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1.
  • Linde, L., et al. (författare)
  • Predictors of DAPSA28 remission in patients with psoriatic arthritis initiating a first TNF inhibitor: results from 13 European registries
  • 2024
  • Ingår i: Rheumatology. - 1462-0324. ; 63:3, s. 751-764
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives In bio-naive patients with PsA initiating a TNF inhibitor (TNFi), we aimed to identify baseline predictors of Disease Activity index for PsA in 28 joints (DAPSA28) remission (primary objective) and DAPSA28 moderate response at 6 months, as well as drug retention at 12 months across 13 European registries. Methods Baseline demographic and clinical characteristics were retrieved and the three outcomes investigated per registry and in pooled data, using logistic regression analyses on multiply imputed data. In the pooled cohort, selected predictors that were either consistently positive or negative across all three outcomes were defined as common predictors. Results In the pooled cohort (n = 13 369), 6-month proportions of remission, moderate response and 12-month drug retention were 25%, 34% and 63% in patients with available data (n = 6954, n = 5275 and n = 13 369, respectively). Five common baseline predictors of remission, moderate response and 12-month drug retention were identified across all three outcomes. The odds ratios (95% CIs) for DAPSA28 remission were: age, per year: 0.97 (0.96-0.98); disease duration, years (<2 years as reference): 2-3 years: 1.20 (0.89-1.60), 4-9 years: 1.42 (1.09-1.84), & GE;10 years: 1.66 (1.26-2.20); men vs women: 1.85 (1.54-2.23); CRP of >10 vs & LE;10 mg/l: 1.52 (1.22-1.89) and 1 mm increase in patient fatigue score: 0.99 (0.98-0.99). Conclusion Baseline predictors of remission, response and adherence to TNFi therapy were identified, of which five were common for all three outcomes, indicating that the predictors emerging from our pooled cohort may be considered generalizable from country level to disease level.
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2.
  • Ørnbjerg, L. M., et al. (författare)
  • Predictors of ASDAS-CRP inactive disease in axial spondyloarthritis during treatment with TNF-inhibitors: Data from the EuroSpA collaboration
  • 2022
  • Ingår i: Seminars in Arthritis and Rheumatism. - : Elsevier BV. - 0049-0172 .- 1532-866X. ; 56
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives: In patients with axial spondyloarthritis (axSpA) initiating their first tumor necrosis factor alpha-inhibitor (TNFi), we aimed to identify common baseline predictors of Ankylosing Spondylitis Disease Activity Score (ASDAS-CRP) inactive disease (primary objective) and clinically important improvement (CII) at 6 months, and drug retention at 12-months across 15 European registries. Methods: Baseline demographic and clinical characteristics were collected. Outcomes were investigated per registry and in pooled data using logistic regression analyses on multiply imputed data. Results: The consistency of baseline predictors in individual registries justified pooling the data. In the pooled dataset (n = 21,196), the 6-month rates for ASDAS inactive disease and ASDAS CII were 26% and 51%, and the 12-month drug retention rate 65% in patients with available data (n = 9,845, n = 6,948 and n = 21,196, respectively). Nine common baseline predictors of ASDAS inactive disease, ASDAS CII and 12-month drug retention were identified, and the odds ratios (95%-confidence interval) for ASDAS inactive disease were: age, per year: 0.97 (0.97–0.98), men vs. women: 1.88 (1.60–2.22), current vs. non-smoking: 0.76 (0.63–0.91), HLA-B27 positive vs. negative: 1.51 (1.20–1.91), TNF start year 2015–2018 vs. 2009–2014: 1.24 (1.06–1.45), CRP>10 vs. ≤10 mg/l: 1.49 (1.25–1.77), one unit increase in health assessment questionnaire (HAQ): 0.77 (0.58–1.03), one-millimeter (mm) increase in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) fatigue and spinal pain: 0.99 (0.99–1.00) and 0.99 (0.99–1.99), respectively Conclusion: Common baseline predictors of treatment response and adherence to TNFi could be identified across data from 15 European registries, indicating that they may be universal across different axSpA populations.
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3.
  • Glintborg, B., et al. (författare)
  • Is the risk of infection higher during treatment with secukinumab than with TNF inhibitors? An observational study from the Nordic countries
  • 2023
  • Ingår i: Rheumatology. - : Oxford University Press (OUP). - 1462-0324 .- 1462-0332. ; 62:2, s. 647-658
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives The positioning of secukinumab in the treatment of axial SpA (axSpA) and PsA is debated, partly due to a limited understanding of the comparative safety of the available treatments. We aimed to assess the risk of the key safety outcome infections during treatment with secukinumab and TNF inhibitors (TNFi). Methods Patients with SpA and PsA starting secukinumab or TNFi year 2015 through 2018 were identified in four Nordic rheumatology registers. The first hospitalized infection during the first year of treatment was identified through linkage to national registers. Incidence rates (IRs) with 95% CIs per 100 patient-years were calculated. Adjusted hazard ratios were estimated through Cox regression, with secukinumab as the reference. Several sensitivity analyses were performed to investigate confounding by indication. Results Among 7708 patients with SpA and 5760 patients with PsA, we identified 16 229 treatment courses of TNFi (53% bionaive) and 1948 with secukinumab (11% bionaive). For secukinumab, the first-year risk of hospitalized infection was 3.5% (IR 5.0; 3.9-6.3), compared with 1.7% (IR 2.3; 1.7-3.0) during 3201 courses with adalimumab, with the IRs for other TNFi lying in between these values. The adjusted HR for adalimumab, compared with secukinumab, was 0.58 (0.39-0.85). In sensitivity analyses, the difference from secukinumab was somewhat attenuated and in some analyses no longer statistically significant. Conclusion When used according to clinical practice in the Nordic countries, the observed first-year absolute risk of hospitalized infection was doubled for secukinumab compared with adalimumab. This excess risk seemed largely explained by confounding by indication.
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4.
  • Hellamand, Pasoon, et al. (författare)
  • Sex Differences in the Effectiveness of First-Line Tumor Necrosis Factor Inhibitors in Psoriatic Arthritis: Results From the European Spondyloarthritis Research Collaboration Network
  • 2024
  • Ingår i: ARTHRITIS & RHEUMATOLOGY. - 2326-5191 .- 2326-5205.
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: Women with psoriatic arthritis (PsA) may have reduced tumor necrosis factor inhibitor (TNFi) effectiveness compared to men. We examined sex differences in treatment response and retention rates during 24 months of follow-up among patients with PsA initiating their first TNFi. Methods: Data from patients with PsA across 13 European Spondyloarthritis Research Collaboration Network registries starting their first TNFi were pooled. Logistic regression was used to analyze the association between sex and treatment response using low disease activity (LDA) according to the Disease Activity Score in 28 joints using the C-reactive protein level (DAS28-CRP) (<3.2) at six months as the primary outcome. Analyses were adjusted for age, country, conventional synthetic disease-modifying antirheumatic drug treatment, and TNFi start year. Retention rates were explored using the Kaplan-Meier estimator. Results: We analyzed the treatment response of 7,679 patients with PsA (50% women) with available data on LDA at six months. At baseline, women and men had similar characteristics, including mean DAS28-CRP (women vs men, 4.4 [SD 1.2] vs 4.2 [SD 1.2]), though patient-reported outcome measures were worse in women. At six months, 64% of women and 78% of men had LDA (relative risk [RR] 0.82; 95% confidence interval [CI] 0.80-0.84). This difference was similar after adjustment (RR 0.83; 95% CI 0.81-0.85). TNFi retention rates were evaluated in 17,842 patients with PsA. Women had significantly lower retention rates than men at all time points (women 79%, 64%, and 50% vs men 88%, 77%, and 64% at 6, 12, and 24 months, respectively). Conclusion: Despite comparable disease characteristics at baseline, women with PsA have reduced treatment response and retention rates to their first TNFi, highlighting the need to consider sex differences in PsA research and management.
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6.
  • Michelsen, Brigitte, et al. (författare)
  • Real-World Six- and Twelve-Month Drug Retention, Remission, and Response Rates of Secukinumab in 2,017 Patients With Psoriatic Arthritis in Thirteen European Countries
  • 2022
  • Ingår i: Arthritis Care and Research. - : Wiley. - 2151-464X .- 2151-4658. ; 74:7, s. 1205-1218
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: There is a lack of real-life studies on interleukin-17 (IL-17) inhibition in psoriatic arthritis (PsA). We assessed real-life 6- and 12-month effectiveness (i.e., retention, remission, low disease activity [LDA], and response rates) of the IL-17 inhibitor secukinumab in PsA patients overall and across 1) number of prior biologic/targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs), 2) years since diagnosis, and 3) European registries. Methods: Thirteen quality registries in rheumatology participating in the European Spondyloarthritis Research Collaboration Network provided longitudinal, observational data collected as part of routine care for secondary use. Data were pooled and analyzed with Kaplan-Meier plots, log rank tests, Cox regression, and multiple linear and logistic regression analyses. Results: A total of 2,017 PsA patients started treatment with secukinumab between 2015 and 2018. Overall secukinumab retention rates were 86% and 76% after 6 and 12 months, respectively. Crude (LUNDEX adjusted) 6-month remission/LDA (LDA including remission) rates for the 28-joint Disease Activity Index for Psoriatic Arthritis, the Disease Activity Score in 28 joints using the C-reactive protein level, and the Simplified Disease Activity Index (SDAI) were 13%/46% (11%/39%), 36%/55% (30%/46%), and 13%/56% (11%/47%), and 12-month rates were 11%/46% (7%/31%), 39%/56% (26%/38%), and 16%/62% (10%/41%), respectively. Clinical Disease Activity Index remission/LDA rates were similar to the SDAI rates. Six-month American College of Rheumatology 20%/50%/70% improvement criteria responses were 34%/19%/11% (29%/16%/9%); 12-month rates were 37%/21%/11% (24%/14%/7%). Secukinumab effectiveness was significantly better for b/tsDMARD-naive patients, similar across time since diagnosis (<2/2–4/>4 years), and varied significantly across the European registries. Conclusion: In this large real-world study on secukinumab treatment in PsA, 6- and 12-month effectiveness was comparable to that in previous observational studies of tumor necrosis factor inhibitors. Retention, remission, LDA, and response rates were significantly better for b/tsDMARD-naive patients, were independent of time since diagnosis, and varied significantly across the European countries.
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7.
  • Roseman, C., et al. (författare)
  • Persistent pain and its predictors after starting anti-tumour necrosis factor therapy in psoriatic arthritis : what is the role of inflammation control?
  • 2024
  • Ingår i: Scandinavian Journal of Rheumatology. - 0300-9742 .- 1502-7732. ; 53:2, s. 94-103
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: While considerable focus has been placed on pain due to inflammation in psoriatic arthritis (PsA), less is reported on pain despite inflammation control. Here, we aimed to investigate the occurrence/predictors of persistent pain, including non-inflammatory components, after starting anti-tumour necrosis factor (anti-TNF) therapy. Method: Bionaïve PsA patients starting a first anti-TNF therapy 2004–2010 were identified (South Swedish Arthritis Treatment Group register; N = 351). Outcomes included unacceptable pain [visual analogue scale (VAS) pain > 40 mm], and unacceptable pain despite inflammation control (refractory pain; VAS pain > 40 mm + C-reactive protein < 10 mg/L + ≤ 1 swollen joint of 28), assessed at 0, 3, 6, and 12 months. Baseline predictors were estimated by logistic regression. Results: Upon starting anti-TNF therapy, 85% of patients reported unacceptable pain, falling to 43% at 3 months and then remaining stable. After 12 months, refractory pain constituted 63% of all unacceptable pain. Higher baseline VAS pain/global, worse physical function and lower health-related quality-of-life were associated with a higher risk of unacceptable/refractory pain at 12 months. More swollen joints and higher evaluator’s global assessment were associated with a lower risk of 12-month refractory pain. Conclusions: A substantial proportion of PsA patients reported unacceptable pain throughout the first anti-TNF treatment year. At 12 months, refractory pain constituted about two-thirds of this remaining pain load. More objective signs of inflammation at anti-TNF initiation were associated with less future refractory pain. This highlights insufficient effect of biologics in patients with inflammation-independent pain, warranting alternative treatments.
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8.
  • Ørnbjerg, Lykke M., et al. (författare)
  • Patient-Reported Outcomes (PROs) and PRO Remission Rates in 12,262 Biologic-Naïve Patients With Psoriatic Arthritis Treated With Tumor Necrosis Factor Inhibitors in Routine Care
  • 2024
  • Ingår i: Journal of Rheumatology. - 0315-162X. ; 51:4, s. 378-389
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective. To evaluate patient-reported outcomes (PROs) after initiation of tumor necrosis factor inhibitor (TNFi) treatment in European real-world patients with psoriatic arthritis (PsA). Further, to investigate PRO remission rates across treatment courses, registries, disease duration, sex, and age at disease onset. Methods. Visual analog scale or numerical rating scale scores for pain, fatigue, patient global assessment (PtGA), and the Health Assessment Questionnaire–Disability Index (HAQ-DI) from 12,262 patients with PsA initiating a TNFi in 13 registries were pooled. PRO remission rates (pain ≤ 1, fatigue ≤ 2, PtGA ≤ 2, and HAQ-DI ≤ 0.5) were calculated for patients still on the treatment. Results. For the first TNFi, median pain score was reduced by approximately 50%, from 6 to 3, 3, and 2; as were fatigue scores, from 6 to 4, 4, and 3; PtGA scores, from 6 to 3, 3, and 2; and HAQ-DI scores, from 0.9 to 0.5, 0.5, and 0.4 at baseline, 6, 12, and 24 months, respectively. Six-month Lund Efficacy Index (LUNDEX)–adjusted remission rates for pain, fatigue, PtGA, and HAQ-DI scores were 24%, 31%, 36%, and 43% (first TNFi); 14%, 19%, 23%, and 29% (second TNFi); and 9%, 14%, 17%, and 20% (third TNFi), respectively. For biologic-naïve patients with disease duration < 5 years, 6-month LUNDEX-adjusted remission rates for pain, fatigue, PtGA, and HAQ-DI scores were 22%, 28%, 33%, and 42%, respectively. Corresponding rates for patients with disease duration > 10 years were 27%, 32%, 41%, and 43%, respectively. Remission rates were 33%, 40%, 45%, and 56% for men and 17%, 23%, 24%, and 32% for women, respectively. For patients aged < 45 years at diagnosis, 6-month LUNDEX-adjusted remission rate for pain was 29% vs 18% for patients ≥ 45 years. Conclusion. In 12,262 biologic-naïve patients with PsA, 6 months of treatment with a TNFi reduced pain by approximately 50%. Marked differences in PRO remission rates across treatment courses, registries, disease duration, sex, and age at onset of disease were observed, emphasizing the potential influence of factors other than disease activity on PROs.
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9.
  • Christiansen, SN, et al. (författare)
  • SECULAR TRENDS IN BASELINE CHARACTERISTICS, TREATMENT RETENTION AND RESPONSE RATES IN 17453 BIONAIVE PSORIATIC ARTHRITIS PATIENTS INITIATING TNFI - RESULTS FROM THE EUROSPA COLLABORATION
  • 2021
  • Ingår i: ANNALS OF THE RHEUMATIC DISEASES. - : BMJ. - 0003-4967 .- 1468-2060. ; 80, s. 131-132
  • Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
    • Knowledge of changes over time in baseline characteristics and tumor necrosis factor inhibitor (TNFi) response in bionaïve psoriatic arthritis (PsA) patients treated in routine care is limited.Objectives:To investigate secular trends in baseline characteristics and retention, remission and response rates in PsA patients initiating a first TNFi.Methods:Prospectively collected data on bionaïve PsA patients starting TNFi in routine care from 15 European countries were pooled. According to year of TNFi initiation, three groups were defined a priori based on bDMARD availability: Group A (1999–2008), Group B (2009–2014) and Group C (2015–2018).Retention rates (Kaplan-Meier), crude and LUNDEX adjusted1 remission (Disease Activity Score (DAS28) <2.6, 28-joint Disease Activity index for PsA (DAPSA28) ≤4, Clinical Disease Activity Index (CDAI) ≤2.8) and ACR50 response rates were assessed at 6, 12 and 24 months. No statistical comparisons were made.Results:A total of 17453 PsA patients were included (4069, 7551 and 5833 in groups A, B and C).Patients in group A were older and had longer disease duration compared to B and C. Retention rates at 6, 12 and 24 months were highest in group A (88%/77%/64%) but differed little between B (83%/69%/55%) and C (84%/70%/56%).Baseline disease activity was higher in group A than in B and C (DAS28: 4.6/4.3/4.0, DAPSA28: 29.9/25.7/24.0, CDAI: 21.8/20.0/18.6), and this persisted at 6 and 12 months. Crude and LUNDEX adjusted remission rates at 6 and 12 months tended to be lowest in group A, although crude/LUNDEX adjusted ACR50 response rates at all time points were highest in group A. At 24 months, disease activity and remission rates were similar in the three groups (Table).Table 1.Secular trends in baseline characteristics, treatment retention, remission and response rates in European PsA patients initiating a 1st TNFiBaseline characteristicsGroup A(1999–2008)Group B(2009–2014)Group C(2015–2018)Age, median (IQR)62 (54–72)58 (49–67)54 (45–62)Male, %514847Years since diagnosis, median (IQR)5 (2–10)3 (1–9)3 (1–8)Smokers, %161717DAS28, median (IQR)4.6 (3.7–5.3)4.3 (3.4–5.1)4.0 (3.2–4.8)DAPSA28, median (IQR)29.9 (19.3–41.8)25.7 (17.2–38.1)24.0 (16.1–35.5)CDAI, median (IQR)21.8 (14.0–31.1)20.0 (13.0–29.0)18.6 (12.7–26.1)TNFi drug, % (Adalimumab / Etanercept / Infliximab / Certolizumab / Golimumab)27 / 43 / 30 / 0 / 036 / 31 / 14 / 5 / 1421 / 40 / 21 / 8 / 10Follow up6 months12 months24 monthsGr AGr BGr CGr AGr BGr CGr AGr BGr CRetention rates, % (95% CI)88 (87–89)83 (82–84)84 (83–85)79 (78–80)72 (71–73)72 (71–73)68 (67–69)60 (59–61)60 (59–62)DAS28, median (IQR)2.7 (1.9–3.6)2.4 (1.7–3.4)2.3 (1.7–3.2)2.5 (1.8–3.4)2.2 (1.6–3.1)2.1 (1.6–2.9)2.1 (1.6–3.1)2.0 (1.6–2.9)1.9 (1.5–2.6)DAPSA28, median (IQR)10.6 (4.8–20.0)9.5 (3.9–18.3)8.7 (3.6–15.9)9.1 (4.1–17.8)7.7 (3.1–15.4)7.6 (2.9–14.4)6.7 (2.7–13.7)6.6 (2.7–13.5)5.9 (2.4–11.8)CDAI, median (IQR)7.8 (3.0–15.2)8.0 (3.0–15.0)6.4 (2.6–12.2)6.4 (2.5–13.0)6.2 (2.5–12.1)5.8 (2.2–11.4)5.0 (2.0–11.0)5.5 (2.0–11.2)5.0 (2.0–9.0)DAS28 remission, %, c/L47 / 4255 / 4661 / 5153 / 4362 / 4566 / 4864 / 4268 / 3775 / 41DAPSA28 remission, %, c/L22 / 1926 / 2228 / 2325 / 2031 / 2232 / 2336 / 2334 / 1938 / 21CDAI remission, %, c/L23 / 2123 / 1926 / 2227 / 2127 / 2029 / 2134 / 2231 / 1735 / 19ACR50 response, %, c/L26 / 2322 / 1824 / 2027 / 2223 / 1721 / 1523 / 1518 / 1014 / 8Gr, Group; c/L, crude/LUNDEX.Conclusion:Over the past 20 years, patient age, disease duration and disease activity level at the start of the first TNFi in PsA patients have decreased. Furthermore, TNFi retention rates have decreased while remission rates have increased, especially remission rates within the first year of treatment. These findings may reflect a greater awareness of early diagnosis in PsA patients, a lowered threshold for initiating TNFi and the possibility for earlier switching in patients with inadequate treatment response.References:[1]Arthritis Rheum 2006; 54: 600-6.Acknowledgements:Novartis Pharma AG and IQVIA for supporting the EuroSpA Research Collaboration Network.Disclosure of Interests:Sara Nysom Christiansen Speakers bureau: BMS and GE, Grant/research support from: Novartis, Lykke Midtbøll Ørnbjerg Grant/research support from: Novartis, Simon Horskjær Rasmussen: None declared, Anne Gitte Loft Speakers bureau: AbbVie, Janssen, Lilly, MSD, Novartis, Pfizer, UCB, Consultant of: AbbVie, Janssen, Lilly, MSD, Novartis, Pfizer, UCB, Grant/research support from: Novartis, Johan K Wallman Consultant of: Celgene, Eli Lilly, Novartis, Florenzo Iannone Speakers bureau: Abbvie, MSD, Novartis, Pfizer and BMS, Brigitte Michelsen Consultant of: Novartis, Grant/research support from: Novartis, Michael J. Nissen Speakers bureau: Novartis, Eli Lilly, Celgene, and Pfizer, Consultant of: Novartis, Eli Lilly, Celgene, and Pfizer, Jakub Zavada: None declared, Maria Jose Santos Speakers bureau: AbbVie, Novartis, Pfizer, Manuel Pombo-Suarez: None declared, Kari Eklund: None declared, Matija Tomsic Speakers bureau: Abbvie, Amgen, Biogen, Medis, MSD, Novartis, Pfizer, Consultant of: Abbvie, Amgen, Biogen, Medis, MSD, Novartis, Pfizer, Björn Gudbjornsson Speakers bureau: Amgen and Novartis, İsmail Sari: None declared, Catalin Codreanu Speakers bureau: AbbVie, Amgen, Egis, Novartis, Pfizer, UCB, Grant/research support from: AbbVie, Amgen, Egis, Novartis, Pfizer, UCB, Daniela Di Giuseppe: None declared, Bente Glintborg Grant/research support from: Pfizer, Biogen, AbbVie, Marco Sebastiani: None declared, Karen Minde Fagerli: None declared, Burkhard Moeller: None declared, Karel Pavelka Speakers bureau: AbbVie, Roche, MSD, UCB, Pfizer, Novartis, Egis, Gilead, Eli Lilly, Consultant of: AbbVie, Roche, MSD, UCB, Pfizer, Novartis, Egis, Gilead, Eli Lilly, Anabela Barcelos: None declared, Carlos Sánchez-Piedra: None declared, Heikki Relas: None declared, Ziga Rotar Speakers bureau: Abbvie, Amgen, Biogen, Medis, MSD, Novartis, Pfizer, Consultant of: Abbvie, Amgen, Biogen, Medis, MSD, Novartis, Pfizer, Thorvardur Love: None declared, Servet Akar: None declared, Ruxandra Ionescu Speakers bureau: Abbvie, Amgen, Boehringer-Ingelheim Eli-Lilly,Novartis, Pfizer, Sandoz, UCB, Gary Macfarlane Grant/research support from: GlaxoSmithKline, Marleen G.H. van de Sande: None declared, Merete L. Hetland Speakers bureau: Abbvie, Biogen, BMS, Celltrion, Eli Lilly, Janssen Biologics B.V, Lundbeck Fonden, MSD, Pfizer, Roche, Samsung Biopies, Sandoz, Novartis., Mikkel Østergaard Speakers bureau: AbbVie, BMS, Boehringer-Ingelheim, Celgene, Eli-Lilly, Centocor, GSK, Hospira, Janssen, Merck, Mundipharma, Novartis, Novo, Orion, Pfizer, Regeneron, Schering-Plough, Roche, Takeda, UCB and Wyeth, Consultant of: AbbVie, BMS, Boehringer-Ingelheim, Celgene, Eli-Lilly, Centocor, GSK, Hospira, Janssen, Merck, Mundipharma, Novartis, Novo, Orion, Pfizer, Regeneron, Schering-Plough, Roche, Takeda, UCB and Wyeth
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10.
  • Exarchou, S., et al. (författare)
  • MORTALITY IN PATIENTS WITH PSORIATIC ARTHRITIS IN SWEDEN
  • 2021
  • Ingår i: Annals of the Rheumatic Diseases. - : BMJ Publishing Group Ltd. - 0003-4967 .- 1468-2060. ; 80, s. 130-131
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
    • In contrast to the increased mortality reported in other inflammatory diseases such as rheumatoid arthritis and psoriasis, prior mortality studies in psoriatic arthritis (PsA) have shown inconsistent results.Objectives:To compare all-cause mortality between PsA patients in Sweden and matched general population controls, and to describe cause of death distributions in the two groups.Methods:All individuals in Sweden with ≥1 main diagnosis of PsA (ICD-10: L40.5/M07.0-M07.3) from outpatient visits to rheumatology or internal medicine clinics at age ≥18 years (y) 2001-2017 were identified from the Swedish National Patient Register. Each case was matched to 5 general population controls based on sex, county and age in the year of the first registered arthritis diagnosis for the case. Cases and controls were followed from 1 Jan, 2007, or from first PsA diagnosis thereafter for index cases, until first occurrence of death (data from the Swedish Cause of Death Register), emigration or 31 Dec, 2018. Mortality was assessed overall, as well as stratified by sex (45% males) and disease duration (PsA diagnosis prior to 2007 [38% of cases] vs. 2007-2017), using matched Cox proportional hazard regression, or – in case the Cox assumption regarding proportionality did not hold – matched Breslow test. To account for potential PsA misclassification (in a previous validation study, 86% of 400 cases fulfilled PsA classification criteria), a sensitivity analysis was performed by randomly replacing 20% of cases with one of their own controls. Moreover, incidence rate ratios (IRR) of death were calculated overall and stratified by sex, disease duration and age. Finally, causes of death (from the Cause of Death Register) were described for PsA cases and controls.Results:Over the 12y follow-up, 3 121 deaths occurred among 33 036 PsA cases (268 402 person-years at risk) and 12 884 deaths among 161 144 controls (1 302 250 person-years), resulting in an increased mortality among the PsA cases (HR 1.11 [95%CI 1.07-1.16], p<0.001, Figure and Table; sensitivity analysis HR 1.09 [1.05-1.14]). The increased mortality was seen mainly among female PsA cases and among cases with longer disease duration (Figure; Table). IRR:s of death were significantly increased for all ages except <40y, with the numerically highest point-estimates for ages 40-49y and 50-59y (Table). Cause of death frequencies among the PsA cases/controls: cardiovascular disease 29/27%; diabetes mellitus 2.1/2.5%; chronic kidney disease 0.4/0.3%; infection 5.7/4.5%; chronic pulmonary disease 5.1/4.1%; malignancy 29/34%; suicide 2.3/2.0%; other 27/26%.Table 1.Mortality rates and incidence rate ratiosPsA casesPopulation controlsNumber of deathsPerson-yearsat riskMortality rate*Number of deathsPerson-yearsat riskMortality rate*Incidence rate ratio (95%CI)Overall3 121268 40211.612 8841 302 2509.91.18 (1.13-1.22)Males1 459120 51712.16 468580 28511.11.09 (1.03-1.15)Females1 662147 88611.26 416721 9668.91.27 (1.20-1.34)Longer disease duration1 943139 37913.97 459670 17411.11.25 (1.19-1.32)Shorter disease duration1 178129 0239.15 425632 0778.61.06 (1.00-1.13)Age intervals (years)<401833 5680.598163 2780.60.89 (0.54-1.48)40-499050 5521.8322246 9551.31.37 (1.08-1.73)50-5928065 8204.31 131321 7303.51.21 (1.06-1.38)60-6972370 22410.33 132341 5879.21.12 (1.04-1.22)70-7996037 23225.84 160178 90923.31.11 (1.03-1.19)≥801 05011 00795.44 04149 79181.21.18 (1.10-1.26)* Per 1000 person-years.Conclusion:In this nationwide 12y assessment, the mortality risk among PsA patients in Sweden was increased by around 10% as compared to the general population, mainly driven by increased risks among females and patients with longer disease duration. Cause of death distributions were numerically similar between PsA cases and controls.References:Disclosure of Interests:Sofia Exarchou Consultant of: AbbVie, Novartis, Daniela Di Giuseppe: None declared, Gerd-Marie Alenius: None declared, Eva Klingberg Speakers bureau: Eli Lilly, Consultant of: Novartis, Grant/research support from: Roche, Valgerdur Sigurdardottir Consultant of: Novartis, Sanofi, Sara Wedrén: None declared, Ulf Lindström: None declared, Carl Turesson Speakers bureau: AbbVie, BMS, Pfizer, Roche, Consultant of: Roche, Grant/research support from: BMS, Lennart T.H. Jacobsson Consultant of: AbbVie, Eli Lilly, Janssen, Novartis, Pfizer, Johan Askling Grant/research support from: For ARTIS: AbbVie, BMS, Eli Lilly, Merck, Pfizer, Roche, Samsung Bioepis, Sanofi, UCB. This study was supported by AbbVie, Amgen, Eli Lilly, Novartis and Pfizer. The sponsors were allowed to comment on the study protocol and were provided with a report of the results, but had no influence on the study design or decision to submit the abstract., Johan K Wallman Consultant of: Celgene, Eli Lilly, Novartis
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12.
  • Glintborg, B., et al. (författare)
  • One-Year Treatment Outcomes of Secukinumab Versus Tumor Necrosis Factor Inhibitors in Spondyloarthritis: Results From Five Nordic Biologic Registries Including More Than 10,000 Treatment Courses
  • 2022
  • Ingår i: Arthritis Care & Research. - : Wiley. - 2151-464X .- 2151-4658. ; 74:5, s. 748-758
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective To describe baseline characteristics and to compare treatment effectiveness of secukinumab versus tumor necrosis factor inhibitors (TNFi) in patients with spondyloarthritis (SpA) using adalimumab as the main comparator. Methods This was an observational, prospective cohort study. Patients with SpA (clinical ankylosing spondylitis, nonradiographic axial SpA, or undifferentiated SpA) starting secukinumab or a TNFi during 2015-2018 were identified from 5 Nordic clinical rheumatology registries. Data on comorbidities and extraarticular manifestations (psoriasis, uveitis, and inflammatory bowel disease) were captured from national registries (data available in 94% of patients) and included in multivariable analyses. We assessed 1-year treatment retention (crude survival curves, adjusted hazard ratios [HRadj] for treatment discontinuation) and 6-month response rates (Ankylosing Spondylitis Disease Activity Score [ASDAS] score <2.1, Bath Ankylosing Spondylitis Disease Activity Index [BASDAI] <40 mm, crude/LUNDEX-adjusted, adjusted logistic regression analyses with odds ratios [ORs]) stratified by line of biologic treatment (first, second, and third plus). Results In total, 10,853 treatment courses (842 secukinumab and 10,011 TNFi, of which 1,977 were adalimumab) were included. The proportions of patients treated with secukinumab during the first, second, and third-plus lines of treatment were 1%, 6%, and 22%, respectively). Extraarticular manifestations varied across treatments, while other baseline characteristics were largely similar. Secukinumab had a 1-year retention comparable to adalimumab as a first or second line of treatment but poorer as a third-plus line of therapy (secukinumab 56% [95% confidence interval (95% CI) 51-61%] versus adalimumab 70% [95% CI 64-75%]; HRadj 1.43 [95% CI 1.12-1.81]). Across treatment lines, secukinumab had poorer estimates for 6-month response rates than adalimumab, statistically significantly only for the third-plus line (adjusted analyses: ASDAS score <2.1 OR 0.56 [95% CI 0.35-0.90]; BASDAI <40 mm OR 0.62 [95% CI 0.41-0.95]). Treatment outcomes varied across the 5 TNFi. Conclusion Secukinumab was mainly used in biologics-experienced patients with SpA. Secukinumab and adalimumab performed similarly in patients who had failed a first biologic, although with increasing prior biologic exposure, adalimumab was superior.
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13.
  • Glintborg, B., et al. (författare)
  • Uptake and effectiveness of newer biologic and targeted synthetic disease-modifying antirheumatic drugs in psoriatic arthritis: results from five Nordic biologics registries
  • 2023
  • Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 82:6, s. 820-828
  • Tidskriftsartikel (refereegranskat)abstract
    • BackgroundWe aimed to describe the uptake of newer biologic or targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs) in psoriatic arthritis (PsA) in the Nordic countries and to compare their retention and effectiveness. MethodsPatients with PsA starting a b/tsDMARD in 2012-2020 in five Nordic rheumatology registers were included. Uptake and patient characteristics were described, with comorbidities identified from linkages to national patient registries. One-year retention and 6-month effectiveness (proportions achieving low disease activity (LDA) on the Disease Activity Index for PSoriatic Arthritis based on 28-joint evaluation) for the newer b/tsDMARDs (abatacept/apremilast/ixekizumab/secukinumab/tofacitinib/ustekinumab) were compared with adalimumab through adjusted regression models stratified by treatment course (first, second/third, and fourth or more). ResultsIn total, 5659 treatment courses with adalimumab (56% biologic-naive) and 4767 courses with a newer b/tsDMARD (21% biologic-naive) were included. The uptake of newer b/tsDMARDs increased from 2014 and plateaued in 2018. Patient characteristics appeared similar across treatments at treatment start. Adalimumab was more often used as the first course and newer b/tsDMARDs more often in biologic-experienced patients. Used as a second/third b/tsDMARD, the retention rate and the proportion achieving LDA were significantly better for adalimumab (rate 65%, proportion 59%) compared with abatacept (45%, 37%), apremilast (43%, 35%), ixekizumab (LDA only, 40%) and ustekinumab (LDA only, 40%), but not significantly different from other b/tsDMARDs. ConclusionUptake of newer b/tsDMARDs occurred mainly in biologic-experienced patients. Regardless of mode of action, only a minority of patients starting a second or later b/tsDMARD course remained on drug and achieved LDA. Superior outcomes for adalimumab indicate that the positioning of newer b/tsDMARDs in the PsA treatment algorithm remains to be established.
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14.
  • Hansen, R. L., et al. (författare)
  • Inflammatory hallmarks of lesser prominence in psoriatic arthritis patients starting biologics: a Nordic population-based cohort study
  • 2021
  • Ingår i: Rheumatology. - : Oxford University Press (OUP). - 1462-0324 .- 1462-0332. ; 60:1, s. 140-146
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives. To assess secular trends in baseline characteristics of PsA patients initiating their first or subsequent biologic DMARD (bDMARD) therapy and to explore prescription patterns and treatment rates of bDMARDs from 2006 to 2017 in the Nordic countries. Methods. PsA patients registered in the Nordic rheumatology registries initiating any treatment with bDMARDs were identified. The bDMARDs were grouped as original TNF inhibitor [TNFi; adalimumab (ADA), etanercept (ETN) and infliximab (IFX)]; certolizumab pegol (CZP) and golimumab (GOL); biosimilars and ustekinumab, based on the date of release. Baseline characteristics were compared for the five countries, supplemented by secular trends with R-2 calculations and point prevalence of bDMARD treatment. Results. A total of 18 089 patients were identified (Denmark, 4361; Iceland, 449; Norway, 1948; Finland, 1069; Sweden, 10 262). A total of 54% of the patients were female, 34.3% of patients initiated an original TNFi, 8% CZP and GOL, 7.5% biosimilars and 0.3% ustekinumab as a first-line bDMARD. Subsequent bDMARDs were 25.2% original TNFi, 9% CZP and GOL, 12% biosimilars and 2.1% ustekinumab. From 2015 through 2017 there was a rapid uptake of biosimilars. The total of first-line bDMARD initiators with lower disease activity increased from 2006 to 2017, where an R2 close to 1 showed a strong association. Conclusion. Across the Nordic countries, the number of prescribed bDMARDs increased from 2006 to 2017, indicating a previously unmet need for bDMARDs in the PsA population. In recent years, PsA patients have initiated bDMARDs with lower disease activity compared with previous years, suggesting that bDMARDs are initiated in patients with a less active inflammatory phenotype.
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15.
  • Hill, Y.R., et al. (författare)
  • Investigating a novel activation-repolarisation time metric to predict localised Vulnerability to reentry using computational modelling
  • 2016
  • Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203 .- 1932-6203. ; 11:3
  • Tidskriftsartikel (refereegranskat)abstract
    • © 2016 Hill et al. Exit sites associated with scar-related reentrant arrhythmias represent important targets for catheter ablation therapy. However, their accurate location in a safe and robust manner remains a significant clinical challenge. We recently proposed a novel quantitative metric (termed the Reentry Vulnerability Index, RVI) to determine the difference between activation and repolarisation intervals measured from pairs of spatial locations during premature stimulation to accurately locate the critical site of reentry formation. In the clinic, the method showed potential to identify regions of low RVI corresponding to areas vulnerable to reentry, subsequently identified as ventricular tachycardia (VT) circuit exit sites. Here, we perform an in silico investigation of the RVI metric in order to aid the acquisition and interpretation of RVI maps and optimise its future usage within the clinic. Within idealised 2D sheet models we show that the RVI produces lower values under correspondingly more arrhythmogenic conditions, with even low resolution (8 mm electrode separation) recordings still able to locate vulnerable regions. When applied to models of infarct scars, the surface RVI maps successfully identified exit sites of the reentrant circuit, even in scenarios where the scar was wholly intramural. Within highly complex infarct scar anatomies with multiple reentrant pathways, the identified exit sites were dependent upon the specific pacing location used to compute the endocardial RVI maps. However, simulated ablation of these sites successfully prevented the reentry re-initiation. We conclude that endocardial surface RVI maps are able to successfully locate regions vulnerable to reentry corresponding to critical exit sites during sustained scar-related VT. The method is robust against highly complex and intramural scar anatomies and low resolution clinical data acquisition. Optimal location of all relevant sites requires RVI maps to be computed from multiple pacing locations. Copyright:
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18.
  • Lindström, Ulf, et al. (författare)
  • Comparison of treatment retention and response to secukinumab versus tumour necrosis factor inhibitors in psoriatic arthritis
  • 2021
  • Ingår i: Rheumatology. - : Oxford University Press (OUP). - 1462-0324 .- 1462-0332. ; 60:8, s. 3635-3645
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives. To compare treatment retention and response to secukinumab vs adalimumab, including the other four TNF inhibitors (TNFi) as comparators, in PsA. Methods. All patients with PsA starting secukinumab or a TNFi in 2015-2018 were identified in the biologic registers of the Nordic countries. Data on comorbidities were linked from national registers. One-year treatment retention and hazard ratios (HRs) for treatment discontinuation were calculated. The proportion achieving a 6 month 28-joint Disease Activity Index for Psoriatic Arthritis (DAPSA28) remission was determined together with odds ratios (ORs) for remission (logistic regression). Both HRs and ORs were calculated with adalimumab as the reference and adjusted for baseline characteristics and concurrent comorbidities. All analyses were stratified by the line of biologic treatment (first, second, third+). Results. We identified 6143 patients contributing 8307 treatment courses (secukinumab, 1227; adalimumab, 1367). Secukinumab was rarely used as the first biologic, otherwise baseline characteristics were similar. No clinically significant differences in treatment retention or response rates were observed for secukinumab vs adalimumab. The adjusted HRs for discontinuation per the first, second and third line of treatment were 0.98 (95% CI 0.68, 1.41), 0.94 (0.70, 1.26) and 1.07 (0.84, 1.36), respectively. The ORs for DAPSA28 remission in the first, second and third line of treatment were 0.62 (95% CI 0.30, 1.28), 0.85 (0.41, 1.78) and 0.74 (0.36, 1.51), respectively. In the subset of patients previously failing a TNFi due to ineffectiveness, the results were similar. Conclusion. No significant differences in treatment retention or response were observed between secukinumab and adalimumab, regardless of the line of treatment. This suggests that even in patients who have failed a TNFi, choosing either another TNFi or secukinumab may be equally effective.
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23.
  • Wallman, J. K., et al. (författare)
  • High degree of classification criteria fulfillment among patients with clinical psoriatic arthritis diagnoses in Sweden
  • 2020
  • Ingår i: Annals of the Rheumatic Diseases. - : BMJ Publishing Group Ltd. - 0003-4967 .- 1468-2060. ; 79, s. 1725-1726
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
    • The clinical diagnosis of psoriatic arthritis (PsA) may be challenging. In Sweden, the vast majority of PsA cases are diagnosed within rheumatology or internal medicine (IM). Knowledge of the correspondence between clinical ICD diagnoses and classification criteria fulfillment is crucial to interpret studies identifying cases based on ICD codes.Objectives:To assess the degree to which patients with clinical PsA diagnoses in Sweden fulfill established PsA classification criteria.Methods:Four hundred patients with ≥1 outpatient physician visit to one of five rheumatology or IM departments (3 university/2 county departments, spread across Sweden) 2013-2015 with a main ICD-10 diagnosis of PsA (L40.5/M07.0-M07.3), were randomly selected from the Swedish National Patient Register (80 cases/site). Based on a structured medical record review, positive predictive values (PPV) of a clinical PsA diagnosis (i.e. ≥1 visit with a PsA ICD-10 code) for fulfillment of the following classification criteria were assessed: CASPAR,[1] Moll & Wright,[2] Vasey & Espinoza,[3] and Modified ESSG criteria for PsA,[4] respectively (as well as for any of these); ASAS criteria for peripheral or axial spondyloarthritis (SpA) [5]; and the 1987 ACR criteria for rheumatoid arthritis (RA).[6] Subanalyses regarding CASPAR fulfillment were also performed restricted to patients with available rheumatoid factor and peripheral X-ray status (central CASPAR items; n=227), and among patients with ≥2 ICD codes for PsA, of which ≥1 from a rheumatology/IM department (n=353).Results:Out of 400 clinically diagnosed PsA patients, 343 (86%) fulfilled any of the 4 PsA classification criteria, with a PPV for CASPAR fulfillment of 69% (rising to 73-82% in the subanalyses;Figure 1). Substantial overlap was seen regarding fulfillment of the 4 PsA criteria (Figure 2A). Moreover, 86% fulfilled the ASAS peripheral or axial SpA criteria, while the 1987 ACR definition of RA was met by 27% – in both cases with the great majority also classifiable as PsA (Figure 2B). Most patients not fulfilling any PsA criteria had either no verified arthritis or polyarticular disease (Table). Overall, only 6.5% of the clinical PsA diagnoses were judged as clearly wrong by the rheumatologists performing the medical record assessments.Conclusion:The validity of clinical ICD-10 diagnoses for PsA in the Swedish National Patient Register is good, with a PPV of 86% for the fulfillment of established PsA classification criteria.References:[1]Arthritis Rheum2006;54:2665-73[2]Semin Arthritis Rheum 1973;3:55-78[3]In: Calin A, editor. Spondyloarthropathies. Orlando: Grune & Stratton; 1984:151-85[4]Ann Rheum Dis2005;64(Suppl II):ii3–ii8[5]Ann Rheum Dis2011;70:25-31[6]Arthritis Rheum1988;31:315-24Patient characteristics (n=400), stratified by classification criteria fulfillmentFulfilling anyPsA criterian=343Not fulfilling anyPsA criterian=57Male sex, %4644Age, yrs; mean (SD)59 (14)62 (15)Symptom duration, yrs; mean (SD)18 (12)16 (13)Psoriasis, %8947Nail psoriasis, %3811Arthritis, %9358 Monoarthritis, %*7.90 Oligoarthritis, %*4522 Polyarthritis, %*4778DIP-joint arthritis, %287.0Dactylitis, %281.8Enthesitis, %4219Inflammatory back pain, %275.3RF positive, %5.814ACPA positive, %4.43.5Arthritic X-ray changes in hands/feet, %3321* % of patients with arthritis of known distribution. Missing data: 0-4%, except forRF (33%), ACPA (37%) and X-ray changes (20%).Acknowledgments:This work was supported by Celgene, Novartis, Pfizer, Reumatikerförbundet and Psoriasisförbundet.Disclosure of Interests:Johan K Wallman Consultant of: AbbVie, Celgene, Eli Lilly, Novartis and UCB Pharma, Gerd-Marie Alenius: None declared, Eva Klingberg Grant/research support from: Roche, Consultant of: Novartis, Speakers bureau: Eli Lilly, Valgerdur Sigurdardottir Consultant of: Novartis, Sara Wedrén: None declared, Sofia Exarchou: None declared, Ulf Lindström: None declared, Daniela Di Giuseppe: None declared, Johan Askling Grant/research support from: JA acts or has acted as PI for agreements between Karolinska Institutet and the following entities, mainly in the context of the ARTIS national safety monitoring programme of immunomodulators in rheumatology: Abbvie, BMS, Eli Lilly, Merck, MSD, Pfizer, Roche, Samsung Bioepis, Sanofi, and UCB Pharma, Lennart T.H. Jacobsson Consultant of: AbbVie, Eli Lilly, Janssen, Novartis and Pfizer
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24.
  • Wallman, J. K., et al. (författare)
  • Validity of clinical psoriatic arthritis diagnoses made by rheumatologists in the Swedish National Patient Register
  • 2023
  • Ingår i: Scandinavian Journal of Rheumatology. - : Informa UK Limited. - 0300-9742 .- 1502-7732. ; 52:4, s. 374-384
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives : Knowledge of the correspondence between clinical ICD diagnoses and classification criteria fulfilment is crucial to interpret studies identifying cases via ICD codes. We assessed the degree to which patients registered with ICD-10 diagnoses of psoriatic arthritis (PsA) in the Swedish National Patient Register (NPR) fulfil established PsA classification criteria. Method Four hundred patients with at least one outpatient visit to one of five rheumatology or internal medicine departments (three university/two county departments across Sweden) in 2013-2015, with a main ICD-10 diagnosis of PsA (L40.5-M07.3), were randomly selected (80 cases/site). Through a structured medical record review, positive predictive values (PPVs) for fulfilment of the following classification criteria were assessed: CASPAR, Moll and Wright, Vasey and Espinoza, and modified ESSG criteria for PsA. A subset analysis regarding CASPAR fulfilment was also performed among cases with available rheumatoid factor and peripheral X-ray status (central CASPAR items; n = 227). Results Of the 400 patients with a main ICD-10 diagnosis of PsA, 343 (86%) fulfilled at least one of the four PsA classification criteria. PPVs for the different criteria were: CASPAR 69% (82% in the subset analysis), Moll and Wright 51%, Vasey and Espinoza 76%, and modified ESSG 64%. Overall, only 6.5% of the 400 PsA diagnoses were judged as clearly incorrect by the medical record reviewers. Conclusion The validity of rheumatologist-made, clinical ICD-10 diagnoses for PsA in the Swedish NPR is good, with PPVs of 69-82% for CASPAR fulfilment and 86% for meeting any established PsA classification criteria.
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26.
  • Coates, Laura C., et al. (författare)
  • Secukinumab efficacy on resolution of enthesitis in psoriatic arthritis : pooled analysis of two phase 3 studies
  • 2019
  • Ingår i: Arthritis Research & Therapy. - : Springer Science and Business Media LLC. - 1478-6354 .- 1478-6362. ; 21:1
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Enthesitis is one of the psoriatic arthritis (PsA) domains. Patients with enthesitis are associated with worse outcomes than those without enthesitis. The effect of secukinumab on the resolution of enthesitis in patients with PsA was explored using pooled data from the FUTURE 2 and 3 studies. METHOD: Assessments of enthesitis through week 104 used the Leeds Enthesitis Index. These post hoc analyses included resolution of enthesitis count (EC = 0), median time to first resolution of enthesitis (Kaplan-Meϊer estimate), and shift analysis (as observed) of baseline EC (1, 2, or 3-6) to full resolution (FR), stable (similar or reduction of EC), or worse (EC > baseline). Efficacy outcomes (ACR, PASI, HAQ-DI, SF-36 PCS, and DAS28-CRP) were assessed in patients with or without baseline enthesitis. Results are reported for secukinumab 300 and 150 mg in the overall population and by prior TNFi treatment. RESULTS: A total of 65% (466/712) of patients had baseline enthesitis. In the overall population, FR was achieved as early as week 16 in 65% (300 mg) and 56% (150 mg) versus 44% (placebo) patients, with further improvements to 91% (300 mg) and 88% (150 mg) at week 104. The majority (89%) of patients without enthesitis at baseline maintained this status at week 104. Median days to resolution of EC were shorter with secukinumab 300 and 150 mg versus placebo (57 and 85 vs 167 days, respectively). In patients with EC of 1 or 2, shift analysis from baseline to week 24 showed that more patients achieved FR with secukinumab 300 mg and 150 mg versus placebo, whereas no difference between secukinumab and placebo was shown in the more severe patients with EC of 3-6. Increases in proportions of patients with FR were observed with secukinumab irrespective of the severity of EC from baseline to week 104. Improvements in efficacy outcomes were similar in patients with or without enthesitis treated with secukinumab 300 mg. CONCLUSION: Secukinumab provided early and sustained resolution of enthesitis in patients with PsA over 2 years. Secukinumab 300 mg provided higher resolution than 150 mg in patients with more severe baseline EC and showed similar overall efficacy in patients with or without enthesitis. TRIAL REGISTRATION: FUTURE 2: ClinicalTrials.gov, NCT01752634 (date of study registration: December 19, 2012), and EudraCT, 2012-004439-22 (date of study registration: December 12, 2012) FUTURE 3: ClinicalTrials.gov, NCT01989468 (date of study registration: November 21, 2013), and EudraCT, 2013-004002-25 (date of study registration: December 17, 2013).
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28.
  • Di Giuseppe, D, et al. (författare)
  • COVERAGE OF THE SWEDISH RHEUMATOLOGY QUALITY REGISTER: TO WHAT DEGREE ARE B/TSDMARD TREATMENTS FOR PSORIATIC ARTHRITIS RECORDED?
  • 2022
  • Ingår i: ANNALS OF THE RHEUMATIC DISEASES. - : BMJ. - 0003-4967 .- 1468-2060. ; 81, s. 858-858
  • Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
    • In a national context, the Swedish Rheumatology Quality register (SRQ) is a major source of information on clinical data for patients treated with biological and targeted synthetic disease-modifying anti-rheumatic drug (b/tsDMARD) for rheumatic diseases. Data from SRQ are fundamental for research on drug effectiveness and safety.ObjectivesTo understand to what degree patients with psoriatic arthritis (PsA) and their dispensed b/tsDMARD treatments are recorded in the SRQ.MethodsWe identified all dispensed oral or subcutaneously administered b/tsDMARDs, approved for use in PsA, from the Swedish Prescribed Drug register (PDR, with 100% coverage) in 2018-2019. We required the patients who received the dispensation to have at least one ICD code for PsA (L405, M070, M071, M072, M073) as main diagnosis from a visit to a rheumatology or internal medicine (IM) unit in the National Patient Register (NPR) before dispensation, but no main diagnosis of rheumatoid arthritis (ICD code: M05, M06 (excluding M06.1 and M06.4), M12.3). Furthermore, to limit the assessment to patients with contemporary contact with the specialized rheumatology care, we also required at least one visit with a PsA main diagnosis from rheumatology/IM during 2017-2019. We then checked if the patients and their treatments were registered in SRQ. In a sensitivity analysis, we excluded patients with a visit in dermatology within 6 weeks prior to the first prescription of each b/tsDMARD, in order to exclude patients being prescribed the drug for cutaneous psoriasis.ResultsIn 2018-2019, a total of 7922 unique b/tsDMARD prescriptions had been dispensed to 6311 patients with PsA, having contemporary contact with the specialized rheumatology care. Of them, 5687 patients were registered in SRQ (90.1%), of which 94.4% with a PsA diagnosis and 95.5% with at least one registration of a b/tsDMARD. The coverage of the single drugs in SRQ, as compared to dispensations in PDR, ranged between 53.5% to 93.3% (69.3% to 95.8% considering only patients also in SRQ), with the tumor necrosis factor inhibitors (TNFi) having the best coverage (79.4-93.3%) (Table 1). In a sensitivity analysis, among the 5290 patients without a main diagnosis of psoriasis before start of treatment, 4919 (93%) were registered in SRQ, of which 94% with a PsA diagnosis and 96% with at least one registration of a b/tsDMARD.Table 1.coverage of the single b/tsDMARD approved for use in PsA patients in the SRQ as compared to the prescribed drug register, 2018-2019ATCDrug*Total patients in PDRPatients with the same drug in SRQPercentagePercentage only considering patients included in SRQL04AB01Etanercept2753234885.3%92.5%L04AB04Adalimumab2436193379.4%88.8%L04AB05Certolizumab pegol24321387.7%89.9%L04AB06Golimumab41839093.3%95.8%L04AA24Abatacept947377.7%83.9%L04AA32Apremilast54729453.7%69.3%L04AC10Secukinumab83365678.8%84.8%L04AC13Ixekizumab1187160.2%74%L04AC05Ustekinumab21913863%76.2%L04AA29Tofacitinib26119474.3%77%* In Sweden intravenously administered drugs are not prescribed and therefore not included in the PDR. Also, some hospitals administer ustekinumab in hospital, due to its high cost. However, all b/tsDMARDs, irrespectively of administration route, can be registered in SRQ.ConclusionThe coverage of b/tsDMARD-treated PsA patients in SRQ as compared to the PDR in Sweden is ranging between 90 and 93%, and SRQ is performing well in the registration of the single drugs, especially for TNFi. These results suggest that research studies based on data from the SRQ are representative of the Swedish b/tsDMARD-treated PsA population.Disclosure of InterestsDaniela Di Giuseppe: None declared, Ulf Lindström: None declared, Johan K Wallman Consultant of: AbbVie, Amgen, Celgene, Eli Lilly, Novartis, Grant/research support from: AbbVie, Amgen, Eli Lilly, Novartis, Pfizer, Lotta Ljung: None declared, Johan Askling Grant/research support from: Abbvie, Astra-Zeneca, BMS, Eli Lilly, MSD, Pfizer, Roche, Samsung Bioepis, Sanofi, and UCB
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29.
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30.
  • Exarchou, Sofia, et al. (författare)
  • The National Prevalence of Clinically Diagnosed Psoriatic Arthritis in Sweden in 2017
  • 2023
  • Ingår i: Journal of Rheumatology. - : The Journal of Rheumatology. - 0315-162X .- 1499-2752. ; 50:6, s. 781-788
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective. Psoriatic arthritis (PsA) prevalence estimates vary across studies; studies based on national data are few. We aimed to estimate the prevalence of clinically diagnosed PsA in Sweden in 2017, overall and stratified by sex, age, education, and geography, and to quantify disease-modifying antirheumatic drug (DMARD) use among those in contact with specialized rheumatology care between 2015 and 2017.Methods. Individuals who were 18 to 79 years of age, alive and residing in Sweden on December 31, 2017, and had a prior PsA diagnosis were identified from the National Patient Register (NPR) and/or the Swedish Rheumatology Quality Register (SRQ). PsA prevalence was estimated according to a base case (BC) defini-tion (ie, & GE; 1 main PsA International Classification of Diseases code from rheumatology or internal medicine departments in the NPR or a PsA diagnosis in the SRQ), according to 4 sensitivity analysis definitions, and for those seen in specialized rheumatology care between 2015 and 2017. In the latter group, DMARD use during 2017 was also assessed. Data for stratifications were retrieved from national registers.Results. The crude national prevalence of PsA for adults, aged 18 to 79 years, was estimated at 0.39%, according to the BC definition; 0.34% after accounting for diagnostic misclassification; and 0.32% to 0.50% across all sensitivity analyses. The prevalence was lower in males and in those with a higher level of education. The prevalence for those seen in specialized rheumatology care between 2015 and 2017 was estimated at 0.24%. During 2017, 32% of patients in this population received biologic or targeted synthetic DMARDs, and 41% received conventional synthetic DMARDs only.Conclusion. The prevalence of clinically diagnosed PsA in adults, aged 18 to 79 years, in Sweden in 2017 was around 0.35%. Among PsA cases in recent contact with specialized rheumatology care, almost three-fourths received DMARD therapy in 2017.
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31.
  • Georgiadis, S, et al. (författare)
  • CAN SINGLE IMPUTATION TECHNIQUES FOR BASDAI COMPONENTS RELIABLY CALCULATE THE COMPOSITE SCORE IN AXIAL SPONDYLOARTHRITIS PATIENTS?
  • 2022
  • Ingår i: ANNALS OF THE RHEUMATIC DISEASES. - : BMJ. - 0003-4967 .- 1468-2060. ; 81, s. 212-213
  • Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
    • In axial spondyloarthritis (axSpA), Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) is a key patient-reported outcome. However, one or more of its components may be missing when recorded in clinical practice.ObjectivesTo determine whether an individual patient’s BASDAI at a given timepoint can be reliably calculated with different single imputation techniques and to explore the impact of the number of missing components and/or differences between missingness of individual components.MethodsReal-life data from axSpA patients receiving tumour necrosis factor inhibitors (TNFi) from 13 countries in the European Spondyloarthritis (EuroSpA) Research Collaboration Network were utilized [1]. We studied missingness in BASDAI components based on simulations in a complete dataset, where we applied and expanded the approach of Ramiro et al. [2]. After introducing one or more missing components completely at random, BASDAI was calculated from the available components and with three different single imputation techniques: possible middle value (i.e. 50) of the component and mean and median of the available components. Differences between the observed (original) and calculated scores were assessed and correct classification of patients as having BASDAI<40 mm was additionally evaluated. For the setting with one missing component, differences arising between missing one of components 1-4 versus 5-6 were explored. Finally, the performance of imputations in relation to the values of the original score was investigated.ResultsA total of 19,894 axSpA patients with at least one complete BASDAI registration at any timepoint were included. 59,126 complete BASDAI registrations were utilized for the analyses with a mean BASDAI of 38.5 (standard deviation 25.9). Calculating BASDAI from the available components and imputing with mean or median showed similar levels of agreement (Table 1). When allowing one missing component, >90% had a difference of ≤6.9 mm between the original and calculated scores and >95% were correctly classified as BASDAI<40 (Table 1). However, separate analyses of components 1-4 and 5-6 as a function of the BASDAI score suggested that imputing any one of the first four BASDAI components resulted in a level of agreement <90% for specific BASDAI values while imputing one of the stiffness components 5-6 always reached a level of agreement >90% (Figure 1, upper panels). As expected, it was observed that regardless of the BASDAI component set to missing and the imputation technique used, correct classification of patients as BASDAI<40 was less than 95% for values around the cutoff (Figure 1, lower panels).Table 1.Level of agreement between the original and calculated BASDAI and correct classification for BASDAI<40 mmLevel of agreement with Dif≤6.9 mm* (%)Correct classification for BASDAI<40 mm** (%)1 missing componentAvailable93.996.9Value 5073.996.3Mean94.296.8Median93.196.82 missing componentsAvailable83.794.8Value 5040.792.8Mean83.594.8Median82.894.73 missing componentsAvailable71.992.6Value 5028.187.3Mean72.292.6Median69.792.2* The levels of agreement with a difference (Dif) of ≤6.9 mm between the original and calculated scores were based on the half of the smallest detectable change. Agreement of >90% was considered as acceptable. ** Correct classification of >95% was considered as acceptable.Figure 1.Level of agreement between the original and calculated BASDAI and correct classification for BASDAI<40 mm as a function of the original scoreConclusionBASDAI calculation with available components gave similar results to single imputation of missing components with mean or median. Only when missing one of BASDAI components 5 or 6, single imputation techniques can reliably calculate individual BASDAI scores. However, missing any single component value results in misclassification of patients with original BASDAI scores close to 40.References[1]Ørnbjerg et al. (2019). Ann Rheum Dis, 78(11), 1536-1544.[2]Ramiro et al. (2014). Rheumatology, 53(2), 374-376.AcknowledgementsNovartis Pharma AG and IQVIA for supporting the EuroSpA collaboration.Disclosure of InterestsStylianos Georgiadis Grant/research support from: Novartis, Myriam Riek Grant/research support from: Novartis, Christos Polysopoulos Grant/research support from: Novartis, Almut Scherer Grant/research support from: Novartis, Daniela Di Giuseppe: None declared, Gareth T. Jones Speakers bureau: Janssen, Grant/research support from: AbbVie, Pfizer, UCB, Amgen, GSK, Merete Lund Hetland Grant/research support from: Abbvie, Biogen, BMS, Celltrion, Eli Lilly, Janssen Biologics B.V, Lundbeck Fonden, MSD, Medac, Pfizer, Roche, Samsung Biopies, Sandoz, Novartis, Mikkel Østergaard Speakers bureau: Abbvie, BMS, Boehringer-Ingelheim, Celgene, Eli-Lilly, Hospira, Janssen, Merck, Novartis, Novo, Orion, Pfizer, Regeneron, Roche, Sandoz, Sanofi, UCB, Consultant of: Abbvie, BMS, Boehringer-Ingelheim, Celgene, Eli-Lilly, Hospira, Janssen, Merck, Novartis, Novo, Orion, Pfizer, Regeneron, Roche, Sandoz, Sanofi, UCB, Grant/research support from: Abbvie, BMS, Merck, Celgene, Novartis, Simon Horskjær Rasmussen Grant/research support from: Novartis, Johan K Wallman Consultant of: AbbVie, Amgen, Celgene, Eli Lilly, Novartis, Bente Glintborg Grant/research support from: Pfizer, Abbvie, BMS, Anne Gitte Loft Speakers bureau: AbbVie, Janssen, Lilly, MSD, Novartis, Pfizer, Roche, UCB, Consultant of: AbbVie, Janssen, Lilly, MSD, Novartis, Pfizer, Roche, UCB, Karel Pavelka Speakers bureau: Pfizer, MSD, BMS, UCB, Amgen, Egis, Roche, AbbVie, Consultant of: Pfizer, MSD, BMS, UCB, Amgen, Egis, Roche, AbbVie, Jakub Zavada Speakers bureau: Abbvie, Elli-Lilly, Sandoz, Novartis, Egis, UCB, Consultant of: Abbvie, Elli-Lilly, Sandoz, Novartis, Egis, UCB, Merih Birlik: None declared, Ayten Yazici Grant/research support from: Roche, Brigitte Michelsen Grant/research support from: Novartis, Eirik kristianslund: None declared, Adrian Ciurea Speakers bureau: AbbVie, Eli Lilly, Merck Sharp & Dohme, Novartis, Pfizer, Consultant of: AbbVie, Eli Lilly, Merck Sharp & Dohme, Novartis, Pfizer, Michael J. Nissen Speakers bureau: AbbVie, Eli Lilly, Janssens, Novartis, Pfizer, Consultant of: AbbVie, Eli Lilly, Janssens, Novartis, Pfizer, Ana Maria Rodrigues Speakers bureau: Abbvie, Amgen, Consultant of: Abbvie, Amgen, Grant/research support from: Novartis, Pfizer, Amgen, Maria Jose Santos Speakers bureau: Abbvie, AstraZeneca, Lilly, Novartis, Pfizer, Gary Macfarlane Grant/research support from: GSK, Anna-Mari Hokkanen Grant/research support from: MSD, Heikki Relas Speakers bureau: Abbvie, Celgene, Pfizer, UCB, Viatris, Consultant of: Abbvie, Celgene, Pfizer, UCB, Viatris, Catalin Codreanu Speakers bureau: AbbVie, Amgen, Boehringer Ingelheim, Ewopharma, Lilly, Novartis, Pfizer, Consultant of: AbbVie, Amgen, Boehringer Ingelheim, Ewopharma, Lilly, Novartis, Pfizer, Corina Mogosan: None declared, Ziga Rotar Speakers bureau: Abbvie, Novartis, MSD, Medis, Biogen, Eli Lilly, Pfizer, Sanofi, Lek, Janssen, Consultant of: Abbvie, Novartis, MSD, Medis, Biogen, Eli Lilly, Pfizer, Sanofi, Lek, Janssen, Matija Tomsic Speakers bureau: Abbvie, Amgen, Biogen, Eli Lilly, Janssen, Medis, MSD, Novartis, Pfizer, Sanofi, Sandoz-Lek, Consultant of: Abbvie, Amgen, Biogen, Eli Lilly, Janssen, Medis, MSD, Novartis, Pfizer, Sanofi, Sandoz-Lek, Björn Gudbjornsson Speakers bureau: Amgen, Novartis, Consultant of: Amgen, Novartis, Arni Jon Geirsson: None declared, Pasoon Hellamand Grant/research support from: Novartis, Marleen G.H. van de Sande Speakers bureau: Eli Lilly, Novartis, UCB, Janssen, Abbvie, Consultant of: Eli Lilly, Novartis, UCB, Janssen, Abbvie, Grant/research support from: Eli Lilly, Novartis, UCB, Janssen, Abbvie, Isabel Castrejon: None declared, Manuel Pombo-Suarez Consultant of: Abbvie, MSD, Roche, Bruno Frediani: None declared, Florenzo Iannone Speakers bureau: Abbvie, Amgen, AstraZeneca, BMS, Galapagos, Janssen, Lilly, MSD, Novartis, Pfizer, Roche, UCB, Consultant of: Abbvie, Amgen, AstraZeneca, BMS, Galapagos, Janssen, Lilly, MSD, Novartis, Pfizer, Roche, UCB, Lykke Midtbøll Ørnbjerg Grant/research support from: Novartis
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33.
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34.
  • Glintborg, B, et al. (författare)
  • UPTAKE OF NEWER BIOLOGIC AND TARGETED SYNTHETIC DMARDS IN PSORIATIC ARTHRITIS, RESULTS FROM FOUR NORDIC BIOLOGIC REGISTRIES
  • 2022
  • Ingår i: ANNALS OF THE RHEUMATIC DISEASES. - : BMJ. - 0003-4967 .- 1468-2060. ; 81, s. 766-767
  • Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
    • The treatment landscape in psoriatic arthritis (PsA) is changing, including newer biologic and targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs) with different modes of action becoming available. However, the most effective treatment strategy in routine care remains to be established.ObjectivesTo explore the uptake and treatment patterns of newer b/tsDMARDs, namely JAK-inhibitors (JAKi; baricitinib, tofacitinib, upadacitinib), IL-17-inhibitors (ixekizumab, secukinumab), abatacept, apremilast, and ustekinumab in PsA patients from the Nordic countries. Furthermore, to describe patient characteristics and extra-musculoskeletal manifestations at treatment start (=baseline).MethodsObservational cohort study, using prospectively collected routine care data from 4 Nordic rheumatology registries. Treatments (newer b/tsDMARDs with tumor-necrosis-factor inhibitors (TNFi) as the reference) initiated from January 2009 until December 2020 and corresponding baseline patient characteristics were identified. Linkage to national patient registries was used to identify previous extra-musculoskeletal manifestations (0-5 years). Country-level data were pooled for analyses. Uptake of each drug was explored as the cumulative number of treatment starts (a) overall, irrespective of previous b/tsDMARD experience, and (b) in b/tsDMARD-naïve patients. Each patient could contribute >1 treatment course.ResultsOverall, 13,364 unique patients contributing 24,325 treatment courses with either a newer b/tsDMARD (4,855, 20%) or a TNFi (19,470, 80%, whereof 10,897 were started year 2015-20) were identified. For the sub-group of 11,892 first b/tsDMARD treatment courses, 1,009 (8%) were a newer b/tsDMARD (10,883 were a TNFi, whereof 5,956 were started year 2015-20).Secukinumab dominated the newer b/tsDMARD uptake (1,848 new-starts, Figure 1). Ustekinumab-uptake increased over time both overall and in b/tsDMARD-naïve patients. In b/tsDMARD-naïve patients, apremilast had the fastest uptake (490 new-starts) (Figure 1). Use of JAKi was limited, especially in b/tsDMARD-naïve patients.Figure 1.Patients starting a newer b/tsDMARD tended to have longer disease duration and slightly higher disease activity at baseline (DAS28, patient-reported outcomes) than TNFi initiators (Table 1). Previous extra-musculoskeletal manifestations (uveitis, IBD) were rare, and with similar distributions across treatments (Table 1).Table 1.Baseline characteristics upon treatment startAbata-ceptApre-milastBari-citinibIxe-kizumabSecuki-numabTofa-citinibUpada-citinibUste-kinumabAny TNFiCumulative uptake, n3629351063421848494669119470Male gender, %334227384033333744Age54 (12)53 (12)55 (13)52 (13)51 (13)54 (13)52 (10)50 (12)49 (13)b/tsDMARD treatment number, %1952911149020562191512262518171925≥3723378746173836219Disease duration, yrs9 (8)8 (8)10 (8)10 (8)9 (9)11 (10)8 (8)8 (9)7 (8)Pain, VAS (0-100)63 (21)61 (23)64 (23)64 (25)63 (24)66 (23)75 (17)64 (23)59 (24)DAS284.73 (1.34)4.04 (1.35)3.95 (1.36)4.24 (1.19)4.13 (1.36)4.49 (1.33)4.74 (0.88)4.19 (1.32)4.07 (1.29)Uveitis, %*323123022IBD, %*113111-31Numbers are mean (SD) unless otherwise statedIBD: inflammatory bowel disease, bDMARD: biologic DMARD, ts: targeted synthetic*0-5 years previously, available all study period for Iceland, Sweden, Finland until 31Dec2018, not available for DenmarkConclusionIn this cross-country collaboration we were able to explore uptake of newer b/tsDMARDs. TNFi still dominates compared to newer b/tsDMARDs in routine care treatment of PsA. Newer b/tsDMARDs are mainly used in patients with several previous treatment failures, i.e. with longer disease duration and higher disease activity, indicating difficult to treat disease. Further studies are planned to explore real-world treatment patterns and outcomes.AcknowledgementsBG and DdiG contributed equally.Partly funded by NordForsk and Foreum grants. On behalf of the Danish DANBIO, Swedish SRQ, Norwegian NOR-DMARD, Finnish ROB-FIN and Icelandic ICEBIO registriesDisclosure of InterestsBente Glintborg Grant/research support from: Pfizer, AbbVie, BMS, Daniela Di Giuseppe: None declared, Johan K Wallman Consultant of: AbbVie, Amgen, Celgene, Eli Lilly, Novartis, Grant/research support from: AbbVie, Amgen, Eli Lilly, Novartis, Pfizer, Dan Nordström: None declared, Björn Gudbjornsson Speakers bureau: Novartis and Amgen, Merete Lund Hetland Grant/research support from: AbbVie, Biogen, BMS, Celltrion, Eli Lilly Denmark A/S, Janssen Biologics B.V, Lundbeck Fonden, MSD, Pfizer, Roche, Samsung Biopis, Sandoz, Novartis., Johan Askling Grant/research support from: Abbvie, Astra-Zeneca, BMS, Eli Lilly, MSD, Pfizer, Roche, Samsung Bioepis, Sanofi, and UCB., Gerdur Gröndal: None declared, Tuulikki Sokka-Isler Grant/research support from: Abbvie, Amgen, BMS, Celgene, Eli Lilly, GSK, Medac, MSD, Novartis, Orion Pharma, Pfizer, Roche, Sandoz, UCB, Sella Aarrestad Provan: None declared, Ulf Lindström: None declared
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35.
  • Hambardzumyan, Karen, et al. (författare)
  • A Multi-Biomarker Disease Activity Score and the Choice of Second-Line Therapy in Early Rheumatoid Arthritis After Methotrexate Failure
  • 2017
  • Ingår i: Arthritis & Rheumatology. - : Wiley. - 2326-5191 .- 2326-5205. ; 69:5, s. 953-963
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: To investigate whether the Multi-Biomarker Disease Activity (MBDA) score predicts optimal add-on treatment in patients with early rheumatoid arthritis (RA) who were inadequate responders to MTX (MTX-IRs). Methods: We analyzed data from 157 MTX-IRs (with a Disease Activity Score using the erythrocyte sedimentation rate [DAS28-ESR] >3.2) from the Swedish Pharmacotherapy (SWEFOT) trial who were randomized to receive triple therapy (MTX plus sulfasalazine plus hydroxychloroquine) versus MTX plus infliximab. The MBDA score as a predictor of the subsequent DAS28-based response to each second-line treatment was analyzed at randomization with the Breslow-Day test for 2 × 2 groups, using both validated categories (low [<30], moderate [30–44], and high [>44]) and dichotomized categories (lower [≤38] versus higher [>38]). Results: Among the 157 patients, 12% had a low MBDA score, 32% moderate, and 56% high. Of those with a low MBDA score, 88% responded to subsequent triple therapy, and 18% responded to MTX plus infliximab (P = 0.006); for those with a high MBDA score, the response rates were 35% and 58%, respectively (P = 0.040). When using 38 as a cutoff for the MBDA score (29% patients with lower scores versus 71% with higher scores), the differential associations with response to triple therapy versus MTX plus infliximab were 79% versus 44% and 36% versus 58%, respectively (P = 0.001). Clinical and inflammatory markers had poorer predictive capacity for response to triple therapy or MTX plus infliximab. Conclusion: In patients with RA who had an inadequate response to MTX, the MBDA score categories were differentially associated with response to subsequent therapies. Thus, patients with post-MTX biochemical improvements (lower MBDA scores) were more likely to respond to triple therapy than to MTX plus infliximab. If confirmed, these results may help to improve treatment in RA.
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36.
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37.
  • Hambardzumyan, K., et al. (författare)
  • Association of female sex and positive rheumatoid factor with low serum infliximab and anti-drug antibodies, related to treatment failure in early rheumatoid arthritis : results from the SWEFOT trial population
  • 2019
  • Ingår i: Scandinavian Journal of Rheumatology. - : Informa UK Limited. - 0300-9742 .- 1502-7732. ; 48:5, s. 362-366
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: Infliximab-treated patients with rheumatoid arthritis (RA) may respond insufficiently due to low serum infliximab (sIFX) levels, caused by anti-drug antibodies (ADAs). However, monitoring of sIFX and ADAs is not routinely implemented, and levels for optimal outcome have not been validated. We searched for predictors for sIFX < 0.2 μg/mL and ADA development in a randomized setting. Methods: In the SWEFOT trial, of 128 patients randomized to methotrexate + IFX therapy, 101 had serum samples at 3, 9, and 21 months that were analysed for sIFX [enzyme-linked immunosorbent assay (ELISA)] and ADAs [ELISA, and precipitation and acid dissociation (PandA) when sIFX > 0.2 μg/mL]. The primary and secondary outcome measures were low disease activity [LDA = 28-joint Disease Activity Score (DAS28) ≤ 3.2] and remission (DAS28 < 2.6). Baseline characteristics were assessed as potential predictors of sIFX < 0.2 μg/mL or ADA positivity, using logistic regression. Results: Categorization of sIFX levels into < 0.2, 0.2–2.9, 3.0–7.0, and > 7.0 μg/mL showed a dose–response association with LDA (30%, 64%, 67%, and 79%, respectively, p = 0.008) and remission (10%, 45%, 39%, and 66%, p = 0.004) at trial cessation (21 months). Female patients had sIFX < 0.2 μg/mL more often than males (35% vs 7%, p = 0.006), with a similar trend for rheumatoid factor (RF)-positive vs RF-negative patients (34% vs 16%, p = 0.059). ADA positivity showed similar patterns, also after adjustment for potential confounders (female sex: p = 0.050; RF positivity: p = 0.067). PandA captured four highly ADA-reactive patients with sIFX > 0.2 μg/mL, of whom three were ADA positive at other time-points, all with high DAS28 at follow-up. Conclusion: In early RA patients receiving IFX as a second-line agent, sIFX < 0.2 μg/mL and ADA development were associated with treatment failure and were more common in females, with a similar trend for RF positivity. Our findings support the use of therapeutic drug monitoring, and PandA in ADA-negative non-responders. Trial registration: SWEFOT NCT00764725 (https://clinicaltrials.gov/ct2/show/NCT00764725).
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38.
  • Hambardzumyan, Karen, et al. (författare)
  • Serum biomarkers for prediction of response to methotrexate monotherapy in early rheumatoid arthritis : Results from the SWEFOT trial
  • 2019
  • Ingår i: Journal of Rheumatology. - : The Journal of Rheumatology. - 0315-162X .- 1499-2752. ; 46:6, s. 555-563
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective. To investigate baseline levels of 12 serum biomarkers that constitute a multibiomarker disease activity test, as predictors of response to methotrexate (MTX) in patients with early rheumatoid arthritis (eRA). Methods. In 298 patients from the Swedish Pharmacotherapy (SWEFOT) clinical trial, baseline serum levels of 12 proteins were analyzed for association with disease activity based on the 28-joint count Disease Activity Score (DAS28) after 3 months of MTX monotherapy using uni-/multivariate logistic regression. Primary outcome was low disease activity (LDA; DAS28 ≤ 3.2). Results. Of 298 patients, 104 achieved LDA after 3 months on MTX. Four of the 12 biomarkers [C-reactive protein (CRP), leptin, tumor necrosis factor receptor I (TNF-RI), and vascular cell adhesion molecule 1 (VCAM-1)] significantly predicted LDA based on stepwise logistic regression analysis. Dichotomization of patients using receiver-operating characteristic curve analysis-based cutoffs for these biomarkers showed significantly higher proportions with LDA among patients with lower versus higher levels of CRP or leptin (40% vs 23%, p = 0.004, and 40% vs 25%, p = 0.011, respectively), as well as among those with higher versus lower levels of TNF-RI or VCAM-1 (43% vs 27%, p = 0.004, and 41% vs 25%, p = 0.004, respectively). Combined score based on these biomarkers, adjusted for known predictors of LDA (smoking, sex, and age), associated with decreased chance of LDA (adjusted OR 0.45, 95% CI 0.32–0.62). Conclusion. Low baseline levels of CRP and leptin, and high baseline levels of TNF-RI and VCAM-1 were associated with LDA after 3 months of MTX therapy in patients with eRA. Combination of these 4 biomarkers increased accuracy of prediction.
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39.
  • Hellamand, Pasoon, et al. (författare)
  • Sex differences in the effectiveness of first-line tumour necrosis factor inhibitors in axial spondyloarthritis: Results from the EuroSpA Research Collaboration Network
  • 2023
  • Ingår i: RMD Open. - 2056-5933. ; 9:4
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective Evidence indicates reduced treatment effectiveness of TNFi in women with axial spondyloarthritis (axSpA) compared with men. We aimed to investigate sex differences in treatment response and retention rates over 24 months of follow-up in axSpA patients initiating their first TNFi. Methods Data from axSpA patients initiating a TNFi in 1 of 15 registries within EuroSpA collaboration were pooled. We investigated the association of sex with treatment response using logistic regression. The primary outcome was clinically important improvement (CII) at 6 months according to Ankylosing Spondylitis Disease Activity Score with C-reactive protein (CRP) (≥1.1 decrease). We adjusted for age, country and TNFi start year. A secondary outcome was retention rates over 24 months of follow-up assessed by Kaplan-Meier estimator. Results In total, 6451 axSpA patients with data on CII were assessed for treatment response; 2538 (39%) were women and 3913 (61%) were men. Women presented at baseline with lower CRP levels but had higher scores on patient-reported outcome measures. At 6 months, 53% of the women and 66% of the men had CII. Women had a lower relative risk of CII compared with men (0.81; 95% CI 0.77 to 0.84). This sex difference was similar in adjusted analysis (0.85; 95% CI 0.82 to 0.88). Retention rates were evaluated in 27 702 patients. The TNFi 6/12/24 months retention rates were significantly lower among women (79%/66%/53%) than men (88%/79%/69%). Conclusion Treatment response and retention rates are lower among women with axSpA initiating their first TNFi. Sex differences in treatment effectiveness were present regardless of the outcome measure used for treatment response, and differences in retention rates transpired early and increased as time progressed.
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40.
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41.
  • Köhler, Stephan J., et al. (författare)
  • Utvärdering av delprogrammet metaller inom miljöövervakning av sjöar : Styrfaktorer och mönster som hjälp för ett reviderat provtagningsprogram
  • 2016
  • Rapport (övrigt vetenskapligt/konstnärligt)abstract
    • Den årliga omfattande provtagningen av programmet omdrev som har pågått mellan 2007 till 2016 har varit mycket värdefull för utvärderingen för av faktorer som styr halter av ett antal metaller (Cd, Co, Cu, Ni, Pb och Zn). Det föreliggande dataset kan vara un-derlag till stöd för länsstyrelsen och kommuner att identifiera höga halter. Regionala skillnader i programmet omdrev har samma mönster som i programmet trendsjöar både med avseende på medianhalter, förekomst av låga värden och trender i påverkade jäm-fört med opåverkade områden. Ett större antal sjöar i omdrevprogrammet är tydligen påverkad av antropogena källor och kan möjligen uteslutas från metallanalyser i framti-den. Möjligen kan dessa sjöar vara referenser för påverkade områden. För följande me-taller fanns det starka (Co, Pb och Zn), svaga (Ni) och inga (Cd, Cu) samband mellan totalhalter och kemiska och landskapsrelaterade styrfaktorer som kan användas för att beräkna förväntade medianhalter i sjöar. Det föreslås att ett större antal sjöar i program-met trendsjöar analyseras 4 gånger per år för att få en bättre uppfattning av den tempo-rala variationen. I områden som är opåverkade av kända punktkällor så kan skattning av biotillgängligheten (Cu, Ni och Zn) eller beräkning av acceptabla gränsvärden (Pb) även fortsättningsvis utföras via metallernas totalhalter och totalhalten organiskt kol (TOC). För metallerna Pb och Zn kan totalhalterna korrigeras via antingen omräkningsfunktion-er eller med hjälp av modelleringsverktyget VisualMinteq som är tillgängligt. Beräk-ningarna antyder att halten TOC samvarierar med den beräknade biotillgängliga frakt-ionen. Osäkerheter som styrs av pH är minst lika stora som osäkerheter som härrör från TOC. Andra osäkerheter i beräkningarna så som halten Al och Fe som också kan bindas upp av TOC bör belysas närmare vid behov. I sjöar med höga pH värden bör biotill-gängligheten av Ni följas upp om totalhalten Ni är ovanligt höga (>25 ppb).
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42.
  • Lee, Heui Chang, et al. (författare)
  • Histological evaluation of flexible neural implants; Flexibility limit for reducing the tissue response?
  • 2017
  • Ingår i: Journal of Neural Engineering. - : IOP Publishing. - 1741-2560 .- 1741-2552. ; 14:3
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective. Flexible neural probes are hypothesized to reduce the chronic foreign body response (FBR) mainly by reducing the strain-stress caused by an interplay between the tethered probe and the brain's micromotion. However, a large discrepancy of Young's modulus still exists (3-6 orders of magnitude) between the flexible probes and the brain tissue. This raises the question of whether we need to bridge this gap; would increasing the probe flexibility proportionally reduce the FBR? Approach. Using novel off-stoichiometry thiol-enes-epoxy (OSTE+) polymer probes developed in our previous work, we quantitatively evaluated the FBR to four types of probes with different softness: silicon (∼150 GPa), polyimide (1.5 GPa), OSTE+Hard (300 MPa), and OSTE+Soft (6 MPa). Main results. We observed a significant reduction in the fluorescence intensity of biomarkers for activated microglia/macrophages and blood-brain barrier (BBB) leakiness around the three soft polymer probes compared to the silicon probe, both at 4 weeks and 8 weeks post-implantation. However, we did not observe any consistent differences in the biomarkers among the polymer probes. Significance. The results suggest that the mechanical compliance of neural probes can mediate the degree of FBR, but its impact diminishes after a hypothetical threshold level. This infers that resolving the mechanical mismatch alone has a limited effect on improving the lifetime of neural implants.
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43.
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44.
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45.
  • Lindstrom, U, et al. (författare)
  • COMPARISON OF TIME FROM METHOTREXATE INITIATION TO START OF A B/TSDMARD IN PSORIATIC ARTHRITIS VERSUS RHEUMATOID ARTHRITIS. A NATIONWIDE REGISTER-BASED STUDY.
  • 2022
  • Ingår i: ANNALS OF THE RHEUMATIC DISEASES. - : BMJ. - 0003-4967 .- 1468-2060. ; 81, s. 254-254
  • Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
    • In Sweden, methotrexate (MTX) is recommended as first-line DMARD for both psoriatic arthritis (PsA) and rheumatoid arthritis (RA). Whereas in RA the use of MTX monotherapy is supported by efficacy data from randomized trials, in PsA no clear efficacy has been demonstrated in placebo-controlled trials. Therefore, the use of MTX in PsA is mostly based on clinical experience and results from studies not primarily designed to evaluate MTX efficacy.ObjectivesTo compare time from MTX initiation until start of a biological or targeted synthetic DMARD (b/tsDMARD), as marker of insufficient MTX response, in previously DMARD-naïve, incident cases with PsA and matched, corresponding, reference subjects with RA.MethodsPatients with PsA, having collected a prescription of MTX as their first ever DMARD any time between 2011 through 2018, and with a first ever PsA diagnosis in the Swedish National Patient Register within two years prior to this date, were included. Each individual was required to have a visit in rheumatology, but no visit in dermatology, within 6 weeks prior to MTX initiation, to ensure that PsA rather than psoriasis was the main reason for MTX treatment. For each individual with PsA, a corresponding individual with incident RA was identified, matched on sex, age, and year of MTX initiation. Only PsA cases with an identified RA comparator were included. All individuals with a diagnosis indicating axial spondyloarthritis prior to MTX start were excluded. The data were enriched through linkage to other national registers.Follow-up was defined as the time from MTX initiation until start of any b/tsDMARD. Censoring was performed at the first of death, migration or 31 Dec 2020. Time until start of a b/tsDMARD was compared for PsA and RA through crude survival curves and conditional Cox-regression, crude and adjusted for comorbidity, level of education and patient global health.Results3098 patients with PsA, and their individually matched RA comparators were included. At initiation of MTX, PsA cases had a mean 28-joint disease activity score (DAS28) of 4.0 and RA-controls of 4.6, while patient-reported global health was 51 (of 100) for both groups and number of swollen joints (28-joint count) 4.0 for PsA and 6.8 for RA, Table 1. The comorbidity burden was similar at baseline.Table 1.Characteristics of PsA cases and matched RA controls at start of MTX.Psoriatic arthritis N=3098Rheumatoid arthritis N=3098Age, mean (sd)55 (14)55 (14)Sex, male49%49%Length of education, yrs <1020%24% 10-1251%49% >1228%26%Diabetes1, 27.4%6.7%Myocardial infarction11.3%1.8%Malignancy14.7%5.0%Congestive heart disease10.2%0.2%Chronic lung disease11.6%2.2%Use of anti-depressive drugs1, 315.4%11.4%DAS28-CRP, mean (sd)44.0 (1.1)4.6 (1.2)Patient global, mean (sd) 451 (23)51 (23)CRP, median (IQR) 47 (14)10 (21)Tender joint count (28), mean (sd) 45.2 (4.9)7.0 (5.7)Swollen joint count (28), mean (sd) 44.0 (4.1)6.8 (5.2)1) Diagnosis within 5 years. 2) Also identified by collecting ≥1 prescription of anti-diabetics in 1 year. 3) Identified by collecting ≥1 prescription within 1 year before methotrexate start. 4) Data on disease activity variables available for 28-36% of PsA and 56-62% of RA.During a mean follow-up of 4.5 and 4.4 years, 34% and 33% of PsA and RA patients, respectively, started a b/tsDMARD, of whom 63% and 84% had also used ≥1 non-MTX conventional synthetic DMARD before the b/tsDMARD initiation. The crude survival curves for time from MTX initiation until start of a b/tsDMARD were identical for PsA and RA, Figure 1A. The adjusted HR for starting a b/tsDMARD in PsA compared with RA was 0.99 (95% CI 0.90-1.09). No calendar time trends were observed (Figure 1B and C).ConclusionIn this study, the risk of escalating treatment from MTX, by adding or switching to a b/tsDMARD, was identical in PsA cases and matched RA controls. This supports a good response to MTX in PsA, similar to that in RA. Due to the matching, neither the results from the PsA nor the RA populations may be fully generalizable.Disclosure of InterestsUlf Lindström: None declared, Daniela Di Giuseppe: None declared, Sofia Exarchou Consultant of: AbbVie, Amgen, Janssen, Novartis, Grant/research support from: AbbVie, Amgen, Eli Lilly, Novartis, Pfizer, Gerd-Marie Alenius: None declared, Tor Olofsson Consultant of: Merck Sharp & Dohme, Eva Klingberg: None declared, Lennart T.H. Jacobsson Speakers bureau: Janssen, Eli Lilly, Novartis, Consultant of: Janssen, Eli Lilly, Novartis, Johan Askling Grant/research support from: Abbvie, Astra-Zeneca, BMS, Eli Lilly, MSD, Pfizer, Roche, Samsung Bioepis, Sanofi, and UCB., Johan K Wallman Consultant of: AbbVie, Amgen, Celgene, Eli Lilly, Novartis, Grant/research support from: AbbVie, Amgen, Eli Lilly, Novartis, Pfizer
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46.
  • Lindstrom, U, et al. (författare)
  • COMPARISON OF TREATMENT RETENTION OF SECUKINUMAB AND TNF-INHIBITORS IN PSORIATIC ARTHRITIS. OBSERVATIONAL DATA FROM A NORDIC COLLABORATION.
  • 2020
  • Ingår i: ANNALS OF THE RHEUMATIC DISEASES. - : BMJ. - 0003-4967 .- 1468-2060. ; 79, s. 427-428
  • Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
    • A head-to-head trial (EXCEED) has indicated similar effectiveness of secukinumab (SEC) and the tumor necrosis factor inhibitor (TNFi) adalimumab (ADA) in psoriatic arthritis (PsA). In the clinical setting, treatment retention serves as a combined measure of overall effectiveness and tolerability.Objectives:To explore baseline patient characteristics, and compare treatment retention rates for SEC and each of etanercept (ETN), infliximab (IFX), golimumab (GOL), certolizimab (CZP) and ADA in PsA.Methods:Patients starting SEC or any TNFi in 2015-2018, in the 5 Nordic countries, were identified in clinical rheumatology registers. Data were pooled for analysis and stratified by 1st, 2ndand ≥3rdline of treatment. One year treatment retention was compared by crude Kaplan-Meier curves and a proportional hazard model for risk of discontinuation, censored at 1 year and adjusted for sex, age, country and baseline CRP, patient global and use of csDMARD, with ADA as reference.Results:In total, 6062 patients with PsA were included, contributing 8172 treatment starts (table 1). SEC was mainly used as 2ndor ≥3rdline treatment. The survival curves and 1-year treatment retention rates, stratified by line of treatment, were similar for SEC compared to the TNFis, with some differences between the different TNFi (fig 1, table 2). Adjusted hazard ratios (HR) also indicated similar risk of SEC withdrawal compared to ADA (table 2).Table 1.Patient characteristics at treatment start1stline2ndline≥3rdlineSECN=164TNFiN=3808SECN=273TNFiN=1767SECN=767TNFiN=1393Females48%47%44%42%36%39%Age, years52 (13)49 (13)50 (12)50 (13)52 (12)51 (12)Disease duration, years12 (10)10 (10)13 (10)13 (10)16 (10)16 (10)Swollen joint count 283 (4)2 (3)2 (3)2 (3)3 (4)2 (3)CRP, mg/L10 (18)10 (17)7 (11)9 (17)13 (22)11 (20)Patient global score57 (24)58 (24)60 (25)59 (26)68 (23)65 (24)Concomitant therapycsDMARD30%60%41%57%49%53% Methotrexate24%49%31%48%40%44% Sulphasalazine2%9%5%5%4%6%Numbers are mean (SD) unless noted otherwiseTable 2.One year treatment retention and hazard of discontinuation for SEC and TNFiLine of treatmentDrugN1 year treatment retention % (95% CI)Adjusted HR (95% CI) for discontinuation1stlineADA56973 (69-76)RefCZP27366 (60-72)1.2 (0.9-1.6)ETN174773 (71-75)0.9 (0.7-1.1)GOL21267 (60-73)1.2 (0.9-1.7)IFX100762 (59-65)1.4 (1.1-1.7)SEC16472 (63-78)1.0 (0.7-1.4)2ndlineADA41569 (63-73)RefCZP17651 (43-58)1.6 (1.2-2.2)ETN70163 (59-66)1.2 (0.9-1.5)GOL15169 (61-76)0.9 (0.6-1.2)IFX32465 (59-70)1.0 (0.8-1.4)SEC27369 (62-74)0.9 (0.7-1.2)≥3rdlineADA34667 (62-72)RefCZP22149 (42-56)1.5 (1.2-2.0)ETN37262 (57-67)1.1 (0.9-1.5)GOL20656 (49-63)1.3 (1.0-1.8)IFX24857 (50-63)1.3 (1.0-1.8)SEC76763 (59-67)1.0 (0.8-1.3)Conclusion:In this large study of bDMARD treatment of PsA in clinical practice, SEC was most often used as 2ndor ≥3rdline treatment, and the treatment retention of SEC was comparable with that of TNFi. Further analyses, taking into account other comorbidities, channeling and effectiveness will be presented.Acknowledgments:UL and BG are shared first, and LJ and LEK shared last authors.Partly funded by Nordforsk and FOREUM.Disclosure of Interests:Ulf Lindström: None declared, Bente Glintborg Grant/research support from: Grants from Pfizer, Biogen and Abbvie, Daniela Di Giuseppe: None declared, Tanja Schjødt Jørgensen Speakers bureau: Abbvie, Pfizer, Roche, Novartis, UCB, Biogen, and Eli Lilly, Björn Gudbjornsson Speakers bureau: Novartis and Amgen, Kathrine L. Grøn Grant/research support from: BMS, Sella Aarrestad Provan Consultant of: Novartis, Brigitte Michelsen: None declared, Merete L. Hetland Grant/research support from: BMS, MSD, AbbVie, Roche, Novartis, Biogen and Pfizer, Consultant of: Eli Lilly, Speakers bureau: Orion Pharma, Biogen, Pfizer, CellTrion, Merck and Samsung Bioepis, Johan K Wallman Consultant of: AbbVie, Celgene, Eli Lilly, Novartis and UCB Pharma, Dan Nordström Consultant of: Abbvie, Celgene, Lilly, Novartis, Pfizer, Roche and UCB., Speakers bureau: Abbvie, Celgene, Lilly, Novartis, Pfizer, Roche and UCB., Nina Trokovic: None declared, Thorvardur Love: None declared, Niels Steen Krogh: None declared, Johan Askling Grant/research support from: JA acts or has acted as PI for agreements between Karolinska Institutet and the following entities, mainly in the context of the ARTIS national safety monitoring programme of immunomodulators in rheumatology: Abbvie, BMS, Eli Lilly, Merck, MSD, Pfizer, Roche, Samsung Bioepis, Sanofi, and UCB Pharma, Lennart T.H. Jacobsson Consultant of: AbbVie, Eli Lilly, Janssen, Novartis and Pfizer, Lars Erik Kristensen Consultant of: UCB Pharma (Advisory Board), Sannofi (Advisory Board), Abbvie (Advisory Board), Biogen (Advisory Board), Speakers bureau: AbbVie, Amgen, Biogen, Bristol-Myers Squibb,Celgene, Eli Lilly, Gilead, Forward Pharma, Janssen Pharmaceuticals, MSD, Novartis, Pfizer, and UCB Pharma
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47.
  • Lindström, Ulf, et al. (författare)
  • Methotrexate treatment in early psoriatic arthritis in comparison to rheumatoid arthritis: an observational nationwide study
  • 2023
  • Ingår i: Rmd Open. - : BMJ Publishing Group Ltd. - 2056-5933. ; 9:2
  • Tidskriftsartikel (refereegranskat)abstract
    • IntroductionWe aimed to compare the proportions of patients with newly diagnosed psoriatic arthritis (PsA) and rheumatoid arthritis (RA) remaining on methotrexate (regardless of other disease-modifying antirheumatic drug (DMARD)-changes), and proportions not having started another DMARD (regardless of methotrexate discontinuation), within 2 years of starting methotrexate, as well as methotrexate effectiveness. MethodsPatients with DMARD-naive, newly diagnosed PsA, starting methotrexate 2011-2019, were identified from high-quality national Swedish registers and matched 1:1 to comparable patients with RA. Proportions remaining on methotrexate and not starting another DMARD were calculated. For patients with disease activity data at baseline and 6 months, response to methotrexate monotherapy was compared through logistic regression, applying non-responder imputation. ResultsIn total, 3642/3642 patients with PsA/RA were included. Baseline patient-reported pain and global health were similar, whereas patients with RA had higher 28-joint scores and evaluator-assessed disease activity. Two years after methotrexate start, 71% of PsA vs 76% of patients with RA remained on methotrexate, 66% vs 60% had not started any other DMARD, and 77% vs 74% had not started specifically a biological or targeted synthetic DMARD. At 6 months, the proportions of patients with PsA versus RA achieving pain-scores <= 15 mm were 26% vs 36%; global health <= 20 mm: 32% vs 42%; evaluator-assessed 'remission': 20% vs 27%, with corresponding adjusted ORs (PsA vs RA) of 0.63 (95% CI 0.47 to 0.85); 0.57 (95% CI 0.42 to 0.76) and 0.54 (95% CI 0.39 to 0.75). DiscussionIn Swedish clinical practice, methotrexate use is similar in PsA and RA, both regarding initiation of other DMARDs and methotrexate retention. On a group level, disease activity improved during methotrexate monotherapy in both diseases, although more so in RA.
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48.
  • Mogard, Elisabeth, et al. (författare)
  • Chronic Pain and Assessment of Pain Sensitivity in Patients With Axial Spondyloarthritis: Results From the SPARTAKUS Cohort
  • 2021
  • Ingår i: Journal of Rheumatology. - : The Journal of Rheumatology. - 0315-162X .- 1499-2752. ; 48:11, s. 1672-1679
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective. To study differences in pain reports between patients with ankylosing spondylitis (AS) and non-radiographic axial spondyloarthritis (nr-axSpA), and to assess how pain sensitivity measures associate with disease and health outcomes. Methods. Consecutive patients with axial SpA (axSpA) were enrolled in the population-based SPARTAKUS cohort (2015-2017) and classified as AS (n = 120) or nr-axSpA (n = 55). Pain was assessed with question-naires (intensity/duration/distribution) and computerized cuff pressure algometry to measure pain sensi-tivity (pain threshold/pain tolerance/temporal summation of pain). Linear regression models were used to compare pain measures between patients with AS and nr-axSpA, and to assess associations between pain sensitivity measures and disease and health outcomes. Results. Of 175 patients with axSpA, 43% reported chronic widespread pain, with no significant differences in any questionnaire-derived or algometry-assessed pain measures between patients with AS and nr-axSpA. Lower pain tolerance was associated with longer symptom duration, worse Ankylosing Spondylitis Disease Activity Score using C-reactive protein (ASDAS-CRP), Bath Ankylosing Spondylitis Functional Index, and Bath Ankylosing Spondylitis Metrology Index (BASMI), more pain regions, unacceptable pain, worse Maastricht AS Enthesitis Score (MASES), fatigue, anxiety, and health-related quality of life. Further, lower pain threshold was associated with worse ASDAS-CRP and MASES, whereas higher temporal summation was associated with longer symptom duration, unacceptable pain, and worse BASMI. Conclusion. Chronic pain is common in axSpA, with no observed differences in any pain measures between patients with AS and nr-axSpA. Further, higher pain sensitivity is associated with having worse disease and health outcomes. The results indicate that patients with AS and nr-axSpA, in line with most clinical char-acteristics, have a similar pain burden, and they highlight large unmet needs regarding individualized pain management, regardless of axSpA subgroup.
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49.
  • Mogard, E., et al. (författare)
  • Chronic Pain in Patients With Established Axial Spondyloarthritis and Assessment of Pain Sensitivity by Computerized Pneumatic Cuff Pressure Algometry : Results from the Spartakus Cohort
  • 2017
  • Ingår i: Annals of the Rheumatic Diseases. - London : BMJ Publishing Group Ltd. - 0003-4967 .- 1468-2060. ; 76:Suppl. 2, s. 651-651
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Pain is a common symptom in all arthritides, and remains a problem also with better treatment options. In axial spondyloarthritis (ax-SpA), data on chronic pain remain scarce.Objectives: To study pain distribution, duration and intensity in ax-SpA, and relate this to disease status and measurement of pressure pain sensitivity.Methods: Consecutive patients (n=115) with clinical ax-SpA diagnoses (ankylosing spondylitis (AS) or undifferentiated axial spondyloarthritis (USpA)) were examined and answered pain questionnaires. Patients were categorised as having no chronic pain (NCP), chronic regional pain (CRP) or chronic widespread pain (CWP). Pressure pain sensitivity was assessed by computerized pneumatic cuff pressure algometry (CPA) on the dominant lower leg, and pain threshold, pain tolerance and temporal summation (assessed by the temporal summation index, TSI) were recorded. Differences in disease status and pressure pain sensitivity between patients with CWP versus NCP were assessed (Chi-square or Mann-Whitney U-test). Pressure pain sensitivity was also compared between patients with/without unacceptable pain levels (VAS pain >40 versus ≤40; Mann-Whitney U-test).Results: Fifty percent of patients reported CWP, irrespective of clinical diagnosis (AS 47%, USpA 53%), and more women than men reported CWP (59% versus 37%, p<0.001). Only 18% of all patients reported NCP. Overall, higher disease activity, pain intensity, worse fatigue, global health and function were observed among patients with CWP compared to those with NCP. There was a trend towards lower pain tolerance in patients with CWP compared to NCP (Table). Lower pain tolerance and higher TSI scores were observed among patients reporting VAS pain >40 versus those with VAS pain scores ≤40 ((mean (SD)) 51.9 (21.2) versus 68.1 (28.1), p=0.007; 0.73 (0.60) versus 0.55 (0.59), p=0.045). 2017, BMJ Publishing Group Limited.
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50.
  • Montelius, L., et al. (författare)
  • Pattern recognition of nerve signals using an artificial neural network
  • 1996
  • Ingår i: ; , s. 1502-1503
  • Konferensbidrag (refereegranskat)abstract
    • By using a microfabricated nerve chip with integrated electrodes through which peripheral nerves can generate and make electrical connects, it should be possible to control a remote prosthesis by processing the detected nerve signals. In this study different artificial neural networks have been employed for classification of such complex patterns of signals. The signals were obtained from four electrodes detecting muscle activity in a rat hindlimb as a consequence of applied stimulus to the rat right hindpaw. These signals recorded at four different sites resembles a situation of a nerve chip with four electrodes, which implies that we might be able to use the same strategy when analyzing data from a four-electrode chip to obtain information from the nervous system. In this paper we will address the usefulness of different network topologies for analyzing measured in-vivo data from an implanted perforated nerve chip.
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