| 1. |
- Lindström, Ulf, et al.
(författare)
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Effectiveness and treatment retention of TNF inhibitors when used as monotherapy versus comedication with csDMARDs in 15 332 patients with psoriatic arthritis. Data from the EuroSpA collaboration
- 2021
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Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 80, s. 1410-1418
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Tidskriftsartikel (refereegranskat)abstract
- Background: Comedication with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) during treatment with tumour necrosis factor inhibitors (TNFi) is extensively used in psoriatic arthritis (PsA), although the additive benefit remains unclear. We aimed to compare treatment outcomes in patients with PsA treated with TNFi and csDMARD comedication versus TNFi monotherapy. Methods: Patients with PsA from 13 European countries who initiated a first TNFi in 2006-2017 were included. Country-specific comparisons of 1 year TNFi retention were performed by csDMARD comedication status, together with HRs for TNFi discontinuation (comedication vs monotherapy), adjusted for age, sex, calendar year, disease duration and Disease Activity Score with 28 joints (DAS28). Adjusted ORs of clinical remission (based on DAS28) at 12 months were calculated. Between-country heterogeneity was assessed using random-effect meta-analyses, combined results were presented when heterogeneity was not significant. Secondary analyses stratified according to TNFi subtype (adalimumab/infliximab/etanercept) and restricted to methotrexate as comedication were performed. Results: In total, 15 332 patients were included (62% comedication, 38% monotherapy). TNFi retention varied across countries, with significant heterogeneity precluding a combined estimate. Comedication was associated with better remission rates, pooled OR 1.25 (1.12-1.41). Methotrexate comedication was associated with improved remission for adalimumab (OR 1.45 (1.23-1.72)) and infliximab (OR 1.55 (1.21-1.98)) and improved retention for infliximab. No effect of comedication was demonstrated for etanercept. Conclusion: This large observational study suggests that, as used in clinical practice, csDMARD and TNFi comedication are associated with improved remission rates, and specifically, comedication with methotrexate increases remission rates for both adalimumab and infliximab. © Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.
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| 2. |
- Nissen, M., et al.
(författare)
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The impact of a csDMARD in combination with a TNF inhibitor on drug retention and clinical remission in axial spondylarthritis
- 2022
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Ingår i: Rheumatology. - : Oxford University Press (OUP). - 1462-0324 .- 1462-0332. ; 61:12, s. 4741-4751
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Tidskriftsartikel (refereegranskat)abstract
- Objectives Many axial spondylarthritis (axSpA) patients receive a conventional synthetic DMARD (csDMARD) in combination with a TNF inhibitor (TNFi). However, the value of this co-therapy remains unclear. The objectives were to describe the characteristics of axSpA patients initiating a first TNFi as monotherapy compared with co-therapy with csDMARD, to compare one-year TNFi retention and remission rates, and to explore the impact of peripheral arthritis. Methods Data was collected from 13 European registries. One-year outcomes included TNFi retention and hazard ratios (HR) for discontinuation with 95% CIs. Logistic regression was performed with adjusted odds ratios (OR) of achieving remission (Ankylosing Spondylitis Disease Activity Score (ASDAS)-CRP < 1.3 and/or BASDAI < 2) and stratified by treatment. Inter-registry heterogeneity was assessed using random-effect meta-analyses, combined results were presented when heterogeneity was not significant. Peripheral arthritis was defined as >= 1 swollen joint at baseline (=TNFi start). Results Amongst 24 171 axSpA patients, 32% received csDMARD co-therapy (range across countries: 13.5% to 71.2%). The co-therapy group had more baseline peripheral arthritis and higher CRP than the monotherapy group. One-year TNFi-retention rates (95% CI): 79% (78, 79%) for TNFi monotherapy vs 82% (81, 83%) with co-therapy (P < 0.001). Remission was obtained in 20% on monotherapy and 22% on co-therapy (P < 0.001); adjusted OR of 1.16 (1.07, 1.25). Remission rates at 12 months were similar in patients with/without peripheral arthritis. Conclusion This large European study of axial SpA patients showed similar one-year treatment outcomes for TNFi monotherapy and csDMARD co-therapy, although considerable heterogeneity across countries limited the identification of certain subgroups (e.g. peripheral arthritis) that may benefit from co-therapy.
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| 3. |
- Christiansen, SN, et al.
(författare)
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SECULAR TRENDS IN BASELINE CHARACTERISTICS, TREATMENT RETENTION AND RESPONSE RATES IN 17453 BIONAIVE PSORIATIC ARTHRITIS PATIENTS INITIATING TNFI - RESULTS FROM THE EUROSPA COLLABORATION
- 2021
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Ingår i: ANNALS OF THE RHEUMATIC DISEASES. - : BMJ. - 0003-4967 .- 1468-2060. ; 80, s. 131-132
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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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| 6. |
- Georgiadis, S, et al.
(författare)
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CAN SINGLE IMPUTATION TECHNIQUES FOR BASDAI COMPONENTS RELIABLY CALCULATE THE COMPOSITE SCORE IN AXIAL SPONDYLOARTHRITIS PATIENTS?
- 2022
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Ingår i: ANNALS OF THE RHEUMATIC DISEASES. - : BMJ. - 0003-4967 .- 1468-2060. ; 81, s. 212-213
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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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| 7. |
- Linde, L., et al.
(författare)
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Predictors of DAPSA28 remission in patients with psoriatic arthritis initiating a first TNF inhibitor: results from 13 European registries
- 2024
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Ingår i: Rheumatology. - 1462-0324. ; 63:3, s. 751-764
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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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| 11. |
- Cordtz, R, et al.
(författare)
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RISK OF HAEMATOLOGICAL MALIGNANCY IN PATIENTS WITH PSORIATIC ARTHRITIS, OVERALL AND IN RELATION TO TNF INHIBITORS - A NORDIC COHORT STUDY
- 2022
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Ingår i: ANNALS OF THE RHEUMATIC DISEASES. - : BMJ. - 0003-4967 .- 1468-2060. ; 81, s. 169-170
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Several autoimmune inflammatory diseases, including rheumatoid arthritis (RA), are associated with increased risk of malignant lymphomas. There is also a longstanding concern of lymphoma development with tumour necrosis factor inhibitor (TNFi) treatment, but most studies in RA to date do not indicate an additionally increased risk. Corresponding studies in psoriatic arthritis (PsA), both with respect to the underlying risks, and risks in relation to treatment with TNFi, are limited. Data on myeloid malignancies in PsA are scarce.ObjectivesTo estimate the risk of haematological malignancy overall and by lymphoid and myeloid types in TNFi treated versus (vs.) biologics-naïve patients with PsA across the five Nordic countries. Additionally, we investigated the underlying risk of haematological malignancies in PsA as compared to the general population.MethodsWe identified patients with PsA starting a first ever TNFi from the clinical rheumatology registers (CRR) in Sweden (SE), Denmark (DK), Norway (NO), Finland (FI), and Iceland (ICE) from 2006 through 2019 (n=10 621). We identified biologics-naïve patients with PsA from a) the CRR (n=18 705, all countries) and b) the national patient registers (NPR, n=27 286, SE and DK only). To estimate the underlying risk of haematological malignancy in PsA, we randomly sampled general population comparators in SE and DK matched on year of birth, sex, and calendar year at start of follow-up, to the patients with PsA.Through linkage to the mandatory national cancer registers in all five countries, we collected information on haematological malignancy overall, and categorised into lymphoid or myeloid types. By applying a modified Poisson regression, we estimated pooled incidence rate ratio (IRR) with 95% confidence intervals (CI) for TNFi treated vs. biologics-naïve PsA and for PsA vs. the general population, adjusted for age (18-55, 56-65, 66-70, >70 years), sex, calendar period (2006-2010, 2011-2019) and country, and using robust standard errors.ResultsWe observed 40 events of haematological malignancies (during 59 827 person-years) among TNFi treated PsA, resulting in a crude incidence rate (IR) of 67 per 100 000 person-years. The corresponding IR was 91 (63 events) for biologics-naïve PsA from the CRR, and 118 (172 events) for biologics-naïve PsA from NPR. This resulted in a pooled IRR of 0.97 (0.69 to 1.37) for TNFi-treated vs. biologics-naïve PsA patients from the CRR, and 0.84 (0.64 to 1.10) vs. biologics-naïve PsA patients from the NPR. The pooled IRR of haematological malignancies in PsA overall vs. the general population was 1.35 (1.17 to 1.55). Throughout, the estimates were largely similar for lymphoid and myeloid malignancies (Figure 1). The crude IR of haematological malignancies were substantially akin across different TNFi agents.Figure 1.Pooled incidence rate ratios (IRRs) (95% CI) of haematological malignancy overall and by lymphoid and myeloid types, in first ever TNFi treated versus biologics-naïve patients with PsA, and versus general population comparators. Legend: Lymphoid malignancies include international classification of diseases (ICD) 10 codes C81-86, C88, C90-91. Myeloid malignancies include ICD10 codes C92-95, D45-D46, D47.1, D47.3-5. Incidence rate ratios adjusted for age (18-55, 56-65, 66-70, >70 years), sex, calendar period (2006-2010, 2011-2019) and country, and using robust standard errors.ConclusionIn this large five-country cohort study, we did not observe any increased risk of haematological malignancies overall, nor for lymphoid and myeloid types, in patients with PsA treated with TNFi. By contrast, there were signals of a moderately increased underlying risk of haematological malignancies, both of lymphoid and myeloid types, in patients with PsA overall as compared to the general population. The findings are of importance from a patient information perspective.AcknowledgementsWe would like to acknowledge the NordForsk and FOREUM, and especially the patient representatives of the NordForsk collaboration for their valuable contribution to this study.Disclosure of InterestsRené Cordtz: None declared, Johan Askling Consultant of: Abbvie, Astra-Zeneca, BMS, Eli Lilly, MSD, Pfizer, Roche, Samsung Bioepis, Sanofi, and UCB, Grant/research support from: Abbvie, Astra-Zeneca, BMS, Eli Lilly, MSD, Pfizer, Roche, Samsung Bioepis, Sanofi, and UCB, Bénédicte Delcoigne: None declared, Karin Ekström Smedby: None declared, Eva Baecklund: None declared, Christine Ballegaard: None declared, Pia Isomäki Speakers bureau: AbbVie, Eli Lilly and Pfizer, Consultant of: AbbVie, Eli Lilly, Pfizer, Roche and ViforPharma, Grant/research support from: Pfizer, Kalle Aaltonen: None declared, Björn Gudbjornsson Speakers bureau: Novartis, not related to this work, Consultant of: Novartis, not related to this work, Thorvardur Love Speakers bureau: Celgene, Sella Aa. Provan: None declared, Brigitte Michelsen Grant/research support from: Novartis, not related to this work, Joe Sexton: None declared, Lene Dreyer Speakers bureau: Eli Lilly, Galderma and Janssen, Grant/research support from: BMS not related to this work, Karin Hellgren: None declared
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| 12. |
- Di Giuseppe, D, et al.
(författare)
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BIOLOGIC REFRACTORY DISEASE IN AXIAL SPONDYLOARTHRITIS - DEFINITION, PREVALENCE AND PATIENT CHARACTERISTICS. A COLLABORATION BETWEEN FIVE NORDIC BIOLOGIC REGISTRIES
- 2021
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Ingår i: ANNALS OF THE RHEUMATIC DISEASES. - : BMJ. - 0003-4967 .- 1468-2060. ; 80, s. 82-83
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- In clinical practice, some patients with axial spondyloarthritis (axSpA) fail several consecutive biological treatments (bDMARDs). How this group of ”refractory” patients should best be defined, how common they are, and what their characteristics are, is poorly understood.Objectives:To explore the point prevalence of bDMARD refractory disease in axSpA over time, according to different definitions, and to describe the characteristics of refractory vs. not-refractory patients upon start of their first bDMARD.Methods:Observational prospective cohort study. Patients with axSpA (ankylosing spondylitis/non-radiographic axial SpA) starting a first bDMARD 2009-2018 were identified in biologic registries in Denmark, Sweden, Finland, Norway and Iceland. Clinical characteristics and treatments were retrieved, and data were pooled for analysis.Refractory disease was defined based on the number of different bDMARD treatments started in individual patients: mild (≥3 bDMARDs), moderate (≥4), and strict (5 or more). Restart of same bDMARD with another bDMARD in between counted as separate courses whereas switch from originator to corresponding biosimilar was ignored.Proportions of patients fulfilling each definition of refractory disease at 2 and 5 years after the start of 1st bDMARD were calculated.Point-prevalence per calendar-year was calculated as the number of patients with refractory disease at the end of each year, divided by the total number of patients ever having starting a first bDMARD before that time-point, and who were still alive and resident in the country.Results:The point prevalence of refractory axSpA increased with calendar-time (Figure). Among 12,037 included axSpA patients (64% male), the point-prevalence of bDMARD refractory disease in 2018 was 16%/7%/3% according to mild/moderate/strict definitions (Table).Table 1.Biologic refractory axSpA according to three definitionsA.Baseline characteristics upon start 1st bDMARDRefractory definitionOverall cohortMILDMODERATESTRICTN120371969832351Age, years42 (13)41 (12)41 (12)41 (12)Male, %64%57%54%56%Disease duration, years7 (10)6 (9)6 (8)5 (8)BASDAI, 0-10053 (28)60 (29)63 (27)66 (35)ASDAS3.3 (1.1)3.5 (1.2)3.6 (1.0)3.7 (1.1)CRP, mg/L16 (23)18 (26)21 (28)23 (32)Patient global, VAS, 0-10059 (25)65 (22)66 (22)67 (23)Patient Pain, VAS, 0-10057 (24)62 (22)63 (22)63 (22)Fatigue, VAS, 0-10059 (27)66 (26)66 (26)68 (25)B.Proportions of patients having refractory disease 2 and 5 years after start of their first bDMARD2 years, %5%1%0%5 years, %13%4%1%Numbers are means (SD) unless otherwise statedUpon start of their 1st bDMARD, patients later fulfilling the definitions for refractory axSpA were more frequently women, had shorter disease duration, higher C-reactive protein and higher patient reported outcomes.Overall, 5%/1%/0% had mild/moderate/strict refractory disease 2 years after start of first bDMARD, after 5 years it was 13%/4%/1% (Table).Conclusion:In this large Nordic observational cohort of axSpA patients treated in routine care, we could demonstrate that a substantial proportion of all patients had used multiple bDMARDs. In 2018, one in six patients had received ≥3 bDMARDs, indicating a bDMARD refractory disease. Multiple switching was more frequent during later years, probably due to more bDMARDs becoming available. The characteristics of refractory axSpA, including sex and disease activity, will have to be further explored, as will the impact of refractory disease on long-term outcomes.Acknowledgements:the DANBIO, SRQ, ICEBIO, ROB-FIN and NOR-DMARD registries.Partly sponsored by Nordforsk and Foreum.Disclosure of Interests:Daniela Di Giuseppe: None declared, Ulf Lindström: None declared, Kalle Aaltonen: None declared, Heikki Relas Speakers bureau: Abbvie, Celgene, MSD, Roche, Sella Aarrestad Provan: None declared, Björn Gudbjornsson Speakers bureau: Amgen and Novartis, Merete L. Hetland Grant/research support from: AbbVie, Biogen, BMS, Celtrion, Eli Lilly Denmark A/S, Janssen Biologics B.V, Lundbeck Fonden, MSD, Pfizer, Roche, Samsung Biopis, Sandoz. MLH chairs the steering committee of the Danish Rheumatology Quality Registry (DANBIO), which receives public funding from the hospital owners and funding from pharmaceutical companies. MLH co-chairs the EuroSpA research collaboration, which generates real-world evidence of treatment of psoriatic arthritis and axial spondyloarthritis based on secondary use of quality data and is partly funded by Novartis., Johan Askling: None declared, Tanja Schjødt Jørgensen: None declared, Lene Dreyer Speakers bureau: Eli-Lilly and Galderma, Grant/research support from: BMS, Dan Nordström: None declared, Brigitte Michelsen: None declared, Arni Jon Geirsson: None declared, Lennart T.H. Jacobsson: None declared, Bente Glintborg Grant/research support from: Abbvie, BMS, Pfizer, Lundbeck foundation
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| 13. |
- Di Giuseppe, D., et al.
(författare)
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The occurrence of multiple treatment switches in axial spondyloarthritis. Results from five Nordic rheumatology registries
- 2022
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Ingår i: Rheumatology. - : Oxford University Press (OUP). - 1462-0324 .- 1462-0332. ; 61:9, s. 3647-3656
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Tidskriftsartikel (refereegranskat)abstract
- Objectives In axial spondyloarthritis (axSpA), switching between multiple biologic or targeted synthetic (b/ts-) DMARDs might indicate difficult-to-treat disease. We aimed to explore the occurrence of multiple switching in routine care axSpA patients using various definitions, and to identify associated clinical characteristics upon start of first b/tsDMARD (baseline). Methods Observational cohort study including patients with axSpA starting a first-ever b/tsDMARD 2009-2018 based on data from five biologic registries (Denmark/Sweden/Finland/Norway/Iceland). Comorbidities and extra-articular manifestations were identified through linkage to national registries. Multi-switching was defined in overlapping categories according to b/tsDMARD treatment history: treatment with >= 3, >= 4 or >= 5 b/tsDMARDs during follow-up. We explored the cumulative incidence of patients becoming multi-switchers with >= 3 b/tsDMARDs stratified by calendar-period (2009-2011, 2012-2013, 2014-2015, 2016-2018). In the subgroup of patients starting a first b/tsDMARD 2009-2015, baseline characteristics associated with multi-switching (within 3 years' follow-up) were explored using multiple logistic regression analyses. Results Among 8398 patients included, 6056 patients (63% male, median age 42 years) started a first b/tsDMARD in 2009-2015, whereof proportions treated with >= 3, >= 4 or >= 5 b/tsDMARDs within 3 years' follow-up were 8%, 3% and 1%, respectively. Calendar-period did not affect the cumulative incidence of multi-switching. Baseline characteristics associated with multi-switching (>= 3 b/tsDMARDs) were female gender, shorter disease duration, higher patient global score, comorbidities and having psoriasis but not uveitis. Conclusion In this large Nordic observational cohort of axSpA patients, multiple switching was frequent with no apparent time-trend. Clinical associated factors included gender, but also previous comorbidities and extra-articular manifestations illustrating the ongoing challenge of treating this patient group.
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| 14. |
- Glintborg, B., et al.
(författare)
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Is the risk of infection higher during treatment with secukinumab than with TNF inhibitors? An observational study from the Nordic countries
- 2023
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Ingår i: Rheumatology. - : Oxford University Press (OUP). - 1462-0324 .- 1462-0332. ; 62:2, s. 647-658
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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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| 15. |
- Glintborg, B., et al.
(författare)
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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
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Ingår i: Arthritis Care & Research. - : Wiley. - 2151-464X .- 2151-4658. ; 74:5, s. 748-758
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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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| 16. |
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| 17. |
- Glintborg, B., et al.
(författare)
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Uptake and effectiveness of newer biologic and targeted synthetic disease-modifying antirheumatic drugs in psoriatic arthritis: results from five Nordic biologics registries
- 2023
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Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 82:6, s. 820-828
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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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| 18. |
- Hellgren, K, et al.
(författare)
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PREGNANCY OUTCOMES IN RELATION TO DISEASE ACTIVITY AND ANTI-RHEUMATIC TREATMENT STRATEGIES IN WOMEN WITH RHEUMATOID ARTHRITIS - A MATCHED COHORT STUDY FROM SWEDEN AND DENMARK
- 2021
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Ingår i: ANNALS OF THE RHEUMATIC DISEASES. - : BMJ. - 0003-4967 .- 1468-2060. ; 80, s. 126-126
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Women with rheumatoid arthritis (RA) are at increased risks of adverse pregnancy outcomes, especially preterm birth (PTB) and small for gestational age (SGA). However, the link between RA disease activity, type and timing of anti-rheumatic treatment, and the risk of these outcomes remains unclear.Objectives:To explore the associations between maternal RA and PTB/SGA in relation to disease activity and use of anti-rheumatic treatment before and during pregnancy.Methods:By linking national medical birth registers to prospective clinical rheumatology registers (CRRs) in Sweden (SRQ) and Denmark (DANBIO), we identified 1739 RA-pregnancies and 17390 control-pregnancies (matched 1:10 on maternal age, birth year, and parity) with delivery 2006-2018. From CRRs and prescribed drug registers, we collected information on RA disease activity (DAS28, CRP and HAQ-score) and anti-rheumatic drugs (biologics, conventional synthetic (cs)DMARDs and oral steroids) nine months before and during pregnancy. Using logistic regression, we estimated adjusted odds ratios (ORs) with 95% confidence intervals (CI) for PTB and SGA in RA-pregnancies vs. control-pregnancies overall, and stratified by disease activity and type of anti-rheumatic treatment before and during pregnancy. Apart from the matching variables we adjusted for body mass index, smoking, educational level and country.Results:Overall, RA-pregnancies were associated with increased ORs of PTB (1.92, 95% CI 1.56-2.35) and SGA (1.93, 95% CI 1.45-2.57). High maternal disease activity during pregnancy strengthened the associations with both PTB and SGA, whereas the ORs approached 1 for low disease activity (control-pregnancies constituting the reference), Table 1. Among RA-pregnancies with available information on DAS28-CRP (n=686, 39%), OR was 2.69 (95% CI 1.37-5.26) for PTB, and 3.39 (95% CI 1.43-8.06) for SGA, comparing DAS28-CRP >=3.2 vs.<3.2 during pregnancy. Stratifying on type of anti-rheumatic treatment did not substantially change the results. Combination therapy with biologics together with oral steroids and/or csDMARDs in the nine months before pregnancy was associated with PTB (ORs spanning 2.57-3.45) and SGA (ORs spanning 2.40-3.81).Table 1.Adjusted odds ratios (ORs)1 for PTB and SGA in RA-pregnancies in relation to disease activity and functional status during pregnancy vs. control pregnanciesPreterm birthSmall for gestational age1Pregnancies, nEvents,n (%)Adjusted OR(95% CI)Pregnancies, nEvents,n (%)Adjusted OR(95% CI)Control-pregnancies217312794 (5)1 (REF)17184418 (2)1(REF)All RA pregnancies21734144 (8)1.92 (1.56-2.35)172275 (4)1.93 (1.45-2.57)DAS28-CRP3,4<3.245926 (6)1.05 (0.64-1.72)45613 (3)0.96 (0.49-1.91)3.2-5.118217 (9)2.40 (1.40-4.11)18113 (7)3.13 (1.64-5.97)>5.1435 (12)2.77 (0.86-8.87)434 (9)4.59 (1.59-13.2)No information105096 (9)2.18 (1.71-2.78)104245 (4)2.06 (1.46-2.90)HAQ-score3<0.533819 (6)1.31 (0.79-2.16)3358 (2)0.93 (0.41-2.12)0.5-0.916615 (9)2.37 (1.34-4.19)1655 (3)1.50 (0.60-3.74)≥119619 (10)1.85 (1.06-3.24)19518 (9)3.70 (2.05-6.67)No information103491 (9)2.06 (1.60-2.64)102744 (4)1.98 (1.39-2.82)CRP, mg/L3<1045521 (5)0.91 (0.55-1.51)45214 (3)1.09 (0.57-2.07)10-2919122 (11)2.58 (1.52-4.38)19012 (6)2.68 (1.38-5.22)≥30579 (16)4.59 (2.28-9.22)575 (9)4.12 (1.68-10.1)No information103192 (9)2.10 (1.64-2.70)102344 (4)2.05 (1.44-2.90)1Missingness on small for gestational age in 12 RA-pregnancies and 128 control-pregnancies 2Only among live births, i.e. stillbirths excluded. 3Maximum value any time during pregnancy 4Defined as DAS28-CRP without patient’s global health VASConclusion:During pregnancy, disease activity rather than treatment, appears to be the most important risk factor for PTB and SGA in RA. The findings highlight the importance of monitoring RA during pregnancy, especially in women receiving extensive anti-rheumatic treatment or with residual disease activity.Acknowledgements:The Nordic clinical rheumatology registers for allowing us to use their clinical data. We also would like to acknowledge the NordForsk and FOREUM, especially the patient representatives of the NordForsk collaboration.Disclosure of Interests:Karin Hellgren Consultant of: UCB, Anne Emilie Secher: None declared, Bente Glintborg Grant/research support from: Pfizer, Biogen and BMS, Ane Lilleoere Rom: None declared, Björn Gudbjornsson Speakers bureau: Amgen and Novartis, Brigitte Michelsen Consultant of: Novartis, Grant/research support from: Novartis, Fredrik Granath: None declared, Merete Lund Hetland Speakers bureau: Biogen, Celltrion, Janssen Biologics B.V, MSD, Pfizer, Samsung Biopis, Consultant of: Biogen, Celltrion, Janssen Biologics B.V, MSD, Pfizer, Samsung Biopis, Grant/research support from: AbbVie, Biogen, BMS, Eli Lilly Danmark A/S, Lundbeck Fonden, Pfizer, Roche, Sandoz, Novartis
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| 19. |
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| 20. |
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| 21. |
- Lindstrom, U, et al.
(författare)
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COMPARISON OF TREATMENT RETENTION OF SECUKINUMAB AND TNF-INHIBITORS IN PSORIATIC ARTHRITIS. OBSERVATIONAL DATA FROM A NORDIC COLLABORATION.
- 2020
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Ingår i: ANNALS OF THE RHEUMATIC DISEASES. - : BMJ. - 0003-4967 .- 1468-2060. ; 79, s. 427-428
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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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| 22. |
- Lindström, Ulf, et al.
(författare)
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Comparison of treatment retention and response to secukinumab versus tumour necrosis factor inhibitors in psoriatic arthritis
- 2021
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Ingår i: Rheumatology. - : Oxford University Press (OUP). - 1462-0324 .- 1462-0332. ; 60:8, s. 3635-3645
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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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- Ornbjerg, LM, et al.
(författare)
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SECULAR TRENDS IN BASELINE CHARACTERISTICS, TREATMENT RETENTION AND RESPONSE RATES IN 27189 BIO-NAIVE AXIAL SPONDYLOARTHRITIS PATIENTS INITIATING TNFI - RESULTS FROM THE EUROSPA COLLABORATION
- 2021
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Ingår i: ANNALS OF THE RHEUMATIC DISEASES. - : BMJ. - 0003-4967 .- 1468-2060. ; 80, s. 217-218
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Knowledge of changes over time in baseline characteristics and tumor necrosis factor inhibitor (TNFi) response in bio-naïve axial spondyloarthritis (axSpA) patients treated in routine care is limited.Objectives:To investigate secular trends in baseline characteristics and retention, remission and response rates in axSpA patients initiating a first TNFi.Methods:Prospectively collected data on bio-naïve axSpA 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 (Ankylosing Spondylitis Disease Activity Score (ASDAS) <1.3, Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) <20) and response (ASDAS Major and Clinically Important Improvement (MI/CII), BASDAI 50) rates were assessed at 6, 12 and 24 months. No statistical comparisons were made.Results:In total, 27189 axSpA patients were included (5945, 11255 and 9989 in groups A, B and C).At baseline, patients in group A were older, had longer disease duration and a larger proportion of male and HLA-B27 positive patients compared to B and C, whereas disease activity was similar across groups.Retention rates at 6, 12 and 24 months were highest in group A (88%/81%/71%) but differed little between B (84%/74%/64%) and C (85%/76%/67%).In all groups, median ASDAS and BASDAI had decreased markedly at 6 months (Table 1). The ASDAS values at 12 and 24 months and BASDAI at 24 months were higher in group A compared with groups B and C. Similarly, crude remission and response rates were lowest in group A. After adjustments for drug retention (LUNDEX), remission and response rates showed less pronounced between-group differences regarding ASDAS measures and no relevant differences regarding BASDAI measures.Conclusion:Nowadays, axSpA patients initiating TNFi are younger with shorter disease duration and more frequently female and HLA-B27 negative than previously, while baseline disease activity is unchanged. Drug retention rates have decreased, whereas crude remission and response rates have increased. This may indicate expanded indication but also a stable disease activity threshold for TNFi initiation over time, an increased focus on targeting disease remission and more available treatment options.References:[1]Arthritis Rheum 2006; 54: 600-6.Table 1.Secular trends in baseline characteristics, treatment retention, remission and response rates in European axSpA patients initiating a 1st TNFiBaseline characteristicsGroup A(1999–2008)Group B(2009–2014)Group C(2015–2018)Age, years, median (IQR)57 (49–66)51 (42–60)46 (37–56)Male, %666057HLA-B27, %877772Years since diagnosis, median (IQR)5 (1–12)2 (0–8)2 (0–7)Smokers, %232425ASDAS, median (IQR)3.5 (2.8–4.1)3.4 (2.8–4.1)3.5 (2.8–4.1)BASDAI, median, (IQR)57 (42–71)59 (43–72)57 (41–71)TNFi drug, % (Adalimumab /Etanercept / Infliximab /Certolizumab / Golimumab)22 / 35 / 43 / 0 / 037 / 21 / 20 / 4 / 1827 / 28 / 24 / 8 / 13Follow up6 months12 months24 monthsGr AGr BGr CGr AGr BGr CGr AGr BGr CRetention rates, %, (95% CI)88 (88–89)84 (83–85)85 (84–86)81 (80–82)74 (74–75)76 (75–76)71 (70–72)64 (63–65)67 (66–68)ASDAS, median, (IQR)1.8 (1.2–2.8)1.9 (1.2–2.8)1.8 (1.2–2.6)1.9 (1.3–2.6)1.7 (1.2–2.5)1.6 (1.1–2.4)1.9 (1.4–2.6)1.7 (1.1–2.4)1.5 (1.1–2.2)ASDAS inactive disease, %, c/L28 / 2528 / 2430 / 2624 / 1932 / 2434 / 2623 / 1634 / 2039 / 23ASDAS CII, %, c/L57 / 5159 / 5063 / 5461 / 5063 / 4767 / 5159 / 4168 / 4074 / 45ASDAS MI, %, c/L31 / 2732 / 2737 / 3232 / 2637 / 2741 / 3130 / 2042 / 2546 / 28BASDAI, median, (IQR)23 (10–40)26 (11–48)24 (10–44)21 (10–38)23 (10–42)20 (8–39)22 (9–40)20 (8–39)16 (6–35)BASDAI remission, %, c/L44 / 4040 / 3443 / 3645 / 3645 / 3450 / 3844 / 3048 / 2956 / 34BASDAI 50 response, %, c/L53 / 4750 / 4253 / 4557 / 4656 / 4258 / 4457 / 3960 / 3563 / 38Gr, Group; c/L, crude/LUNDEX adjusted.Acknowledgements:Novartis Pharma AG and IQVIA for supporting the EuroSpA Research Collaboration Network.Disclosure of Interests:Lykke Midtbøll Ørnbjerg Grant/research support from: Novartis, Sara Nysom Christiansen Speakers bureau: BMS and GE, 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, Ulf Lindström: None declared, Jakub Zavada: None declared, Florenzo Iannone: None declared, Fatos Onen: None declared, Michael J. Nissen Speakers bureau: Novartis, Eli Lilly, Celgene, and Pfizer, Consultant of: Novartis, Eli Lilly, Celgene, and Pfizer, Brigitte Michelsen Consultant of: Novartis, Grant/research support from: Novartis, Maria Jose Santos Speakers bureau: AbbVie, Novartis, Pfizer, Gary Macfarlane Grant/research support from: GlaxoSmithKline, Dan Nordström Consultant of: Abbvie, BMS, MSD, Novartis, Pfizer, Roche, UCB, Manuel Pombo-Suarez: None declared, Catalin Codreanu Speakers bureau: AbbVie, Amgen, Egis, Novartis, Pfizer, UCB, Grant/research support from: AbbVie, Amgen, Egis, Novartis, Pfizer, UCB, Matija Tomsic Speakers bureau: Abbvie, Amgen, Biogen, Medis, MSD, Novartis, Pfizer, Consultant of: Abbvie, Amgen, Biogen, Medis, MSD, Novartis, Pfizer, Irene van der Horst-Bruinsma Speakers bureau: Abbvie, BMS, MSD, Novartis, Pfizer, Lilly, UCB, Björn Gudbjornsson Speakers bureau: Amgen and Novartis, Johan Askling: None declared, Bente Glintborg Grant/research support from: Pfizer, Biogen, AbbVie, 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, Elisa Gremese: None declared, Nurullah Akkoc: None declared, Adrian Ciurea Speakers bureau: Abbvie, Eli-Lilly, MSD, Novartis, Pfizer, Eirik kristianslund: None declared, Anabela Barcelos: None declared, Gareth T. Jones Grant/research support from: Pfizer, AbbVie, UCB, Celgene, Amgen, GSK, Anna-Mari Hokkanen Grant/research support from: MSD, Carlos Sánchez-Piedra: None declared, Ruxandra Ionescu Speakers bureau: Abbvie, Amgen, Boehringer-Ingelheim Eli-Lilly,Novartis, Pfizer, Sandoz, UCB, Ziga Rotar Speakers bureau: Abbvie, Amgen, Biogen, Medis, MSD, Novartis, Pfizer, Consultant of: Abbvie, Amgen, Biogen, Medis, MSD, Novartis, Pfizer, Marleen G.H. van de Sande: None declared, Arni Jon Geirsson: None declared, 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, Merete L. Hetland Speakers bureau: Abbvie, Biogen, BMS, Celltrion, Eli Lilly, Janssen Biologics B.V, Lundbeck Fonden, MSD, Pfizer, Roche, Samsung Biopies, Sandoz, Novartis.
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