| 31. |
- Eriksson, Jonas K., et al.
(författare)
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Biological vs Conventional Combination Treatment and Work Loss in Early Rheumatoid Arthritis A Randomized Trial
- 2013
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Ingår i: JAMA Internal Medicine. - : American Medical Association (AMA). - 2168-6114 .- 2168-6106. ; 173:15, s. 1407-1414
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Tidskriftsartikel (refereegranskat)abstract
- IMPORTANCE The introduction of biological tumor necrosis factor inhibitors has improved the treatment of rheumatoid arthritis (RA) but at a substantial cost. These drugs have been shown to lead to superior radiological outcomes compared with a combination of conventional disease-modifying antirheumatic drugs over 2 years. OBJECTIVE To investigate whether radiological superiority translates into better work loss outcomes. DESIGN, SETTING, AND PARTICIPANTS Multicenter, 2-arm, parallel, randomized, active-controlled, open-label trial. Patients with early RA (symptom duration <1 year) were recruited from 15 rheumatology clinics in Sweden from October 1, 2002, through December 31, 2005. The study population was restricted to working-age patients (aged <63 years). INTERVENTIONS Patients who did not achieve low disease activity after 3 to 4 months of methotrexate therapy were randomized to receive additional biological treatment with infliximab or conventional combination treatment with sulfasalazine plus hydroxychloroquine. MAIN OUTCOMES AND MEASURES Monthly sick leave and disability pension days 21 months after randomization retrieved from the nationwide Swedish Social Insurance Office register. Main analyses were by intention to treat, including all patients, and adjusted for baseline sick leave and disability pension. RESULTS Of 204 eligible patients, 105 were randomized to biological and 99 to conventional treatment. Seven patients in the biological and 4 in the conventional treatment group never received the study drug, and 72 and 52 patients, respectively, followed the study per protocol for 21 months. The baseline mean (SD) work loss was 17 (13) d/mo (median, 16 d/mo) in both groups (mean difference, 0.6 d/mo; 95% CI, -3.0 to 3.9). The mean changes in work loss at 21 months were -4.9 d/mo in the biological and -6.2 d/mo in the conventional treatment group (adjusted mean difference, 1.6 d/mo; 95% CI, -1.2 to 4.4). Including only patients receiving at least 1 dose of assigned treatment, the adjusted mean difference was 1.5 d/mo (95% CI, -1.5 to 4.4), and in per-protocol analysis the adjusted mean difference was 0.3 d/mo (95% CI, -2.8 to 3.8). CONCLUSIONS AND RELEVANCE The radiological superiority of biological compared with conventional combination therapy did not translate into better work loss outcomes in patients with early RA who had experienced an insufficient response to methotrexate.
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| 32. |
- Eriksson, Jonas K, et al.
(författare)
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Infliximab Versus Conventional Combination Treatment and Seven-Year Work Loss in Early Rheumatoid Arthritis : Results of a Randomized Swedish Trial
- 2016
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Ingår i: Arthritis Care and Research. - : Wiley. - 2151-4658 .- 2151-464X. ; 68:12, s. 1758-1766
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Tidskriftsartikel (refereegranskat)abstract
- Objective To compare long-term work loss in methotrexate-refractory early rheumatoid arthritis (RA) randomized to addition of infliximab or conventional combination treatment. Methods Multicentre, two-arm, parallel, randomized, active-controlled, open-label trial. RA patients with <1y symptom duration were recruited from 15 rheumatology clinics in Sweden between 2002-2005. Patients who did not achieve low disease activity after 3-4 months methotrexate therapy were randomized to addition of infliximab or conventional combination treatment with sulfasalazine+hydroxychloroquine. Yearly sick leave and disability pension days over 7 years after randomization were retrieved from nationwide registers kept by the Swedish Social Insurance Agency. Results Of 210 working age patients, 109 were randomized to infliximab (mean age=48.4y, 73% women) and 101 to conventional treatment (48.7y, 77%). The year before randomization the mean number of annual work days lost was 127 in the infliximab arm and 118 in the conventional treatment group (mean difference, 9; 95%CI, -23 to 39). Compared to the year before randomization, the mean changes at 7 years were -25 days in the infliximab and -26 days in the conventional treatment group (adjusted mean difference, 10; 95%CI, -25 to 46). The mean cumulative work loss days was 846 in the infliximab group and 701 in the conventional treatment group (adjusted mean difference, 104; 95%CI, -56 to 284). Conclusions Long-term work loss improved significantly in early RA randomized to infliximab+methotrexate or conventional combination therapy. No difference was detected between strategies, and the level of work loss days remained twice that observed in the general population.TRIAL REGISTRATION NUMBER: NCT00764725 This article is protected by copyright. All rights reserved.
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| 33. |
- Fanouriakis, Antonis, et al.
(författare)
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EULAR recommendations for the management of systemic lupus erythematosus : 2023 update
- 2024
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Ingår i: Annals of the Rheumatic Diseases. - : HighWire Press. - 0003-4967 .- 1468-2060. ; 83:1, s. 15-29
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: To update the EULAR recommendations for the management of systemic lupus erythematosus (SLE) based on emerging new evidence.METHODS: An international Task Force formed the questions for the systematic literature reviews (January 2018-December 2022), followed by formulation and finalisation of the statements after a series of meetings. A predefined voting process was applied to each overarching principle and recommendation. Levels of evidence and strengths of recommendation were assigned, and participants finally provided their level of agreement with each item.RESULTS: The Task Force agreed on 5 overarching principles and 13 recommendations, concerning the use of hydroxychloroquine (HCQ), glucocorticoids (GC), immunosuppressive drugs (ISDs) (including methotrexate, mycophenolate, azathioprine, cyclophosphamide (CYC)), calcineurin inhibitors (CNIs, cyclosporine, tacrolimus, voclosporin) and biologics (belimumab, anifrolumab, rituximab). Advice is also provided on treatment strategies and targets of therapy, assessment of response, combination and sequential therapies, and tapering of therapy. HCQ is recommended for all patients with lupus at a target dose 5 mg/kg real body weight/day, considering the individual's risk for flares and retinal toxicity. GC are used as 'bridging therapy' during periods of disease activity; for maintenance treatment, they should be minimised to equal or less than 5 mg/day (prednisone equivalent) and, when possible, withdrawn. Prompt initiation of ISDs (methotrexate, azathioprine, mycophenolate) and/or biological agents (anifrolumab, belimumab) should be considered to control the disease and facilitate GC tapering/discontinuation. CYC and rituximab should be considered in organ-threatening and refractory disease, respectively. For active lupus nephritis, GC, mycophenolate or low-dose intravenous CYC are recommended as anchor drugs, and add-on therapy with belimumab or CNIs (voclosporin or tacrolimus) should be considered. Updated specific recommendations are also provided for cutaneous, neuropsychiatric and haematological disease, SLE-associated antiphospholipid syndrome, kidney protection, as well as preventative measures for infections, osteoporosis, cardiovascular disease.CONCLUSION: The updated recommendations provide consensus guidance on the management of SLE, combining evidence and expert opinion.
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| 34. |
- Ferreira, Isabel, et al.
(författare)
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Nitrated nucleosome levels and neuropsychiatric events in systemic lupus erythematosus; a multi-center retrospective case-control study
- 2017
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Ingår i: Arthritis Research and Therapy. - : Springer Science and Business Media LLC. - 1478-6354 .- 1478-6362. ; 19:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: In patients with systemic lupus erythematosus (SLE) there is no serological test that will reliably distinguish neuropsychiatric (NP) events due to active SLE from those due to other causes. Previously we showed that serum levels of nitrated nucleosomes (NN) were elevated in a small number of patients with NPSLE. Here we measured serum NN in samples from a larger population of patients with SLE and NP events to see whether elevated serum NN could be a marker for NPSLE. Methods: We obtained serum samples from patients in the Systemic Lupus International Collaborative Clinics (SLICC) inception cohort. This included 216 patients with NP events and two matched controls with SLE but no NP events for each of these patients. For the NP patients we tested samples taken before, during and after the NP event. Results: Twenty-six patients had events attributed to SLE according to the most stringent SLICC attribution rule. In these patients there was no association between onset of event and elevated serum NN. In 190 patients in whom events were not attributed to SLE by the SLICC rules, median serum NN was elevated at the onset of event (P = 0.006). The predominant clinical features in this group of 190 patients were headache, mood disorders and anxiety. Conclusions: Serum NN levels rise at the time of an NP event in a proportion of patients with SLE. Further studies are needed to determine the value of serum NN as a biomarker for NPSLE.
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| 35. |
- Fisher, Benjamin A., et al.
(författare)
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Antibodies to citrullinated α-enolase peptide 1 and clinical and radiological outcomes in rheumatoid arthritis
- 2011
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Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 70:6, s. 1095-1098
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION:The anticyclic citrullinated peptide 2 (anti-CCP2) assay is a generic test for antibodies to citrullinated proteins, among which there is a subset of about 50% with antibodies to citrullinated enolase peptide 1 (CEP-1). The anti-CEP-1 positive subset is strongly associated with the HLA-DRB1 shared epitope and its interaction with smoking.OBJECTIVE:To investigate whether anti-CEP-1 antibodies may be helpful in predicting outcome.METHODS: Anti-CEP-1 and anti-CCP2 antibodies were measured in two prospective cohorts of patients (Karolinska n=272, Norfolk Arthritis Register (NOAR) n=408) with early rheumatoid arthritis (RA). Outcomes measured were C-reactive protein, erythrocyte sedimentation rate, visual analogue scales for pain and global assessment of disease activity, Health Assessment Questionnaire, physician's assessment, swollen and tender joint counts and radiological progression.RESULTS: Anti-CCP2 antibodies were present in 57% and 50%, and anti-CEP-1 in 27% and 24% of the Karolinska and NOAR cohorts, respectively. Importantly, no statistically significant differences in clinical outcomes were demonstrated between the anti-CEP-1-/CCP2+ and the anti-CEP-1+/CCP2+ subsets in either cohort, or in radiological outcomes in the Karolinska cohort.CONCLUSION: Although antibodies to specific citrullinated proteins may have distinct genetic and environmental risk factors, the similarity in clinical phenotype suggests that they share common pathways in the pathogenesis of joint disease in RA.
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| 36. |
- Gabay, Cem, et al.
(författare)
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Tocilizumab monotherapy versus adalimumab monotherapy for treatment of rheumatoid arthritis (ADACTA) : a randomised, double-blind, controlled phase 4 trial.
- 2013
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Ingår i: The Lancet. - 0140-6736 .- 1474-547X. ; 381:9877
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Roughly a third of patients with rheumatoid arthritis treated with biological treatments receive them as monotherapy. Tocilizumab--an inhibitor of interleukin 6 receptor signalling--has been studied as monotherapy in several clinical trials. We assessed the efficacy and safety of tocilizumab monotherapy compared with adalimumab monotherapy for patients with rheumatoid arthritis.METHODS: We did this randomised, double-blind, parallel-group, phase 4 superiority study in 76 centres in 15 countries in North and South America, Australasia, and Europe. We enrolled patients who were aged at least 18 years, had severe rheumatoid arthritis for 6 months or more, and were intolerant to methotrexate or were inappropriate for continued methotrexate treatment. Patients were randomly assigned (1:1; block size of four) to receive tocilizumab 8 mg per kg bodyweight intravenously every 4 weeks plus placebo subcutaneously every 2 weeks or adalimumab 40 mg subcutaneously every 2 weeks plus placebo intravenously every 4 weeks for 24 weeks. Investigators, patients, and sponsor personnel were masked to assignment. The primary endpoint was change in disease activity score using 28 joints (DAS28) from baseline to week 24. This trial is registered with ClinicalTrials.gov, number NCT01119859.FINDINGS: We screened 452 patients and enrolled 326 patients. The intention-to-treat population contained 325 patients (163 assigned to tocilizumab, 162 assigned to adalimumab). Week 24 mean change from baseline in DAS28 was significantly greater in the tocilizumab group (-3·3) than in the adalimumab group (-1·8) patients (difference -1·5, 95% CI -1·8 to -1·1; p<0·0001). 16 of 162 (10%) patients in the adalimumab group versus 19 of 162 (12%) in the tocilizumab group had serious adverse events. More patients in the tocilizumab group than in the adalimumab group had increased LDL-cholesterol, increased alanine aminotransferase concentrations, and reduced platelet and neutrophil counts.INTERPRETATION: Tocilizumab monotherapy was superior to adalimumab monotherapy for reduction of signs and symptoms of rheumatoid arthritis in patients for whom methotrexate was deemed inappropriate. The adverse event profiles of tocilizumab and adalimumab were consistent with previous findings.FUNDING: F Hoffmann-La Roche.
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| 37. |
- Gunnarsson, Iva, et al.
(författare)
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Histopathologic and clinical outcome of rituximab treatment in patients with cyclophosphamide-resistant proliferative lupus nephritis
- 2007
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Ingår i: Arthritis and Rheumatism. - : John Wiley & Sons. - 0004-3591 .- 1529-0131. ; 56:4, s. 1263-1272
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Rituximab is a monoclonal antibody directed against the CD20 marker of B cells. Because of its ability to deplete B lymphocytes, it has been suggested that the drug could be of benefit in B cell-dependent diseases, including systemic lupus erythematosus (SLE). The purpose of this study was to investigate the histopathologic and clinical effects of combination treatment with rituximab and cyclophosphamide (CYC) in patients with CYC-resistant proliferative lupus nephritis.METHODS: Seven female patients with proliferative lupus nephritis were treated with rituximab in combination with CYC. Renal biopsies were performed before treatment and during followup. SLE activity was evaluated by the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) and the British Isles Lupus Assessment Group index. In 6 of the 7 patients, immunostaining of lymphocyte subpopulations in the renal tissue was performed before treatment and during followup.RESULTS: At 6 months of followup, significant clinical improvement was noted, with a reduction in SLEDAI scores (from a mean of 15 to 3), anti-double-stranded DNA antibody levels (from a mean of 174 IU/ml to 56 IU/ml), and anti-C1q antibody levels (from a mean of 35 units/ml to 22 units/ml). On repeat renal biopsy, improvement in the histopathologic class of nephritis occurred in a majority of patients, and a decrease in the renal activity index was noted (from 6 to 3). A reduction in the number of CD3, CD4, and CD20 cells in the renal interstitium was noted in 50% of the patients on repeat biopsy.CONCLUSION: At 6 months of followup, all patients had responded both clinically and histopathologically to combination therapy. For patients with proliferative lupus nephritis who fail to respond to conventional immunosuppressive therapy including CYC, combined treatment with rituximab and CYC may constitute a new treatment option.
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| 38. |
- Hallert, Eva, 1947-
(författare)
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Disease activity, function and costs in early rheumatoid arthritis
- 2006
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Rheumatoid arthritis (RA) is a major cause of progressive joint damage and disability, and is associated with decline in quality of life, reduced ability to work and increased health care utilisation. The economic consequences of the disease are substantial for the individuals and their families and for the society as a whole. This thesis describes a 5-year follow up of 320 patients with early RA, enrolled between January 1996 and April 1998 in the Swedish multi-centre inception cohort TIRA (early interventions in rheumatoid arthritis). Health status, function and costs were investigated. Predictors of high costs were calculated, and an algorithm was constructed to predict future need for TNFinhibitor treatment in patients not responding to traditional disease-modifying antirheumatic drugs (DMARDs). Clinical and laboratory data, measures of functional capacity and self-reported assessments were collected regularly. In addition, patients completed biannual/annual questionnaires concerning all health care utilisation and days lost from work due to the disease. Within 3 months, improvements were seen regarding all variables assessing disease activity and functional ability, but 15% of the patients had sustained high or moderate disease activity throughout the study period. The scores of ‘health assessment questionnaire’ (HAQ) were similar for men and women at baseline, but had a less favourable course in women, who also had DMARDs more frequently prescribed.Ambulatory care accounted for 76% of the direct costs during the first year. Women had more ambulatory care visits and higher usage of complementary medicine compared to men. Men ≥65 years had low costs compared to younger men and compared to women of all ages. In multiple logistic regression tests, HAQ, high levels of IgM-class rheumatoid factor (RF), and poor hand function increased the odds of incurring high direct costs. Poor hand function and pain increased the odds of incurring high indirect costs.Indirect costs exceeded direct costs all three years. The average direct costs were €3,704 (US$ 3,297) year 1 and €2,652 (US$ 2,360) year 3. All costs decreased over the years, except those for medication and surgery. The indirect costs were €8,871 (US$ 7,895) year 1 and remained essentially unchanged, similarly for both sexes. More than 50% were on sick leave or early retirement at inclusion. Sick leave decreased but was offset by increase in early retirement. 14 patients (5%) were prescribed TNF-inhibitors at the 3- year follow up, thus increasing drug costs substantially. However, they incurred higher costs even before prescription of anti-TNF therapy.At the 5-year follow-up (2001-2003), 31 patients (12%) were prescribed TNFinhibitors. Baseline values of erythrocyte sedimentation rate, C-reactive protein, anti-CCP antibodies and morning stiffness were significantly higher in this group. These patients were also to a larger extent RF-positive and carriers of the ‘shared epitope’ (SE). Anti-TNF treated patients were significantly younger and more often women. For men, a predictive model was constructed using baseline data including SE+ and IgA-RF >100 U/L and anti-CCP >240 U/L yielding a specificity of 98% and a sensitivity of 71%. For women, disease activity score (DAS28) at the 3-month follow-up proved to be a better predictor, and the final model comprised SE+ and 3-month DAS28>5.2, giving a specificity of 95% and a sensitivity of 59%.
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| 39. |
- Hambardzumyan, Karen, et al.
(författare)
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A Multi-Biomarker Disease Activity Score and the Choice of Second-Line Therapy in Early Rheumatoid Arthritis After Methotrexate Failure
- 2017
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Ingår i: Arthritis & Rheumatology. - : Wiley. - 2326-5191 .- 2326-5205. ; 69:5, s. 953-963
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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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| 40. |
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