Continued inhibition of structural damage over 2 years in patients with rheumatoid arthritis treated with rituximab in combination with methotrexate (original) (raw)
Related papers
Annals of the Rheumatic Diseases, 2012
BackgroundIn the IMAGEstudy, rituximab plus methotrexate (MTX) inhibited joint damage and improved clinical outcomes at 1 year in MTX-naïve patients with early active rheumatoid arthritis.ObjectiveThe aim of this study was to assess joint damage progression and clinical outcomes over 2 years.MethodsPatients (n=755) were randomised to receive rituximab 2×500 mg+MTX, 2×1000 mg+MTX or placebo+MTX. The placebo-controlled period continued to week 104. Two-year end points were defined as secondary or exploratory and included change in total Genant-modified Sharp score (mTSS), total erosion score and joint space narrowing score from baseline to week 104. Clinical efficacy and physical function end points were also assessed.ResultsAt 2 years, rituximab 2×1000 mg+MTX maintained inhibition of progressive joint damage versus MTX alone (mTSS change 0.41 vs 1.95; p<0.0001 (79% inhibition)), and a higher proportion of patients receiving rituximab 2×1000 mg+MTX had no radiographic progression o...
Annals of the Rheumatic Diseases, 2012
Background/objective Progression of joint damage is linked to disease activity. This link is dissociated upon treatment with tumour necrosis factor (TNF)-or IL-6inhibitors plus methotrexate (MTX). It is hitherto unknown if this may also be true for therapies targeting B-cells. We thus evaluated if rituximab (RTX) therapy inhibits joint damage irrespective of its effects on disease activity. Methods We used a random 90% sample of data from two arms of the IMAGE trial comprising patients with active early rheumatoid arthritis (RA) receiving MTX (n=188) or MTX+RTX 1000 mg (n=204). Patients were divided into low, moderate and high disease activity at one year of treatment by simplified disease activity index (low disease activity (LDA), moderate disease activity (MDA), high disease activity (HDA)), or by swollen joint count (SJC) or C reactive protein (CRP) tertiles. Progression of damage by the Genant modified total Sharp score (TGSS) was compared between therapies (Kruskal-Wallis, Wilcoxon tests) for each of these subgroups. Results In patients treated with MTX, 1-year progression of TGSS In LDA, MDA and HDA was 0.40±0.88, 1.04 ±1.73, and 1.31±3.02, respectively. In contrast, on RTX +MTX, TGSS progression was 0.38±1.07, 0.39±1.28, and −0.05±0.44, respectively (for MDA and HDA the progression of TGSS was significantly lower in the combined group than in the MTX group: p=0.003 and p=0.05, respectively). Additional analyses (tertiles of SJC, CRP, and matching for disease activity) confirmed the primary analysis. Conclusions In early RA, progression of joint damage increases with increasing disease activity on MTX. RTX plus MTX retards damage independently of its effects on disease activity, since even in HDA destruction is halted, contrasting MTX monotherapy. This indicates that beyond cytokine blockade (TNF-and IL-6 inhibitors), also celldirected therapy (anti-CD20 antibody) conveys profound anti-destructive effects and dissociates the link between disease activity and joint damage.
Rheumatology (Oxford, England), 2013
The most cost-effective dosing regimen for rituximab treatment in RA is currently unknown. The objective of this study is to determine whether low rituximab serum levels are associated with progression of structural damage in RA patients. Sixty-two RA patients were treated with rituximab in three different centres. Structural damage was assessed on radiographs of hands and feet before and 1 year after therapy using the Sharp-van der Heijde scoring method (SHS). Patients were divided into progressors vs non-progressors based on different cut-off values. Rituximab serum levels were measured by sandwich ELISA after 4 and 12 weeks (Leiden University Medical Center and University Medical Centre, Utrecht cohorts) or 4 and 16 weeks (Academic Medical Center/University of Amsterdam cohort). There was no difference in rituximab levels between progressors and non-progressors 4 weeks and 12 or 16 weeks after initiation of treatment in the different cohorts. There was also no correlation between...
Annals of the rheumatic diseases, 2014
To evaluate changes in structural damage and joint inflammation assessed by MRI following rituximab treatment in a Phase 3 study of patients with active rheumatoid arthritis (RA) despite methotrexate (MTX) who were naive to biological therapy. Patients were randomised to receive two infusions of placebo (n=63), rituximab 500 mg (n=62), or rituximab 1000 mg (n=60) intravenously on days 1 and 15. MRI scans and radiographs of the most inflamed hand and wrist were acquired at baseline, weeks 12 (MRI only), 24 and 52. The primary end point was the change in MRI erosion score from baseline at week 24. Patients treated with rituximab demonstrated significantly less progression in the mean MRI erosion score compared with those treated with placebo at weeks 24 (0.47, 0.18 and 1.60, respectively, p=0.003 and p=0.001 for the two rituximab doses vs placebo) and 52 (-0.30, 0.11 and 3.02, respectively; p<0.001 and p<0.001). Cartilage loss at 52 weeks was significantly reduced in the rituxim...
2015
Citation for published version (APA): Peterfy, C., Emery, P., Tak, P. P., Østergaard, M., DiCarlo, J., Otsa, K., ... Gabriele, A. (2016). MRI assessment of suppression of structural damage in patients with rheumatoid arthritis receiving rituximab: results from the randomised, placebo-controlled, double-blind RA-SCORE study. Annals of the Rheumatic Diseases, 75(1), 170177. https://doi.org/10.1136/annrheumdis-2014-206015
Joint Bone Spine, 2014
Introduction: Rituximab (RTX) is a monoclonal anti-CD20 antibody approved for the treatment of rheumatoid arthritis (RA) in association with methotrexate (MTX). Objectives: To evaluate the efficacy and safety of RTX-MTX combination therapy compared with RTX alone in the treatment of RA. Methods: We analyzed data from a prospective cohort study, the Italian biologic register GISEA, to investigate the efficacy and safety of rituximab. Moreover, the adverse events (AE) and the causes of discontinuation therapy were analyzed. Results: We identified 338 RA patients, 162 treated with RTX and 176 with RTX-MTX. After 52 and 104 weeks of therapy the disease activity score in 28 joints and the Health Assessment Questionnaire Score were available in 168 patients (78 with RTX-MTX and 60 with RTX alone), showing significant reduction without differences among the two groups. AE were reported in 142 patients (42%), for a total * Corresponding author. Please cite this article in press as: Sebastiani M, et al. Efficacy and safety of rituximab with and without methotrexate in the treatment of rheumatoid arthritis patients: Results from the GISEA register. Joint Bone Spine (2014), http://dx.
The Journal of Rheumatology, 2012
Objective.This 5-year observational posthoc analysis of the REFLEX study and its open-label extension assessed clinical efficacy, radiographic response, and safety of rituximab (RTX) in patients with rheumatoid arthritis (RA) who had an inadequate response to tumor necrosis factor (TNF) inhibitors.Methods.Patients in REFLEX were originally randomized to placebo (PBO) + methotrexate (MTX; PBO-randomized) or RTX + MTX (RTX-randomized). PBO-randomized patients were rescued with RTX as appropriate. Patients responding to initial RTX treatment could receive further RTX courses. For clinical efficacy and safety analyses, PBO-randomized patients were re-baselined prior to first RTX treatment and the data were pooled with RTX-randomized patient data. Efficacy outcomes 24 weeks after each course were calculated relative to first RTX pretreatment baseline. Radiographic outcomes were assessed relative to randomization baseline for both PBO-randomized and RTX-randomized groups.Results.A total o...
Joint Bone Spine, 2012
Rituximab has been shown to be efficient in the treatment of rheumatoid arthritis (RA) when associated with methotrexate (MTX). The purpose of this study was to evaluate the response to this treatment in daily practice in the following three specific situations: rheumatoid factor (RF)-negative RA patients, rituximab monotherapy patients and TNF␣ inhibitors-naive patients. Methods: This retrospective observational study is an exploratory analysis of the response to rituximab. One thousand milligrams (1000 mg) of rituximab was administered twice at an interval of 15 days. Therapeutic response was determined at mean 20 weeks after the infusion on the basis of DAS28 scores and EULAR response criteria. Results: One hundred and eight patients were included in the study and the responses of 95 of these were evaluated. Of the latter, 75% were EULAR responders. There was no significant difference in EULAR response between patients treated with rituximab and MTX (73.8%) and those who had received rituximab alone (79.3%). Similarly, there was no difference in the number of EULAR responders between patients who had received TNF inhibitor beforehand (74.1%) and those who had not (78.6%). However, interval to retreatment was significantly shorter in TNF inhibitor-naive patients. Lastly, a significant difference (P = 0.02) in EULAR response rate was observed between RF-positive patients (84.8%) and RFnegative patients (57.9%). Interval to retreatment was also significantly shorter in RF-negative patients. Conclusion: In our experience, while our RTX efficacy findings appear to be consistent with the results of comparable controlled trials, whether or not in association with MTX, or with prior administration of one or several TNF inhibitors, RF-positive RA patients exhibited a higher EULAR response rate than RF-negative RA patients.