Rituximab for rheumatoid arthritis refractory to anti–tumor necrosis factor therapy: Results of a multicenter, randomized, double-blind, placebo-controlled, phase III trial evaluating primary efficacy and safety at twenty-four weeks

Radiant Research, Dallas, Texas 75235, USA.
Arthritis & Rheumatology (Impact Factor: 7.87). 09/2006; 54(9):2793-806. DOI: 10.1002/art.22025
Source: PubMed

ABSTRACT In addition, for the first time in a patient population who had an inadequate response to 1 or more anti-TNF agents, an exploratory analysis of radiographic data at 24 weeks demonstrated a trend toward less progression of structural joint damage. The mean increases from baseline in the total Genant-modified Sharp scores, erosion scores, and joint space narrowing scores at 24 weeks in rituximab-treated patients were half those in placebo-treated patients, with the joint space narrowing score reaching statistical significance at week 24. It is important to recognize that this portion of the trial was only 6 months in duration, allowed rescue therapy between weeks 16 and 24 (with 40% of the placebo group and 13% of the rituximab group entering the rescue protocol at or after week 16), and included intravenous and oral steroids for the first 2 weeks in both the placebo and rituximab groups. While glucocorticoids have been shown to reduce the rate of radiographic progression of RA (31), all patients in this trial received glucocorticoids. Therefore, the effects of glucocorticoids on radiographic progression could not be assessed. Additionally, all patients had previously taken anti-TNF agents. Glucocorticoid administration and previous therapy with anti-TNF agents may have affected the ability to detect significant differences in radiographic changes between treatment groups. The effect of rituximab on radiographic progression will be further evaluated in longer-term followup from this study as well as in an additional study.


Available from: Paul Emery, Sep 23, 2014
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Rheumatoid arthritis (RA) is a chronic inflammatory disease with unknown etiology that affects various pathways within the immune system, involves many other tissues and is associated with joint destruction. Current treatments fail to address pathophysiological and biochemical mechanisms involved in joint degeneration and the induction of pain. Moreover, RA patients are extremely heterogeneous and require specific treatments, the choice of which is complicated by the fact that not all patients respond to treatment. At present, patient assessment involving clinical, immunological, and radiological traits does not permit the prediction of the anti-rheumatic treatment response in approximately half of RA subjects. Recent data suggest that patient stratification, in accordance with the level of pro-inflammatory gene expression, may help to predict response to RA therapy.
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Objectives. The following study aims to evaluate the monotherapy with biologic agents: Infliximab (IFX), Etanercept (ETA), Adalimumab (ADA) and Rituximab (RTX) in patients diagnosed with rheumatoid arthritis (RA). Methods. To achieve these objectives, the database of "Dr. I. Cantacuzino" Clinical Hospital, Department of Internal Medicine and Rheumatology, was used. The study was retrospective and descriptive, covering 168 patients with RA, followed for 12 months, from January 2012 to January 2013. Admission criteria for the study were the following: patients diagnosed with RA according to ACR 1987/ EULAR 2010 criteria, disease activity score (DAS 28)> 5.1, positive inflammation tests, presence of RA refractory to classic remitting treatment administered at least 6 months prior to the initiation of biological therapy, on patients treated with RTX. They were considered non-responders after 6 months of treatment with anti tumor necrosis factor alpha (anti-TNF) and decided to switch agents with anti CD-20. Results . Comparing values between any two points in time (baseline - 6 months -12 months) for any type of therapy, there were significant decreases in the values of erythrocyte sedimentation rate (ESR), reactive C protein (CRP) and disease activity score (DAS 28). There were no significant differences between therapies regarding ESR at 6 months (p = 0.070, ANOVA) and 12 months (p = 0.375, Kruskal-Wallis), significant differences were regarding CRP at 6 and 12 months (p = 0.000, Kruskal-Wallis) and DAS 28 at 6 months (p = 0.000, Kruskal- Wallis) and 12 months (p = 0.018, Kruskal-Wallis). Conclusion . All 4 therapies have proven efficient, prognostic markers decreasing gradually at 6 and 12 months. Abbreviations: RA = rheumatoid arthritis, IFX = Infliximab, ETA = Etanercept, ADA = Adalimumab, RTX = Rituximab, ESR = erythrocyte sedimentation rate, CRP = reactive C protein, DAS 28 = disease activity score, anti TNF = inhibitor of tumor necrosis factor.
    Journal of medicine and life 01/2015; 8(1):79-84.
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Pro-inflammatory cytokines are directly implicated in the pathogenesis of Rheumatoid arthritis (RA). Variable clinical response to cytokine targeted therapies as TNFalpha and IL-6, strongly highlights the heterogeneity of inflammatory process in RA. Another cytokine, IL-15 has also been related to the inflammatory process in RA. Recently we described for the first time, the presence of its specific receptor, IL-15Ralpha, in synovial fluid (SF). The aim of this work was to compare the expression profile of IL-15Ralpha, its ligand IL-15, TNFalpha and IL-6 and how these cytokines are correlated in SF from RA patients taking as a reference Osteoarthritis (OA), an articular but not autoinmmune disease. Synovial fluids were obtained from the knee joints of 60 patients, 30 with confirmed diagnosis of RA and 30 with OA diagnosis. The levels of TNFalpha, IL-6, IL-15 and IL-15Ralpha were measured by ELISA. A statistical analysis was performed with GraphPad Prism v5.0 using the Mann-Whitney U test and Spearman's rank correlation. A cluster analysis was run in MeV software v4.9.0 and differences across clusters were evaluated by an ANOVA including post-test analysis. We found higher and significant levels of TNFalpha, IL-6 and IL-15Ralpha but not of IL-15 in RA compared with the OA group. Additionally, a high inter-individual variability in the levels of these 4 cytokines was observed in RA, although we identified 4 patients' subgroups by cluster analysis of cytokines concentration in SF. We also found a positive correlation between IL-15Ralpha-IL-6 and IL-15Ralpha-IL-15, but not for other pairs of cytokines in RA. In addition we found correlation between the value of IL-15Ralpha in SF and disease activity score, DAS28. In our current work we found a high inter-individual variability in the levels of TNFalpha, IL-6, IL-15 and IL-15Ralpha in SF of RA patients and were identified four principal clusters of cytokines concentration in SF, suggesting the importance of identifying disease subset of patients for personalized treatment. Finally, we found a correlation between IL-15Ralpha-IL-6, IL-15Ralpha-IL-15, but we did not find any correlation between other pairs of studied cytokines in SF.
    BMC Musculoskeletal Disorders 12/2015; 16(1):516. DOI:10.1186/s12891-015-0516-3 · 1.90 Impact Factor