Real-World Predictors of Success of Rituximab in RA: Viewpoint

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Highest Clinical Efficacy of Rituximab in Autoantibody-Positive Patients With Rheumatoid Arthritis and in Those for Whom No More Than One Previous TNF Antagonist Has Failed: Pooled Data From 10 European Registries

Chatzidionysiou K, Lie E, Nasonov E, et al
Ann Rheum Dis. 2011;70:1575-1580.

Background

Rituximab is a B-cell-depleting therapy that has been widely used over the past several years for the treatment of rheumatoid arthritis (RA). Typically, rituximab is used for RA after another biologic disease-modifying antirheumatic drug (DMARD) such as an anti-tumor necrosis factor agent has failed to control RA; however, it is still not clear what the optimal treatment strategy for rituximab should be. These authors used a large-scale pooled database of patients with RA in Europe that were treated with rituximab to investigate the real-world predictors of efficacy of this agent.

Study Summary

The authors identified 2019 patients from 10 European countries treated with rituximab at a dose of 2 1000 mg infusions given 2 weeks apart. They evaluated the 3- and 6-month efficacies of this treatment measured by the 28-joint count Disease Activity Score (DAS28).

The mean age of these subjects at the time of rituximab treatment was 54-years-old, 80% were female, the mean duration of RA was approximately 12 years, approximately 86% were rheumatoid factor positive, and approximately 77% were cyclic citrullinated peptide antibody (CCP) positive (although not all patients had CCP assessed). At the time of first use of rituximab, the mean DAS28 at baseline was 5.8, approximately 77% were on concomitant DMARDs, and from data on 1844 patients, 63% had failed at least 1 biologic agent.

Overall, the DAS28 improved in most patients after they received rituximab, and by 6 months, the number of patients with high disease activity (DAS28 > 5.1) had decreased from 73% to 26% (but there were substantial numbers of subjects without available data at the 6-month mark). In multivariate analyses, the predictors of a good EULAR response (DAS improved by > 1.2, and an overall score of ≤ 3.2^[1]) before initiation of rituximab were: (a) use of ≤ 1 biologic DMARD, (b) lower baseline DAS28 level, and (c) and anti-CCP positivity. The authors also found that there was a trend for patients using concomitant oral DMARDs to have improved DAS28 scores at 3 and 6 months when compared with those not taking DMARDs.

The authors conclude that rituximab was most effective in seropositive patients when used as the first biologic agent, or before the failure of > 1 anti-tumor necrosis factor agent.

Viewpoint

Controlled clinical trials can provide only limited amounts of information about drug efficacy; therefore, the approach these authors used to evaluate the "real-world" efficacy of rituximab for RA is to be applauded. Take-home points from their study are that certain patient groups may have better responses to rituximab therapy, including those treated with rituximab as a first-line biologic or before the use of multiple anti-tumor necrosis factor agents, those taking concomitant DMARDs, and those with CCP positivity (supporting findings of other studies^[2,3]; although the improvement seen in this study in patients that were sero-negative suggests that rituximab is still effective even in absence of rheumatoid factor/CCP positivity). However, because this is not a controlled trial, these findings should be interpreted with some caution because there may other factors not accounted for that influence these findings, although this study should help set the stage for additional studies that can provide more specific guidance for the use of rituximab in RA.

Highest clinical effectiveness of rituximab in autoantibody-positive patients with rheumatoid arthritis and in those for whom no more than one previous TNF antagonist has failed: pooled data from 10 European registries.

Ann Rheum Dis.  2011; 70(9):1575-80 (ISSN: 1468-2060)

Chatzidionysiou K; Lie E; Nasonov E; Lukina G; Hetland ML; Tarp U; Gabay C; van Riel PL; Nordström DC; Gomez-Reino J; Pavelka K; Tomsic M; Kvien TK; van Vollenhoven RF
Correspondence to Katerina Chatzidionysiou, Arbetargatan 28A, 1tr, c/o Gunilla Johansson, 11245 Stockholm, Sweden; aikaterini.chatzidionysiou@karolinska.se.

OBJECTIVE: To assess the 6-month effectiveness of the first rituximab (RTX) course in rheumatoid arthritis (RA) and to identify possible predictors of response.

METHOD: 10 European registries submitted anonymised datasets (baseline, 3- and 6-month follow-up) from patients with RA who had started RTX, and datasets were pooled and analysed. Heterogeneity between countries was analysed by analysis of variance. Predictors of response were identified by logistic regression.

RESULTS: 2019 patients were included (mean age/disease duration 53.8/12.1 years, 80.3% female, 85.6% rheumatoid factor (RF) positive and 76.8% (456/594 patients) anti-cyclic citrullinated peptide antibodies (anti-CCP) positive). For these patients an average of 2.7 disease-modifying antirheumatic drugs (DMARDs) (range 0-10) had failed, and RTX was given as the first biological agent in 36.6% of patients. There was significant heterogeneity between countries for several baseline characteristics, including the number of previous biological agents. Disease Activity Score based on 28 joint counts (DAS28) decreased from 5.8±1.4 at baseline to 4.2±1.4 at 6 months (p<0.0001) and 22.2%/42.5% achieved European League Against Rheumatism (EULAR) good/moderate response. Larger 6-month improvement in DAS28 was observed in RF-positive and anti-CCP-positive versus seronegative patients. The following predictors of EULAR good response at 6 months were identified in a multivariate analysis: anti-CCP positivity (OR=2.86, p=0.003), number of previous DMARDs (OR=0.84, p=0.06), ≤1 previous biological agents (OR=1.89, p=0.04), baseline DAS28 level (OR=0.74, p=0.003).

CONCLUSION: In this large observational cohort of patients with RA treated with RTX, seropositive patients achieved significantly greater reductions in DAS28 at 6 months than seronegative patients. Effectiveness was best when RTX was used as the first biological agent or after failure of no more than one anti-tumour necrosis factor agent.