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Real-World Predictors of Success of Rituximab in RA

Kevin Deane, MD
Posted: 08/30/2011

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.

Abstract

References

1. Fransen J, van Riel PL. The disease activity score and the EULAR response criteria. Clin Exp Rheumatol.
2005;23:S93-S99.
2. Cohen SB, Emery P, Greenwald MW, et al. 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. Arthritis Rheum. 2006;54:2793-2806.
3. Quartuccio L, Fabris M, Salvin S, et al. Rheumatoid factor positivity rather than anti-CCP positivity, a lower disability
and a lower number of anti-TNF agents failed are associated with response to rituximab in rheumatoid arthritis.
Rheumatology (Oxford). 2009;48:1557-1559.

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