Inflammation and autoantibody markers identify rheumatoid arthritis patients with
enhanced clinical benefit following rituximab treatment.
Author(s): Lal P, Su Z, Holweg CT, Silverman GJ, Schwartzman S, Kelman A, Read S, Spaniolo
G, Monroe JG, Behrens TW, Townsend MJ.
Affiliation(s): Genentech, South San Francisco, California 94080, USA.
Publication date & source: 2011, Arthritis Rheum. , 63(12):3681-91
OBJECTIVE: Rituximab significantly improves the signs and symptoms of rheumatoid
arthritis (RA) and slows the progression of joint damage. The aim of this study
was to identify clinical characteristics and biomarkers that identify patients
with RA in whom the clinical benefit of rituximab may be enhanced.
METHODS: The study group comprised 1,008 RA patients from 2 independent
randomized placebo-controlled phase III clinical trials (REFLEX [Randomized
Evaluation of Long-Term Efficacy of Rituximab in Rheumatoid Arthritis] and SERENE
[Study Evaluating Rituximab's Efficacy in Methotrexate Inadequate Responders]). A
novel threshold selection method was used to identify baseline candidate
biomarkers present in at least 20% of patients that enriched for
placebo-corrected American College of Rheumatology 50% improvement (ACR50
response; a high clinical efficacy bar) at week 24 after the first course of
rituximab.
RESULTS: The presence of IgM rheumatoid factor (IgM-RF), IgG-RF, IgA-RF, and IgG
anti-cyclic citrullinated peptide (anti-CCP) antibodies together with an elevated
C-reactive protein (CRP) level were associated with enhanced placebo-corrected
ACR50 response rates in the REFLEX patients with RA who had an inadequate
response to anti-tumor necrosis factor therapies. These findings were
independently replicated using samples from patients in SERENE who had an
inadequate response to disease-modifying antirheumatic drug treatment. The
combination of an elevated baseline CRP level together with an elevated level of
any RF isotype and/or IgG anti-CCP antibodies was further associated with an
enhanced benefit to rituximab.
CONCLUSION: The presence of any RF isotype and/or IgG anti-CCP autoantibodies
together with an elevated CRP level identifies a subgroup of patients with RA in
whom the benefit of rituximab treatment may be enhanced. Although the clinical
benefit of rituximab was greater in the biomarker-positive population compared
with the biomarker-negative population, the clinical benefit of rituximab
compared with placebo was also clinically meaningful in the biomarker-negative
population.
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