Drs. Lal, Su, Holweg, Kelman, Read, Spaniolo, Monroe, Behrens, and Townsend own stock or stock options in Genentech/Roche.
Inflammation and autoantibody markers identify rheumatoid arthritis patients with enhanced clinical benefit following rituximab treatment†
Version of Record online: 29 NOV 2011
Copyright © 2011 by the American College of Rheumatology
Arthritis & Rheumatism
Volume 63, Issue 12, pages 3681–3691, December 2011
How to Cite
Lal, P., Su, Z., Holweg, C. T. J., Silverman, G. J., Schwartzman, S., Kelman, A., Read, S., Spaniolo, G., Monroe, J. G., Behrens, T. W. and Townsend, M. J. (2011), Inflammation and autoantibody markers identify rheumatoid arthritis patients with enhanced clinical benefit following rituximab treatment. Arthritis & Rheumatism, 63: 3681–3691. doi: 10.1002/art.30596
ClinicalTrials.gov identifiers: NCT00468546 (REFLEX [Randomized Evaluation of Long-Term Efficacy of Rituximab in Rheumatoid Arthritis]) and NCT00299130 (SERENE [Study Evaluating Rituximab's Efficacy in Methotrexate Inadequate Responders]).
- Issue online: 29 NOV 2011
- Version of Record online: 29 NOV 2011
- Accepted manuscript online: 30 AUG 2011 10:08AM EST
- Manuscript Accepted: 2 AUG 2011
- Manuscript Received: 28 JUN 2010
- Hoffmann-La Roche
- Biogen Idec
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.
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.
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.
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.