ACR Meeting Abstracts

ACR Meeting Abstracts

Abstract Number: 1280

Sustained Efficacy Responses and a Consistent Safety Profile with Rituximab Repeat Treatment Over 5 Years in Patients with Rheumatoid Arthritis and an Inadequate Response to Tumour Necrosis Factor Inhibitors

Edward Keystone1, Stanley B. Cohen2, Paul Emery3, Joel M. Kremer4, Maxime R. Dougados5, James E. Loveless6, Carol Chung7, Pamela Wong7, Patrica B. Lehane8 and Helen Tyrrell8, 1The Rebecca MacDonald Centre for Arthritis and Autoimmunity, Mount Sinai Hospital, Toronto, ON, Canada, 2Metroplex Clinical Research Center, Dallas, TX, 3Division of Rheumatic & Musculoskeletal Disease, University of Leeds, Leeds, United Kingdom, 4Center for Rheumatology, Albany Medical College, Albany, NY, 5Hopital Cochin, René Descartes University, Paris, France, 6St Luke's Rheumatology, Boise, ID, 7Genentech, Inc., South San Francisco, CA, 8Roche Products Limited, Welwyn Garden City, United Kingdom

Meeting: 2012 ACR/ARHP Annual Meeting

Keywords:

Session Information

Title: Rheumatoid Arthritis Treatment - Small Molecules, Biologics and Gene Therapy

Session Type: Abstract Submissions (ACR)

Background/Purpose: In the REFLEX study conducted in anti-TNF inadequate responder (TNF-IR) patients with RA, a single course of rituximab (RTX) in combination with methotrexate (MTX) significantly improved disease activity at 24 weeks vs placebo (PBO) + MTX. Patients were eligible for continued RTX treatment in an open-label extension (OLE). Efficacy and safety outcomes from REFLEX and its OLE over 5 years are presented.

Methods: This was an observational, post-hoc analysis of REFLEX from baseline to 5 years, open label from the second study treatment. Patients originally randomized to PBO were rescued with RTX as appropriate and included in the OLE. Patients with a response to initial RTX treatment were eligible for further RTX treatment courses. RTX retreatment was administered as needed based on SJC and TJC ≥8 and at the discretion of the physician (≥24 weeks following first RTX course and ≥16 weeks following additional courses). PBO patients were re-baselined prior to their first RTX treatment and for this analysis PBO data were pooled with RTX patient data from time of first RTX treatment. Efficacy outcomes 24 weeks after each RTX course were calculated relative to first RTX pre-treatment baseline. No imputations were made for missing data. Safety data included rates of AEs, serious AEs (SAEs), infections, and serious infections (SIEs).

Results: Overall, 480 patients received at least one course of RTX. Subsequent RTX courses were given to 317 (≥2 courses), 259 (≥3 courses), 195 (≥4 courses), and 122 (≥5 courses) patients. Most withdrawals occurred after course 1, mainly for non-safety reasons. ACR responses were improved after the first course of RTX and were maintained over 5 courses (Table) with a similar trend observed for EULAR responses.

ACR response rates (% patients) at 24 weeks after each course
Clinical measure Course 1
(n=400)		 Course 2
(n=279)		 Course 3
(n=225)		 Course 4
(n=161)		 Course 5
(n=91)
ACR20 62.0 72.8 72.4 65.8 70.3
ACR50 30.8 41.2 47.6 44.7 41.8
ACR70 13.0 19.4 26.2 24.2 22.0

The proportion of patients achieving a minimal clinically important difference in HAQ-DI was maintained over 5 courses (66.0–71.1%). Over the 5 years, rates of AEs, SAEs, and infections did not increase and generally remained stable in the RTX-treated population (1768 pt-yrs), with overall rates per 100 pt-yrs (95% CI) of 344.87 (336.32–353.64) for AEs, 22.34 (20.24–24.65) for SAEs, 97.50 (93.01–102.21) for all infections, and 5.60 (4.60–6.82) for SIEs. The most frequent SIE was pneumonia, affecting 2% of RTX patients.

Conclusion: This post-hoc analysis shows that RTX repeat treatment is associated with 24-week clinical efficacy responses, sustained to 5 courses, with a trend towards improved efficacy over time. The safety profile of RTX was comparable with published RTX long-term safety data and with that of other biologics in RA populations. No increased incidence of significant AEs was observed in spite of RTX exposure and peripheral B-cell depletion over many years. The results confirm RTX as an effective long-term treatment option in this refractory RA population.

Disclosure:

E. Keystone,

Abbott, Amgen, AstraZeneca, Bristol-Meyers Squibb, Centocor, Roche, Genzyme, Merck, Novartis, Pfizer, UCB,

2,

Abbott, AstraZeneca, Biotest, Bristol-Meyers Squibb, Centocor, Roche, Genentech, Merck, Nycomed, Pfizer, UCB,

5;

S. B. Cohen,

Abbott, Amgen, AstraZeneca, Bristol-Meyers Squibb, Centocor, Roche, Genzyme, Merck, Novartis, Pfizer, UCB,

2,

Amgen, Bristol-Meyers Squibb, Roche/Genentech, Merck, Pfizer,

5;

P. Emery,

Pfizer, Merck, Abbott, BMS, Roche, UCB,

5;

J. M. Kremer,

Roche, Genentech,

2,

Genentech,

5;

M. R. Dougados,

Roche, Abbott, Pfizer, BMS, UCB, Novartis, Merck,

2,

Roche, Abbott, Pfizer, BMS, UCB, Novartis, Merck,

5;

J. E. Loveless,

Roche,

2,

Roche, Genentech,

5,

Roche,

8;

C. Chung,

Genentech, Inc (full time),

3;

P. Wong,

Genentech, Inc (full time),

3;

P. B. Lehane,

Roche,

3;

H. Tyrrell,

Roche ,

1,

Roche,

3.

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