RESEARCH - Rituximab inhibits structural joint damage in RA patients with an inadequate response to TNF inhibitor therapies

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Ann Rheum Dis. Published Online First: 3 April 2008. doi:10.1136/ard.2007.085787

Copyright © 2008 BMJ Publishing Group Ltd & European League Against

Rheumatism

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Extended Report

Rituximab inhibits structural joint damage in rheumatoid arthritis

patients with an inadequate response to tumour necrosis factor

inhibitor therapies

C Keystone 1*, Emery 2, G fy 3,

Tak 4, Stanley Cohen 5, Mark C Genovese 6, Maxime Dougados 7, Gerd R

Burmester 8, Greenwald 9, Tore K Kvien 10, 11,

Hagerty 12, W Cravets 12 and Tim Shaw 11

1 Mount Sina Medical School, United States

2 Leeds General Infirmary, United Kingdom

3 Synarc Inc.,, United States

4 Academic Medical Center/University of Amsterdam, Netherlands

5 St. University Hospital, United States

6 Stanford University, United States

7 Hôpital Cochin, France

8 Charité – University of Medicine Berlin, Germany

9 Desert Medical Advances, United States

10 Diakonhjemmet Hospital, Norway

11 Roche Products Ltd., United Kingdom

12 Biogen Idec Inc., United States

Abstract

Objective: To determine if treatment with a B cell-targeted therapy

can inhibit the progression of structural joint damage in patients

with rheumatoid arthritis (RA), exhibiting an inadequate response to

tumour necrosis factor (TNF) inhibitors.

Methods: In this Phase III study, patients with an inadequate response

to a TNF inhibitor and receiving methotrexate were randomised to

rituximab or placebo. Radiographs were obtained at baseline, Week 24

and Week 56 after randomisation. Patients with an inadequate response

to their randomised therapy could receive rescue medication from Week

16. From Week 24, eligible patients from both treatment arms could

receive open-label rituximab. Patients were analysed according to

their original treatment group. Radiographs were scored using the

Genant-modified Sharp method. The primary radiographic endpoint was

change in total Genant-modified Sharp score at Week 56.

Results: Rituximab treatment caused significant reduction in joint

damage progression compared with placebo. The mean change from

baseline in the total Genant-modified Sharp score at Week 56 was

significantly lower for rituximab-treated patients treated than for

placebo-treated patients (1.00 vs 2.31; p = 0.005), and was supported

by changes in erosion score (0.59 and 1.32 for rituximab plus

methotrexate vs placebo plus methotrexate, respectively; p = 0.011)

and joint space narrowing score (0.41 and 0.99, respectively; p <

0.001).

Conclusions: This study provides the first evidence that a B

cell-targeted therapy—rituximab—can significantly inhibit the

progression of structural joint damage in RA patients with

long-standing, active, and treatment-resistant disease.

http://ard.bmj.com/cgi/content/abstract/ard.2007.085787v1?papetoc

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