Genentech Inc, Biogen Idec and Roche announced the results of a phase II study showing that two doses of Rituxan (Rituximab), administered two weeks apart, improved symptoms in patients with moderate-to-severe rheumatoid arthritis (RA) for up to 48 weeks when combined with methotrexate (MTX), compared to MTX alone.

Preliminary findings from this study, first presented at the 2002 and 2003 meetings of the American College of Rheumatology (ACR), included both a primary analysis of patients at week 24 and an exploratory analysis at week 48.

The randomized, double blind, placebo-controlled study demonstrated that patients with moderate-to-severe RA receiving the combination of Rituxan with MTX and a brief course of corticosteroids produced higher ACR 20, 50 and 70 responses than with MTX alone. A subsequent exploratory analysis also demonstrated that responses were sustained for up to 48 weeks.

"The study provides support for the concept that B-lymphocytes play a central role in rheumatoid arthritis and suggests that B-lymphocyte targeted therapy has potential," said Professor Jonathan Edwards, University College of London, lead investigator for the study.

In the study, investigators administered patients with two infusions of Rituxan on day one and day 15 and followed patients for up to 104 weeks to assess the response of Rituxan alone or in combination with MTX or cyclophosphamide (CTX) compared to MTX alone (control arm). The primary efficacy results at 24 weeks showed that the proportion of patients reaching the primary endpoint of improving by at least 50 per cent in disease scores (ACR 50) was significantly greater in the Rituxan- combination-treated groups compared with patients in the control arm of the study.

The study included 161 patients from 11 countries with moderate-to-severe, active, long-standing RA (mean duration 10.4 years) who had previously failed one to five disease-modifying anti-rheumatic drugs (DMARDs) and responded inadequately to MTX at the time of entering the study.

"Our study reveals the role that B-cells may play in a wide range of immunological or autoimmune diseases such as lupus and multiple sclerosis," said Hal Barron, Genentech senior vice president of Development and Chief Medical Officer. "We are committed to understanding the underlying mechanisms by which these diseases progress to help provide potential new therapies for patients and physicians," he added.

"RA affects over two million Americans, and despite recent advances in therapy, many patients do not respond or respond inadequately to current treatments," said Burt Adelman, executive vice president, Development, Biogen Idec.

According to the investigators, the study's safety results indicate that all three Rituxan regimens had similar levels and type of adverse events compared to MTX-alone arm. Peripheral blood immunoglobulin levels remained within the normal range throughout the treatment cycle. Most adverse events were reported during the initial 15 days, and many were associated with the first infusion of Rituxan. Overall, the infusion reactions were less frequent and severe than those observed in studies with non-Hodgkin's lymphoma (NHL) patients.

The majority of events were mild-to-moderate in severity. They included transient hypo- and hypertension, cough, pruritus and rash. At week 48, the incidence and types of events, including infections, were evenly balanced between all groups. During the period of week 24 to week 48, a total of four additional serious adverse events were reported. These included two serious infections (arytenoiditis, infection of the cartilage in the back of the wind pipe, in the Rituxan+CTX group and viral gastroenteritis in the Rituxan-alone group). The other events were goitre (Rituxan-alone) and replacement of a renal stent (Rituxan+MTX).