Bristol-Myers Squibb Company has announced that the European Commission approved a new indication for Orencia (abatacept), in combination with methotrexate (MTX), for the treatment of moderate to severe active rheumatoid arthritis (RA) in adult patients who have responded inadequately to previous therapy with one or more disease-modifying anti-rheumatic drugs (DMARDs) including MTX or a TNF-alpha inhibitor.

"This is a very welcome decision from the European Commission and one which will potentially have a positive impact on treatment outcomes for RA patients who have already experienced inadequate response to a first DMARD," said Dr. Manuela Le Bars, European Medical Lead for Immunoscience, Bristol-Myers Squibb. "There is a growing body of evidence to show that earlier use of Orencia may have significant benefits for patients - for both short-term and long-term efficacy. This new indication means patients have the potential to benefit sooner from incremental improvements in function and quality of life provided by Orencia."

The approval of Orencia as a first line biologic after DMARD inadequate response was supported by data from a two-year open-label study from a trial in methotrexate (MTX)-naïve RA patients (AGREE), as well as by long-term open-label data from the core RA clinical trial programme in MTX inadequate responders (IR) (AIM, ATTEST, and a Phase IIb study) and in anti-TNF-IRs (ATTAIN and ARRIVE). These data indicate that Orencia may provide improved outcomes in short-term efficacy as well as durable and sustained long-term efficacy (up to seven years as demonstrated in the Phase IIb study) when used with MTX earlier in the RA treatment paradigm. In addition, a sustained reduction in the rate of progression of structural damage up to five years was demonstrated in the AIM trial.

In the AGREE trial in MTX-naïve patients, 53% of patients with RA who had not previously received treatment with a DMARD and were subsequently treated with Orencia plus MTX (n=256) achieved ACR50 at six months, compared to 38% of patients who were treated with placebo plus MTX (n=253) (p<0.001); In the AIM trial in MTX-IR, 40% of patients with RA who had an inadequate response to MTX alone and were subsequently treated with Orencia plus MTX (n=424) achieved ACR50 at six months, compared to 17% of patients who were treated with placebo plus MTX (n=214) (p<0.001); In the ATTAIN trial in TNF-IR, 20% of patients with RA who had an inadequate response to TNF inhibitors and were subsequently treated with Orencia plus DMARDs (n=256) achieved ACR50 at six months compared to 4% of patients who were treated with placebo plus DMARDs (n=133) (p<0.001).

In the ATTEST trial, which was a randomized double-blind study to assess the efficacy and safety of Orencia or infliximab versus placebo in MTX-IR, it was demonstrated that the efficacy of Orencia and of infliximab vs. placebo was similar at six months. Further improvement was observed with Orencia at 12 months. At six months, the incidences of infections were 48.1% (75), 52.1% (86) and 51.8% (57) and the incidences of infections were 1.3% (2), 4.2% (7) and 2.7% (3) for the Orencia, infliximab and placebo groups, respectively. At 12 months, the incidences of infections were 59.6% (93), 68.5 (113) and the incidences of infections were 1.9% (3) and 8.5% (14) for the Orencia and infliximab groups, respectively. In those patients who initially received infliximab and then switched to Orencia, the reductions in the mean Disease Activity Score (DAS28)† from baseline were 3.29 at day 729 and 2.48 at day 365.

"Control of the disease in all its aspects is the goal of treatment in RA," said Prof. Dr. René Westhovens, of the University of Leuven in Belgium. "As with other DMARDs, Orencia has the potential to help patients reach a state of remission. The expanded indication of Orencia into an earlier line of RA treatment is part of the wider evolution of RA management that will increasingly allow us to slow the progression of the disease."

Orencia is a selective co-stimulation modulator of T-cell activation. Orencia is designed to prevent full T-cell activation and inhibit the release of chemicals leading to joint inflammation and destruction as observed in RA and pJIA.

Orencia is the first biologic discovered and developed in Bristol-Myers Squibb research centres and was first approved for adult RA in May 2007 by the European Commission.

Orencia in combination with MTX is indicated for the treatment of moderate to severe active RA in adult patients who responded inadequately to previous therapy with one or more DMARDs including MTX or a TNF-alpha inhibitor. A reduction in the progression of joint damage and improvement of physical function have been demonstrated during combination treatment with Orencia and MTX.

Orencia, in combination with MTX, is also indicated for the treatment of moderate to severe active polyarticular Juvenile Idiopathic Arthritis in paediatric patients six years of age and older who have had an insufficient response to other DMARDS, including at least one TNF inhibitor. Orencia has not been studied in children under six years old.

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