Abatacept (Orencia) Approved for the Treatment of Refractory Rheumatoid
Arthritis

On Dec. 27, the FDA approved abatacept (Orencia injection, made by
Bristol-Myers Squibb Company), for reducing signs and symptoms, inducing
major clinical response, slowing the progression of structural damage, and
improving physical function in adult patients with moderately to severely
active rheumatoid arthritis (RA).

Abatacept is indicated for use in patients who have had inadequate response
to one or more disease-modifying antirheumatic drugs (DMARDS) such as
methotrexate or tumor necrosis factor (TNF) antagonists. It may be used
alone or concomitantly with DMARDs other than TNF antagonists; concurrent
use of anakinra is not recommended.

A selective costimulator modulator, abatacept binds to CD80 and CD86 to
block the interaction with CD28 required for full T lymphocyte (T cell)
activation. Activated T cells have been found in the synovium of patients
with RA and are implicated in the pathogenesis of the disease.

The approval was based on data from three double-blind, randomized,
placebo-controlled, phase 3 clinical studies: Abatacept in Inadequate
responders to Methotrexate (AIM); Abatacept Trial in Treatment of Anti-TNF
Inadequate responders (ATTAIN); and Abatacept Study of Safety in Use with
other RA thErapies (ASSURE).

Results of the two efficacy studies (AIM and ATTAIN) showed that the
addition of abatacept to methotrexate or non-biologic DMARDs yielded
significant and sustained improvements in RA signs and symptoms, relative to
use of the respective agents alone, as measured by ACR 20, 50, and 70 scores
at 6 months.

Significant improvements in physical function were also observed in the
abatacept arm of both trials, and patients reported significant improvements
in health-related quality of life for all 8 domains of the short form 36
(SF-36) questionnaire.

In addition, a significant proportion of patients receiving abatacept plus
methotrexate (MTX) in the AIM study achieved a major clinical response
(defined as maintaining an American College of Rheumatology (ACR) 70 score
for 6 consecutive months), compared with those receiving MTX alone (14% vs
2%, P < .001).

The most commonly observed adverse events occurring in at least 10% of
patients treated with abatacept included headache, upper respiratory tract
infection, nasopharyngitis, and nausea. Infusion reactions occurred in 9% of
patients, and the incidence of dizziness, headache, and hypertension ranged
from 1 to 2%. Significant infection, experienced by 3% of those taking
abaracept compared with 1.9% of those taking placebo, is one of the most
serious adverse reactions, as is a higher rate of lymphoma and other
malignancies when compared to the general population. Live vaccines should
not be given within 3 months of use of abatacept and caution should be
exercised when using this drug in those with an underlying condition that
predisposes them to infections. Treatment should be discontinued if serious
infection develops.

Abatacept is administered as a 30-minute infusion at a fixed dose based on
weight range (approx. 10-mg/kg) at day 0, 2 weeks, and every 4 weeks
thereafter. Although premedication was not required in clinical trials,
appropriate support measures should be available for immediate use in the
event of a hypersensitivity reaction.

According to a company news release, the product is expected to be available
for commercial use by the end of February 2006.

I was in the trial during 2 years.

Wil

Belgium