CHMP Backs Abatacept (Orencia) for MTX-Naive Patients With RA

Troy Brown, RN


July 26, 2016

The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) recommended adding marketing authorization for a new indication for abatacept (Orencia, Bristol-Myers Squib Pharma EEIG) on July 21, according to a company news release.

The new indication is for abatacept by intravenous infusion or subcutaneous injection in combination with methotrexate (MTX) for the treatment of adults with highly active or progressive rheumatoid arthritis (RA) who have not previously been treated with MTX.

Abatacept is already approved in the European Union in combination with MTX for the treatment of adults with moderate to severe active RA who have responded inadequately to previous treatment with one or more disease-modifying antirheumatic drugs (DMARDs), including MTX or a tumor-necrosis factor-α inhibitor.

Abatacept is approved in the United States as monotherapy or concomitantly with DMARDs other than tumor necrosis factor antagonists.

Combination treatment with abatacept and MTX has been shown to reduce the progression of joint damage and improve physical function.

"This CHMP recommendation is particularly notable because it is the first time that MRI-detected structural and inflammatory measures of disease severity are cited as support for the proposed RA indication," Paul Emery, MD, Arthritis Research UK Professor of Rheumatology and head of the Academic Division of Musculoskeletal Disease, Leeds Institute of Molecular Medicine, University of Leeds, United Kingdom, said in the company news release.

"This is consistent with mounting evidence supporting a paradigm shift in how and when we initiate different forms of RA therapy, particularly for those patients with progressive disease accompanied by certain poor prognostic markers," Dr Emery added.

The committee's decision follows analysis of data from two phase 3 studies.

AGREE (Abatacept study to Gauge Remission and joint damage progression in MTX-naive patients with Early Erosive RA) was a 12-month, multinational, double-blind, randomized, phase 3B study of MTX-naive patients with early, quickly progressing RA. The study evaluated intravenous abatacept in combination with MTX compared with MTX alone in patients with moderate to severe RA.

The study's primary endpoints were the proportion of patients who achieved Disease Activity Score 28–C-Reactive Protein (DAS28-CRP) less than 2.6 at 1 year (41% vs 23%; P < .001) and inhibited radiographic progression at 1 year (mean change in total Sharp score, 0.6 vs 1.1; P = .04).

The AVERT (Assessing Very Early Rheumatoid Arthritis Treatment) study compared abatacept, 125 mg subcutaneous, plus MTX combination therapy; abatacept, 125 mg subcutaneous monotherapy; and MTX monotherapy in induction of DAS28-defined remission after 12 months of treatment in 351 adults with moderately to highly active early RA (mean DAS28 CRP, 5.4; mean symptom duration,<6.7 months) who had not been previously treated with MTX or other disease-modifying antirheumatic drugs (MTX-naive).

These patients also had factors that suggested their disease would progress rapidly (positive for anti–cyclic citrullinated peptide antibodies and/or rheumatoid factor, with presence of baseline joint erosions). The study's primary endpoints were the proportion of patients with DAS28-defined remission (DAS28 CRP < 2.6) at month 12 and both months 12 and 18 for abatacept plus MTX compared with MTX monotherapy. At 12 months, significantly more patients in the combination therapy group achieved DAS28-defined remission compared with those in the MTX-only group (60.9% for abatacept plus MTX; 45.2% for MTX alone).

Abatacept plus MTX combination therapy was also more effective than MTX monotherapy at 12 months for Boolean remission (37.0% for abatacept plus MTX; 22.4% for MTX alone), Clinical Disease Activity Index remission (42% for abatacept plus MTX; 27.6% for MTX alone), and Simple Disease Activity Index remission (42% for abatacept plus MTX; 25% for MTX alone).

The most commonly reported adverse events, which occurred at a rate of at least 10% in those who took abatacept in the adult RA clinical studies, were headache, upper respiratory tract infection, nasopharyngitis, and nausea.

The European Commission will review the committee's opinion and decide whether to approve the additional indication for abatacept.

An updated summary of product characteristics will be published in the revised European public assessment report after the European Commission grants marketing authorization for abatacept. It will be available in all official European Union languages and will provide detailed recommendations for the use of abatacept.

Dr Emery is a coinvestigator of the AVERT study.

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