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Orencia Combo Tops in Early, Severe RA

MedpageToday

PARIS -- In a study of patients with poor-prognosis early rheumatoid arthritis, more patients treated with abatacept (Orencia) plus methotrexate were in remission at 1 year than were those on methotrexate alone, a researcher reported here.

At 12 months, 60.9% of patients receiving the combination had achieved remission, which was defined as a disease activity score in 28 joints below 2.6, as did 42.5% of those on abatacept monotherapy and 45.2% of those given only methotrexate, according to , of the University of Leeds in England, and colleagues.

Action Points

  • Note that this study was published as an abstract and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.

The odds ratio for 12-month remission with combination treatment versus methotrexate was 2.01 (95% CI 1.18-3.43, P=0.01), he reported at the annual

This was a phase IIIb randomized study known as AVERT, or Assessing Very Early Rheumatoid Arthritis Treatment, which evaluated the safety and efficacy of subcutaneous abatacept for 1 year. In addition, the trial considered whether response could be maintained for an additional 6 months after withdrawal of all rheumatoid arthritis medications.

Abatacept was given weekly in doses of 125 mg, with or without methotrexate. Participants had active synovitis in at least two joints for 2 months or more, had baseline disease activity scores in 28 joints (DAS28) above 3.2, and had disease duration of less than 2 years.

A total of 351 patients with highly active disease were included. Their mean disease duration was roughly 6 months, mean DAS28 was 5.4, mean Health Assessment Questionnaire score was 1.4, and 95.2% were seropositive for both rheumatoid factor and anti-cyclic citrullinated protein antibodies.

"These patients had bad disease," Emery said.

Those whose DAS28 was below 3.2 at 12 months had all their arthritis treatments withdrawn, but if they experienced a flare by 15 months, open-label abatacept plus methotrexate was restarted.

At most time points throughout the study, efficacy was highest in the abatacept plus methotrexate group, with efficacy in the abatacept monotherapy arm falling between the combination and methotrexate-only arms.

The rates of patients whose DAS28 was below 2.6 at both 12 and 18 months were 14.8% for the combination group, 12.4% for the abatacept monotherapy group, and 7.8% for the methotrexate group.

Accordingly, approximately 25% of patients on abatacept who were in remission at 12 months were still in remission at 18 months after the withdrawal of treatment, Emery said.

The odds ratio for remission at both time points in the combination group was 2.51 (95% CI 1.02-6.18, P=0.045) versus methotrexate alone, and 2.04 (95% CI 0.81-5.14) for abatacept alone.

During the randomized phase of the study, serious adverse events occurred in 6.7%, 12.1%, and 7.8% of the combination, abatacept-only, and methotrexate groups, respectively. Serious infections occurred in 0.8%, 3.4%, and 0%.

A post-hoc analysis found that patients whose DAS28 was below 2.6 at both 12 and 18 months had numerically lower DAS28 and HAQ scores at baseline, and had shorter symptom duration.

"This was the first study to show sustained remission after withdrawal of all RA medications, including biologics, methotrexate, and steroids," Emery said.

"These patients had very early but very active disease. With milder disease we might have had more dramatic carryover after medication withdrawal," he noted.

Disclosures

Emery and colleagues disclosed financial relationships with multiple companies, including Bristol-Myers Squibb, AbbVie, Merck, Pfizer, Roche, Takeda, Novartis, UCB, Lilly, Amgen, Pfizer, Actelion, Gilead, sanofi-aventis, and Abbott.

Primary Source

European League Against Rhematism

Source Reference: Emery P, et al "Induction of clinical remission followed by drug-free withdrawal with abatacept combination and monotherapy in early RA: results from the AVERT study over 18 months" EULAR 2014; Abstract OP0026.