Alice Goodman

June 23, 2014

PARIS — After 12 months of treatment with abatacept, some adults with highly active early rheumatoid arthritis (RA) and a poor prognosis achieved drug-free remission at 18 months in a new phase 3b study.

"AVERT is the first study to show sustained remission following the withdrawal of all RA therapy, including biologics, methotrexate, and steroids," said investigator Paul Emery, MD, from the University of Leeds in the United Kingdom.

"Abatacept-treated patients with shorter symptom duration, lower baseline disease activity, or longer sustained DAS remission prior to treatment withdrawal were more likely to sustain drug-free remission," he explained. "These results support the first-line treatment of adults with RA with abatacept."

Dr. Emery, who is past president of the European League Against Rheumatism (EULAR), presented the AVERT results here at the EULAR Congress 2014.

In AVERT, investigators assessed the ability of abatacept, with or without methotrexate, to induce remission at 12 months and to maintain it after the rapid withdrawal of all RA treatments.

The 351 adults enrolled in the study had symptoms of RA for less than 2 years, had anti-cyclic citrullinated peptide antibodies, had a disease activity score in 28 joints (DAS28) based on C-reactive protein (CRP) above 3.2, and had not been previously treated with methotrexate or biologic therapies for RA.

The coprimary end points of the study were the proportion of patients with disease remission (DAS28 CRP <2.6) at month 12 and month 18.

Patients were randomly assigned 1 of 3 treatments for 12 months: combination therapy with abatacept 125 mg plus methotrexate, abatacept 125 mg monotherapy, or methotrexate monotherapy.

At 12 months, patients with low disease activity (DAS28 CRP <3.2) entered the 12-month withdrawal phase of the study, and all study drugs and any RA treatment, including steroids, were rapidly withdrawn.

During the withdrawal phase, 79.4% of patients went back on therapy because of worsening RA symptoms.

At 18 months, drug-free remission rates were higher in the combination and abatacept monotherapy groups than in the methotrexate monotherapy group (14.2% vs 12.4% vs 7.8%).

Findings on MRI scans used to assess joint changes paralleled those seen on clinical assessment.

No new safety concerns were raised during the study, and safety was comparable in the combination and abatacept monotherapy groups.

Table 2. Events at 12 Months

Event Combination Therapy, % Abatacept Monotherapy, % Methotrexate Monotherapy, %
Serious adverse event 6.7 12.1 7.8
Treatment discontinuation 1.7 4.3 2.6

 

The mechanism of action of abatacept might explain why some patients were able to achieve drug-free remission for extended periods of time, said EULAR president Gerd Burmester, MD, from the Charité-Universitätsmedizin in Berlin, Germany, who was one of the AVERT investigators.

"As we have learned, T-cells are the 'brain' of RA. Abatacept interferes with the binding of autoantigen-presenting cells to T-cells," he told Medscape Medical News.

"The beauty of this study is that it used MRI to assess joint progression in a large patient population, which gave a good picture of what is going on with early changes in RA," he explained.

"I think x-rays will not be used in the future because they give us answers too late in the course of disease to detect changes and intervene early. The secret in rheumatology is to treat as early as possible," he said.

"These results support the concept of early combination therapy in many patients with severe active arthritis. In the long term, it does seem that therapy can be somewhat de-escalated," said Eric Matteson, MD, chair of rheumatology at the Mayo Clinic in Rochester, Minnesota, who was not involved in the study, in an email to Medscape Medical News.

"The study results point out, again, that we need better biomarkers to identify patients who are most likely to benefit from combination therapy," he added.

Dr. Emery reports financial relationships with AbbVie, BMS, Merck, Pfizer, Roche, and Takeda. Dr. Burmester reports financial relationships with BMS, AbbVie, Pfizer, MedImmune, MSD, Novartis, Roche, UCB, and Lilly. Dr. Matteson has disclosed no relevant financial relationships.

European League Against Rheumatism (EULAR) Congress 2014: Abstract OP0026. Presented June 12, 2014.

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