Abatacept and Adalimumab Equally Effective in RA

Kate Johnson

June 13, 2012

June 13, 2012 (Berlin, Germany) — Abatacept (Orencia, Bristol-Myers Squibb) and adalimumab (Humira, Abbott) were shown to be equal in the first head-to-head comparison of biologic disease-modifying antirheumatic drugs, according to research reported here at the European League Against Rheumatism (EULAR) Congress 2012.

"We can say at the end of the day that the efficacy was parallel, the kinetics were parallel, the x-ray data were parallel, and the safety was close," said Michael Schiff, MD, from the University of Colorado in Denver, and lead investigator of the AMPLE (Abatacept Versus Adalimumab Comparison in Biologic-Naive RA Subjects With Background Methotrexate) trial.

"What we were really trying to do is show that one can have a choice between a T-cell inhibitor and a TNF [tumor necrosis factor] inhibitor," Dr. Schiff said during a press conference. Until now, "there have really not been head-to-head studies looking at different biologic agents — AMPLE is the first to look at this in a standard-of-care setting," he explained.

The AMPLE trial is clinically relevant because it directly compared abatacept and adalimumab in combination with methotrexate, which is how they are normally used, Dr. Schiff added.

"We were trying to answer a standard-of-care question," he said. "Methotrexate is still the anchor therapy. It will continue to be the anchor therapy for years to come; we're comfortable with it, we know its safety profile, we know how to deal with it, and we have excellent clinical response in about one third of patients."

The AMPLE trial is a phase 3b randomized investigator-blinded noninferiority study that is scheduled to run for 24 months. The primary end point is efficacy, defined as meeting the American College of Rheumatology 20% improvement criteria (ACR20) at 12 months.

The study involved 646 biologic-naïve patients with active RA and an inadequate response to methotrexate monotherapy. All patients received a stable dose of methotrexate, and were randomized to either subcutaneous abatacept 125 mg weekly (without an intravenous load) or to subcutaneous adalimumab 40 mg biweekly.

At 12 months, the ACR20 response rates were 64.8% for abatacept and 63.4% for adalimumab, Dr. Schiff reported. The pattern was similar for the ACR50 response (46.2% vs 46.0%) and for the ACR70 response (29.2% vs 26.2%). "Abatacept and adalimumab track exactly the same. Also, when we see the kinetics of this, they look much the same...and rapidity of response is quite important here," he said. At week 4 of the trial, ACR20 response was 42.5% for abatacept and 47.6% for adalimumab.

Radiographic nonprogression was similar in the abatacept and adalimumab groups (84.8% vs 88.6%) at 12 months, he said. "Both drugs have been shown to slow radiographic progression, but in this head-to-head trial, we found that there was no difference [between the drugs], and most patients did not progress. We were able to inhibit radiologic progression."

Rates of adverse and serious adverse events, serious infections, and malignancies were also similar between the groups, although they were slightly higher in the adalimumab group, noted Dr. Schiff.

Specifically, there was less discontinuation related to adverse events in the abatacept group than in the adalimumab group (3.5% vs 6.1%); the same was true for discontinuations related to serious adverse events (1.3% vs 3.0%) and those related to infections (0.0% vs 1.5%). There were also fewer injection-site reactions in the abatacept group than in the adalimumab group (3.8% vs 9.1%; P = .006).

Although this was designed as a noninferiority trial, Dr. Schiff explained that they did do a superiority analysis on injection-site reactions, which showed the superiority of abatacept. Other than this, there was very little difference between the 2 drugs.

"We have done subanalyses looking at men vs women, older vs younger, higher vs lower disease activity score, duration of disease.... There was no difference.... AMPLE is evidence that we have 2 very powerful drugs in our armamentarium for patients with RA," he concluded.

"Today, we have a clear choice between the 2," said Xavier Mariette, MD, PhD, from Hôpital Bicêtre in Paris, France, and EULAR scientific chair, in an interview with Medscape Medical News.

However, it is important to remember that there is a different mechanism of action for each drug, he said. Abatacept is a T-cell inhibitor, whereas adalimumab is a TNF inhibitor.

"With anti-TNF inhibitors, we have long-term safety data. We don't have long-term data with the new biologics. Now the challenge is to find which patient is going to benefit more from which drug."

Dr. Schiff reports being a consultant for Bristol-Myers Squibb, and being on the speakers bureau of Abbott. Several of his coauthors have ties to Bristol-Myers Squibb and Abbott, and several are employees of Bristol-Myers Squibb, with shares in the company. Dr. Mariette has disclosed no relevant financial relationships.

European League Against Rheumatism (EULAR) Congress 2012: Abstract OP0022. Presented June 7, 2012.

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