MADRID, Spain — Abatacept (Orencia, Bristol-Myers Squibb) and adalimumab (Humira, Abbott), 2 popular biologics, have similar efficacy and safety in patients with moderate to severe rheumatoid arthritis (RA), according to the first head-to-head trial comparing the agents.
Results of the trial, known as AMPLE, are a "leap forward," said lead investigator Michael Schiff, MD, from the University of Colorado in Denver, because they show a second agent, abatacept, is as effective as the current favorite, adalimumab, when patients experience an incomplete response to methotrexate.
"This is a special study because adalimumab is the most commonly used drug to treat RA worldwide, and abatacept is also widely used," Dr. Schiff said here at the European League Against Rheumatism Congress 2013. "The robust dataset demonstrates that subcutaneous abatacept and adalimumab are equally efficacious in clinical, functional, and radiographic outcomes in moderate to severe RA. This gives clinicians the data to make an informed choice about which biologic agent to add.
"The first head-to-head study to compare one biologic with another is historic," Ulf Müller-Ladner, from the University of Geissen in Germany, who was not involved in the study, told Medscape Medical News. "This blinded study provides useful data for clinicians in selecting treatment for real-world patients."
The AMPLE trial is a phase 3 randomized study of 646 biologic-naïve patients with active RA on a stable dose of methotrexate. The researchers randomized patients 1:1 to abatacept or adalimumab treatment for 2 years.
First-year results presented in 2012 and published earlier this year, as reported by Medscape Medical News, showed that 64.8% of the abatacept-treated patients and 63.4% of the adalimumab-treated patients achieved at least a 20% response, according to American College of Rheumatology criteria (Arthritis Rheum. 2013;65:28-38). About 85% experienced inhibition of radiographic progression.
Final 2-year results comparing the antitumor necrosis factor inhibitors show the responses seen at year 1 were maintained. Both drugs achieved similar clinical efficacy and inhibition of radiographic disease progression.
Table. AMPLE Responses at 2 Years
| American College of Rheumatology Criteria | Abatacept (%) | Adalimumab (%) |
| ACR20 | 59.7 | 60.1 |
| ACR50 | 44.7 | 46.6 |
| ACR70 | 31.1 | 29.3 |
| ACR90 | 14.5 | 8.2 |
At 2-years, about 85% of patients were free of radiographic progression, Dr. Schiff reported. "The main question for patients is whether side effects mean that they will discontinue the drug."
Similar numbers of adverse events were reported in the 2 groups, but there were fewer discontinuations with abatacept. There were also fewer adverse events leading to discontinuation with abatacept than with adalimumab (3.8% vs 9.5%). The same was true for serious adverse events (1.6% vs 4.9%).
The rate of infections leading to discontinuation was very low in both the abatacept and adalimumab groups (0.0% vs 0.6%); there were 2 cases of tuberculosis in the adalimumab group.
Dr. Schiff said that it is expensive and time-consuming to conduct trials like AMPLE, but more such studies are needed. "It would be really helpful to conduct a head-to-head trial when we have multiple choices of treatments. Hopefully, these trials will happen," he added.
Many clinical trials compare a new drug to placebo, "but patients don't care how placebo works," Dr. Schiff pointed out. "They want to know how the new drug works compared with standard therapy. Now that we have so many biologics available for RA, clinicians need direct comparisons to aid in the selection of therapy."
When asked by Medscape Medical News to comment on the slight safety signal favoring abatacept, Dr. Müller-Ladner said that it is not important because the adverse effects of both drugs were in line with previous experience; therefore, these safety data should not affect decision-making.
"There was no new safety signal for either drug," he said. "We really can choose between these 2 subcutaneous drugs. This study provides proof for what we are already doing with patients."
Dr. Schiff reports receiving funding from Bristol-Myers Squibb, the maker of abatacept, and Abbott, the manufacturer of adalimumab. Dr. Muller-Ladner reports receiving financial support from every company that markets biologic therapies.
European League Against Rheumatism (EULAR) Congress 2013: Abstract OP0044. Presented June 13, 2013.
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Cite this: Abatacept, Adalimumab Equal Head-to-Head for RA at 2 Years - Medscape - Jun 14, 2013.
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