“But based on some newer trial data on conventional synthetic DMARD combination therapy,” he continued, “the task force more explicitly endorses combination of conventional synthetic DMARDs, also, early on. Preference to combination is not given because of possible limitations in designs of these trials and conflicting trial data.”
Robert Landewe, MD, PhD, professor of rheumatology at the Academic Medical Center Amsterdam, and a task force member, acknowledged that the 2010 task force has “been bashed by many comments in the literature.”
“We felt the role of glucocorticoids in the trials that were available was dominant,” he said. “And we felt trials solely investigating DMARD combination therapy at that point in time were not convincing.”
For instance, he said, the Swefot trial, which explored triple combination therapy versus methotrexate plus infliximab after a target response was not achieved after three months of methotrexate alone, dropped its intended per-arm cohort to 130 from 200.1 Plus, it involved unblinded physicians and had reduced statistical power. Moreover, it was designed as a superiority trial, but in the end was presented as a noninferior trial.
“These factors make Swefot less appropriate for considering if triple-combo should be advocated as an option before methotrexate plus biologicals,” Dr. Landewe said.
Another trial, TEAR, set out to investigate whether new-onset RA patients should be treated with step-up therapy or immediate combination therapy. But the trial missed its primary endpoint and was beset by attrition and data were missing for 37% of the patients, Dr. Landewe said.
“Making recommendations is a process that should involve all pillars of evidence-based medicine”—including patients and clinical experience—“not only ‘science,’” Dr. Landewe said. “Even the science of randomized controlled trials is subject to interpretation.”
Thomas Collins is a freelance medical writer based in Florida.
