The sooner top-level rheumatoid arthritis treatment starts, the better a patient’s chances for remission, according to a new analysis reported last week at the annual European Congress of Rheumatology, EULAR, in Rome.
Two years ago, results from the COMET study showed that starting RA patients on a combined regimen of methotrexate and etanercept led to significantly more remissions after 1 year on treatment than methotrexate alone. The new, post-hoc analysis divided the 400+ patients in the study, who began treatment 3-24 months after their RA diagnosis, into two subgroups: patients who began treatment within 4 months after their RA diagnosis, and patients who started treatment beyond 4 months.
The striking results, reported last week by Paul Emery, a rheumatologist at the University of Leeds, U.K., showed that patients begun on the tumor necrosis factor (TNF) inhibitor etanercept plus methotrexate within the first 4 months following diagnosis achieved a 70% remission rate after 1 year compared with a 48% rate in patients started on the same regimen but after the first 4 months passed. This time-dependent effect on remission rates did not appear in patients begun on methotrexate alone. In the methotrexate arms about 1/3 of patients reached remission after a year regardless of when the methotrexate started.
The 70% remission rate in the very-early treatment group jumps out as remarkably good, a “dreamed of” response rate, Prof. Emery said. The findings also reveal a clear window of opportunity. Newly diagnosed RA patients hit early with top-level treatment stand the best chance for their disease to fully resolve, a finding that extends the growing trend in rheumatology to diagnose and treat patients asap.
But the finding also sets up a tension between the potential reward from giving a TNF inhibitor plus methotrexate upfront and early and the potential downside that this strategy will put many patients on an expensive TNF inhibitor who would never need it. After all, a third of the patients in the methotrexate-only arm went into remission without ever seeing a TNF inhibitor. Will rheumatologists now need to decide between taking advantage of a transient opportunity to get the most out of treatment and the risk of giving patients a drug they might never really need?
Not necessarily. COMET ran during 2004-2006, so patients had their RA diagnosed by now obsolete criteria. New RA diagnostic criteria introduced by EULAR and the American College of Rheumatology last October aim to diagnose RA patients much earlier, and in these patients the treatment window of opportunity may be longer.
Second, even if patients start on a TNF inhibitor and methotrexate, another recent report from the Leeds group suggests that once in remission some patients can withdraw from the TNF inhibitor and remain in remission. And third, hopefully in the near future researchers will find factors that identify the patients who will not optimally respond to methotrexate alone so that adding a TNF inhibitor will not need to be done universally and in some cases needlessly.
—Mitchel Zoler (on Twitter @mitchelzoler)