AT ACR 2017
SAN DIEGO (FRONTLINE MEDICAL NEWS) – Despite the well-recognized role of methotrexate in the management of rheumatoid arthritis, about 30% of patients with RA discontinue treatment with methotrexate 1-2 years after starting it, according to results from a registry study.
“We know that methotrexate is an acceptable and certainly well-characterized treatment for RA,” study author Jeffrey R. Curtis, MD, said at the annual meeting of the American College of Rheumatology. “Despite, this, though, patterns of persistence, intolerance, and inadequate response with methotrexate [MTX] are not well characterized in real-world settings. We all get the sense that there are patients who greatly dislike it.”
In an effort to compare the characteristics and reasons for MTX discontinuation in patients with RA who received MTX either as monotherapy or in combination with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), Dr. Curtis and his associates drew from the U.S. Corrona RA registry, an independent, observational database of patients with inflammatory arthritides. The registry is comprised of 174 practices in 41 U.S. states; it includes 686 participating rheumatologists and data on 46,544 patients.
The researchers analyzed patients not previously treated with a biologic DMARD (bDMARD) or a targeted synthetic DMARD (tsDMARD). They compared 1,488 patients who initiated MTX monotherapy with 656 patients who initiated MTX in combination with csDMARDs during October 2001 through February 2017 and had at least one follow-up visit after treatment initiation.
The mean age of patients was 57 years, 75% were female, and 84% were white. Patients in the MTX combination therapy group were more likely to be white, better educated, and employed, but were slightly less likely to have active disease. Dr. Curtis reported that the proportion of MTX monotherapy patients who discontinued MTX was 24% at 1 year, 37% at 2 years, and 46% at 3 years, and was not significantly different from the figures for the combination MTX therapy group (P = .99). “The survival curve was overlapping and nonsignificant,” said Dr. Curtis, professor of medicine in the division of clinical immunology and rheumatology at the University of Alabama at Birmingham. “For example, at 12 months, 24.4% of people stopped methotrexate if they had started it alone, but it was 26% if they were on combination therapy. Flipping that around, 75% stayed on MTX at 1 year’s time.”
In contrast, the researchers also found that patients in the MTX monotherapy group were significantly more likely to start a bDMARD or a tsDMARD earlier than patients in the MTX combination therapy group (P less than .001). In an adjusted Cox proportional hazards model, higher risk for MTX discontinuation was associated with being disabled (hazard ratio, 1.33), being retired (HR, 1.37), or using alcohol regularly (the HR ranged from 1.22 to 2.03 depending on the mean units consumed per day). MTX discontinuation was less likely in patients with older age (HR, 0.94), longer duration of RA (HR, 0.92), or higher baseline Clinical Disease Activity Index score (HR, 0.96).
About 20% of physicians in the registry provided reasons for discontinuation of MTX. The top reasons they gave were the presence of infection and cancer (about 85% and 15%, respectively). The reasons patients gave for discontinuation of MTX were wide ranging and included unusual fatigue (about 67%), followed by stomach problems (48%), hair loss (about 36%), mental fog (about 29%), sores in the mouth (about 25%), nausea (about 19%), and diarrhea (about 19%). “Patients are telling us very different things about why this drug is being stopped,” Dr. Curtis said. “Doctors in this registry could specify a reason for stopping that would map to these reasons, and yet they didn’t.”
He acknowledged certain limitations of the study, including the potential for missing data and the possibility that some of the patients may have reinitiated MTX. “We know from other data that people may stop MTX for a period of time but then may resume it,” Dr. Curtis said. Going forward, he called for strategies “to better identify patients with suboptimal persistence to MTX and predict those most likely to not tolerate MTX, to optimize overall RA treatment.”
The study was supported by Corrona, and the analysis was funded by Pfizer. Dr. Curtis reported that he has received research grants from Amgen, Corrona, Crescendo Bioscience, and Pfizer, and consulting fees from AbbVie, Amgen, Bristol-Myers Squibb, Corrona, Myriad, Pfizer, Roche/Genentech, and UCB.