Methotrexate Underutilized in RA

Methotrexate, considered the anchor treatment for rheumatoid arthritis because of its effectiveness, tolerability and cost, is substantially underutilized in both its oral and subcutaneous formulations. While the latter has been shown to be tolerable with superior efficacy as compared with oral methotrexate, its use as a strategy preceding the switch to a biologic, has increased only marginally in recent years.

These findings, published in the Nov. 18 online issue of Arthritis Care & Research, suggest the need for efforts to change methotrexate prescribing practices.

While guidelines from both the American College of Rheumatology and the European League Against Rheumatism name methotrexate as first-line therapy, European League Against Rheumatism guidelines also recommend that methotrexate doses should be sufficient at 25-30 mg per week - but they do not specify the route of administration, Rohr, et al. point out.

Researchers, led by James R. O’Dell, M.D., of the University of Nebraska Medical Center, conducted a retrospective analysis of methotrexate prescribing practices in the United States between 2009 and 2012 for rheumatoid arthritis patients. The analysis included 35,640 methotrexate-naive patients who were started on oral methotrexate and had a five-year follow-up. For 25 percent of patients (13,270), a biologic was given as initial therapy and subcutaneous methotrexate was prescribed to 7 percent (3,800) patients.

Of the 35,640 patients who started on oral methotrexate, 15,599, or 44 percent, remained on this therapy for five years. But for 17,528 patients, or 87 percent, adding or switching to a biologic was the next step as compared to 2,513 patients, or 13 percent, who were switched to subcutaneous methotrexate. Of the 2,513 patients who switched from oral to subcutaneous methotrexate, 72 percent remained on this therapy for the rest of the study.

In terms of dosing, patients receiving oral methotrexate - who were either switched to a biologic or added a biologic to their treatment regimen - were initially receiving an average oral dose of methotrexate of 15.3 mg per week. Only 37 percent were placed on doses greater than 15 mg per week.

In terms of switching to a biologic, or adding a biologic to treatment, this occurred in the first three months of treatment for 41 percent of patients (or, 51 percent in the first six months).

Rohr et al. also compared prescription patterns in 2012 versus 2009 to identify changes in methotrexate dosing among those patients who had biologics added or who were switched to them. Only a small increase in mean oral methotrexate dose was detected, from 15.3 mg per week in 2009 to 15.9 mg per week in 2012. The mean dose of oral methotrexate in patients switched to subcutaneous methotrexate increased slightly from 16.1mg per week in 2009 to 16.7 mg per week in 2012. Also, subcutaneous methotrexate use increased slightly but significantly (p < 0.0001) after failure of oral methotrexate from  13 percent of patients in 2009 to 16 percent in 2012.

The Treatment of Early Aggressive Rheumatoid Arthritis Trial (TEAR) showed that patients with early onset poor prognosis rheumatoid arthritis should be given a six-month trial of methotrexate before the decision to add conventional disease modifying anti-rheumatic drugs or a biologic, the researchers wrote. TEAR found that patients treated in this way fared as well clinically and radiographically after two years as compared those assigned to either combination therapy.

“This study highlights that this anchor drug is dramatically underutilized in clinical practice with suboptimal dosing, inadequate duration of monotherapy and failure to administer it in its most bioavailable way - subcutaneously,” the authors wrote. They urge efforts to change methotrexate prescribing practices.

References:

Melanie K. Rohr, MD, Ted R. Mikuls, MD, MSPH, et al. “The Underuse of Methotrexate in the Treatment of RA:  A National Analysis of Prescribing Practices in the U.S,” Arthritis Care & Research. Accepted: Nov 15, 2016. DOI: 10.1002/acr.23152.