SAN FRANCISCO, CA—Methotrexate is frequently under-dosed, administered for an inadequate duration, and rarely switched to subcutaneous injection prior to initiating biologic therapy, James R. O’Dell, MD, from the University of Nebraska Medical Center, Omaha, NE, reported at the 2015 ACR/ARHP Annual Meeting.

“There are some major concerns here,” Dr. O’Dell said. “Methotrexate is the anchor DMARD for rheumatoid arthritis (RA) treatment. It’s the best drug we have.”

When patients do not respond at lower doses, it is recommended at doses of up to 20–25 mg, he noted. 

But not much is known about methotrexate’s appropriate use in real-world clinical settings. To better understand how methotrexate is utilized for RA treatment in the United States, Dr. O’Dell and colleagues used Symphony Health Solutions’ anonymized patient-level claims data, representing 274 million patients and 92% of all prescription drug writers in the USA. 

Patients with RA who started treatment with oral methotrexate in 2009 were identified by ICD-9 codes 714.0 and 714.30, and were followed to 2014. Clinical information obtained included switches from oral to subcutaneous methotrexate and/or biologics (with or without concomitant methotrexate), timing of treatment changes, and oral or subcutaneous methotrexate dosing at times of switches/additions or at the end of follow-up.

In total, the study included 35,640 patients who began oral methotrexate therapy for RA in 2009. Of these patients, 44% (n=15,599) continued on oral methotrexate alone (Group 1) through the end of the 5-year follow-up period, and 49.2% (n=17,528) added or switched to a biologic agent (Group 2). Only 7% of patients switched from oral to subcutaneous methotrexate (Group 3) after a median of 530 days on oral therapy.

“Of those patients that had a treatment change, 87% added a biologic instead of trying subcutaneous methotrexate,” noted Dr. O’Dell. “Patients switched to biologics quickly, with 41% switched in 3 months or less.”

Furthermore, “the mean oral methotrexate dose at the time of adding [a biologic] was only 15.3mg/week,” suggesting that patients were switched to biologics before methotrexate dose escalation was attempted, he noted. 

Switching to a biologic “may be premature for many patients,” he said. 

When patients were switched to subcutaneous methotrexate instead of a biologic, most continued that treatment for the entire study period, he noted. In general, 72% of patients who switched from oral to subcutaneous methotrexate stayed on this treatment for 5 years The other 28% eventually needed a biologic, at a median 289 days on subcutaneous methotrexate, he said.

Switching to subcutaneous methotrexate can prevent the need for–or significantly extend the time to–a biologic. Dr. O’Dell added, “More appropriate optimization of methotrexate could lead to better control of RA and would be expected to produce significant cost savings.”

“Oral methotrexate is underdosed in clinical practice, and subcutaneous methotrexate is underutilized,” he concluded. “Subcutaneous methotrexate is used as initial therapy in only 9% of patients and after oral methotrexate before a biological in only 7% of patients.” 

Yet subcutaneous methotrexate was “successful in 72% of patients,” he noted.