Subcutaneous vs. oral methotrexate safer, better-tolerated in routine practice
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Subcutaneous methotrexate is safe in clinical practice, and is continued longer and better tolerated than other therapy groups, particularly oral methotrexate, according to data published in Arthritis Care & Research.
“Oral [methotrexate (MTX)] is used extensively in rheumatology due to efficacy, ease of administration and low cost,” Christien K.H. Li, MBBS, of the Translational and Clinical Research Institute at Newcastle University in the United Kingdom, and colleagues wrote. “However, oral MTX is often poorly tolerated in a minority of patients, primarily from gastrointestinal side effects. Therefore, use and feasibility of subcutaneous MTX have witnessed great interest in recent years, especially with the underuse of both oral and subcutaneous MTX in the United States.
“Current evidence suggests subcutaneous is more effective than oral MTX, with fewer treatment failures, although there are few randomized controlled trials (RCTs) comparing these options,” they added. “Furthermore, data concerning the applicability of these findings to unselected patient populations in routine clinical practice are lacking.”
To examine the safety and efficacy of subcutaneous methotrexate compared with oral methotrexate, alternative DMARDs and combination therapy in routine care, Li and colleagues retrospectively studied clinical and laboratory data from patients attending rheumatology clinics at a large secondary care trust in the Northeast England, serving a population of 550,000.
In all, Li and colleagues included 8,394 patients who started, or were already established on, DMARDs from January 2014 to January 2018 in their study. Among these patients, 2,093 received oral methotrexate and 949 were treated with subcutaneous methotrexate. The researchers calculated adverse and stop event rates — transaminitis or neutropenia — adjusting for the duration of DMARD exposure.
According to the researchers, the median oral methotrexate dose was 15 mg, while the median subcutaneous dose was 20 mg (P < .0001). Patients who received subcutaneous doses demonstrated higher continuation rates, when adjusted for followup duration (RR = 1.54; 95% CI, 1.41.7). Regarding safety, 2,382 patients experienced 4,358 adverse events, including 1,711 cases of transaminitis and 2,647 cases of neutropenia. Patients who received subcutaneous doses as monotherapy experienced significantly fewer adverse events, compared with those treated with biologic and combination DMARD regimens (P < .01).
Subcutaneous methotrexate was associated with a nonsignificant trend toward lower rates of neutropenia, but only a slightly higher rate of transaminitis (RR = 1.26; 95% CI, 1.071.48), compared with oral doses, despite significantly higher doses.
“In our cohort, subcutaneous MTX is associated with a comparable rate of neutropenia to oral MTX, with only a small increase in transaminitis events, even at the higher doses achievable by this route of administration,” Li and colleagues wrote. “Furthermore, we observe subcutaneous MTX is safer and better tolerated, with significantly better continuation rates (after adjustment for follow-up duration) and lower stop events from intolerance and secondary inefficacy compared to oral MTX.”
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