Safety and tolerability of subcutaneous methotrexate in routine clinical practice.

OBJECTIVES To show safety and efficacy of subcutaneous (sc) methotrexate (MTX) compared to oral MTX, alternative disease-modifying anti-rheumatic drugs (DMARD) monotherapy, and combinations (biologic monotherapy, conventional and biologic combination groups) in routine clinical practice. METHODS Clinical and laboratory data were retrospectively analysed for rheumatology clinic attendances at a large North-East England hospital trust between January 2014-January 2018. Adverse and stop event rates (transaminitis [serum alanine aminotransferase >80U/l] or neutropenia [neutrophils <2.0x109 /l]) were calculated, adjusted for duration of DMARD exposure. RESULTS 8394 patients received DMARDs: 2093 oral MTX; 949 sc MTX. Median (Interquartile range - IQR) oral MTX dose was 15 (10-20) mg, and sc MTX was 20 (15-25) mg (p<0.0001). Continuation rates were higher for sc MTX when adjusted for follow-up duration (RR=1.54, 95% CI: 1.40-1.70; p<0.0001). 2382 patients experienced 4358 adverse events (1711 transaminitis, 2647 neutropenia). Significantly fewer adverse events were observed for sc MTX monotherapy versus biologic and combination DMARD therapies (p<0.01). Compared to oral MTX, sc MTX was associated with a non-significant trend to lower rates of neutropenia, but only slightly higher rate of transaminitis (RR=1.26, 95% CI: 1.07-1.48; p=0.006) despite significantly higher doses. CONCLUSIONS Subcutaneous MTX is safe in routine practice. This is the largest study yet reported and provides observational data that sc MTX is continued longer and better tolerated compared to other therapy groups, especially oral MTX.