medwireNews: Real-world study results suggest that patients with rheumatoid arthritis (RA) who initiate treatment with oral methotrexate achieve similar disease control to those taking the subcutaneous formulation.
“Together with the known lower costs and patient burden, our data suggest that starting with oral [methotrexate] should be the preferred strategy,” say Janne Heuvelmans (Sint Maartenskliniek, Nijmegen, the Netherlands) and fellow researchers in Rheumatology.
The team analyzed data from 640 patients with RA who initiated treatment with either oral (n=259) or subcutaneous (n=381) methotrexate at a starting dose of at least 15 mg/week (maximum 25 mg/week) at Sint Maartenskliniek between 2012 and 2019. In the oral group, 11.0% took split-dose methotrexate throughout the study, while 9.3% switched from single-dose to split-dose methotrexate over the course of follow-up, and 13.0% switched to subcutaneous methotrexate. More than 70% of patients in both groups were taking concomitant hydroxychloroquine.
Average DAS28-CRP scores at baseline were 3.78 points in the oral methotrexate group and 3.70 points in the subcutaneous group. During an average follow-up of approximately 140 days, these scores decreased by 1.21 and 1.24 points, respectively, giving a nonsignificant between-group difference of 0.13 points after adjustment for potentially confounding factors.
These findings remained consistent when concomitant hydroxychloroquine use was added as an interaction term to the analysis, and in a sensitivity analysis including only patients who used single-dose methotrexate throughout the study.
In an analysis of secondary outcomes, Heuvelmans et al found that the average weekly methotrexate dose at follow-up was significantly lower among patients taking the oral versus the subcutaneous formulation (18.0 vs 19.9 mg). A numerically smaller proportion of people in the oral group stopped taking methotrexate during the study period (8.1 vs 12.3%), but the between-group difference did not reach statistical significance.
The researchers report that the safety profile of oral methotrexate was “somewhat better” than that of subcutaneous methotrexate, with 40.5% and 51.7% of patients, respectively, experiencing adverse events (AEs).
The most commonly reported AEs in the oral and subcutaneous groups were gastrointestinal symptoms (27.0 vs 29.4%), hair loss (4.3 vs 3.9%), skin symptoms (2.3 vs 4.7%), mucositis (2.3 vs 4.5%), headache (1.9 vs 4.5%), and fatigue (1.2 vs 3.9%).
Heuvelmans and team suggest that the higher incidence of AEs in the subcutaneous group “may be associated with the higher dose.” They also highlight imbalances in laboratory measures among patients taking oral versus subcutaneous methotrexate, with hematologic abnormalities more common in the oral group but alanine aminotransferase and creatinine abnormalities more frequent in the subcutaneous group.
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