Parenteral methotrexate therapy is more successful than oral methotrexate in achieving optimal disease activity control in rheumatoid arthritis, with no increased adverse effects, say researchers writing in PLoS One this month.
The American College of Rheumatology (ACR) and the European League Against Rheumatism both recommend methotrexate monotherapy as the first strategy for early rheumatoid arthritis and to increase the dose until disease control has been achieved, and up to 25 mg daily. The bioavailability of methotrexate is higher with parenteral formulations, without an increase in adverse effects, but it is important to understand whether this method of delivery also has greater efficacy. While studies suggest that parenteral methotrexate may be more efficacious, these studies are poorly controlled. or biased. Meanwhile, trials comparing methotrexate with biologics may be biased towards showing a greater efficacy for biologics, due to the use of a suboptimal methotrexate dose and route of administration.
This meta-analysis compared the efficacy of oral versus parenteral methotrexate in rheumatoid arthritis, using the ACR20 response at six months as the primary endpoint. Relative treatment effects were generated as an odds ratio (OR), with an OR greater than 1 indicating a benefit for parenteral therapy.
“Given the important impact that route of administration may have on the bioavailability and efficacy of methotrexate, its beneficial cost and side effect profile compared with biologics, along with the lack of rigorous data, the aim of our meta-analysis was to assemble the randomized trial data directly comparing the same dose of oral versus parenteral methotrexate, to compare their efficacy and safety,” wrote the authors, led by Andreea Bujor, M.D, Ph.D., of Boston University School of Medicine in Massachusetts.
Out of a search result of 357 papers, researchers found four studies that met inclusion criteria; this included a total of 703 patients randomized to either treatment. Methotrexate dosing started at 15mg per week week and was increased up to 25mg per week.
The odds of achieving ACR20 was higher using parenteral methotrexate compared with oral methotrexate with an OR of 3.02 (95% CI 1.41, 6.46). Participants taking parenteral methotrexate had a 20% greater odds of attaining ACR20 improvement (95% CI 5.0%, 35.3%) compared with those on oral methotrexate. Overall there were no significant differences in adverse events between groups.
“We propose that parenteral methotrexate is more effective than weekly oral methotrexate; its widespread use may lead to better control of disease and a decrease in demand for biologic agents,” the authors wrote.
Andreea M. Bujor, Sahar Janjua, Michael P. LaValley, et al. “Comparison of oral versus parenteral methotrexate in the treatment of rheumatoid arthritis: A meta-analysis.” PLoS One. September 6, 2019. doi: 10.1371/journal.pone.0221823