Triple Therapy for Rheumatoid Arthritis

Most people diagnosed with rheumatoid arthritis (RA) start on the disease-modifying medication methotrexate, but if that drug fails to sufficiently control disease activity, then a biologic drug often gets added to the mix. Biologic drugs, including TNF inhibitors like infliximab (Remicade) or etanercept (Enbrel) or adalimumab (Humira), work well, but there are downsides — namely the cost and increased risk of infections.

“Triple therapy” — which entails taking methotrexate along with two other disease-modifying anti-rheumatic drugs, hydroxychloroquine and sulfasalazine — is far more affordable compared to methotrexate and a pricey biologic, and research has previously suggested that it’s usually as effective as taking methotrexate with a TNF inhibitor. But is it equally safe?

To find out, researchers used data from Truven MarketScan that included info on 45,208 RA patients who were using methotrexate plus a TNF inhibitor between 2003 and 2014 and compared them to 1,387 RA patients who were on triple therapy during the same timeframe. They determined that there was “no substantially different risk of any serious infection, bacterial infection, or herpes zoster,” which is also known as shingles, between the two groups.

The study was published in the journal Arthritis Care & Research.

These results suggest that RA patients would fare equally well in terms of infection risk with either drug regimen. “By examining a large database representing the middle-aged working population in the U.S., our results provide informative real-world evidence on the comparative infectious risk between [TNF inhibitors plus methotrexate] versus triple therapy,” the authors wrote.

The authors did note that the number of study participants using triple therapy was very small compared to the large number of those taking a TNF inhibitor and methotrexate. That imbalance in sample size might have skewed the results, though the researchers adjusted for 50 possibly influential factors (such as age, having another chronic condition, and previous history of serious infection).

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