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Is the Jury Still Out on Triple Therapy vs. MTX + TNF inhibitor?

There are several trials that test the efficacy and safety of combination tumor necrosis factor inhibitor (TNFi) plus methotrexate against triple therapy (methotrexate plus hydroxychloroquine plus sulfasalazine) in patients with rheumatoid arthritis (RA).

Trials like TEAR, RACAT and SWEFOT have show similar and disparate results.

Researchers preformed a systematic review and network meta-analysis (NMA) of randomised controlled trials comparing TNFi-methotrexate or triple therapy. Interestingly, the primary endpoint of this analysis was an ACR 70% response (ACR70) at 6 months. 

Researchers analyzed 33 studies in patients with inadequate response to methotrexate (established RA) and 19 in patients naive to methotrexate (early RA).

Established RA - Inadequate response to MTX

Figure 2

In inadequate responders, triple therapy was associated with lower odds of achieving ACR70 at 6 months compared with TNFi-methotrexate (OR 0.35, 95% credible interval (CrI) 0.19 to 0.64). Although several secondary endpoints trended towards favoring the TNFi-methotrexate arm, there was no significant advantage for either therapy.

For those who were MTX naive, there was no advantage of either therapy with regard to the primary endpoint. Although those treated with TNFi–methotrexate were more likely to achieve ACR70 and have less X-ray progression at 2 years, this was only seen in the fixed-effects analyses and not the random-effects models. The magnitude of this effect was not felt to not be clinically relevant. 

With regard to safety, infections were lower with triple therapy than with TNFi-methotrexate (OR 0.08, 95% CrI 0.00 to 0.57). There were no differences observed between the two regimens in patients naive to methotrexate.

For those with an inadequate response to methotrexate, triple therapy was associated with 65% lower odds of achieving ACR70 at 6 months compared with TNFi-methotrexate in patients.

The author has received compensation as an advisor or consultant on this subject

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