Biologics, Triple Therapy a Good Follow-Up to Failed First-Line Methotrexate Treatment


Patients with rheumatoid arthritis who switched to biologics or triple therapy had a longer time to treatment failure versus augmented oral methotrexate.

After failing initial methotrexate treatment, patients with rheumatoid arthritis (RA) who took biologics or triple therapy had a longer time to failure than patients who took methotrexate oral monotherapy, according to findings presented at the 2017 American College of Rheumatology/Association of Rheumatology Health Professionals

Annual Meeting.

“This study was motivated because some feel that though the medical community agrees that methotrexate (MTX) is the cornerstone therapy for RA, there are not always clear guidelines for what to choose next when MTX is not enough,” said Sasha Bernatsky, MD, PhD, associate professor in the Department of Medicine, Division of Rheumatology at McGill University in Montreal. “Since RA is such a serious disease with a huge impact on health, this is a real knowledge gap. So, we compared treatment strategies in early RA patients who had initiated MTX and then required a therapy change (ie, was MTX ineffective or—less commonly—associated with a severe adverse event).”

In this study, Bertnasky and colleagues included 911 adults with RA enrolled in a multicenter early arthritis cohort who failed initial methotrexate therapy and then changed treatment. The time of medication change became “time zero” for the survival analysis of the second treatment.

The most common second treatments were methotrexate and another disease modifying anti-rheumatic drug (DMARD, 32.9%) and non-methotrexate DMARDs (26.1%).

Patients who switched to biologics or triple therapy had a longer time to treatment failure versus those who took augmented oral methotrexate, according to Bernatsky.

Patients on MTX subcutaneous at time zero had an adjusted hazard ratio (HR) of 0.91 (95% CI, 0.61-1.35). Those prescribed methotrexate plus another DMARD had an adjusted HR of 0.87 (95% CI, 0.62-1.22). In comparison, triple therapy patients had an adjusted HR of 0.64 (95% CI, 0.44-0.94) while patients on biologics had an adjusted HR of 0.31 (95% CI, 0.20-0.49).

“This underlines the message that aggressive therapy has benefits in RA,” Bernatsky told Specialty Pharmacy Times. “There was a trend for better results for patients given biologics +/-DMARDs, as opposed to those given triple therapy, which just missed meeting statistical significance.

“We could not confirm clear differences with respect to MTX (dual or triple) combinations (eg, MTX plus hydroxychloroquine dual therapy or MTX/hydroxychloroquine/sulfasalazine triple therapy), but these options seemed better than switching completely away from MTX to another DMARD (instead of adding something to MTX),” Bernatsky continued. “This could possibly be interpreted as confirming, in part, MTX’s role as cornerstone therapy.”

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