Despite Positive Study Results, Triple Therapy Rarely Used in RA


Triple therapy in RA is infrequent, despite mounting evidence that this more cost-effective option might be as effective as treatment intensification with biologic disease-modifying antirheumatic drugs.

Rheumatoid arthritis (RA) treatment intensification to triple therapy, with methotrexate, sulfasalazine and hydroxychloroquine, is infrequent. That’s despite mounting evidence that this more cost-effective option might be as effective as rheumatoid arthritis treatment intensification with biologic disease-modifying antirheumatic drugs (DMARDs), according to a new study.

Researchers looked at Aetna U.S. insurance claims data from 2009 to 2014 to study patterns of intensification to triple therapy in rheumatoid arthritis patients after they had been treated initially with nonbiologic prescriptions.

Analyzing a total of 24,576 patients with prescriptions for nonbiologic DMARDs, the researchers found that while 89 percent of those studied were initially prescribed methotrexate, sulfasalazine or hydroxychloroquine, only 0.7 to 0.9 percent went on to receive triple therapy for their rheumatoid arthritis. Among the patients in the database, rheumatoid arthritis treatment was intensified to biologic DMARDs in 2,739 patients, or 11.1 percent. Put another way, of the patients whose rheumatoid arthritis treatment was intensified, 93.8 percent received biologic DMARDs.

Physicians’ use of triple therapy for rheumatoid arthritis in routine clinical practice didn’t increase, despite the publishing of seminal randomized controlled trials showing similar efficacy between triple therapy and biologic DMARDs during the study period.

The researchers point to factors that seem to make physicians more or less inclined to prescribe triple therapy. Where patients lived made a difference. For example, rheumatoid arthritis patients in the Northeast whose treatment was intensified were 33 percent less likely to use triple therapy compared to patients in the South. There was a trend toward more use of triple therapy with increasing patient age. Rheumatoid arthritis patients who received glucocorticoids in the 180 days before intensification were more likely to receive triple therapy. And those initially prescribed combination nonbiologic DMARDs were significantly more likely to receive triple therapy.

Patients who had serious infections or had received antimicrobial agents before intensification were not more likely to be prescribed triple therapy, despite the serious infection risk associated with biologic DMARDs.

The authors, who include two employees of CVS Health and on employee of Aetna, write that there are several study limitations.

“Since our study included insurance beneficiaries throughout the entire U.S., our findings may reflect routine clinical care for patients with RA. However, because all of the patients in our study were insured, the findings may not be generalizable to underinsured or uninsured patients, for whom generic oral drugs may be a preferable option,” they write.

Because of this and other limitations, the findings might actually overestimate triple therapy use in U.S. rheumatoid arthritis patients. More research needs to be done looking at barriers to and facilitators of triple therapy use in rheumatoid arthritis, according to the study.



Sparks JA, Krumme AA. et al. “Brief Report: Intensification to Triple Therapy After Treatment With Nonbiologic Disease-Modifying Antirheumatic Drugs for Rheumatoid Arthritis in the United States From 2009 to 2014,” Arthritis and Rheumatology. July 2016. DOI: 10.1002/art.39617.


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