Intensification to triple therapy non-biologic disease-modifying antirheumatic drugs for rheumatoid arthritis in the United States from 2009 to 2014

Objective. Several trials suggest that triple therapy (methotrexate, sulfasalazine, and hydroxychloroquine) and biologic disease-modifying antirheumatic drugs (bDMARD) have similar efficacy in rheumatoid arthritis (RA). We investigated intensification to triple therapy after initial non-biologic (nbDMARD) prescription among patients with RA. Methods. We used US insurance claims data to evaluate triple therapy use from 20092014. Patients with a visit for RA and initial nbDMARD prescription were included. Frequencies and rates to intensification to triple therapy or bDMARD were calculated. We evaluated whether sociodemographic, temporal, geographic, clinical, and healthcare utilization factors were associated with triple therapy intensification using Cox regression. Among those who intensified therapy, we investigated factors associated with triple therapy use by logistic regression. Results. There were 24,576 patients initially with mean age of 50.3 (SD 12.3) years, and 78% were female. During the study period, 2,739 (11.1%) intensified treatment to bDMARD compared to 181 (0.7%) who intensified to triple therapy. There was no significant change in triple therapy use across calendar years. Patients who intensified to triple therapy were more likely to use glucocorticoids (HR 1.91, 95%CI 1.41-2.60) compared to no glucocorticoids and more likely to use nonsteroidal anti-inflammatory drugs (NSAID, HR 1.48, 95%CI 1.10-1.99) compared to no NSAID use within 180 days of initial nbDMARD prescription. Among those who intensified treatment to triple therapy or bDMARD, significant associations for triple therapy use included older age, US Page 2 of 25 John Wiley & Sons Arthritis & Rheumatology This article is protected by copyright. All rights reserved. 3 region (highest odds for triple therapy use in the West, lowest odds for triple therapy use in the Northeast), glucocorticoid use, and lower number of outpatient visits within 180 days of initial nbDMARD prescription. Conclusion. Despite reports published during the study period suggesting equivalent efficacy of triple therapy and bDMARDs for RA, the use of triple therapy was infrequent and did not increase over time in this large nationwide study. Page 3 of 25 John Wiley & Sons Arthritis & Rheumatology This article is protected by copyright. All rights reserved. 4 Several randomized controlled trials demonstrate that triple therapy (combination of methotrexate, sulfasalazine, and hydroxychloroquine) is non-inferior to biologic disease-modifying antirheumatic drugs (bDMARDs) for the treatment of rheumatoid arthritis (RA) (1-3). Compared to bDMARDs, triple therapy use has been shown to have superior cost effectiveness and similar quality of life measures (4-6). Despite the growing number of bDMARDs for RA, triple therapy may have an important role in the treatment of RA by optimizing efficacy and cost. In part due to recent efforts advocating treatment to target of remission for RA, clinicians are now faced with complex treatment decisions for RA balancing efficacy, safety, and cost of a variety of options for DMARDs (7). The 2012 American College of Rheumatology guidelines for RA treatment recommended triple therapy as a therapeutic option for patients with RA after failure of initial non-biologic (nbDMARD) monotherapy or as initial therapy for patients with high disease activity and poor prognosis (8). Initial triple therapy at RA diagnosis may reduce disease activity compared to methotrexate