Persistence With Conventional Triple Therapy Versus a Tumor Necrosis Factor Inhibitor and Methotrexate in US Veterans With Rheumatoid Arthritis

Abstract

Objective: To compare persistence and adherence to triple therapy with the nonbiologic disease-modifying antirheumatic drugs (DMARDs) methotrexate (MTX), hydroxychloroquine, and sulfasalazine, versus a tumor necrosis factor inhibitor (TNFi) plus MTX in patients with rheumatoid arthritis (RA).

Methods: Administrative and laboratory data were analyzed for US Veterans with RA initiating triple therapy or TNFi + MTX between January 2006 and December 2012. Treatment persistence 365 days postindex was calculated using 3 definitions. Definition 1 required no gap in therapy of ≥90 days for any drug in the original combination. Definition 2 required no added or switched DMARD, no decrease to nonbiologic DMARD monotherapy, and no termination of all DMARD therapies. Definition 3 was similar to definition 2 but allowed a switch to another drug within the same class. Adherence used a proportion of days covered of ≥80%. Propensity-weighted analysis with matched weights was used to balance covariates.

Results: The analysis included 4,364 RA patients (TNFi + MTX, n = 3,204; triple therapy, n = 1,160). In propensity-weighted analysis, patients in the TNFi + MTX group were significantly more likely than patients in the triple therapy group to satisfy all persistence criteria in definition 1 (risk difference [RD] 13.1% [95% confidence interval (95% CI) 9.2-17.0]), definition 2 (RD 6.4% [95% CI 2.3-10.5]), and definition 3 (RD 9.5% [95% CI 5.5-13.6]). Patients in the TNFi + MTX group also exhibited higher adherence during the first year (RD 7.2% [95% CI 3.8-10.5]).

Conclusion: US Veterans with RA were significantly more likely to be persistent and adherent to combination therapy with TNFi + MTX than triple therapy with nonbiologic DMARDs.

Figure 1

Propensity score analysis with standardized difference scores before and after application of matched weights. VA = Veterans Affairs; NSAID = nonsteroidal antiinflammatory drug; CCS = Clinical Classification System; HIV = human immunodeficiency virus; RDCI = rheumatic disease comorbidity index; CCP  = cyclic citrullinated peptide; ED = emergency department.

Figure 2

Kaplan‐Meier plot for persistence with matching weights, definition 1: no gap in therapy of ≥90 days for any drug in the original combination. TNFi = tumor necrosis factor inhibitor; MTX = methotrexate. Color figure can be viewed in the online issue, which is available at http://onlinelibrary.wiley.com/journal/doi/10.1002/acr.22944/abstract.

Figure 3

Kaplan‐Meier plot for persistence with matching weights, definition 2: no added or switched disease‐modifying antirheumatic drug (DMARD), no decrease to nonbiologic DMARD monotherapy, and no termination of all DMARD therapies. TNFi = tumor necrosis factor inhibitor; MTX = methotrexate. Color figure can be viewed in the online issue, which is available at http://onlinelibrary.wiley.com/journal/doi/10.1002/acr.22944/abstract.

Figure 4

Kaplan‐Meier plot for persistence with matching weights, definition 3: similar to definition 2, but allowed a switch to another drug within the same class. TNFi = tumor necrosis factor inhibitor; MTX = methotrexate. Color figure can be viewed in the online issue, which is available at http://onlinelibrary.wiley.com/journal/doi/10.1002/acr.22944/abstract.