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

Abstract

ObjectiveTo 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).MethodsAdministrative 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.ResultsThe 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]).ConclusionUS Veterans with RA were significantly more likely to be persistent and adherent to combination therapy with TNFi + MTX than triple therapy with nonbiologic DMARDs.

Low Persistence Rates in Patients With Rheumatoid Arthritis Treated With Triple Therapy and Adverse Drug Events Associated With Sulfasalazine

“…In summary, this observational cohort study demonstrated that in US veterans with RA, persistence and adherence rates remained relatively low when escalating from MTX to combination MTX‐TNFi and triple therapy, findings that mirror a larger recent study published by our group involving a larger cohort of US veterans . However, the current study also helped elucidate via chart abstraction the reasons why patients discontinue their combination medications for their RA.…”

“…However, our findings are consistent with a prior study by Bonafede et al , in which persistence rates were 29.4% for MTX‐TNFi and 23.2% for triple therapy at 1 year, and adherence rates were 27.9% for MTX‐TNFi versus 18.2% for triple therapy. Other studies have shown relatively low adherence to RA treatment in real‐world clinical practice, including a recent publication by our group, using a larger cohort of US veterans . Lower persistence and adherence rates represent a greater extent of unrealized treatment benefit and poorer clinical outcomes in RA.…”

“…Therefore, gaps of ≥90 days between fills were used as surrogate markers for lapses in medication use. Use of a 90‐day selection is relatively arbitrary, but this period had been used in previous studies by our coauthors . Persistence was calculated for each medication.…”

“…Recent studies have shown substantially better cost effectiveness with triple therapy compared to combination therapy with MTX‐TNFi . A recent study by our group showed that overall persistence and adherence rates were significantly lower in US veterans taking triple therapy as compared with MTX‐TNFi therapy . In the previous study, however, there were no restrictions placed on how patients started triple or MTX‐TNFi therapy; for example, subjects may have sequentially added a DMARD at 3 different instances to qualify for triple therapy.…”

Rheumatoid Arthritis Treatment After Methotrexate: The Durability of Triple Therapy Versus Etanercept

“…Since the publication of these results, questions have surfaced regarding adherence and durability of triple therapy. Results from 2 separate retrospective studies using administrative data from the Veterans Affairs (VA) health system (a major source of RACAT trial participants) have suggested that patients taking triple therapy have lower adherence and lower treatment persistence than patients on methotrexate‐TNF inhibitor , for former observations contrasting with similar adherence rates reported from RACAT . The present study is an open‐label followup to the RACAT trial and explores the subsequent durability of triple therapy versus methotrexate‐etanercept in randomized patients following completion of the 48‐week double‐blinded study.…”