Impact of concomitant use of DMARDs on the persistence with anti-TNF therapies in patients with rheumatoid arthritis: results from the British Society for Rheumatology Biologics Register

Abstract

Objective: To evaluate the effect of different concomitant disease modifying antirheumatic drugs (DMARDs) on the persistence with antitumour necrosis factor (anti-TNF) therapies in patients with rheumatoid arthritis (RA).

Method: This analysis included 10 396 patients with RA registered with the British Society for Rheumatology Biologics Register, a prospective observational cohort study, who were starting their first anti-TNF therapy and were receiving one of the following DMARD treatments at baseline: no DMARD (n=3339), methotrexate (MTX) (n=4418), leflunomide (LEF) (n=610), sulfasalazine (SSZ) (n=308), MTX+SSZ (n=902), MTX+ hydroxychloroquine (HCQ) (n=401) or MTX+SSZ+HCQ (n=418). Kaplan-Meier survival analysis was used to study the persistence with anti-TNF therapy in each DMARD subgroup up to 5 years. Multivariate Cox proportional hazard models, stratified by anti-TNF used and start year and adjusted for a number of potential confounders, were used to compare treatment persistence overall and according to the reason for discontinuation between each of the DMARD subgroups, using MTX as reference.

Results: One-year drug survival (95% CI) for the first anti-TNF therapy was 71% (71% to 72%) but this dropped to 42% (41% to 43%) at 5 years. Compared with MTX, patients receiving no DMARD, LEF or SSZ were more likely to discontinue their first anti-TNF therapy while patients receiving MTX in combination with other DMARDs showed better treatment persistence.

Conclusions: These results support the continued use of background DMARD combinations which include MTX. Consideration should be given to the discontinuation of LEF and SSZ monotherapy at the time anti-TNF therapies are started, with the possible exception of the SSZ+ETN combination.

Conflict of interest statement

Competing interests The British Society for Rheumatology (BSR) commissioned the Biologics Register (BSRBR) as a UK-wide national project to investigate the safety of biological agents in routine medical practice. DPMS and KLH are principal investigators on the BSRBR. BSR receives restricted income from UK pharmaceutical companies, presently Abbott Laboratories, Amgen, Roche, Schering Plough and Wyeth Pharmaceuticals. This income finances a wholly separate contract between the BSR and the University of Manchester who provide and run the BSRBR data collection, management and analysis services. The principal investigators and their team have full academic freedom and are able to work independently of pharmaceutical industry influence. All decisions about analyses, interpretation and publication are made autonomously of any industrial contribution. Members of the Manchester team, BSR trustees, committee members and staff complete an annual declaration in relation to conflicts of interest. The PhD work of MMS was supported by the Egyptian Government. The authors declare no other conflicts of interest.

Figures

Figure 1

Kaplan–Meier estimates of crude persistence with anti-tumour necrosis factor (anti-TNF) therapies overall and by reason for discontinuation.

Figure 2

Kaplan–Meier estimates of crude persistence with anti-tumour necrosis factor (anti-TNF) therapies according to baseline disease-modifying antirheumatic drug(s). HCQ, hydroxychloroquine; LEF, leflunomide; MTX, methotrexate; SSZ, sulfasalazine.