Is background methotrexate advantageous in extending TNF inhibitor drug survival in elderly patients with rheumatoid arthritis? An analysis of the British Society for Rheumatology Biologics Register.

OBJECTIVE

To evaluate drug survival with monotherapy compared with combination therapy with MTX in RA older adults.

METHODS

Patients from the British Society for Rheumatology Biologics Register, a prospective observational cohort, who were biologic naïve and commencing their first TNF inhibitors (TNFi) were included. The cohort was stratified according to age: <75 and ≥75. Cox-proportional hazards models compared the risk of TNFi discontinuation from (i) any-cause, (ii) inefficacy and (iii) adverse events, between patients prescribed TNFi-monotherapy compared with TNFi MTX combination.

RESULTS

The analysis included 15 700 patients. Ninety-five percent were <75 years old. Comorbidity burden and disease activity were higher in the ≥75 cohort. Fifty-two percent of patients discontinued TNFi therapy during the follow-up period. Persistence with therapy was higher in the <75 cohort. Patients receiving TNFi monotherapy were more likely to discontinue compared with patients receiving concomitant MTX [hazard rate 1.12 (1.06-1.18) P <0.001]. This finding only held true in patients <75 [hazard rate (HR) 1.11 (1.05-1.17) vs ≥75 [HR 1.13 (0.90-1.41)]. Examining TNFi discontinuation by cause revealed patients ≥75 receiving TNFi monotherapy were less likely to discontinue TNFi due to inefficacy [HR 0.66 (0.43-0.99) P=0.04] and more likely to discontinue therapy from adverse events [HR 1.41(1.02-1.96) P =0.04]. These results were supported by the multivariate adjustment in complete case and imputed analyses.

CONCLUSION

TNFi monotherapy is associated with increased treatment failure. In older adults, the disadvantage of TNFi monotherapy on drug survival is no longer seen. Patients ≥75 have fewer discontinuations due to inefficacy than adverse events compared with younger patients. This likely reflects greater disposition to toxicity but perhaps also a decline in immunogenicity associated with immunosenescence.