Does TNFi Monotherapy for RA Become More Efficacious With Age?

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Findings in this study should help alleviate concerns about TNFi monotherapy immunogenicity in older patients with RA.

In older adults initiating their first tumor necrosis factor inhibitor (TNFi), TNFi monotherapy is not associated with increased treatment failure. Rather, patients 75 and older had lower rates of discontinuation due to drug inefficacy than younger patients, but higher risk of discontinuation due to adverse events, according to a study published in Rheumatology.

This prospective observational cohort study analyzed data from the British Society for Rheumatology Biologics Register of older adults who were biologic naïve initiating their first TNFi. After participants were stratified by age (<75 and ≥75), the risk of TNFi discontinuation from (1) any cause, (2) inefficacy, and (3) adverse events was compared between participants prescribed TNFi monotherapy and those prescribed TNFi-methotrexate (MTX) combination using Cox-proportional hazards models.

Of the 15,700 participants (95% aged <75 years), 52% (n=8206) discontinued TNFi treatment during the follow-up period, with an overall discontinuation incidence rate (IR) of 18.4 (95% CI, 18.0-18.8) per 100 patient-years (PY). The most common reasons cited were adverse events (40%) and inefficacy (41%). The crude IR for TNFi discontinuation per 100 PY was higher in participants 75 and older compared with those under 75 (all cause, 25.5 [95% CI, 23.2-27.9] vs 18.1 [95% CI, 17.7-18.5]; inefficacy: 8.4 [95% CI, 7.2-9.9] vs 7.4 [95% CI, 7.2-7.7]; and adverse events: 11.8 [95% CI, 10.3-13.6] vs 7.1 [95% CI, 6.9-7.4]).

Overall, participants on monotherapy were more likely to discontinue compared with participants on combination therapy (hazard rate [HR], 1.12; 95% CI, 1.06-1.18; P <.001). This finding was maintained when analysis was restricted to participants aged <75 but not for analyses including those aged ≥75,with no statistically significant difference seen in the HR for discontinuation between monotherapy and combination therapy.

When discontinuation was examined by cause, participants aged ≥75on TNFi monotherapy were 34% less likely to discontinue TNFi due to inefficacy compared with participants on combination therapy (HR, 0.66; 95% CI, 0.43-0.99; P =.04); this finding was not seen in participants aged <75.

In regard to adverse events, both cohorts were more likely to discontinue TNFi therapy when prescribed monotherapy compared with combination therapy (>75: HR, 1.41; 95% CI, 1.02-1.96; P =.04; and <75: HR, 1.21; 95% CI, 1.11-1.32; P <.001). In multivariable analyses, all results remained significant.

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Study investigators conclude that considering “these data provide evidence to support TNFi monotherapy strategies in the [patients aged ≥75] in the wider context of a desire to reduce polypharmacy burden, the findings in this study should help alleviate physician concerns about drug immunogenicity in older patients.”

Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.


Bechman K, Oke A, Yates M, et al. 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 [published online January 30, 2020]. Rheumatology (Oxford). doi:10.1093/rheumatology/kez671