TNF Inhibitor Monotherapy Not Associated With Treatment Failure in Older Adults

elderly woman holding pills
Patients over 75 have fewer discontinuations due to inefficacy than adverse events compared with younger patients on TNF inhibitor monotherapy.

Although tumor necrosis factor inhibitor (TNFi) monotherapy has been associated with increased treatment failure in rheumatoid arthritis (RA), according to research results published in Rheumatology, this disadvantage is not observed in patients 75 years or older, with patients in this cohort experiencing fewer treatment discontinuations due to inefficacy.

Researchers investigated drug survival rates with TNFi monotherapy compared with methotrexate combination therapy in a population of older adults. They obtained data from the British Society of Rheumatology Biologics Register for RA, a national, prospective, observational cohort study established in 2001 to monitor the long-term safety of biologic therapy.

Overall, 23,411 patients were included in the registry. Of those, 15,700 were biologic naïve and beginning their first TNFi therapy. Among all patients, 95% were younger than 75 years of age (mean 55±12.9 years), with a median disease duration of 10 years (interquartile range 5-18). Baseline mean Disease Activity Score in 28 Joints was 6.42±1.06.

Compared with younger patients, participants >75 years had more comorbidities, including cardiac and respiratory diseases, increased RA disease activity scores, and their elevated erythrocyte sedimentation rates. Older patients were more likely to be prescribed TNFi monotherapy over combination therapy with conventional synthetic disease-modifying antirheumatic drugs (DMARDs; 35% vs 24%).

Within the cohort, 52% of patients discontinued their first TNFi therapy during the follow-up period. Over 44,642 person-years of follow-up, investigators noted an overall incidence of discontinuation of 18.4 (95% CI, 18.0-18.8) per 100 patient-years. The primary reasons for discontinuation included adverse events or treatment inefficiency.

The persistence of TNFi therapy was higher in the younger cohort, with crude incidence rates per 100 patient-years elevated in the ≥75 vs <75 age group. Overall, patients who received TNFi monotherapy were more likely to discontinue TNF blockade compared with patients who were receiving combination TNFi-methotrexate therapy (hazard rate 1.12; 95% CI, 1.06-1.18). Findings persisted even after restricting analysis to the younger cohort.

Patients in the ≥75 cohort who received TNFi monotherapy were 34% less likely to discontinue TNFi therapy because of inefficacy compared with patients who received TNFi-methotrexate combination therapy; this finding was not noted in the younger cohort. Patients in both groups were more likely to discontinue therapy when prescribed TNFi monotherapy compared with TNFi-methotrexate combination therapy.

Analyses that investigated other TNFi/conventional synthetic DMARD combinations showed a greater risk of discontinuing TNF blockade in the cohort aged <75 years if the participants were co-prescribed leflunomide rather than methotrexate. These patients were also less likely to discontinue anti-TNF therapy when it was co-prescribed with 2 conventional synthetic DMARDs compared with methotrexate alone.

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Study limitations included the small number of individuals in ≥75-year cohort despite large overall sample size, the inability to externally verify the reason for TNFi discontinuation, and medication switching during the study period.

“These data provide evidence to support TNFi monotherapy strategies in the over-75s in the wider context of a desire to reduce polypharmacy burden,” the researchers concluded. “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 of Rheumatology Biologics Register [published online January 30, 2020]. Rheumatology. doi: 10.1093/rheumatology/kez671