Is Age a Factor in Determining TNFi Discontinuation in RA?

Identifying appropriate biologic DMARDs for elderly patients with RA is becoming increasingly important.

Retrospectively acquired registry data suggest that tumor necrosis factor inhibitor (TNFi) retention rates among eldery and young patients with rheumatoid arthritis (RA) are comparable, however identified causes behind drug discontinuation differed between these patient groups.1   

Since their introduction in the late 1990s, TNFis have improved outcomes for many patients with RA. Meanwhile, the mean patient age at RA diagnosis has increased from approximately 50 years to 58 years, according to a previous observational study, and life expectancy in industrialized nations continues to rise.2 Though these trends indicate a growing number of elderly patients with RA, they may be less likely to receive the current mainstay of RA treatment due to concerns about age-related adverse effects and comorbidities.

Despite these potential issues, this group is “inadequately represented in RA clinical trials because of the exclusion criteria that are commonly applied,” and thus “patients with RA in clinical practice might differ from patients selected for inclusion in clinical trials,” wrote the authors of a new study published in BMC Musculoskeletal Disorders.2

High Yield Data Summary

  • Comparable TNFi retention rates were found amongst elderly and young patients with RA
  • Notable differences in reasons for discontinuing TNFi therapy in the 2 groups were found

To address this gap, scientists at the Hanyang University Hospital for Rheumatic Diseases in Seoul Korea investigated the safety and rate of retention of TNFis in 107 RA patients aged 60 years or older vs 322 patients who were younger than 60 years old.

Data was obtained retrospectively from the hospital’s medical records, and patients’ charts were thoroughly reviewed by trained health professionals. Information regarding demographics, disease activity, treatment, numerous comorbidities at the start of disease-modifying antirheumatic drug (DMARD) therapy, and laboratory results were noted. The observation period began with the initial dose of TNFi and spanned approximately 2 years.

The comparison of baseline characteristics showed that there were more males in the older group than in the younger group (22.4 % vs 11.2 %, P=.01), as well as a higher number of prior non-biologic DMARDs (4.4±1.7 vs 3.9±1.5, P=.01). While the mean disease activity score was not significantly different between groups at the start of treatment, the older group had a greater number of comorbidities compared with the younger group (P<.001), as follows:

·         Cardiovascular disease (7.5%   vs 1.2%)

·         Pulmonary disease (15.9% vs 1.9%)

·         Diabetes mellitus (18.7% vs 6.5%)

·         Hypertension (46.7% vs 14.0%)

While 3-year retention rates did not differ significantly between groups (P=.33), there were differences in the main reasons for TNFI discontinuation: adverse effects in the older patients (34.3%) vs ineffectiveness in the younger patients (41.7%). There was a higher overall incidence rate of serious adverse effects in the older vs younger group (incidence rate ratio [IRR] 1.20, 95% CI 0.63-2.29).

For the older group, age predicted discontinuation (hazard ratio [HR] 1.09, CI 1.02-1.16), and the presence of comorbidities were found to have a protective effect against discontinuation (HR 0.37, CI 0.15-0.91). For the younger group, first use of a TNFI predicted discontinuation (HR 1.75, CI 1.06-2.94), and longer disease duration had a protective effect (HR 0.97, CI 0.94 – 0.997).

Summary and Clinical Applicability

Though additional studies with larger sample sizes and various data sources are needed to assess long-term safety of TNFi for elderly patients, results of the current study show that retention rates are similar in patients younger than 60 years compared with those aged 60 years and older. 

Limitations and Disclosures

The small sample size of elderly patients was one limitation of the study, and it also did not consider age of RA onset, which has been linked with divergent disease manifestations. Finally, because of the small sample size, the authors were unable to evaluate outcomes for each TNFi. 

This study was supported in part by a grant from the BMS pharmaceutical company Korea Limited. The authors declare that they have no competing interests.

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  1. Cho SK, Sung YK, ,Kim D, et al. Drug retention and safety of TNF inhibitors in elderly patients with rheumatoid arthritis. BMC Musculoskelet Disord. 2016; 17:333.
  2. Kaipiainen-Seppänen O, Aho K, Isomäki H, et al. Shift in the incidence of rheumatoid arthritis toward elderly patients in Finland during 1975–1990. Clin Exp Rheumatol. 1996; 14:537–42.

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