Background The concerns about development of adverse events (AEs) in elderly RA patients as a result of age-related changes in drug metabolism and the presence of comorbid illnesses are emphasizing due to increasing prevalence of rheumatoid arthritis (RA) in old age. However, they tend to be inadequately represented in RA clinical trials because of the exclusion criteria that are commonly applied. The tolerability and safety of TNF inhibitors in elderly patients have not been also evaluated in clinical practice.
Objectives This study aimed to determine the safety of TNF inhibitors and predictors of its discontinuation in elderly RA patients.
Methods We recruited 429 RA patients [838 patients-year (PY)] treated with TNF inhibitors from a retrospective biologics registry in Korea of REtrospective study for Safety and Effectiveness of Anti-RA treatment with biologiCs (RESEARCh). We divided patients into two groups of elderly (age ≥65 years) and young RA patients (age <65 years). The period of observation for evaluating safety was defined as the time between starting of TNF inhibitors and termination of treatment. Incidence rate (IR) of serious adverse events (SAEs) in elderly patients was compared to that of young patients. Drug retention rates of both groups were compared using Kaplan-Meier analysis. Potential predictors of discontinuation of TNF inhibitors were also examined using multivariate logistic regression analyses.
Results Among total RA patients treated with TNF inhibitors (n=429), the 13.5% of patients (n=58, 110 PY) was classified in elderly group and 371 patients (728 PY) were included in young group. At the baseline, the elderly group had more male than young group (27.6% v.s. 11.9%, p=0.003) and were treated with lower dosage of methotrexate (13.0±3.64 v.s. 14.2±3.55 mg/week, p<0.001). Elderly patients had more comorbid condition such as pulmonary disease, diabetes mellitus and hypertension (p<0.001) and pulmonary tuberculosis history (p=0.017). For the safety, IR of SAE were slightly higher in elderly patients (7.27/100 PY) than young patients (5.22/100 PY). In elderly group, IR of malignancy (1.82/100 PY v.s. 0.96/100 PY) and respiratory disorder (1.82/100 PY v.s. 0.41/100 PY) were higher than young group. In the analysis of retention rates of TNF inhibitors, there was no significant difference between elderly and young patients (p=0.553 by log-rank test). However, there was a difference in the frequent reasons of discontinuation; development of AE (26.32%) and patients' need (26.32%) in elderly patients, while that was ineffectiveness (34.93%) in young patients. The predictors of discontinuation were also differ in two groups; age (OR 2.01, CI 1.10-1.45) and glucocorticoid use ≥5mg (OR 4.33, CI 1.01-18.60) in elderly group, while short disease duration (OR 2.01, CI 1.10-1.45), first user (v.s. switcher, OR 1.96, CI 1.19-3.13) and infliximab use (v.s. etanercept, OR 1.67, CI 1.05-2.64) in young group.
Conclusions The IR of malignancy and respiratory disorder could be increased in elderly patients treated with TNF inhibitors. The retention rate of TNF inhibitors in elderly RA patients was comparable with young patients.
Acknowledgements This study was supported by a grant of the Korea Healthcare technology R&D Project, Ministry of Health and Welfare, Republic of Korea.(HI10C2020).
Disclosure of Interest None declared
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