Background/Purpose: After more than a decade using biological agents (BA), is widely known their efficacy in the treatment of Rheumatoid Arthritis (RA) and their relationship with Adverse Drug reaction (ADR). We know that drugs metabolism changes with age and, thus, the AE but we have no concrete information about AE with BA in these patients in real life. The purpose of our study was to describe the incidence and characteristics of moderate and severe ADR to BA in a cohort of elderly patients with RA.

Methods: Observational longitudinal study from 1999 to 2013 was conducted. RA patients followed in outpatient clinic at Hospital Clinico San Carlos, which started BA treatment after 65 years of age, were included. Primary outcome: discontinuation due to an ADR (moderate: suspension of the drug regardless of the impact; severe: suspension and hospitalization or death) related to BA (Etanercept (ETN); Infliximab (INF); Adalimumab (ADA); Rituximab (RTX); and other BA [Golimumab, Certolizumab, Abatacept and Tozilizumab]). Co variables: sociodemographic, clinical and therapy.  Incidence rates of discontinuation due to ADR (IR) per 100 patient-years were estimated using survival techniques with their respective 95% confidence interval [95% CI]. Comparison between BA ADR discontinuation rates and other associated factors were run by Cox regression models.

Results: We included 286 courses of BA therapy in 146 patients (604 patient-years). Of these, 78% were women with a mean age at diagnosis of 66.5 ± 7 years and a median time to the start of the first BA of 6 ± 4 years. ADA (27.3%), followed by INF (22.4%), ETN (21.3%), and RTX (19.2%) were the most frequently used. Treatment was suspended due to ADRs in 111 cases (IR: 18.3 [15.2 -22.1]), 56% of them were severe (IR: 10.3 [8-13.2), with 16 deaths during the study period (IR: 2.6 [1.6-4.2]. The retention rate for discontinuation due to ADR was 71%, 50%, 35% and 20% for the first, third, fifth and tenth year. The most frequent cause for ADR was infection (50.5%; IR: 9.3 [7.1-12]). The crude IR of discontinuation was lower for ETN (IR for all ADRs: 14.5 [9-23.3]; IR for severe:  5.1 [2.3-11.4]) compared to TNF- antagonists and RTX. In the multivariate analysis for all ADRs after adjusting by calendar time, age and sex: a) for all ADRs: INF was the BA with the highest risk of ADR development, compared to ETN. No other BAs comparisons achieved statistical signification. Concomitant triple therapy with DMARDs, corticoids, functional loss, and specific comorbidities were other independent factors found; b) for severe ADRs: INF achieved the highest risk of ADR development, compared to ETN, ADA and RTX. ETN also had lower risk compared to RTX. Age of the patient, concomitant corticoids, and specific comorbidities were also associated. 

Conclusion: After 5 years of treatment, two thirds of the patients over 65 years have discontinuated BA due to ADRs, mainly related to infections. 18.4 % and 10.3% patient * year discontinued BAs due to all ADR and severe ADRs respectively. The mortality rate in our study was 2.7%. We have found differences in discontinuation rates among BA due to ADRs, being Infliximab the BA with the highest risk.  We have also found other clinical factors that modify their survival due to ADRs.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/adverse-events-to-biologic-agents-in-elderly-patients-with-rheumatoid-arthritis-cohort-with-13-years-of-follow-up/