Does Older Age have an Impact on Rituximab Efficacy and Safety? Results from the NOR-DMARD Register

• Published in: Drugs & aging Vol. 37; no. 8; pp. 617 - 626
• Main Authors: Mielnik, Pawel, Sexton, Joseph, Lie, Elisabeth, Bakland, Gunnstein, Loli, Liz P., Kristianslund, Eirik K., Rødevand, Erik, Lexberg, Åse S., Kvien, Tore K.
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing 01-08-2020; Springer Nature B.V
• Subjects: Adult; Age; Age Factors; Aged; Antirheumatic Agents - administration & dosage; Antirheumatic Agents - adverse effects; Antirheumatic Agents - therapeutic use; Arthritis, Rheumatoid - drug therapy; Arthritis, Rheumatoid - immunology; Biological products; Drug-Related Side Effects and Adverse Reactions - epidemiology; Drug-Related Side Effects and Adverse Reactions - etiology; Female; Geriatrics/Gerontology; Humans; Immunosenescence - drug effects; Immunotherapy; Infections; Internal Medicine; Male; Medicine; Medicine & Public Health; Middle Aged; Monoclonal antibodies; NCT; NCT01581294; Norway; Original Research Article; Patients; Pharmacology/Toxicology; Pharmacotherapy; Pneumonia; Registration; Registries; Rheumatoid arthritis; Rituximab - administration & dosage; Rituximab - adverse effects; Rituximab - therapeutic use; Severity of Illness Index; Treatment Outcome; Tumor necrosis factor-TNF; Norway
• ISSN: 1170-229X; 1179-1969
• DOI: 10.1007/s40266-020-00782-x

Objective
The objective of this study was to compare the efficacy and safety of rituximab in older vs younger patients with rheumatoid arthritis.
Methods
Data on 367 patients with rheumatoid arthritis treated with rituximab in the Norwegian Disease-Modifying Antirheumatic Drug (NOR-DMARD) register were analysed, comparing patients aged ≥ 65 years (
n
 = 91) with patients aged < 65 years (
n
 = 276). Drug survival was compared using a Kaplan–Meier analysis and Cox proportional hazard models. Disease activity, as assessed by the Disease Activity Score based on 28 joints and erythrocyte sedimentation rate (DAS28-ESR) and the Simplified Disease Activity Index, was analysed with linear mixed models. The occurrence of adverse events was analysed by quasi-Poisson regression models.
Results
Drug survival was similar in the two age groups. The proportion of patients who remained taking rituximab over 2 years was 72% in those under aged 65 years vs 74% in those aged ≥ 65 years. No statistically significant association with age was found for drug survival in either the unadjusted (hazard ratio 1.13,
p
 = 0.65) or adjusted Cox proportional hazard analyses for the model with DAS28-ESR as a confounder (effect size 1.11,
p
 = 0.73). Models including the Simplified Disease Activity Index instead of DAS28-ESR yielded similar results. Age was furthermore not significantly associated with disease activity over time, although there was a tendency towards a poorer response in older patients. In the older age group, there was a higher incidence of pneumonia (107 vs 51 per 1000 patient-years) and other serious infections (142 vs 66 per 1000 patient-years).
Conclusions
Rituximab is a reasonable therapeutic option for older patients with rheumatoid arthritis although vigilance is needed with regard to the infection profile.
Trial Registration
ClinicalTrials.gov Identifier: NCT01581294.