The RESIST Study: Do TNF Inhibitors Protect Against Cognitive Decline in Rheumatoid Arthritis Patients With Mild Cognitive Impairment?

Abstract

AbstractBackgroundRheumatoid arthritis (RA) is an autoimmune disease characterised by chronic inflammation in the joint synovium. Considering growing research interest into the role that systemic inflammation might play in the pathogenesis of Alzheimer’s disease (AD), studying cognitive decline in RA patients can provide important insights into the potential effects of inflammation on cognitive health. Furthermore, evidence suggests that biological drugs used to treat RA, specifically TNF inhibitors (TNFi), may protect against AD progression by reducing systemic inflammation. The rheumatoid arthritis medication and memory study (RESIST) is a multicentre longitudinal observational study which aims to compare rates of cognitive decline in adults with both RA and mild cognitive impairment who are on either a conventional synthetic disease modifying anti‐rheumatic drug (csDMARD) or a TNFi.Method251 participants were recruited (160 on csDMARDs, 91 on TNFis). Participants completed assessments at six‐month intervals for eighteen months. The primary outcome was performance on the Free and Cued Selective Reminding Test (FCSRT). It was hypothesised that the rate of decline in FCSRT score would be lower among participants taking TNFis.ResultBetween‐groups ANCOVA was conducted to compare mean FCSRT scores at 12/18 months, adjusting for baseline score, age, disease activity, pain, wellbeing, depressive symptoms and physical function. Results showed that neither group declined in FCSRT free recall score on average over the 18 month follow‐up period, and that there was no significant difference between groups at 12 (mean difference = 0.59, 95% CI = ‐1.54, 2.72) or 18 months (mean difference = 1.24, 95% CI = ‐0.99, 3.47).ConclusionThe absence of decline in FCSRT performance in either group was unexpected. These findings raise the possibility that both csDMARDs and TNFis may protect against cognitive decline However, a major limitation of the study was attrition due to the COVID‐19 pandemic, which may have influenced results – those who experienced a greater degree of cognitive decline may have been more likely to withdraw from the study. Additional planned analyses will examine the potential moderating effect of APOE genotype, and the relationship between peripheral serum C reactive protein, cytokine levels and cognitive outcomes.