Background/Purpose: There is growing interest regarding the role of neuroinflammation in the development of dementia and the potential role for anti-inflammatory therapy, including TNF-inhibitors (TNFi), in its prevention. Previous studies suggest that inflammatory diseases like rheumatoid arthritis (RA) can increase risk for dementia, yet the effect of DMARDs on reducing this risk is unclear. The objective of this study was to evaluate the risk of incidence dementia associated with the use of biologics or targeted synthetic DMARDs (b/tsDMARD) compared to csDMARDS only in RA patients.

Methods: This longitudinal analysis used 2006-2017 Medicare claims data. Patients must have had continuous enrollment >12 months in Medicare Part A, B, and D, be ≥40 years old and have no prior diagnosis of dementia. RA defined as: two RA diagnoses (ICD-9-CM 714.xx/ICD-10 M0.5.x or M06.x) by a rheumatologist > 7 and < 365 days apart. Patients had to meet RA definition on or before DMARD initiation. Person-time was classified as either: 1) b/tsDMARD exposed, which included TNFi-bDMARDs, non-TNFi-bDMARDs or tsDMARDs with or without csDMARDs; 2) csDMARD-exposed: any csDMARD without b/tsDMARD. Patients could contribute time to different exposure groups if they changed medications. Incident dementia was defined as: 1 inpatient claim for dementia (ICD-9-CM codes for 290.xx, 294.1x, or 331.xx and ICD-10 codes for F00.x, F01.x, F03.x,G30.x, G31.x) OR 2 outpatient claims for dementia OR prescription of a dementia specific medication (rivastigmine, galantamine, memantine, donepezil, tacrine). Incidence rates (IR) were estimated using Poisson models. Cox proportional hazard models (HR) were used to examine the risk for incident dementia among patients receiving b/tsDMARDs compared to those receiving csDMARD, adjusting for the competing risk of death. A sensitivity analysis was done that re-grouped the b/tsDMARD category as TNFi-bDMARDs, non-TNFi-bDMARDs and tsDMARDs.

Results: We identified 141,326 eligible RA patients; 80% female and 75.3% white, median age 67 years and a mean (SD) exposure time of 1.1 (1.5) years. Censoring events included incident dementia, death, change in bDMARD and discontinuation of fee for service. There were 233,271 initiations of c/b/tsDMARDS and 3,794 events of incident dementia (Table 1). The crude IR of dementia was 2.0 (95% CI 1.9-2.1) per 100 person-years for patients on csDMARDs and 1.3 (95% CI 1.2-1.4) for patients on any bDMARD (Table2). Patients on b/tsDMARDs had an adjusted 17% lower risk for dementia than patients on csDMARDs [HR 0.83 (95% CI 0.78-0.89)]. Sensitivity analysis found comparable risks between TNFi, non-TNFi, and tsDMARDs on the risk of dementia (Table 2).

Conclusion: The incidence of dementia in patients with RA was lower in patients receiving b/tsDMARDs when compared to patients on csDMARD only. No differences were observed between different classes of b/tsDMARDs, suggesting that decreased risk is possibly explained by the overall decrease in inflammation rather than a specific mechanism of action.

Table 1. Characteristics of Patients with RA and Incident Dementia

Table 2. Events, person-years, crude, and age-adjusted incidence rates (IRs), and crude and adjusted hazard ratios (HRs) for incident dementia

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/incidence-of-dementia-in-patients-with-rheumatoid-arthritis-and-association-with-dmards-analysis-of-a-national-claims-database/