Fig. 2: Cumulative incidence of clinically diagnosed Alzheimer’s and related dementia (ADRD) in rheumatoid arthritis patients treated with methotrexate or hydroxychloroquine, medicare data 2007–2017.

A new-user active comparator design with propensity score (PS)-based adjustment for confounding, was used to estimate treatment effects in four alternative analyses. Analyses indicate that cumulative incidence of ADRD among HCQ initiators compared to MTX initiators diverged after approximately 2 years of treatment wherein individuals on HCQ had lower cumulative incidence of ADRD compared to MTX users. The four analyses were designed to address various uncertainties associated with claims-based analyses of ADRD risk: Analysis 1: ‘As-treated’ follow-up approach (MTX: N patients = 54,562, N outcomes = 1096, N person years = 71,029; HCQ: N patients = 54,562, N outcomes = 774, N person years = 56,891); Analysis 2: ‘As-started’ follow-up approach incorporating a 6-month induction period (MTX: N patients = 30,615, N outcomes = 1391, N person years = 68,504; HCQ: N patients = 30,615, N outcomes = 1206, N person years = 68,329); Analysis 3: Incorporating a 6-month ‘symptom to diagnosis’ period’ period (MTX: N patients = 25,072, N outcomes = 798, N person years = 43,254; HCQ: N patients = 25,072, N outcomes = 609, N person years = 39,808); and Analysis 4: Alternate outcome definition (MTX: N patients = 54,562, N outcomes = 416, N person years = 71,669; HCQ: N patients = 54,562, N outcomes = 275, N person years = 57,349). See Methods for additional description of analytic approach. HCQ hydroxychloroquine, MTX methotrexate.