Polypharmacy can be associated with poor outcomes in chronic diseases. Our objective is to determine the prevalence of polypharmacy and its association with disease control in patients with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). An observational study was conducted using the SARD database of the CHU de Québec. Participants newly diagnosed with RA or SLE enrolled in the database after 24 months were included. Collected data included number and type of medications, Charlson Comorbidity Index, and medication adherence (proportion of days covered during the first 180 days). Polypharmacy was defined as the simultaneous use ≥5 medications. Multivariable logistic and linear regressions were used to determine the association between polypharmacy and disease control (DAS28CRP, SLEDAI-2 K). The study included 111 participants (RA = 81
SLE = 30). Medication count increased at two years in RA (mean ± SD): 4.6 ± 3.3 to 6.9 ± 3.6
and SLE: 6.5 ± 4.6 to 7.80 ± 4.82. Polypharmacy prevalence increased at two years: RA: from 43 to 74%
SLE: from 47 to 73%. Mean medication adherence exceeded 85%. For RA participants, polypharmacy was associated with a better DAS28CRP score at one year [adjusted odds ratio of achieving a poor outcome: 0.17 (95%CI 0.04-0.71)], but this association was lost at two years [2.88 (0.45-18.29)]. For SLE, polypharmacy was not associated with disease activity based on the SLEDAI-2 K at one year [7.36 (0.26-211.16)] or two years [0.32 (0.05-1.99)]. Overall, polypharmacy is very prevalent in RA and SLE and could be positively associated with the level of disease control in the year after a diagnosis of RA.