Predictors of unsuccessful hydroxychloroquine tapering and discontinuation: Can we personalize decision-making in systemic lupus treatment?

Objective Hydroxychloroquine (HCQ) is a key systemic lupus (SLE) drug, making concerns of drug shortages grave. We evaluated factors associated with poor outcomes after HCQ taper or discontinuation in SLE. Methods We studied five Canadian SLE cohorts between 1999-2019, following patients from date of HCQ tapering (cohort 1) or discontinuation (cohort 2). A composite outcome was defined as any of the following: need for therapy augmentation, increase (of at least 4 points) in SLEDAI-2K, or hospitalization for SLE. In each cohort, multivariable Cox regression was used to identify demographic and clinical factors associated with time to the earliest of these events. A third cohort remaining on HCQ was also studied, to assess if the same factors influenced the outcome even when HCQ dose was unchanged. Results The poor outcome rate, per 100 person-years, was 35.7 (95% CI 31.6, 40.3) in the HCQ taper cohort (N=398), 29.0 (95% CI 25.5, 33.0) in the discontinuation cohort (N=395), and 16.1 (95%CI 13.2, 19.6) in the maintenance cohort (N=395). In patients tapering HCQ, baseline prednisone use was independently associated with greater risk of poor outcomes. In the discontinuation cohort, risk of poor outcomes was greater for blacks and those diagnosed with SLE at age ≤25 years. Among those maintaining HCQ, baseline immunosuppressive use and First Nation ethnicity were associated with poor outcomes. Conclusions We identified demographic and clinical factors associated with poor outcomes after HCQ taper/discontinuation. This information is critical in the current setting of potential shortages, but long-term, this could inform personalized therapies.