Flares after hydroxychloroquine reduction or discontinuation: results from the Systemic Lupus International Collaborating Clinics (SLICC) inception cohort

Objectives: To evaluate systemic lupus (SLE) flares following hydroxychloroquine (HCQ) reduction or discontinuation, versus HCQ maintenance.

Methods: We analyzed prospective data from the Systemic Lupus International Collaborating Clinics (SLICC) cohort, enrolled from 33 sites within 15 months of SLE diagnosis and followed annually (1999-2019). We evaluated person-time contributed while on the initial HCQ dose (‘maintenance’), comparing this to person-time contributed after a first dose reduction, and after a first HCQ discontinuation. We estimated time to first flare, defined as either subsequent need for therapy augmentation, increase of ≥4 points in the SLE Disease Activity Index-2000, or hospitalization for SLE. We estimated adjusted hazard ratios (aHRs) with 95% confidence intervals (CIs) associated with reducing/discontinuing HCQ (versus maintenance). We also conducted separate multivariable hazard regressions in each HCQ sub-cohort to identify factors associated with flare.

Results: We studied 1460 (90% female) patients initiating HCQ. Adjusted HRs for first SLE flare were 1.20 (95% CI 1.04, 1.38) and 1.56 (95% CI 1.31, 1.86) for the HCQ reduction and discontinuation groups, respectively, versus HCQ maintenance. Patients with low educational level were at particular risk of flaring after HCQ discontinuation (aHR 1.43, 95% CI 1.09, 1.87). Prednisone use at time-zero was associated with over 1.5-fold increase in flare risk in all HCQ sub-cohorts.

Conclusions: Versus HCQ maintenance, SLE flare risk was higher after HCQ taper/discontinuation. Decisions to maintain, reduce or stop HCQ may affect specific subgroups differently, including those on prednisone and/or with low education. Further study of special groups (e.g. seniors) may be helpful.