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

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Abstract
Objectives To evaluate systemic lupus erythematosus (SLE) flares following hydroxychloroquine (HCQ) reduction or discontinuation versus HCQ maintenance. Methods We analysed 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 with 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 hospitalisation for SLE. We estimated adjusted HRs (aHRs) with 95% CIs associated with reducing/discontinuing HCQ (vs maintenance). We also conducted separate multivariable hazard regressions in each HCQ subcohort to identify factors associated with flare. Results We studied 1460 (90% female) patients initiating HCQ. aHRs for first SLE flare were 1.20 (95% CI 1.04 to 1.38) and 1.56 (95% CI 1.31 to 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 to 1.87). Prednisone use at time-zero was associated with over 1.5-fold increase in flare risk in all HCQ subcohorts. Conclusions SLE flare risk was higher after HCQ taper/discontinuation versus HCQ maintenance. 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 (eg, seniors) may be helpful.
Funding Information
  • National Institute for Health Research (NIHR)/Wellcome Trust (N/A)
  • Gigtforeningen (A3865)
  • National Research Foundation of Korea (NRF-2017M3A9B4050335)
  • Birmingham Clinical Research Facility (N/A)
  • Arthritis Society (N/A)
  • Sandwell and West Birmingham Hospitals NHS Trust (N/A)
  • Montreal General Hospital (N/A)
  • University of Calgary (N/A)
  • Manchester Clinical Research Facility (N/A)
  • National Institute for Health Research (N/A)
  • National Institutes of Health (5UL1TR001422–02, AR-43727, AR-69572, K24-AR-02318, P60AR064464, RR00046, UL-1RR-025741)
  • Novo Nordisk (A05990)
  • Fonds de Recherche du Québec Santé (N/A)
  • NHS (N/A)
  • Canadian Institutes of Health Research (N/A)
  • Research Institute of the McGill University Health Centre (N/A)
  • National Institute for Health Research (N/A)
  • Wellcome Trust (N/A)
  • Centers for Disease Control and Prevention (U01DP005119)
  • Arthritis Research UK (N/A)

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