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

Celline C. Almeida-Brasil, John G. Hanly, Murray Urowitz, Ann Elaine Clarke, Guillermo Ruiz-Irastorza, Caroline Gordon, Rosalind Ramsey-Goldman, Michelle Petri, Ellen M. Ginzler, D. J. Wallace, Sang Cheol Bae, Juanita Romero-Diaz, Mary Anne Dooley, Christine Peschken, David Isenberg, Anisur Rahman, Susan Manzi, Søren Jacobsen, Sam Lim, Ronald F. van VollenhovenOla Nived, Andreas Jönsen, Diane L. Kamen, Cynthia Aranow, Jorge Sanchez-Guerrero, Dafna D. Gladman, Paul R. Fortin, Graciela S. Alarcón, Joan T. Merrill, Kenneth Kalunian, Manuel Ramos-Casals, Kristján Steinsson, Asad Zoma, Anca Askanase, Munther A. Khamashta, Ian N. Bruce, Murat Inanc, Michal Abrahamowicz, Sasha Bernatsky

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish (US)
Pages (from-to)370-378
Number of pages9
JournalAnnals of the rheumatic diseases
Issue number3
StatePublished - Mar 2022

ASJC Scopus subject areas

  • General Biochemistry, Genetics and Molecular Biology
  • Rheumatology
  • Immunology and Allergy
  • Immunology


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