Flares after hydroxychloroquine reduction or discontinuation: results from the Systemic Lupus International Collaborating Clinics (SLICC) inception cohort
Almeida-Brasil CC., Hanly JG., Urowitz M., Clarke AE., Ruiz-Irastorza G., Gordon C., Ramsey-Goldman R., Petri M., Ginzler EM., Wallace DJ., Bae SC., Romero-Diaz J., Dooley MA., Peschken C., Isenberg D., Rahman A., Manzi S., Jacobsen S., Lim S., van Vollenhoven RF., Nived O., Jönsen A., Kamen DL., Aranow C., Sanchez-Guerrero J., Gladman DD., Fortin PR., Alarcón GS., Merrill JT., Kalunian K., Ramos-Casals M., Steinsson K., Zoma A., Askanase A., Khamashta MA., Bruce IN., Inanc M., Abrahamowicz M., Bernatsky S.
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.