Background/Purpose: Physicians and patients often consider reducing or discontinuing hydroxychloroquine (HCQ) among SLE patients in remission or very low disease activity to limit HCQ-induced toxicity. We evaluated how disease activity status is associated with SLE flare after HCQ reduction or discontinuation, compared with HCQ maintenance.

Methods: We analyzed prospective data from the SLICC cohort (33 sites in Europe, Asia, and North America), which enrolls patients within 15 months of diagnosis and follows them annually since 1999. In patients initially receiving HCQ, we identified events of HCQ dose reduction and discontinuation. We created two cohorts of person-time, with time zero being date of first HCQ reduction in one cohort, and discontinuation in the other. For each cohort, we formed a comparison cohort of person-time on HCQ maintenance, matched on HCQ duration at time-zero (Figure 1). Patients were censored at death, lost to follow-up, end of study (April 2019), or when they started contributing person-time to the other cohorts. SLE flare was defined as either subsequent SLE therapy augmentation (steroids, immunosuppressives, HCQ, chloroquine, or biologics), increase of ≥4 points in the SLE Disease Activity Index-2000 (SLEDAI-2K) or hospitalization for SLE (information available only after 2014, for 60% of patients). We estimated crude flare rates, adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) of the first flare in the HCQ reduction and discontinuation cohorts (vs HCQ maintenance). Analyses were then stratified by low disease activity state or clinical remission (see the definitions in the footnote to Table 1). All models were adjusted for demographics and clinical characteristics at time-zero.

Results: A total of 1460 patients were included (89% female, 52% Caucasian). The HCQ reduction cohort contributed 1063 person-years (N=564) and were compared with 1242 HCQ maintenance person-years (N=778). The HCQ discontinuation cohort contributed 657 person-years (N=389) and were compared with 924 maintenance person-years (N=577). We estimated that 5% of patients may have reduced HCQ therapy as result of the AAO guidelines, 55% because of low disease activity state, and the remainder (40%) for other reasons (possibly intolerance or patient preference). Among those who discontinued HCQ, 4% had retinal changes of concern, 15% were in clinical remission and the remainder stopped for unknown reasons (possibly intolerance, or patient preference). Cohorts reducing or discontinuing HCQ tended to have more SLE flares versus those maintaining HCQ (Table 1). Maintaining HCQ was associated with lower SLE flares particularly among patients already in low disease activity state or in remission at time zero (Table 1). However, patients who were not in remission or low activity state, were likely to flare if HCQ was either maintained or reduced, but the flare risk was higher if they discontinued HCQ (Table 1).

Conclusion: Maintaining HCQ was associated with a lower flare risk in all subgroups evaluated. Even among SLE patients in remission, lowering or stopping HCQ was associated with a 2-fold increase in flare risk compared to HCQ maintenance.

« Back to ACR Convergence 2021

ACR Meeting Abstracts - https://acrabstracts.org/abstract/impact-of-systemic-lupus-disease-activity-state-on-flare-risk-after-hydroxychloroquine-maintenance-reduction-or-discontinuation-in-a-multinational-inception-cohort/