Long-term outcomes of hydroxychloroquine dose reduction in Puerto Ricans with systemic lupus erythematosus: 6-year follow-up

Background/objective To reduce the risk of hydroxychloroquine (HCQ)-induced retinopathy, the American Academy of Ophthalmology recommends a maximum HCQ dose of ≤5.0 mg/kg/day. Previously, we reported that reducing HCQ to this threshold did not affect clinical outcomes in Puerto Rican patients with systemic lupus erythematosus (SLE) after 2 years. To evaluate longer term effects, we extended follow-up to 6 years post-HCQ dose adjustment. Methods We conducted a retrospective study on a cohort of Puerto Rican SLE patients whose HCQ doses were adjusted to ≤5.0 mg/kg/day. Disease activity (per-Systemic Lupus Erythematosus Disease Activity Index), lupus exacerbations, hospitalisations, disease damage (per SLICC/ACR Damage Index) and pharmacologic treatments were assessed. Outcomes during the 4-year extension were compared with preadjustment and initial 2-year postadjustment periods. A control group of SLE patients who did not require HCQ dose adjustment was also included. Results Among the 304 patients included in the study, 60 required HCQ dose adjustment, whereas 244 patients did not require modification of their HCQ regimen and served as controls. During the 4-year extension period, a small but statistically significant increase in disease damage was observed in patients who underwent HCQ dose adjustment compared with earlier follow-up periods. Tacrolimus exposure significantly increased, whereas other immunosuppressive therapies remained stable. No increase in disease activity, lupus exacerbations or hospitalisations was observed. Clinical features were comparable between patients who underwent HCQ dose adjustment and those who did not, although patients in the adjusted-dose group had lower weight-based daily HCQ dosing and were less likely to develop HCQ-induced retinopathy. Conclusions In this cohort, reducing HCQ to ≤5.0 mg/kg/day was associated with a slight increase in long-term disease damage. No adverse outcomes on disease activity, exacerbations or hospitalisations were observed, supporting the long-term safety of HCQ dose adjustment in Puerto Rican SLE patients.