Hydroxychloroquine Maintenance Associated With Lower Flare Risk in Patients With SLE

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Researchers assessed the association between disease activity status and SLE flare risk after hydroxychloroquine reduction or discontinuation vs maintenance.

The following article is a part of conference coverage from the American College of Rheumatology (ACR) Convergence 2021, being held virtually from November 3 to 10, 2021. The team at Rheumatology Advisor will be reporting on the latest news and research conducted by leading experts in rheumatology. Check back for more from the ACR Convergence 2021.


In patients with systemic lupus erythematosus (SLE), reduction or discontinuation of hydroxychloroquine (HCQ) is associated with a 2-fold increased risk for flares, even during remission, according to study results presented at the American College of Rheumatology (ACR) Convergence 2021, held virtually from November 3 to 10, 2021.

Although reducing or discontinuing HCQ in patients with SLE with low disease activity or remission can limit HCQ toxicity, it may also lead to flares.

In a prospective study, researchers compared SLE flare risk after reduction or discontinuation of HCQ compared with HCQ maintenance.

Researchers analyzed data from the Systemic Lupus Erythematosus International Collaborating Clinics (SLICC) cohort, which includes the enrollment of patients within 15 months of SLE diagnosis and an annual follow-up. Patients with reduction or discontinuation of HCQ were placed into 2 cohorts of person-time, with time zero being the date of reduction or discontinuation. Each cohort was matched with an HCQ maintenance cohort based on duration of drug use at time zero.

SLE flare was defined as augmentation in SLE therapy, increase in the SLE Disease Activity Index-2000 (SLEDAI-2K), or hospitalization due to SLE. Hazard ratios (HR) were calculated to assess flare risk based on the first flare observed after reduction or discontinuation of HCQ. Researchers also assessed risk stratified by low disease activity state or clinical remission at baseline.

Among 1460 patients with SLE (89% women; 52% White), 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).

Flare risk was found to be higher with HCQ reduction (HR, 1.13; 95% CI, 0.98-1.30) and discontinuation (HR, 1.41; 95% CI, 1.19-1.67) compared with HCQ maintenance. When stratified by disease activity and remission, flare risk in patients with low disease activity and who were in remission was higher with HCQ reduction (HR, 1.26; 95% CI, 1.04-1.51 and HR, 2.14; 95% CI, 1.34-3.43, respectively) and discontinuation (HR, 1.52; 95% CI, 1.21-1.91 and HR, 2.77; 95% CI, 1.46-5.26, respectively). Flare risk in patients with higher disease activity and who were not in remission at time zero was similar to HCQ maintenance, if HCQ was reduced (HR, 1.00; 95% CI, 0.80-1.23 and HR, 1.07; 95% CI, 0.92-1.24, respectively), but higher if HCQ was discontinued (HR, 1.37; 95% CI, 1.06-1.77 and HR, 1.35; 95% CI, 1.13-1.62, respectively).  

Estimated reasons for HCQ reduction included American Academy of Ophthalmology guidelines (5%) and low disease activity (55%). Reasons for HCQ discontinuation included retinal changes (4%) and clinical remission (15%). The remainder of patients in each cohort reduced or discontinued HCQ for other reasons, including intolerance or patient preference. 

The researchers concluded, “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.”

Disclosure: Several study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of the disclosures.


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Brasil C, Hanly J, Urowitz M, et al. Impact of systemic lupus disease activity state on flare risk after hydroxychloroquine maintenance, reduction or discontinuation in a multinational inception cohort. Presented at: ACR Convergence 2021; November 3-10, 2021. Abstract 0959.