HCQ Tapering, Discontinuation Heighten Flare Risk in Some Patients With SLE

The new study suggests certain sub-categories of patients are at particularly high risk.

Patients with systemic lupus erythematosus (SLE) tend to have a higher risk of flares if they taper or discontinue use of hydroxychloroquine (HCQ) versus continuing maintenance therapy, according to a new study.

However, the authors said the choice of whether to taper the medication could depend on whether the patient fits into certain subgroups, since outcomes and risk varied somewhat among these cohorts. The study was published in the Annals of Rheumatic Diseases.

Sasha Bernatsky, MD, PhD, of McGill University, and colleagues, noted that a pivotal study from 2 decades ago suggested that HCQ withdrawal was ill-advised, since the drug appeared to greatly reduce flares. Yet, the investigators said, the study did not answer the question of whether indefinite maintenance of HCQ was the best fit for all patients, specifically for those in remission or with low disease activity.

“For years, physicians have attempted to identify a subgroup of patients in whom it would be safe to stop or reduce HCQ, such as seniors,” wrote Bernatsky, the study’s corresponding author, and colleagues.

To better understand the impacts of dose reduction among different subgroups of patients with SLE, the investigators examined prospective data from the Systemic Lupus International Collaborating Clinics Cohort, which began in 1999 and followed newly diagnosed patients with SLE through 2019. The patients came from 33 participating sites, and all were enrolled within 15 months of diagnosis. The authors compared patient outcomes while on the initial HCQ maintenance dose with outcomes when and if patients had their dose reduced or stopped taking HCQ altogether.

Data from 1460 patients who were prescribed HCQ was included in the analysis. Ninety percent of patients in the study were female. A total of 592 of the patients in the cohort reduced HCQ during the study period and 407 discontinued HCQ during that time. The HCQ reduction cohort was followed for 2 years on average and the discontinuation and HCQ maintenance cohorts were followed for about 1.7 years, the authors said. Over that time, 78.7% of patients in the reduction cohort and 72% in the discontinuation cohort experienced flaring. Just 50% of patients in the control cohorts had flares.

Flares were defined as subsequent need for therapy augmentation, increase of ≥4 points in the SLE Disease Activity Index—2000, or hospitalization for SLE.

That translated to an adjusted hazard ratio for a first SLE flare of 1.2 (95% Confidence Interval [CI], 1.04-1.38) for the HCQ reduction group and 1.56 (95% CI, 1.31-1.86) for the discontinuation group compared with HCQ maintenance groups.

Despite the overall increased risk among patients tapering or discontinuing HCQ, the investigators said some patients were more at-risk than others. For instance, patients who were taking prednisone or immunosuppressors were at a higher flare risk, as were patients with lower levels of education.

“Low education is a well-known predictor of poor adherence to long-term therapies including in SLE,” the investigators wrote. “Subjects who discontinued HCQ (particularly those with low education) may have been non-adherent with other medications and physician advice, perhaps due to mistrust or not understanding physician recommendations.”

Overall, the authors said their study affirms the idea that HCQ maintenance typically leads to lower flare risk. However, Bernatsky and colleagues added that the issue does not lend itself to one-size-fits-all solutions. They said whether to continue, taper, or discontinue HCQ is a question that needs to be made on a personalized basis following a clear conversation about the trade-offs at play.


Almeida-Brasil CC, Hanly JG, Urowitz M, et al. Flares after hydroxychloroquine reduction or discontinuation: results from the systemic lupus international collaborating clinics (SLICC) inception cohort. Ann Rheum Dis. Published online December 15, 2021. doi:10.1136/annrheumdis-2021-221295