Reducing, stopping hydroxychloroquine spikes flare risk for lupus patients in remission
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Hydroxychloroquine maintenance, compared with reducing or discontinuing, is associated with a lower risk for flare among patients with systemic lupus erythematosus in remission or very low disease activity, according to data presented here.
“Though hydroxychloroquine is a cornerstone lupus drug, physicians and patients often consider lowering or stopping the drug, especially during remission or low disease activity, in order to limit long-term toxicity, such as that due to retinal damage or other organ damage,” Sasha Bernatsky, MD, PhD, of McGill University, in Montréal, Canada, told attendees at ACR Convergence 2021. “In another presentation, we interviewed a number of lupus patients and confirmed about 75% of them had at some point, over the course of their lupus, either lowered or stopped, or both, their hydroxychloroquine.”
“Interestingly, 25% of the time, this was done without consultation with the physician,” she added. “In those who maintained with hydroxychloroquine, a large number will in fact still have a preference to lower or stop their hydroxychloroquine, but not discuss this with physicians. It’s always the tension between wanting to remain in good control of the disease vs. wanting to be on as few medications as possible.”
To examine the association between disease activity and SLE flare following the reduction or discontinuation of hydroxychloroquine, compared with therapy maintenance, Bernatsky and colleagues analyzed prospective data from the Systemic Lupus Erythematosus International Collaborating Clinics (SLICC) cohort. Established in 1999, SLICC enrolls patients within 15 months of diagnosis, from 33 sites in Europe, Asia and North America, and follows up annually.
For their study, the researchers included 1,460 patients initially receiving hydroxychloroquine, and identified instances of dose reduction and discontinuation. They created two cohorts of person-time, with “time zero” set as the date of first reduction in one cohort, and of discontinuation in the other. For each group, the researchers formed a comparison cohort of person-time on hydroxychloroquine maintenance, matched based on therapy duration at time zero.
The reduction cohort included 564 patients and contributed 1,063 person-years. These patients were compared with 778 maintenance patients with 1,242 person-years.
Meanwhile, the discontinuation cohort of 389 patients contributed 657 person-years, and were compared with 577 maintenance patients with 924 person-years.
Patients were removed from the analysis at death, lost follow-up, upon the end of the study in April 2019, or when they began contributing person-time data to other cohorts. The researchers defined flare as either subsequent SLE therapy augmentation, an increase of at least four points on the SLE Disease Activity Index-2000 (SLEDAI-2K), or SLE hospitalization.
Analyses included estimated crude flare rates, adjusted hazard ratios and confidence intervals for the first flare in the reduction and discontinuation cohorts, compared with maintenance. Data were then stratified by LDA or remission status, with all models adjusted for demographics and clinical characteristics at time zero.
According to the researchers’ estimations, 5% of patients may have reduced their hydroxychloroquine therapy as a result of American Academy of Ophthalmology guidelines. As many as 55% may have reduced their dosage due to LDA, while the remaining 40% did so for other reasons, possibly intolerance or patient preference, the researchers wrote.
Among those who discontinued, 4% demonstrated concerning retinal changes and 15% were in clinical remission. The remaining stopped for unknown reasons, possibly intolerance or patient preference, according to the researchers.
Patients who reduced or discontinued hydroxychloroquine tended to demonstrate more SLE flares, compared with those who maintained their therapy. Maintaining hydroxychloroquine was associated with lower SLE flares particularly in patients who were already in LDA or remission status at time zero. In particular, the researchers found that, among patients in remission, lowering or stopping hydroxychloroquine was linked to a twofold increase in flare risk compared to maintenance therapy.
However, those who were not in remission or LDA status were likely to flare regardless of whether hydroxychloroquine was maintained or reduced. Nonetheless, flare risk was higher among patients who discontinued.
“Given the limitations of observational methods, I still think these results suggest that maintaining hydroxychloroquine is associated with lower flare risk than in most subgroups we’ve evaluated to date,” Bernatsky said. “I’m going to be using these results in discussions with my patients regarding what the potential implications are of lowering or stopping hydroxychloroquine; I think in the end this information should be in their hands so that they can be the ones to make these decisions with us. Of course, given the significant flare rates even in remission, we need to keep on working on optimizing lupus treatments.”
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Bernatsky S. Abstract 0959. Presented at: ACR Convergence 2021; November 5-9, 2021 (virtual meeting).
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