PHILADELPHIA – Patients with systemic lupus erythematosus treated with lower doses of hydroxychloroquine (HCQ) had an increased risk for hospitalization for flares, according to study results presented during a press conference at the annual meeting of the American College of Rheumatology.
HCQ is a cornerstone treatment for SLE as it has been shown to increase survival and decrease disease flares.
Doses decreased with changing guidelines
Guidelines over the years have recommended decreasing doses of HCQ. In 2011, ophthalmology guidelines recommended limiting HCQ dosing to 6.5 mg/kg per day or less of ideal body weight to reduce the chance of retinopathy. For many patients, this required a dose lower than 400 mg/day, an amount frequently used to treat lupus.
In 2016, updated guidelines further lowered the dosage of HCQ, recommending 5 mg/kg or less of patient’s actual body weight.
The effects that lower dosing has had on SLE-associated hospitalizations was unknown, which inspired Dr. Nestor’s research.
The team conducted a case-crossover study within the Mass General Brigham SLE cohort.
Hospitalizations studied over a decade
Dr. Nestor and colleagues identified patients with SLE (via electronic health records) who had at least one visit for SLE and were prescribed HCQ between January 2011 and December 2021, the period over which the recommendations were made.
They identified patients who had been hospitalized during that decade with SLE as the primary discharge diagnosis.
Patients were excluded if they had non-SLE indications, such as kidney transplant or infection without a concomitant SLE flare.
Of 2,971 patients with SLE who used HCQ, 576 had at least one hospitalization with primary discharge diagnosis of SLE.
Of these, 108 were hospitalized for an SLE flare and had used HCQ prior to that hospitalization and had at least one control period with HCQ use during the study period.
All of the patients in the study had to have a case period and a control period, Dr. Nestor explained. The case period was 6 months on HCQ ending in hospitalization for lupus and the control period was 6 months on HCQ that did not end in hospitalization for lupus.
Significantly increased hospitalizations
Low-dose HCQ by weight-based dose (≤ 5 vs. > 5 mg/kg per day) and by non–weight-based dose (< 400 vs. 400 mg per day) were both associated with significantly increased hospitalizations for SLE (adjusted odds ratio, 4.41; 95% confidence interval, 1.50-12.98; and AOR, 3.48; 95% CI, 1.33-9.13, respectively).
The average age of the hospitalized group was 36 years. Most patients (92%) were female, 43.5% were White, and 32.4% were Black.
In calling for reassessment of the dosing, Dr. Nestor said, “We are protecting our patients against a very long-term side effect of hydroxychloroquine retinopathy. [It] typically takes 10-20 years to develop in our patients. But by doing that, we’re missing many of the short-term benefits from hydroxychloroquine in our patients, leading to more lupus flares, which leads to more end-organ damage.”
She said patients taking HCQ for lupus are asked to see an ophthalmologist once a year to monitor for the side effect, adding that rheumatologists and ophthalmologists could work together to adjust the guidelines.
Dr. Nestor suggested it’s possible that patients need higher doses of HCQ earlier in their disease and lower doses later. “Perhaps it’s just the patients who are particularly active who need the higher doses,” she said.