'Study: Keep Hydroxychloroquine Doses High in Lupus'

 

• Hydroxychloroquine is linked with serious adverse effects, most notably retinopathy, with long-term use, but nevertheless the drug is the mainstay of treatment for lupus.
• This study examined risks for adverse effects both from hydroxychloroquine and from lupus itself in national data from Taiwan.
• It found that doses of ≥400 mg/day in lupus patients were associated with lower risks for cardiovascular disease and no increased risk for retinopathy in patients younger than 45 as compared with lower doses.

Hydroxychloroquine (HCQ) doses of at least 400 mg/day provided better symptom relief for Taiwanese people with systemic lupus erythematosus (SLE) compared with lower doses, with the added benefit of less risk for cardiovascular problems, researchers said.

Moreover, according to Meng-Yu Weng, MD, PhD, of National Cheng Kung University in Tainan, Taiwan, and colleagues, their population-based analysis showed no extra risk for retinopathy with higher HCQ dosing, at least for patients younger than 45.

"Our study emphasizes the need for weighing the benefits and risks of optimal HCQ dosage in managing SLE," the group wrote in Arthritis & Rheumatology.

Their findings may ease decision-making for clinicians and patients, as they walk the tightrope between the risks for retinopathy and other adverse effects from HCQ in chronic administration with the need to maintain symptom control to limit organ damage. Previous studies have shown that underdosing is a longstanding problem in clinical practice, driven in part by fear of HCQ side effects.

Indeed, the data reported by Weng and colleagues highlight the problem. Analyzing records from Taiwan's universal health insurance system for some 23,000 SLE patients, just 3.8% were on HCQ doses of 400 mg/day or more. Published treatment guidelines commonly call for doses of 200-400 mg/day, or sometimes a weight-based approach that sets 6.5 mg/kg/day as a target (recognizing that HCQ typically comes in 200-mg pills). Either way, that 96% of patients in the current study were taking less than 400 mg/day suggests that their dosing was suboptimal.

More importantly, however, was that, with median follow-up of about 5-6 years, patients on the higher doses had lower rates of coronary artery disease (CAD) and venous thromboembolism (VTE), which are among SLE's more severe manifestations:

• CAD incidence rates: 1.48 vs 1.73 per 100 patient-years (HR 0.86, 95% CI 0.80-0.93)
• VTE incidence rates: 0.13 vs 0.32 per 100 patient-years (HR 0.40, 95% CI 0.33-0.49)

But no dose-related differences were seen for ischemic stroke, end-stage renal disease, or malignancies, Weng's group reported.

Overall, there was also no significant difference in rates of retinopathy attributable to HCQ, at 0.12 with higher doses and 0.14 with lower doses, both per 100 person-years. But for patients 45 and older, retinopathy risk was nearly doubled with doses ≥400 mg/day (HR 1.87, 95% CI 1.45-2.42).

Another subgroup analysis for retinopathy risk was more forgiving to the higher dose. Patients who got eye exams in the first year after starting HCQ showed nearly identical retinopathy rates (14.4% vs 14.8%); and while rates rose with longer follow-up, they still didn't differ significantly at year 3 or year 5.

Patients with SLE diagnoses in the national database were included in the analysis if they were over 10 years old and were starting HCQ for the first time, with no other autoimmune diagnoses. Mean age was 39 in the higher-dose group and 43.7 in the lower-dose group, and body weight averaged 60 kg; as expected, more than 80% were women. Most patients were also taking corticosteroids, and drugs for non-lupus illnesses such as depression and cardiovascular conditions were used by substantial minorities.

Weng and colleagues structured the analysis as a "target trial emulation" in which patients' data were treated as though they came from a randomized trial.

Since that wasn't actually the case, one limitation to the analysis was that unmeasured confounders (such as subtle indicators leading to the dosing decisions) could have influenced the results. As well, the results may not be fully generalizable to non-Taiwanese populations.

Disclosures

The study had no external funding.

The authors declared they had no relevant financial interests.

Primary Source

Arthritis & Rheumatology

Source Reference: Li B, et al "Weighing dose-related benefits and risks of hydroxychloroquine treatment in systemic lupus erythematosus patients" Arthritis Rheumatol 2025; DOI: 10.1002/art.70022.

https://www.medpagetoday.com/rheumatology/lupus/119135