Baseline prednisone use tied to poor outcomes in tapering hydroxychloroquine for lupus
Baseline prednisone use is associated with an increased risk for poor outcomes among patients with systemic lupus erythematosus who are tapering hydroxychloroquine, according to data published in Arthritis Care & Research.
“Systemic lupus is a serious, chronic autoimmune disease that causes very high burden, including premature mortality,” Sasha Bernatsky, MD, PhD, of the McGill University Health Center in Montreal, Canada, told Healio Rheumatology. “Treatment is complex, but hydroxychloroquine is a cornerstone drug, used by almost all SLE patients. Some doctors advocate that all patients should remain on HCQ ‘indefinitely’, because if patients do flare, some will have potentially life-threatening complications including kidney failure or death. However, the doctrine of lifelong HCQ use in SLE patients remains open to question.
“Some people feel that since SLE is not a curable disease, we need to figure out when and whether HCQ should be tapered, to prevent long-term complications that can arise over decades of HCQ use,” she added. “Up to now, it’s been difficult to discuss with patients the potential risk-to-benefit ratios of tapering or discontinuing HCQ. This is a struggle for every SLE patient and every rheumatologist in North America, since there is little information to guide individual decision making about when to adjust and/or stop HCQ. Our project helps fill these knowledge gaps.”
To analyze which factors are associated with poor outcomes among patients with SLE who taper or discontinue hydroxychloroquine, Bernatsky and colleagues studied five Canadian lupus cohorts. These clinical SLE cohorts included the McGill University Health Center, Centre Hospitalier Universitaire de Québec-Université Laval, Dalhousie University, the University of Manitoba and the Southern Alberta Registry for Lupus Erythematosus at the University of Calgary. All five centers enrolled unselected adult patients with SLE at presentation, with follow-up spanning from January 1999 to January 2019.
In all, 1,389 patients with SLE received care at the participating cohorts during the enrollment and follow-up period. Among these participants, 1,344 received hydroxychloroquine, with 398 later tapering the drug and 395 who ultimately discontinued. In addition, among the 629 patients who maintained hydroxychloroquine, 395 were matched to those who tapered or discontinued, based on previous disease duration and time receiving the drug. A total of 240 patients were lost to follow-up, 62 withdrew consent and 35 died during follow-up.
The researchers used a composite outcome, defined as any of the following: The need for therapy augmentation, a SLEDAI‐2K increase of at least four points or hospitalization for SLE. Bernatsky and colleagues used multivariate Cox regression to identify demographic and clinical factors associated with time to earliest of these events in both the tapering and discontinued groups. The researchers also examined the patients who maintained hydroxychloroquine to assess whether these same factors affected the outcome even when provided a steady dose.
According to the researchers, the rate of poor outcomes, per 100 person‐years, was 35.7 (95% CI, 31.6-40.3) among patients who tapered hydroxychloroquine, 29 (95% CI, 25.5-33) among those who discontinued and 16.1 (95% CI, 13.2-19.6) among those who maintained their dose.
In those who tapered, baseline prednisone use was independently associated with a greater risk for poor outcomes. In the discontinuation group, the risk for poor outcomes was greater among Black patients and those diagnosed with SLE at age 25 years or younger. Among those who maintained their dose, baseline immunosuppressive use and First Nation ethnicity were associated with poor outcomes.
“Almost half of the lupus patients we follow at our center have lowered their HCQ dose during follow-up, and up to a third of patients stop their HCQ at some point in time,” Bernatsky said. “Patients may do this on their own, without necessarily knowing the potential risk or harms, or they may be advised to lower/stop HCQ by a health care provider — for example, due to side effects. When doctors and patients discuss whether or not to lower dose or stop HCQ therapy, they can ‘personalize’ that decision-making process by considering some patient-related factors — eg, non-Caucasian race/ethnicity — and how well the disease is currently controlled.
“This includes whether the patients have evidence of active SLE and/or are on prednisone or immunosuppressants like mycophenolate,” she added. “Tapering or stopping HCQ in Asian of Black SLE patients, or with patients with active lupus, may occasionally still sometimes be necessary — if for example a patient has side effects from the drug — but in such a case, the patient and physician should monitor for signs and symptoms of SLE flare. That could include following up with lab tests to detect asymptomatic anemia, low platelets or proteinuria.”