Nonadherence to HCQ Associated With Flares, Damage, and Mortality in SLE

Severe nonadherence to hydroxychloroquine (HCQ) therapy is associated with risk for flares, damage, and mortality among patients with systemic lupus erythematosus (SLE), according to results of a longitudinal cohort study published in Arthritis & Rheumatology.

Investigators assessed the relationship between lack of adherence to HCQ treatment, as determined by serum levels of the drug, and risk for SLE flares, damage, and mortality during 5 years of follow‑up.

Data were sourced from the multinational Systemic Lupus Erythematosus International Collaborating Clinics (SLICC) Inception Cohort.

Serum analysis of patients who had been prescribed HCQ for at least 3 months was conducted to determine the presence of severe treatment nonadherence, defined as serum HCQ levels less than 106 ng/mL for prescribed HCQ doses of 400 mg/d or as levels less than 53 ng/mL for prescribed HCQ doses of 200 mg/d.

The associations between low serum levels and the risk for SLE flare were then assessed using logistic regression analysis. An SLE flare was defined as an increase in the SLE Disease Activity Index 2000 (SLEDAI-2K) of at least 4 points, initiation of treatment with prednisone or immunosuppressive drugs, or new kidney disease.

Associations between low serum levels of HCQ and damage or mortality were analyzed with separate Cox proportional hazard models. Damage was defined as the presence of the first increase of at least 1 point on the SLICC/American College of Rheumatology Damage Index.

A total of 660 patients were included in the analysis, 88% of whom were women. The  median serum HCQ was 388 ng/mL (interquartile [IQ] range, 244-566 ng/mL), and 48 patients (7.3%) were considered severely nonadherent to HCQ treatment.

No demographic, clinical, or laboratory-based factors were associated with severe nonadherence.

Severe nonadherence was found to be independently associated with both SLE flare (odds ratio, 3.38; 95% CI, 1.80-6.42) and an increase in the damage index (hazard ratio [HR], 1.92; 95% CI, 1.05-3.50), both within the first 3 years of the 5-year study period.

Throughout the entire 5-year study period, 11 patients died, 3 of whom were considered severely nonadherent (crude HR, 5.41; 95% CI, 1.43-20.39).

This study was limited by the exclusion of more than 60% of the patient cohort who lacked an HCQ prescription lasting at least 3 months, as well as rounding of daily HCQ doses to the nearest threshold category, which may have introduced bias. Further limitations included the questionable stability of HCQ in serum during the prolonged interval between sampling and assay, the inclusion of several women whose pregnancies may have adversely affected their adherence, and potential unreported SLE flares that may have occurred between annual follow-up visits.

The study authors concluded, “As severe non-adherence is often unknown by the physician and since no predictive clinical or biological factors have been identified, our results underline the benefits of systematically testing to detect severe non-adherence and identify the patients at risk.”

Disclosure: One or more study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.