Study investigates anti-rheumatic drug dose and incident retinopathy

28th January 2023

The risk of retinopathy from hydroxychloroquine is less than 10% over 15 years for most patients, with cases generally mild in nature

Hydroxychloroquine-induced vision-threatening retinopathy occurs in only a small proportion of patients over time with the majority of cases of mild severity according to the findings of a long-term cohort study by US and Canadian researchers.

As an anti-rheumatic treatment, hydroxychloroquine provides a survival benefit for patients with autoimmune diseases such as systemic lupus erythematosus. However, a recognised adverse effect of the drug is retinopathy although the summary of product characteristics (SPC) of the drug suggests that this complication is very uncommon, provided that the recommended daily dose is not exceeded. Despite this assertion, there is a lack of data on the incidence of retinopathy associated with longer term use.

In the present study, researchers undertook a cohort study, including patients aged 18 years and older who were prescribed hydroxychloroquine between 2004 and 2020 and who participated in retinal screening. The primary outcome for the study was hydroxychloroquine induced retinopathy. The risk of developing retinopathy was estimated over a 15-year period based on a weight-based dose of the drug, i.e., > 6 mg/kg/day (which is not advised by the SPC), 5 to 6 mg or < 5 mg/kg/day.

Hydroxychloroquine and development of retinopathy

A total of 3,325 individuals with a mean age of 58.2 years (82.7% female) were included and who had used the drug between 2004 and 2014 and then continued for a further 5 years. Overall, 65.4% were given a dose of 5 mg/kg or less and 18.6% received more than 6 mg/kg/day.

Among the entire cohort, 81 individuals developed retinopathy; 56 with mild disease, 17 moderate and 8 severe. The authors calculated a cumulative incidence of retinopathy of 2.5% over 10 years and 8.6% over 15 years.

Among patients prescribed doses in excess of 6 mg/kg/day, the cumulative risk was much higher at 21.6% compared to only 2.7% for a dose of 5 mg/kg/day. In addition, the risk for severe retinopathy at 15 years was only 1.1%.

The authors concluded that the overall risk of hydroxychloroquine retinopathy was 8.6% after 15 years and that most cases were mild, though cautioned that higher doses were associated with a greater incident risk.

Citation
Melles RB et al. Hydroxychloroquine Dose and Risk for Incident Retinopathy : A Cohort Study. Ann Intern Med 2023

Short-term use of hydroxychloroquine safe in COVID

1st October 2020

Several drugs have been used in an effort to treat the symptoms of COVID-19 including anti-malarials such as hydroxychloroquine (HCQ) although there have been concerns expressed about the safety of the drug, in particular, its prolongation of the QT interval which is associated with arrhythmias.

Now in an analysis by the European Society of Cardiology, it appears that HCQ can be safely administered for a short period of time in a range of clinical settings. The authors examined the effects of HCQ in three different settings: home management; medical wards; and intensive care units. For patients managed at home, the drug was initiated in a hospital setting. Eligible patients were required to have a pre-HCQ 12-lead ECG available and a second ECG which was defined as early (within 5 days before the first dose of HCQ) or late (either 36-72 hours or 96 hours after the first dose). For all patients, various parameters were collected including demographics, cardiovascular comorbidities, ECG readings et and stored in a de-identified database. The team also collected PQ, QRS and QTc durations before and after HCQ administration as well as ventricular arrhythmic events from healthcare records. Arrhythmia safety was assessed with regard to malignant QT-prolong arrhythmias. In cases where patients had died, a committee of three members (blinded to the treatment at the time of occurrence of the arrhythmic event) judged the relationship with HCQ administration.

Findings
In total, 649 patients were enrolled with a mean age of 61.9 years (46% male) and HCQ was administered at home (19.4%), in hospital wards (76.3%) and at intensive care units (4.3%). For patients with late ECG readings (36-72 hours and 96+ hours after the first dose), a significant QT/QTc interval prolongation was observed but the magnitude of the increase was modest at +13 ms. In addition, baseline QT/QTc length and the presence of fever at admission were the most important determinants of QT/QTc prolongation and there were no arrhythmic-related deaths reported. The incidence of ventricular arrhythmias was low (1.1%) and these events were found to be not related to QT or HCQ therapy. Finally, the authors reported no difference in QT/QTc prolongation across the different settings.

They concluded that HCQ is safe in the short-term for those with COVID-19 provided that a baseline ECG is taken and a patient risk assessment performed.

Reference
Gasperetti A et al. Arrhythmic safety of hydroxychloroquine in COVID-19 patients from different clinical settings. Europace 2020;0, 1–9 doi:10.1093/europace/euaa216