LAUSR

Background: Hydroxychloroquine (HCQ) is a disease-modifying anti-rheumatic drug (DMARD) used as a long-term treatment for rheumatoid arthritis (RA) patients. Cardiotoxicity is a rare but potentially life-threatening side effect of HCQ and may present as conduction disorders, cardiomyopathy, and resulting heart failure (HF). The evidence of cardiotoxicity associated with the use of HCQ largely relies on case reports and case series while large cohort studies on the subject are lacking. Objectives: To examine the relationship between the use of HCQ and risk of developing HF in RA. Methods: In this nested case-control study, cases were Olmsted county, Minnesota residents with incident RA (based on 1987 ACR criteria) in 1980-2013 who developed HF after RA incidence. Each case was matched on year of birth, sex and year of RA incidence with an RA control who did not develop HF. Each non-HF control was assigned an index date corresponding to the HF diagnosis date of the case. Controls were allowed to later become cases to avoid bias. HF was defined using the Framingham criteria. Data on HCQ use including start and stop dates and dose changes was manually abstracted via medical record review, and used to calculate HCQ duration and cumulative dose. Age-adjusted logistic regression models were used to examine the association between HCQ and HF. Results: From a cohort of 1078 subjects, the study identified 143 RA cases diagnosed with HF (mean age 65.8, 62% females) and 143 non-HF RA controls (mean age 64.5, 62% female). Cases and controls had similar RA duration, proportion of patients positive for rheumatoid factor (RF) and/ or cyclic citrullinated antibody (CCP), body mass index, and smoking status (Table). The duration of HCQ use prior to the diagnosis of HF was 2.8 years in cases and 2.6 years in controls. A total of 71 cases and 69 controls used HCQ at some time before index date. Among these, the median (interquartile range) duration of HCQ use was 2.8 (0.6, 10.0) years for cases and 2.5 (0.7, 8.2) for controls. The median cumulative dose of HCQ was 371 g and 302 g in cases and controls, respectively, with 55% of cases receiving a cumulative dose of ≥ 300 g compared to 54% in controls. HCQ cumulative dose was not associated with HF (Odds Ratio [OR]: 0.96 per 100g increase in cumulative dose, 95% confidence interval [95% CI]: 0.90-1.03). Likewise, no association was found for patients with a cumulative dose ≥300g (OR 0.92, 95% CI 0.41-2.08). The duration of use of HCQ prior to index was not associated with HF (OR 0.98, 95% CI 0.91-1.05). Retinal toxicity rates were similar in cases and controls. Conclusion: Use of HCQ was not associated with development of HF in patients with RA in this study. While there was no statistically significant association between the cumulative dose of HCQ and HF, the confidence interval for HCQ dose ≥300 g was wide suggesting that more studies are needed to understand the impact of higher doses of HCQ on development of HF in RA. Disclosure of Interests: Ahmed Sorour: None declared, Youssef Shahin: None declared, Cynthia S. Crowson Grant/research support from: Pfizer research grant, Reto Kurmann: None declared, Sara Achenbach: None declared, Rekha Mankad: None declared, Elena Myasoedova: None declared