Association Of Hydroxychloroquine Use Research Articles

Association of Hydroxychloroquine Use with a Dose-Dependent Decrease in Mortality Risk in Patients with Elderly-Onset Rheumatoid Arthritis.

Elderly-onset rheumatoid arthritis (EORA) is associated with an increased mortality risk; however, the effect of conventional synthetic, biologics or targeted synthetic disease-modifying anti-rheumatic drugs (csDMARDs, bDMARDs or tsDMARDs) on the EORA-specific mortality risk is unknown. In this study, we investigated the risk factors for all-cause mortality of patients with EORA. Data of EORA patients diagnosed with RA at age > 60years between January 2007 and June 2021 were extracted from the electronic health record of Taichung Veterans General Hospital, Taiwan. Multivariable Cox regression was used to calculate the hazard ratio (HR) and 95% confidence interval (CI). The survival of patients with EORA was analyzed by Kaplan-Meier method. Among the 980 EORA patients who were enrolled (survivors 852 and non-survivor 128), the significant mortality-associated risk factors [HR (95% CI)] included higher age (1.10 [1.07-1.12], p < 0.001), male sex (1.92 [1.22-3.00], p = 0.004), current smoker (2.31 [1.10-4.87], p = 0.027) and underlying malignancy (1.89 [1.20-2.97], p = 0.006). Hydroxychloroquine treatment conferred protection against mortality in patients with EORA (HR 0.30, 95% CI 0.14-0.64, p = 0.002). Patients with malignancy who did not receive hydroxychloroquine treatment had the highest mortality risk compared with their counterparts. Patients with a monthly cumulative dose of hydroxychloroquine dose < 1374.5mg had the lowest survival rate compared to patients who received hydroxychloroquine 1374.5-5778.5 and ≥ 5778.5mg. Hydroxychloroquine treatment is associated with survival benefits in patients with EORA, and prospective studies are needed to validate the abovementioned findings.

Association of Hydroxychloroquine Use With Decreased Incident Atrial Fibrillation in Systemic Lupus Erythematosus.

To study the relationship between hydroxychloroquine (HCQ) use and new-onset atrial fibrillation in patients with systemic lupus erythematosus (SLE). A retrospective cohort of adult patients with SLE was constructed from December 1, 2014 to May 30, 2017. Patients were categorized as either HCQ users or nonusers. The primary outcome was incident atrial fibrillation. Secondary outcomes included incident ventricular arrhythmias (composite of ventricular tachycardia, ventricular fibrillation, or torsades de pointes). Outcomes were adjudicated by review of the electronic health record. Statistical analyses included simple and multivariable logistic regression tests to estimate the association between HCQ use and incident atrial fibrillation after adjusting for relevant confounders. Propensity score matching analysis was completed. Our study included 1,647 patients with SLE, of which 917 were HCQ users and 730 were nonusers. A total of 23 atrial fibrillation events occurred, including 3 in HCQ users and 20 in nonusers. Logistic regression analysis showed an odds ratio (OR) of 0.12 (95% confidence interval [95% CI] 0.034-0.39, P = 0.0005) for incident atrial fibrillation and 2.39 (95% CI 0.25-23.0, P = 0.45) for ventricular arrhythmias. Results remained significant in the fully adjusted and propensity score-matched models. In this exploratory study, HCQ use was associated with an 88% decrease in the risk of incident atrial fibrillation in patients with SLE. Considering the increased cardiovascular risk in SLE, incorporation of HCQ into the regimen may be beneficial for both disease manifestations and reducing the risk of atrial fibrillation. Further studies would be needed to confirm the antifibrillatory benefit of this relatively safe and low-cost medication.

Association of Hydroxychloroquine use and Hemolytic Anemia in Patients With Low Levels of Glucose-6-Phosphate Dehydrogenase.

Glucose-6-phosphate dehydrogenase deficiency (G6PD) is linked to hemolytic anemia with certain medications and is the most common enzyme deficiency worldwide. Although the American College of Rheumatology does not recommend routine testing for G6PD prior to initiation of hydroxychloroquine (HCQ), the package insert for HCQ does recommend careful use in patients with G6PD deficiency. We identified eligible subjects seen at our tertiary care, urban medical center between 1997 and 2018. Case records were analyzed for G6PD deficiency, HCQ use, length of exposure to HCQ, demographic characteristics, and laboratory evidence of hemolysis. We found 5264 patients who were prescribed HCQ, of which 49.5% (2605 patients) were screened for G6PD deficiency. Of the screened patients, 36 were found to be G6PD-deficient. Of the G6PD-deficient patients, 18 were exposed to HCQ. No evidence of hemolysis was found in these exposed patients. Despite more than 500 months of cumulative exposure time to HCQ, there were no cases of hemolysis. These findings are in line with recently published data and suggest that this interaction is not associated with clinically significant hemolysis in our population of mainly African American and Hispanic patients. Limitations to our study are potential bias due to case review design and lack of prior assessment of episodes of hemolysis before HCQ exposure. A high proportion of our patients were Hispanic, suggesting no increase of adverse events in this subgroup. A larger longitudinal trial would be needed to definitively answer the question of the safety of HCQ in G6PD-deficient patients.

Hydroxychloroquine Use and Risk of CKD in Patients with Rheumatoid Arthritis.

Hydroxychloroquine is widely used in patients with rheumatoid arthritis. However, large-scale studies examining the long-term effects of hydroxychloroquine on the development of kidney disease in patients with rheumatoid arthritis are lacking. We aimed to assess the long-term association of hydroxychloroquine use with the risk of developing CKD in this population. We conducted an observational cohort study for patients with newly diagnosed rheumatoid arthritis who were enrolled prospectively in Taiwan's National Health Insurance Research Database between January 1, 2000 and December 31, 2013. We used multivariable Cox proportional hazard regression to analyze the association of hydroxychloroquine use with incident CKD. A total of 2619 patients, including 1212 hydroxychloroquine users and 1407 hydroxychloroquine nonusers, were analyzed. Incident CKD was reported in 48 of 1212 hydroxychloroquine users and 121 of 1407 hydroxychloroquine nonusers. The incidence rate of CKD was lower in hydroxychloroquine users than in hydroxychloroquine nonusers (10.3 versus 13.8 per 1000 person-years). After multivariable adjustment, hydroxychloroquine users still had a lower risk of incident CKD (adjusted hazard ratio, 0.64; 95% confidence interval, 0.45 to 0.90; P=0.01) than hydroxychloroquine nonusers. The lower risk of subsequent CKD development was dose dependent and consistent across subgroup analyses. Hydroxychloroquine use in patients with newly diagnosed rheumatoid arthritis is associated with a significantly lower risk of incident CKD compared with in nonusers.

Systemic lupus erythematosus in three ethnic groups: XVI. Association of hydroxychloroquine use with reduced risk of damage accrual

To examine whether hydroxychloroquine (HCQ) usage is associated with a reduced risk of damage accrual in patients with systemic lupus erythematosus (SLE). Patients (n = 518) meeting the American College of Rheumatology criteria for diagnosis of SLE and with </=5 years disease duration at study entry were followed up annually. Socioeconomic, demographic, clinical, and serologic manifestations as well as disease activity (by the Systemic Lupus Activity Measure [SLAM]) and damage (by the Systemic Lupus International Collaborating Clinics damage index [SDI]) were measured. Propensity scores were calculated to adjust for confounding factors affecting treatment assignment. A Cox proportional hazards model was used to compare the risk of developing new damage according to HCQ use at enrollment into the study. Fifty-six percent of the patients were treated with HCQ at the time of study enrollment. Patients who were not treated with HCQ on enrollment had higher SLAM and SDI scores than patients who were treated. Untreated patients were significantly more likely to have major organ involvement such as renal disease (P < 0.0001) or central nervous system disease (P < 0.0025). Results of unadjusted analysis suggested that treated patients were less likely to accrue damage (hazard ratio [HR] 0.68). With adjustment for differences in treatment assignment, HCQ usage was still associated with a reduced risk of developing new damage, with an HR of 0.68 (95% confidence interval [95% CI] 0.53-0.93) (P = 0.014). With adjustment for differences in treatment assignment, HCQ usage was still associated with a reduced risk of developing new damage (HR 0.73 [95% CI 0.52-1.00]) (P = 0.05). However, patients receiving HCQ who had no damage at study entry had a statistically significant decrease in the risk of damage accrual (HR 0.55 [95% CI 0.34-0.87]) (P = 0.0111), whereas those receiving HCQ who had damage at study entry did not (HR 1.106 [95% CI 0.70-1.74]) (P = 0.6630). These findings indicate that, after adjustment for propensity to receive HCQ, HCQ usage is independently associated with a reduced risk of damage accrual in SLE patients who had not yet accrued damage at the time of treatment initiation.