Whole blood drug levels do not correlate with QTc intervals in hydroxychloroquine-treated systemic lupus erythematosus patients.

OBJECTIVES: HCQ is recommended for all patients with SLE, but reports of cardiac toxicity in severe acute respiratory syndrome coronavirus 2 patients raised concerns. We aimed to study the relationship between HCQ blood levels and QTc intervals. METHODS: A retrospective review of 90 SLE patients (cohort 1) was conducted with data collected regarding demographics, QTc interval and chronic kidney disease (CKD). A prospective study of 84 SLE patients (cohort 2) was conducted with data collected regarding demographics, dose of HCQ, duration of HCQ treatment, presence of echocardiographic abnormalities and CKD simultaneous with whole blood HCQ levels measured by HPLC. Statistical analysis utilized one-way analysis of variance, Pearson's correlation coefficient and t tests. RESULTS: In cohort 1 there was no significant difference in mean QTc based on 75 HCQ-treated [437.91 msec (s.d. 20.02)] as compared with 15 untreated patients [434.6 msec (s.d. 27.49)]. In patients with CKD, the mean QTc in HCQ users [448 (s.d. 23.37)] as compared with non-users [444.5 msec (s.d. 24.61)] also had no significant difference. In cohort 2, HCQ levels did not correlate with QTc interval (r = 0.017) and this applied regardless of the dose prescribed (r = 0.113 for 400 mg and r = 0.06 for 200 mg), duration of exposure (P = 0.36 for 0-5, >5-10 or >10 years), CKD (r = 0.482) or underlying cardiac abnormalities (r = 0.430). CONCLUSIONS: This is the first study relying on measured blood levels demonstrating the absence of a clinically consequential increase in QTc levels in HCQ-treated SLE patients.

Evaluation of Immune Response and Disease Status in Systemic Lupus Erythematosus Patients Following SARS-CoV-2 Vaccination.

OBJECTIVE: To evaluate seroreactivity and disease flares after COVID-19 vaccination in a multiethnic/multiracial cohort of patients with systemic lupus erythematosus (SLE). METHODS: Ninety SLE patients and 20 healthy controls receiving a complete COVID-19 vaccine regimen were included. IgG seroreactivity to the SARS-CoV-2 spike receptor-binding domain (RBD) and SARS-CoV-2 microneutralization were used to evaluate B cell responses; interferon-γ (IFNγ) production was measured by enzyme-linked immunospot (ELISpot) assay in order to assess T cell responses. Disease activity was measured by the hybrid SLE Disease Activity Index (SLEDAI), and flares were identified according to the Safety of Estrogens in Lupus Erythematosus National Assessment-SLEDAI flare index. RESULTS: Overall, fully vaccinated SLE patients produced significantly lower IgG antibodies against SARS-CoV-2 spike RBD compared to fully vaccinated controls. Twenty-six SLE patients (28.8%) generated an IgG response below that of the lowest control (<100 units/ml). In logistic regression analyses, the use of any immunosuppressant or prednisone and a normal anti-double-stranded DNA antibody level prior to vaccination were associated with decreased vaccine responses. IgG seroreactivity to the SARS-CoV-2 spike RBD strongly correlated with the SARS-CoV-2 microneutralization titers and correlated with antigen-specific IFNγ production determined by ELISpot. In a subset of patients with poor antibody responses, IFNγ production was similarly diminished. Pre- and postvaccination SLEDAI scores were similar in both groups. Postvaccination flares occurred in 11.4% of patients; 1.3% of these were severe. CONCLUSION: In a multiethnic/multiracial study of SLE patients, 29% had a low response to the COVID-19 vaccine which was associated with receiving immunosuppressive therapy. Reassuringly, severe disease flares were rare. While minimal protective levels remain unknown, these data suggest that protocol development is needed to assess the efficacy of booster vaccination.