Comparison of three commercially available ELISA assays for anti-infliximab antibodies.

Three commercially available assays for the measurement of antibodies to infliximab (ATI) are approved for clinical use in Australia: Promonitor anti-infliximab (Grifols), Lisa Tracker anti-infliximab (Theradiag) and Ridascreen anti-IFX (R-Biopharm). All are bridging ELISA assays. Measurement of ATI has been incorporated into treatment algorithms for assessing loss of response to infliximab in patients with inflammatory bowel disease, but results obtained by the three ATI assays have not been systematically compared. We performed a series of experiments to allow comparison of results between the assays. Forty-two patient samples known to be positive for ATI by the Lisa Tracker assay were run on the Promonitor assay in singlicate, of which 26 were run on the Ridascreen assay in duplicate, according to the manufacturers' instructions. The Spearman correlation coefficient for all three pairwise assay comparisons was 0.95. Results were not numerically comparable between the assays. The coefficient of variation (CV) was 2.3% for the Lisa Tracker assay, 7.6% for the Promonitor assay and 7.4% for the Ridascreen assay. The presence of infliximab interfered with all three assays in a dose dependent manner. The cut-point for loss of response to infliximab dose intensification, previously demonstrated to be 200 ng/mL on the Lisa Tracker assay, is equivalent to approximately 60 ng/mL on the Ridascreen assay and between 22.9 and 41 AU/mL on the Promonitor assay. All three assays are suitable for clinical use.

Tocilizumab for severe COVID-19 pneumonia: Case series of 5 Australian patients.

AIM: To describe the first Australian cases of severe acute respiratory syndrome-coronavirus 2 (SARS-CoV2) disease (COVID-19) pneumonia treated with the interleukin-6 receptor antagonist tocilizumab. METHODS: Retrospective, open-label, real-world, uncontrolled, single-arm case series conducted in 2 tertiary hospitals in NSW, Australia and 1 tertiary hospital in Victoria, Australia. Five adult male patients aged between 46 and 74 years with type 1 respiratory failure due to COVID-19 pneumonia requiring intensive care unit (ICU) admission and biochemical evidence of systemic hyperinflammation (C-reactive protein greater than 100 mg/L; ferritin greater than 700 µg/L) were administered variable-dose tocilizumab. RESULTS: At between 13 and 26 days follow-up, all patients are alive and have been discharged from ICU. Two patients have been discharged home. Two patients avoided endotracheal intubation. Oxygen therapy has been ceased in three patients. Four adverse events potentially associated with tocilizumab therapy occurred in three patients: ventilator-associated pneumonia, bacteremia associated with central venous catheterization, myositis and hepatitis. All patients received broad-spectrum antibiotics, 4 received corticosteroids and 2 received both lopinavir/ritonavir and hydroxychloroquine. The time from first tocilizumab administration to improvement in ventilation, defined as a 25% reduction in fraction of inspired oxygen required to maintain peripheral oxygen saturation greater than 92%, ranged from 7 hours to 4.6 days. CONCLUSIONS: Tocilizumab use was associated with favorable clinical outcome in our patients. We recommend tocilizumab be included in randomized controlled trials of treatment for patients with severe COVID-19 pneumonia, and be considered for compassionate use in such patients pending the results of these trials.

Use of direct oral anticoagulants for treatment of atrial fibrillation in patients with HIV: a review.

PURPOSE OF REVIEW: Atrial fibrillation is increasingly common in the ageing population. Patients with atrial fibrillation and HIV have a higher stroke risk, with guidelines recommending anticoagulation in the majority. Whilst anticoagulation options have diversified in the last decade for the general population, there is limited evidence for the safety and efficacy of these medications when used concurrently with antiretroviral therapy. We review the potential for patients with HIV on antiretroviral therapy to have direct-acting oral anticoagulations (DOACs). RECENT FINDINGS: Several case reports have been published in the past 5 years, as well as theoretical analyses of anticipated drug interactions, which provide a starting point to guide use of DOACs with antiretroviral medications. SUMMARY: Caution is needed when prescribing DOACs in patients with atrial fibrillation and HIV due to potential drug interactions. Studies are lacking and current advice is based on case reports, expert opinion and knowledge of theoretical interactions.