METHODS: In the randomized, double-blind, time-to-event, phase 3 PREVENT trial, 143 adults received eculizumab (maintenance dose, 1200 mg/2 weeks) or placebo (2:1), with stable-dose concomitant immunosuppressive therapy (IST) permitted (except rituximab and mitoxantrone). Post hoc analyses of relapses and adverse events were performed for prespecified and post hoc subgroups based on concomitant IST and prior rituximab use, demographic and disease characteristics, and autoimmune comorbidity.
RESULTS: The significant reduction in relapse risk observed for eculizumab versus placebo in the overall PREVENT population was consistently maintained across subgroups based on concomitant IST and previous rituximab use, age, sex, region, race, time since clinical onset of NMOSD, historical annualized relapse rate, baseline Expanded Disability Status Scale score, and history of another autoimmune disorder. The serious infection rate was lower with eculizumab than placebo regardless of rituximab use in the previous year, concomitant IST use, or history of another autoimmune disorder.
CONCLUSION: Across a wide range of clinically relevant AQP4+ NMOSD patient subgroups in PREVENT, eculizumab therapy was consistently effective versus placebo in reducing relapse risk, with no apparent increase in serious infection rate.
TRIAL REGISTRATION: NCT01892345 (ClinicalTrials.gov).
METHODS: We systematically searched five electronic databases (PubMed, CENTRAL, Embase, Global Health, and PsycINFO) from date of inception to September 30, 2022, for studies reporting on the effect of bebtelovimab in SARS-CoV-2 infection, using a combination of search terms around -bebtelovimab‖, -LY-CoV1404‖, -LY3853113‖, and -coronavirus infection‖. All citations were screened independently by two researchers. Data were extracted and thematically analyzed based on study design by adhering to the stipulated scoping review approaches.
RESULTS: Thirty-nine studies were included, thirty-four non-clinical studies were narratively synthesized, and five clinical studies were meta-analyzed. The non-clinical studies revealed bebtelovimab not only potently neutralized wide-type SARS-CoV-2 and existing variants of concern such as B.1.1.7 (Alpha), B.1.351 (Beta), P.1 (Gamma), and B.1.617.2 (Delta), but also retained appreciable activity against Omicron lineages, including BA.2.75, BA.4, BA.4.6, and BA.5. Unlike other monoclonal antibodies, bebtelovimab was able to bind to epitope of the SARS-CoV-2 S protein by exploiting loop mobility or by minimizing side-chain interactions. Pooled analysis from clinical studies depicted that the rates of hospitalization, ICU admission, and death were similar between bebtelovimab and other COVID-19 therapies. Bebtelovimab was associated with a low incidence of treatment-emergent adverse events.
CONCLUSION: Preclinical evidence suggests bebtelovimab be a potential treatment for COVID-19 amidst viral evolution. Bebtelovimab has comparable efficacy to other COVID-19 therapies without evident safety concerns.
CASE REPORT: We report a case of a patient with advanced non-small cell lung cancer and underlying active psoriasis who experienced a remarkable response, without developing psoriasis flares, following treatment with a single dose of atezolizumab and first-line chemotherapy.
MANAGEMENT AND OUTCOME: The patient remained asymptomatic 10 months since treatment discontinuation, without disease progression, despite having received only a single dose of atezolizumab and six cycles of chemotherapy.
DISCUSSION: Little is known about the optimum duration required to achieve a durable response with immunotherapy. Patients with autoimmune disease are commonly excluded from immunotherapy trials owing to a higher risk of autoimmune disease flares or immune-related adverse events. The remarkable outcome observed in this case offers some insights into the possible durable response with limited doses of immunotherapy and a safer approach for administering immunotherapy in patients with autoimmune disease. Initiating chemotherapy to induce remission in active autoimmune disease prior to administering immunotherapy could potentially be an ideal approach that facilitates the use of immunotherapy in this patient population.