ABSTRACT
Background: SARS-CoV-2 is a highly contagious respiratory virus responsible for COVID-19 pandemic. To understand the role of antibodies in neutralization, our study quantified circulating levels of IgA/IgG and IgG subtypes induced at different days post onset of symptoms, in severe and non severe patients. Objective(s): To quantify circulating levels of IgA, IgG and IgG subclass in severe and non severe patients induced at different days post onset of symptoms. Material(s) and Method(s): Serum or plasma samples collected from 79 COVID-19 patients were used. Indirect SARS-CoV-2 specific IgA, IgG, and IgG subclass specific ELISAs were performed. Antibody titers between severe and non severe patients were compared at different times post onset of clinical symptoms. Titers in ELISA were correlated to neutralizing antibody titers. Results and Conclusion(s): Over 75% patients were positive for IgA and IgG antibodies in the first week. The ELISA titers did not differ during the first week of infection. However, patients with severe disease exhibited raised titers. Neutralizing antibody titers correlated with the ELISA titers in mild presentation but not in severe disease. IgA and IgG1 antibodies correlated stronger with neutralizing antibodies. The findings highlighted that IgA together with IgG play an important in SARS-CoV-2 neutralization.
ABSTRACT
Background: Bimekizumab (BKZ) is a monoclonal IgG1 antibody used in the treatment of psoriasis which selectively inhibits interleukin (IL)-17F in addition to IL-17A.1,2 Data pooled over two years have indicated that BKZ is generally well-tolerated.3 We report three-year BKZ pooled safety data in patients with moderate-to-severe plaque psoriasis. Method(s): Safety data were evaluated for all patients who received one or more dose BKZ in four Phase 3 trials (BE SURE [NCT03412747], BE VIVID [NCT03370133], BE READY [NCT03410992], and their ongoing open-label extension BE BRIGHT open-label extension [NCT03598790;data cut-off : 10/23/2021]) and four Phase 2 trials (BE ABLE 1 [NCT02905006], BE ABLE 2 [NCT03010527], PS0016 [NCT03025542], PS0018 [NCT03230292]). Safety data were evaluated separately for patients receiving BKZ dosed 320mg every four weeks (Q4W) or every eight weeks (Q8W). Exposureadjusted incidence rates (EAIRs) for treatmentemergent adverse events (TEAEs) are the incidence of new cases per 100 patient-years (PY). Result(s): Total BKZ exposure was 4,245.3 PY (N=1,789) across Phase 2/3 trials, and 3,876.4 PY (N=1,495) in Phase 3 trials. TEAEs occurred at a rate of 186.1 across Phase 2/3 trials, serious TEAEs at 5.6, and TEAEs leading to discontinuation at 3.5. Eighteen deaths occurred (0.4/100 PY), all unrelated to study treatment except one (relationship unknown). TEAEs occurred less frequently in Q8W- than Q4W-treated patients in Phase 3 trials. Consistent with previous reports, most common TEAEs (EAIR) in Phase 2/3 trials were nasopharyngitis (15.3), oral candidiasis (10.2), and upper respiratory tract infection (7.1).3 EAIR of serious infections was 1.2. Most frequently reported were serious coronavirus infections (0.2). There were no cases of active tuberculosis. EAIR of oral candidiasis was 10.2, decreased vs two-year data (12.6),3 and was less common with BKZ Q8W vs Q4W. The vast majority of oral candidiasis events were mild or moderate (99.4%);none were serious. EAIRs of hepatic events (4.0) and elevated liver enzymes (3.4) were decreased vs. two-year data (4.3 and 3.6, respectively).3 EAIRs for inflammatory bowel disease (0.1), adjudicated major adverse cardiac events (0.6), and adjudicated suicidal ideation and behavior (0.1) were low. EAIRs for other safety topics of interest were also low and were similar to or lower than two-year EAIRs.3 Conclusion(s): BKZ was well-tolerated over three years. No safety signals were identified;EAIRs of TEAEs did not increase compared with data from two years.3.
ABSTRACT
The 2022 American Society for Clinical Pharmacology and Therapeutics (ASCPT) Annual Meeting held virtually, with "Disruptive innovation" as the motto, offered attendees an outstanding scientific program focused on clinical pharmacology, translational medicine, drug discovery and drug development. It is the most important event for scientists involved in clinical pharmacology and translational medicine. The ASCPT conference offers scientists from different professional scopes and around the world the perfect opportunity to discuss emerging science. It focuses on improving the understanding and use of existing drug therapies and developing safer and more effective treatments for the future. Oral and poster presentations were available for participants during the running of the conference to accommodate the different time zones. Presentations covered the latest research with the option to ask questions after each presentation via a chat function. Discussion boards were available to provide networking opportunities for virtual attendees.