ADVERSE EVENTS RELATED TO STUDY DRUGS IN FINDING THE OPTIMAL REGIMEN FOR MYCOBACTERIUM ABSCESSUS TREATMENT (FORMAT) TRIAL

Abstract

Introduction/Aim: Treatment for Mycobacterium abscessus pulmonary disease (MABS-PD) is characterised by prolonged use of multiple antibiotics, toxicity, poor effectiveness and evidence free treatment guidelines. The FORMaT Trial intervention program consist of intensive phase (IP) with intravenous therapies and consolidation phase (CP) using oral and inhaled therapies, based on standard of care (13 drugs). We aim to explore the frequency and severity of adverse events (AEs)/serious adverse events (SAEs) within IP and CP. Methods: AEs/SAEs are reported by investigators at trial sites, coded and graded according to the Common Terminology Criteria for Adverse Events (CTCAE) and reviewed by a pharmacovigilance team. All AEs/SAEs defined as 'possibly', 'probably' or 'definitely' related to study medications were analysed within CTCAE system organ class (SOC). Results: Data from the first 37 participants enrolled into the intervention program of FORMaT were analysed. 190 and 112 AEs related to study medications were reported during IP and CP, respectively. 4 AEs during IP and 7 AEs during CP were classified as “Severe” (grade 3). Most AEs were grouped within SOCs Gastrointestinal Disorders and Investigations. Most common AE CTCAE terms coded were nausea (n = 40), diarrhoea (n = 22) and elevated aspartate aminotransferase levels (n = 19). 9 and 13 SAEs were reported during IP and CP, respectively, with SOCs Ear and Labyrinth Disorders and Investigations most common. “Severe” (Grade 3) was assigned to 8 SAEs during IP and 11 SAEs during CP. Most frequently coded SAE CTCAE terms were hearing impairment (n = 5), electrocardiogram QT-corrected interval prolonged (n = 2), alanine aminotransferase increased (n = 2) and gamma-glutamyl transferase increased (n = 2) Figure 1 (Left): AE by grade during IP and CP Conclusion: The high toxicity and treatment burden of current standard of care treatment for MABS-PD cannot be overstated. Ongoing pharmacovigilance surveillance of the FORMaT trial will inform decisions on the removal and substitution of toxic treatments to allow for novel treatments to be tested in future iterations of the trial.