Monitoring the Signs and Symptoms of Variant Creutzfeldt-Jakob Disease Among Patients with Multiple Myeloma Treated with Ixazomib Capsules in China: A Real-World Pharmacovigilance Survey

Introduction: Variant Creutzfeldt-Jakob disease (vCJD) is a fatal and transmittable neurodegenerative disorder in humans, associated with ingestion of products from cattle affected with bovine spongiform encephalopathy (BSE).^1,2 Since April 2018, National Medical Products Administration has approved ixazomib for the treatment of multiple myeloma (MM) in China. The gelatin used for encapsulating ixazomib capsules prior to March 2019 was sourced from countries with BSE outbreaks. Here we present physician survey results from a retrospective analysis conducted to describe physician-observed signs and symptoms as well as concerns and awareness of signs and symptoms, which may be related to vCJD in patients with MM, treated with ixazomib before December 2019 in China.

Methods: This multicentre, cross-sectional, web-based survey was conducted in China. Licensed physicians who have prescribed ixazomib capsules for MM patients before December 2019 participated in the survey and completed an online questionnaire with close-ended multiple-choice questions related to patients' clinical characteristics, responder characteristics, awareness of vCJD-related signs and symptoms, concern about vCJD risk, and willingness to prescribe ixazomib in the future. This report is based on the collective results of the survey program conducted in three phases over a period of three years. Physicians' concern about patients with MM, who have consumed contaminated ixazomib to get vCJD was measured on a 10-point scale, in which 0 stands for no concern and 10 stands for extreme concern.

Results: The analysis included 318 physicians in Phase 1, 311 physicians in Phase 2, and 310 physicians in Phase 3 of the survey. In general, the respondents reported moderate concern for their MM patients who received NINLARO® capsule before December 2019 to develop vCJD-related adverse events (AEs) in Phase 1 (Mean ± SD: 4.6 ± 2.72), while the concern lessened over time in Phase 2 (4.2 ±1.88) and 3 (3.8 ±1.82). Since the physicians became more aware of the limited potential risk of the NINLARO® capsule their willingness to prescribe NINLARO® increased across time, reaching 70.1%, 87.8% and 89.7% of the respondents in Phases 1, 2 and 3, respectively. In addition, a respondent reported 1 death due to severe diarrhea, and with a probable association with NINLARO® and not related to vCJD. One respondent reported two patients in Phase 2 presenting at least 4 of 5 pre-specified symptoms for vCJD. On further inquiry, the respondent reported that the symptoms were not related to vCJD and no tests were performed further to confirm a vCJD diagnosis. No additional AEs related to vCJD symptoms were reported in Phase 3.

Conclusion: This study suggested that the physicians had no concerns on the potential risks of vCJD, therefore their willingness to prescribe ixazomib was unaffected. The potentially contaminated product should no longer be a cause of concern and impact physicians' prescription decisions.

Reference

1.Sitammagari KK, Masood W. Creutzfeldt Jakob Disease. In: StatPearls. Treasure Island (FL): StatPearls Publishing; January 30, 2024.

2.Porter MC, Leemans M. Creutzfeldt-Jakob disease. Continuing Education in Anaesthesia, Critical Care & Pain, 2013.

Li:Takeda (China) International Trading Co., Ltd: Current Employment. Liu:Takeda (China) International Trading Co., Ltd: Current Employment.