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Aim: Hepatic safety data assessment from the TURALIO® (pexidartinib) Risk Evaluation and Mitigation Strategy (tREMS) Program. Methods: Retrospective 3-year assessment (August 2019 to June 2022) of hepatic events from the TURALIO® (pexidartinib) Risk Evaluation and Mitigation Strategy Program. Results: A total of 451 patients, 369 prescribers, 2 wholesalers/distributors and 2 pharmacies were enrolled and certified. Twenty-one (4.7%) patients met the criteria for a hepatic adverse event or laboratory abnormality suggestive of serious and potentially fatal liver injury, all with onset within 2 months of therapy. No new hepatic safety signals were identified. Conclusion: Results are consistent with the phase 3 ENLIVEN trial data. Liver enzyme monitoring, combined with early intervention, including dose modification and discontinuation, conducted in patients treated with pexidartinib mitigate the risk of potential hepatotoxicity. Plain Language Summary Safety findings from the 3-year data collected in the TURALIO® Risk Evaluation and Mitigation Strategy Program Pexidartinib (TURALIO®) is an oral drug that is used to treat adults with tenosynovial giant cell tumor (TGCT) that cannot be fixed with surgery. TGCTs are rare, noncancerous tumors that cause pain, stiffness and difficulty moving. Pexidartinib works by blocking a protein that helps these tumors grow. Before pexidartinib, there were no good treatments for TGCT and surgery often could not remove all the tumors, so they would frequently grow back. Pexidartinib was approved in 2019 after a clinical trial showed it worked well in adults with TGCT. However, pexidartinib can sometimes cause serious liver harm for some patients. To handle this risk, a program called the tREMS (TURALIO® Risk Evaluation and Mitigation Strategy) was established to ensure that pexidartinib is used safely. The tREMS Program teaches doctors, pharmacists and patients about the safe use of pexidartinib and potential liver risks and enrolls patients in a registry to watch their health. Doctors and pharmacies must be certified, and patients need regular liver tests. In the first 3 years, 451 patients and 369 doctors joined the program. Unintended liver issues were found in around 5% of patients, a rate that is about the same as that seen in pexidartinib clinical trials, and no new safety concerns were found. About half of patients with liver issues could reverse them by stopping pexidartinib. No patient had permanent liver damage, needed a transplant or died from liver problems. These results show that the tREMS Program is working well to keep patients with TGCT safe while taking pexidartinib. Article highlights The TURALIO® Risk Evaluation and Mitigation Strategy (tREMS) Program was established in August 2019 to mitigate the risk of hepatotoxicity associated with the administration of pexidartinib. A retrospective 3-year (August 2019 to June 2022) hepatic safety assessment was performed. A total of 451 patients, 369 prescribers, 2 wholesalers/distributors and 2 pharmacies were enrolled and certified in the tREMS Program during this period. A total of 21 (4.7%) patients met the criteria for a liver adverse event (AE) or laboratory abnormalities suggestive of serious and potentially fatal liver injury, all with event onset within 2 months of therapy. Of the 21 patients with liver AEs, 20 permanently discontinued pexidartinib therapy and the dose was interrupted for 1 patient. No AEs of irreversible liver injury, transplant or hepatotoxicity-related death were reported during the study period. No new hepatic safety signals were identified. These hepatic safety data are consistent with the results from the pexidartinib phase 3 ENLIVEN trial and the known safety profile of pexidartinib. These 3-year retrospective hepatic safety assessment data show that the goal of the tREMS Program, to mitigate the risk of serious and potentially fatal liver injury, is being met. Infographic [ABSTRACT FROM AUTHOR] |
