Atsushi Tanaka1, Junko Hirohara2, Toshiaki Nakano2, Kosuke Matsumoto3, Olivier Chazouillères4, Hajime Takikawa5, Bettina E Hansen6, Fabrice Carrat7, Christophe Corpechot8. 1. Department of Medicine, Teikyo University School of Medicine, Tokyo, Japan. Electronic address: a-tanaka@med.teikyo-u.ac.jp. 2. The Third Department of Internal Medicine, Kansai Medical University, Osaka, Japan. 3. Department of Medicine, Teikyo University School of Medicine, Tokyo, Japan. 4. Reference Center for Inflammatory Biliary Diseases and Autoimmune Hepatitis (MIVB-H), Saint-Antoine Hospital, European Reference (ERN) Network Rare-Liver, Saint-Antoine Research Center (CRSA), Assistance Publique - Hôpitaux de Paris (APHP), Sorbonne University, Paris, France. 5. Faculty of Medical Technology, Teikyo University, Tokyo, Japan. 6. Toronto Centre for Liver Disease, Toronto General Hospital, University Health Network & IHPME, University of Toronto, Toronto, Ontario, Canada. 7. Sorbonne Université, Institut National de la santé et de la Recherche Médicale, Institut Pierre Louis d'Epidémiologie et de Santé Publique, APHP.Sorbonne Université, Département de santé Publique, Hôpital Saint-Antoine, Paris, France. 8. Reference Center for Inflammatory Biliary Diseases and Autoimmune Hepatitis (MIVB-H), Saint-Antoine Hospital, European Reference (ERN) Network Rare-Liver, Saint-Antoine Research Center (CRSA), Assistance Publique - Hôpitaux de Paris (APHP), Sorbonne University, Paris, France. Electronic address: christophe.corpechot@aphp.fr.
Abstract
BACKGROUND & AIMS: A beneficial effect of bezafibrate (BZF) on symptoms and biochemical features of primary biliary cholangitis (PBC) has been reported in patients with an incomplete response to ursodeoxycholic acid (UDCA), but long-term effects on survival remain unknown. In Japan, BZF has been used as a de facto second-line therapy for PBC since 2000. Herein, we compared the survival rates between patients treated with and those without BZF in a large nationwide Japanese PBC cohort. METHODS: All consecutively registered patients of this cohort who started UDCA therapy from 2000 onwards and had a follow-up ≥1 year were included. Association between BZF exposure and mortality or need for liver transplantation (LT) was assessed using time-dependent, multivariable-and propensity score-adjusted Cox proportional hazards models. Clinical benefit was quantified using the number needed to treat (NNT). RESULTS: Of 3,908 eligible patients, 3,162 (81%) received UDCA only and 746 (19%) UDCA and BZF over 17,360 and 3,932 patient-years, respectively. During follow-up, 183 deaths (89 liver-related) and 21 LT were registered. Exposure to combination therapy was associated with a significant decrease in all-cause and liver-related mortality or need for LT (adjusted hazard ratios: 0.3253, 95% CI 0.1936-0.5466 and 0.2748, 95% CI 0.1336-0.5655, respectively; p <0.001 for both). This association was consistent across various risk groups at baseline. The NNTs with combination therapy to prevent 1 additional death or LT over 5, 10, and 15 years were 29 (95% CI 22-46), 14 (10-22), and 8 (6-15), respectively. CONCLUSIONS: In a large retrospective cohort study of treatment effects in patients with PBC, the addition of BZF to UDCA was associated with improved prognosis. LAY SUMMARY: The long-term efficacy of bezafibrate (BZF) on liver transplantation (LT) - free survival in patients with PBC and an incomplete response to ursodeoxycholic acid (UDCA) remains to be determined. In this Japanese nationwide retrospective cohort study, the use of UDCA-BZF combination therapy, compared to UDCA alone, was associated with a lower risk of all-cause and liver-related mortality or need for LT. These results indicate that BZF is so far the only drug in PBC to have demonstrated efficacy in improving symptoms, biochemical markers, and long-term outcomes.
BACKGROUND & AIMS: A beneficial effect of bezafibrate (BZF) on symptoms and biochemical features of primary biliary cholangitis (PBC) has been reported in patients with an incomplete response to ursodeoxycholic acid (UDCA), but long-term effects on survival remain unknown. In Japan, BZF has been used as a de facto second-line therapy for PBC since 2000. Herein, we compared the survival rates between patients treated with and those without BZF in a large nationwide Japanese PBC cohort. METHODS: All consecutively registered patients of this cohort who started UDCA therapy from 2000 onwards and had a follow-up ≥1 year were included. Association between BZF exposure and mortality or need for liver transplantation (LT) was assessed using time-dependent, multivariable-and propensity score-adjusted Cox proportional hazards models. Clinical benefit was quantified using the number needed to treat (NNT). RESULTS: Of 3,908 eligible patients, 3,162 (81%) received UDCA only and 746 (19%) UDCA and BZF over 17,360 and 3,932 patient-years, respectively. During follow-up, 183 deaths (89 liver-related) and 21 LT were registered. Exposure to combination therapy was associated with a significant decrease in all-cause and liver-related mortality or need for LT (adjusted hazard ratios: 0.3253, 95% CI 0.1936-0.5466 and 0.2748, 95% CI 0.1336-0.5655, respectively; p <0.001 for both). This association was consistent across various risk groups at baseline. The NNTs with combination therapy to prevent 1 additional death or LT over 5, 10, and 15 years were 29 (95% CI 22-46), 14 (10-22), and 8 (6-15), respectively. CONCLUSIONS: In a large retrospective cohort study of treatment effects in patients with PBC, the addition of BZF to UDCA was associated with improved prognosis. LAY SUMMARY: The long-term efficacy of bezafibrate (BZF) on liver transplantation (LT) - free survival in patients with PBC and an incomplete response to ursodeoxycholic acid (UDCA) remains to be determined. In this Japanese nationwide retrospective cohort study, the use of UDCA-BZF combination therapy, compared to UDCA alone, was associated with a lower risk of all-cause and liver-related mortality or need for LT. These results indicate that BZF is so far the only drug in PBC to have demonstrated efficacy in improving symptoms, biochemical markers, and long-term outcomes.
Authors: Maja Mijic; Ivona Saric; Bozena Delija; Milos Lalovac; Nikola Sobocan; Eva Radetic; Dora Martincevic; Tajana Filipec Kanizaj Journal: Can J Gastroenterol Hepatol Date: 2022-07-22