Impact of long‐term administration of maralixibat on children with cholestasis secondary to Alagille syndrome
Abstract There is growing interest in, but limited data about, intestinal bile acid transport inhibitors as treatment for cholestatic liver disease. The current analyses combine two similar randomized placebo‐controlled trials with subsequent extension phases investigating the impact of maralixibat...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Wolters Kluwer Health/LWW
2022-08-01
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| Series: | Hepatology Communications |
| Online Access: | https://doi.org/10.1002/hep4.1992 |
| _version_ | 1797935657618767872 |
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| author | Benjamin L. Shneider Catherine A. Spino Binita M. Kamath John C. Magee Rosalinda V. Ignacio Suiyuan Huang Simon P. Horslen Jean P. Molleston Alexander G. Miethke Rohit Kohli Daniel H. Leung M. Kyle Jensen Kathleen M. Loomes Saul J. Karpen Cara Mack Philip Rosenthal Robert H. Squires Alastair Baker Sanjay Rajwal Deirdre Kelly Ronald J. Sokol Richard J. Thompson for ChiLDReN and UK IMAGO/IMAGINE Investigators |
| author_facet | Benjamin L. Shneider Catherine A. Spino Binita M. Kamath John C. Magee Rosalinda V. Ignacio Suiyuan Huang Simon P. Horslen Jean P. Molleston Alexander G. Miethke Rohit Kohli Daniel H. Leung M. Kyle Jensen Kathleen M. Loomes Saul J. Karpen Cara Mack Philip Rosenthal Robert H. Squires Alastair Baker Sanjay Rajwal Deirdre Kelly Ronald J. Sokol Richard J. Thompson for ChiLDReN and UK IMAGO/IMAGINE Investigators |
| author_sort | Benjamin L. Shneider |
| collection | DOAJ |
| description | Abstract There is growing interest in, but limited data about, intestinal bile acid transport inhibitors as treatment for cholestatic liver disease. The current analyses combine two similar randomized placebo‐controlled trials with subsequent extension phases investigating the impact of maralixibat in children with severe cholestasis secondary to Alagille Syndrome (n = 57). The primary outcomes were measures of pruritus (ItchRO[Obs]) and clinician scratch scale (CSS), both increasing in severity from 0 to 4) and quality of life (QoL) (Parent PedsQL and Multidimensional Fatigue Scale module [MFS] scaled 0–100 with increased QoL) at week 48 of the extension phase relative to the baseline of the placebo‐controlled trials (week 13). Secondary assessments included other clinical and biochemical parameters assessed in participants at week 72 or end of treatment (after week 48). At week 48, statistically and clinically significant least square mean (95% CI) improvements in pruritus and QoL were observed (ItchRO[Obs] −1.59 [−1.81, −1.36], CSS −1.36 [−1.67, −1.05], PedsQL +10.17 [4.48, 15.86], and multidimension fatigue [MFS] +13.97 [7.85, 20.08]). At week 48, serum bile acids, platelet count, and cholesterol decreased, whereas alanine aminotransferase (ALT) increased and total bilirubin (TB) and albumin were stable. Changes were durable at week 72 and end of treatment. There were no deaths; 2 participants underwent liver transplantation. Study drug was discontinued in 9 participants after treatment‐emergent adverse events, 6 of which were events of increased ALT or TB. Conclusion: Maralixibat administration was associated with marked improvement in pruritus and QoL. Interpretation of these findings is complicated by the complex natural history of severe cholestasis in Alagille syndrome. |
| first_indexed | 2024-04-10T18:17:33Z |
| format | Article |
| id | doaj.art-ff927fac8c8f49b3872a5335a74a6819 |
| institution | Directory Open Access Journal |
| issn | 2471-254X |
| language | English |
| last_indexed | 2024-04-10T18:17:33Z |
| publishDate | 2022-08-01 |
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| record_format | Article |
| series | Hepatology Communications |
| spelling | doaj.art-ff927fac8c8f49b3872a5335a74a68192023-02-02T08:19:12ZengWolters Kluwer Health/LWWHepatology Communications2471-254X2022-08-01681922193310.1002/hep4.1992Impact of long‐term administration of maralixibat on children with cholestasis secondary to Alagille syndromeBenjamin L. Shneider0Catherine A. Spino1Binita M. Kamath2John C. Magee3Rosalinda V. Ignacio4Suiyuan Huang5Simon P. Horslen6Jean P. Molleston7Alexander G. Miethke8Rohit Kohli9Daniel H. Leung10M. Kyle Jensen11Kathleen M. Loomes12Saul J. Karpen13Cara Mack14Philip Rosenthal15Robert H. Squires16Alastair Baker17Sanjay Rajwal18Deirdre Kelly19Ronald J. Sokol20Richard J. Thompson21for ChiLDReN and UK IMAGO/IMAGINE InvestigatorsDivision of Gastroenterology, Hepatology, and Nutrition Department of Pediatrics Baylor College of Medicine and Texas Children's Hospital Houston Texas USAUniversity of Michigan Ann Arbor Michigan USAThe Hospital for Sick Children Toronto Ontario CanadaUniversity of Michigan Ann Arbor Michigan USAUniversity of Michigan Ann Arbor Michigan USAUniversity of Michigan Ann Arbor Michigan USADepartment of Pediatrics Seattle Children's Hospital University of Washington School of Medicine Seattle Washington USADivision of Gastroenterology, Hepatology, and Nutrition Department of Pediatrics Riley Hospital for Children Indiana University Indianapolis Indiana USADivision of Gastroenterology, Hepatology, and Nutrition Department of Pediatrics University of Cincinnati Cincinnati Ohio USAKeck School of Medicine University of Southern California Los Angeles California USADivision of Gastroenterology, Hepatology, and Nutrition Department of Pediatrics Baylor College of Medicine and Texas Children's Hospital Houston Texas USADepartment of Pediatrics University of Utah Salt Lake City Utah USADivision of Gastroenterology, Hepatology, and Nutrition The Children's Hospital of Philadelphia and Department of Pediatrics Perelman School of Medicine at the University of Pennsylvania Philadelphia Pennsylvania USADivision of Gastroenterology, Hepatology, and Nutrition Department of Pediatrics Children's Healthcare of Atlanta and Emory University School of Medicine Atlanta Georgia USADepartment of Pediatrics‐Gastroenterology, Hepatology, and Nutrition University of Colorado School of Medicine and Children's Hospital Colorado Aurora Colorado USADepartment of Pediatrics University of California, San Francisco San Francisco California USADivision of Gastroenterology, Hepatology, and Nutrition Department of Pediatrics University of Pittsburgh, School of Medicine and Children's Hospital of Pittsburgh of University of Pittsburgh Medical Center Pittsburgh Pennsylvania USADepartment of Child Health The Pediatric Liver Center King's College Hospital London UKChildren's Liver & GI Unit The Leeds Hospital Leeds UKLiver Unit Birmingham Women's & Children's Hospital Birmingham UKDepartment of Pediatrics University of California, San Francisco San Francisco California USADepartment of Child Health The Pediatric Liver Center King's College Hospital London UKAbstract There is growing interest in, but limited data about, intestinal bile acid transport inhibitors as treatment for cholestatic liver disease. The current analyses combine two similar randomized placebo‐controlled trials with subsequent extension phases investigating the impact of maralixibat in children with severe cholestasis secondary to Alagille Syndrome (n = 57). The primary outcomes were measures of pruritus (ItchRO[Obs]) and clinician scratch scale (CSS), both increasing in severity from 0 to 4) and quality of life (QoL) (Parent PedsQL and Multidimensional Fatigue Scale module [MFS] scaled 0–100 with increased QoL) at week 48 of the extension phase relative to the baseline of the placebo‐controlled trials (week 13). Secondary assessments included other clinical and biochemical parameters assessed in participants at week 72 or end of treatment (after week 48). At week 48, statistically and clinically significant least square mean (95% CI) improvements in pruritus and QoL were observed (ItchRO[Obs] −1.59 [−1.81, −1.36], CSS −1.36 [−1.67, −1.05], PedsQL +10.17 [4.48, 15.86], and multidimension fatigue [MFS] +13.97 [7.85, 20.08]). At week 48, serum bile acids, platelet count, and cholesterol decreased, whereas alanine aminotransferase (ALT) increased and total bilirubin (TB) and albumin were stable. Changes were durable at week 72 and end of treatment. There were no deaths; 2 participants underwent liver transplantation. Study drug was discontinued in 9 participants after treatment‐emergent adverse events, 6 of which were events of increased ALT or TB. Conclusion: Maralixibat administration was associated with marked improvement in pruritus and QoL. Interpretation of these findings is complicated by the complex natural history of severe cholestasis in Alagille syndrome.https://doi.org/10.1002/hep4.1992 |
| spellingShingle | Benjamin L. Shneider Catherine A. Spino Binita M. Kamath John C. Magee Rosalinda V. Ignacio Suiyuan Huang Simon P. Horslen Jean P. Molleston Alexander G. Miethke Rohit Kohli Daniel H. Leung M. Kyle Jensen Kathleen M. Loomes Saul J. Karpen Cara Mack Philip Rosenthal Robert H. Squires Alastair Baker Sanjay Rajwal Deirdre Kelly Ronald J. Sokol Richard J. Thompson for ChiLDReN and UK IMAGO/IMAGINE Investigators Impact of long‐term administration of maralixibat on children with cholestasis secondary to Alagille syndrome Hepatology Communications |
| title | Impact of long‐term administration of maralixibat on children with cholestasis secondary to Alagille syndrome |
| title_full | Impact of long‐term administration of maralixibat on children with cholestasis secondary to Alagille syndrome |
| title_fullStr | Impact of long‐term administration of maralixibat on children with cholestasis secondary to Alagille syndrome |
| title_full_unstemmed | Impact of long‐term administration of maralixibat on children with cholestasis secondary to Alagille syndrome |
| title_short | Impact of long‐term administration of maralixibat on children with cholestasis secondary to Alagille syndrome |
| title_sort | impact of long term administration of maralixibat on children with cholestasis secondary to alagille syndrome |
| url | https://doi.org/10.1002/hep4.1992 |
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