cholestyramine (A3384) / Ipsen - LARVOL DELTA

A retrospective study assessing the diagnosis and management strategies for bile acid diarrhoea across different specialties in tertiary care hospitals (BSG 2025) - "While existing treatment modalities have proven effective in managing this condition, they remain poorly tolerated. Our study confirms that colesevelam demonstrates improved tolerability compared to colestyramine"

Retrospective data • Constipation • Gastroenterology • Gastrointestinal Disorder

Leflunomide in Combination With Steroids for the Treatment of Acute Graft-versus-Host Disease After Donor Stem Cell Transplant for Hematologic Malignancies (clinicaltrials.gov) - P1 | N=18 | Recruiting | Sponsor: City of Hope Medical Center | Trial completion date: Jul 2025 ➔ Jan 2027 | Trial primary completion date: Jul 2025 ➔ Jan 2027

Trial completion date • Trial primary completion date • Acute Graft versus Host Disease • Graft versus Host Disease • Hematological Malignancies • Immunology • Oncology • Transplantation

Primary sclerosing cholangitis with PLKR and UGT1A1 mutation manifested as recurrent bile duct stones: A case report. (PubMed, Medicine (Baltimore)) - "Close and dynamic detection of the patient's biliary ductal lesions play an important role in the diagnosis of PSC. In the event of relatively rare biliary complications, attention should be paid to the presence of gene mutation."

Journal • Cholestasis • Fibrosis • Gastroenterology • Gastrointestinal Disorder • Hepatology • Immunology • Infectious Disease • Inflammation • Inflammatory Bowel Disease • Primary Biliary Cholangitis • Transplantation • Ulcerative Colitis • UGT1A1

Leflunomide for the Treatment of High-Risk Smoldering Multiple Myeloma in African-American and European-American Patients (clinicaltrials.gov) - P2 | N=56 | Recruiting | Sponsor: City of Hope Medical Center | Trial completion date: Dec 2025 ➔ Jul 2026 | Trial primary completion date: Dec 2025 ➔ Jul 2026

Trial completion date • Trial primary completion date • Hematological Malignancies • Multiple Myeloma • Oncology • Smoldering Multiple Myeloma

DMARD preconception counselling and reinforcement should be a norm in all rheumatology clinics (BSR-CBC 2024) - "Introduction: Leflunomide is known to be teratogenic in animal studies, particularly in rats, with increased risk of malformations and reduced foetal viability...She was diagnosed with seropositive RA in 2016 and was managed on methotrexate for the first two years but was stopped due to hair loss. She was started on hydroxychloroquine and sulfasalazine with partial response...She had to come off adalimumab in 2021 after brief use due to weight gain...She was started on rituximab infusion in June 2022 in view of high DAS-28 score of 6.57 and subsequent received IM depomedrone injection in August 2022.She was reviewed in a routine rheumatology clinic in November 2022 when she informed us that she was 15 weeks pregnant...Although the manufacturer recommends an 11-day washout using colestyramine or activated charcoal, this was not recommended by UKTIS in this case, as the patient was 14+ weeks gestation...This should be treated as never-events and easily avoidable.• Although..."

Alopecia • Gynecology • Immunology • Inflammatory Arthritis • Long-acting Reversible Contraceptives • Obstetrics • Rheumatoid Arthritis • Rheumatology

Colesevelam is effective and well-tolerated for bile acid diarrhoea in Australia (AGW-GESA 2024) - "Commercially available bile-acid sequestrants such as colestyramine have, in recent times, been difficult to access and have high rates of intolerance. In this cohort, the majority of patients remained on treatment with colesevelam despite previous intolerances to currently available bile-acid sequestrants. Colesevelam is a well-tolerated, efficacious bile acid sequestrant for use in BAD and efforts to improve access to colesevelam for Australian patients are warranted."

Crohn's disease • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammatory Bowel Disease • Pain

Managing bile acid diarrhea: aspects of contention. (PubMed, Expert Rev Gastroenterol Hepatol) - "They are relatively inexpensive, and better-quality data is now available for colesevelam...The GLP-1 receptor agonist, liraglutide, is also effective, although mechanisms of action and whether this effect is common to other class members is unclear...The role of dietary factors in symptom development is a major patient concern, needing more formal studies. To build on recent findings, bile acid diarrhea needs further investment into causes, diagnosis and therapy to guide present and future patient care."

Journal • Review • Gastrointestinal Disorder • Inflammation

Should SeHCAT be routinely adopted `for working up patients with chronic diarrhoea? (BSG 2024) - "The two commonly used bile acid sequestrants were colesevelam and cholestyramine...68.75% of patients responded with colesevelam and 29.69% with colestyramine.View this table:View inline View popup 286 Table 1 Conclusion Of the 448 patients who underwent a SeHCAT scan, 234 (52.2%) patients had a positive test confirming a diagnosis of bile acid diarrhoea...Making a positive diagnosis will in return be economically beneficial, as patients will be less likely to undergo further unnecessary investigations. A diagnosis of bile acid diarrhoea should no longer be missed given the availability of SeHCAT scan."

Clinical

Gemcitabine and Leflunomide in Patients With Advanced Unresectable Pancreatic Cancer (clinicaltrials.gov) - P1 | N=19 | Recruiting | Sponsor: City of Hope Medical Center

Metastases • New P1 trial • Gastrointestinal Cancer • Hepatology • Oncology • Pancreatic Cancer • Solid Tumor

It might not be the enzymes! A single centre experience of investigating bile acid malabsorption (ECFS 2024) - "5/10 patients were diagnosed with BAM; moderate n=4, mild n=1 and prescribed treatment Colestyramine n=3, Colesevelam n=2. Of those diagnosed, 3/10 are PI. Adults with CF and significant abdominal symptoms should be referred for SeHCAT once more common causes of symptoms have been excluded. This includes those who are pancreatic sufficient or those who are PI and continue to experience abdominal symptoms despite PERT optimisation. In response to more adult patients experiencing gastrointestinal symptoms, we have incorporated an abdominal symptom pathway into our dietetic annual review."

Clinical • Cystic Fibrosis • Gastroenterology • Gastrointestinal Disorder • Genetic Disorders • Immunology • Pain • Pulmonary Disease • Respiratory Diseases • ELANE

Leflunomide for the Treatment of High-Risk Smoldering Multiple Myeloma in African-American and European-American Patients (clinicaltrials.gov) - P2 | N=56 | Recruiting | Sponsor: City of Hope Medical Center | N=20 ➔ 56 | Trial completion date: Dec 2024 ➔ Dec 2025 | Trial primary completion date: Dec 2024 ➔ Dec 2025

Enrollment change • Trial completion date • Trial primary completion date • Hematological Malignancies • Multiple Myeloma • Oncology

Evaluation of Alternative Treatment Strategies for Bile Acid Malabsorption in Inflammatory Bowel Disease Patients: A Network Meta-Analysis. (PubMed, J Clin Med Res) - "Compared to colesevelam and the placebo, liraglutide was more efficient in decreasing fecal bile acid concentration (liraglutide; MD = -19, 95% CI (-37.61, -0.39)). Tropifexor has been identified as the most successful medication in mitigating BAM symptoms. To ensure more accurate results, there is a need for randomized controlled clinical trials that involve a larger participant pool."

Clinical • Journal • Retrospective data • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammation • Inflammatory Bowel Disease • FGF19

Diarrhea is not a VIP guest (BWG 2024) - "Treatment with somatostatin analogue such as Somatuline autogel at a dosage of 120mg every 28 days was initiated with disease control until April 2023, where a thoraco-abdominal CT scan showed progression of liver lesions...Stool cultures revealed a Blastocystis hominis infection treated with Flagyl without any clinical improvement...Empirical treatment with colestyramine showed no efficacy. A combination of treatment with loperamide, pancreatic enzyme supplementation and codein syrup resulted in a mild reduction in diarrhea...For liver-dominant disease, targeted treatment is recommended, such as bland embolization, radiofrequency ablation, and radioembolization. Other treatments such as Everolimus, Sunitinib, peptide receptor radionuclide therapy (PRRT) or chemotherapy are alternatives for metastatic or unresectable disease."

Acute Kidney Injury • Endocrine Cancer • Hepatology • Hypotension • Infectious Disease • Metabolic Disorders • Neuroendocrine Tumor • Oncology • Renal Disease • Solid Tumor

The Epidemiology of Bile Acid Diarrhea in Denmark. (PubMed, Clin Epidemiol) - "Since the International Classification of Diseases diagnosis code for BAD was not used until 2021, we identified the BAD population by referral to SeHCAT testing followed by a prescription of a bile acid sequestrant (colestyramine, colestipol or colesevelam) within 365 days. The BAD population had more co-morbidities and more health care contacts as well as lower levels of education and income compared with age- and sex-matched controls from the general population. Using the Danish registries, we identified a BAD population, which seems to be inferior in health care and socio-economic parameters compared with the Danish general population."

Journal

Combined, elobixibat, and colestyramine reduced cholesterol toxicity in a mouse model of metabolic dysfunction-associated steatotic liver disease. (PubMed, Hepatol Commun) - "Excessive free cholesterol in the liver can promote fatty liver disease. Herein, combination therapy with EC effectively reduced free cholesterol levels in MASH model mice. Our study provides strong evidence for combination therapy as an effective treatment for MASH."

Journal • Preclinical • Atherosclerosis • Cardiovascular • Dyslipidemia • Fibrosis • Hepatology • Immunology • Metabolic Disorders • Oncology • APOE

LOW DOSE LIRAGLUTIDE WITH PRAGMATIC DOSE ESCALATION ACHIEVES REMISSION IN MORE THAN HALF OF 27 PATIENTS WITH SEQUESTRANT-REFRACTORY BILE ACID DIARRHOEA: A CASE SERIES (UEGW 2023) - "The patients were either intolerant to or had treatment failure of sequestrants (colestyramine and/or colesevelam) and fulfilled the Hjortswang diarrhoea criteria (3 or more stools or 1 or more watery stool per day). Second-line liraglutide with pragmatic dose-escalation achieved remission in 15 of 27 patients with bile acid diarrhoea intolerant or with insufficient treatment response to conventional sequestrants. Of the 15 in remission, 11 did not need maximum liraglutide dosing. Proper diagnosis of bile acid diarrhoea is needed to enable second-line therapy."

Clinical • Crohn's disease • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammatory Bowel Disease

Leflunomide in Combination With Steroids for the Treatment of Acute Graft-versus-Host Disease After Donor Stem Cell Transplant for Hematologic Malignancies (clinicaltrials.gov) - P1 | N=18 | Recruiting | Sponsor: City of Hope Medical Center | Trial completion date: Oct 2023 ➔ Jul 2025 | Trial primary completion date: Oct 2023 ➔ Jul 2025

Combination therapy • Trial completion date • Trial primary completion date • Acute Graft versus Host Disease • Bone Marrow Transplantation • Graft versus Host Disease • Hematological Disorders • Hematological Malignancies • Immunology • Oncology • Transplantation

"What’s the data for colestyramine as maintenance therapy?" (@drkeithsiau)

Clinical

Leflunomide in Combination With Steroids for the Treatment of Acute Graft-versus-Host Disease After Donor Stem Cell Transplant for Hematologic Malignancies (clinicaltrials.gov) - P1 | N=18 | Recruiting | Sponsor: City of Hope Medical Center | Initiation date: Mar 2023 ➔ Jun 2023

Combination therapy • Trial initiation date • Acute Graft versus Host Disease • Bone Marrow Transplantation • Graft versus Host Disease • Hematological Disorders • Hematological Malignancies • Immunology • Oncology • Transplantation

Combined, Elobixibat and Colestyramine Safely Reduced Cholesterol and Bile Acid Toxicity in the Liver of Nonalcoholic Steatohepatitis Mouse Model (APASL 2023) - "Objectives: Cholesterol levels and bile acid metabolism are important drivers of Nonalcoholic Steatohepatitis (NASH) progression. We found that combination therapy with elobixibat and cholestyramine was effective in reducing free cholesterol levels in a mouse model of NASH. Our study provides strong evidence for combination therapy as an effective treatment for NASH. 885"

Preclinical • Fibrosis • Hepatology • Immunology • Liver Cirrhosis • Liver Failure • Non-alcoholic Steatohepatitis

"In terms of intermediate parameters ; the FDA allowed colestyramine , all statins , ezetimibe , anti-PCSK9 Mabs , inclisiran and bempedoic acid to be prescribed on the basis of clinically relevant LDL lowering and robust safety ; 6 different mechanisms .." (@JohnKastelein)

Clinical

Leflunomide in Combination With Steroids for the Treatment of Acute Graft-versus-Host Disease After Donor Stem Cell Transplant for Hematologic Malignancies (clinicaltrials.gov) - P1 | N=18 | Recruiting | Sponsor: City of Hope Medical Center | Not yet recruiting ➔ Recruiting

Combination therapy • Enrollment open • Acute Graft versus Host Disease • Bone Marrow Transplantation • Graft versus Host Disease • Hematological Disorders • Hematological Malignancies • Immunology • Oncology • Transplantation

Leflunomide in Combination With Steroids for the Treatment of Acute Graft-versus-Host Disease After Donor Stem Cell Transplant for Hematologic Malignancies (clinicaltrials.gov) - P1 | N=18 | Not yet recruiting | Sponsor: City of Hope Medical Center

Combination therapy • New P1 trial • Acute Graft versus Host Disease • Bone Marrow Transplantation • Graft versus Host Disease • Hematological Disorders • Hematological Malignancies • Immunology • Oncology • Transplantation

Leflunomide for the Treatment of High-Risk Smoldering Multiple Myeloma in African-American and European-American Patients (clinicaltrials.gov) - P2 | N=20 | Recruiting | Sponsor: City of Hope Medical Center | Initiation date: Jul 2022 ➔ Mar 2022

Trial initiation date • Hematological Malignancies • Multiple Myeloma • Oncology

Leflunomide for the Treatment of High-Risk Smoldering Multiple Myeloma in African-American and European-American Patients (clinicaltrials.gov) - P2 | N=20 | Recruiting | Sponsor: City of Hope Medical Center | Trial completion date: Dec 2023 ➔ Dec 2024 | Initiation date: Nov 2021 ➔ Jul 2022 | Trial primary completion date: Dec 2023 ➔ Dec 2024

Trial completion date • Trial initiation date • Trial primary completion date • Hematological Malignancies • Multiple Myeloma • Oncology