Number needed to treat with ursodeoxycholic acid therapy to prevent liver transplantation or death in primary biliary cholangitis

Objective The clinical benefit of ursodeoxycholic acid (UDCA) in primary biliary cholangitis (PBC) has never been reported in absolute measures. The aim of this study was to assess the number needed to treat (NNT) with UDCA to prevent liver transplantation (LT) or death among patients with PBC. Methods The NNT was calculated based on the untreated LT-free survival and HR of UDCA with respect to LT or death as derived from inverse probability of treatment weighting-adjusted Cox proportional hazard analyses within the Global PBC Study Group database. Results We included 3902 patients with a median follow-up of 7.8 (4.1–12.1) years. The overall HR of UDCA was 0.46 (95% CI 0.40 to 0.52) and the 5-year LT-free survival without UDCA was 81% (95% CI 79 to 82). The NNT to prevent one LT or death within 5 years (NNT5y) was 11 (95% CI 9 to 13). Although the HR of UDCA was similar for patients with and without cirrhosis (0.33 vs 0.31), the NNT5y was 4 (95% CI 3 to 5) and 20 (95% CI 14 to 34), respectively. Among patients with low alkaline phosphatase (ALP) (≤2× the upper limit of normal (ULN)), intermediate ALP (2–4× ULN) and high ALP (>4× ULN), the NNT5y to prevent one LT or death was 26 (95% CI 15 to 70), 11 (95% CI 8 to 17) and 5 (95% CI 4 to 8), respectively. Conclusion The absolute clinical efficacy of UDCA with respect to LT or death varied with baseline prognostic characteristics, but was high throughout. These findings strongly emphasise the incentive to promptly initiate UDCA treatment in all patients with PBC and may improve patient compliance.

[1]  D. Crabb,et al.  Diagnosis and Treatment of Alcohol‐Associated Liver Diseases: 2019 Practice Guidance From the American Association for the Study of Liver Diseases , 2020, Hepatology.

[2]  F. Nevens,et al.  Ursodeoxycholic acid therapy and liver transplant-free survival in patients with primary biliary cholangitis. , 2019, Journal of hepatology.

[3]  B. Srivastava,et al.  FRI-057-A review of primary biliary cholangitis practice in Wales: Time for specialist care , 2019, Journal of Hepatology.

[4]  K. Lindor,et al.  Increasing Prevalence of Primary Biliary Cholangitis and Reduced Mortality With Treatment , 2017, Clinical Gastroenterology and Hepatology.

[5]  G. Hirschfield,et al.  EASL Clinical Practice Guidelines: The diagnosis and management of patients with primary biliary cholangitis. , 2017, Journal of hepatology.

[6]  D. Thorburn,et al.  Pharmacological interventions for primary sclerosing cholangitis: an attempted network meta-analysis. , 2017, The Cochrane database of systematic reviews.

[7]  D. Thorburn,et al.  Pharmacological treatments for primary biliary cirrhosis: a network meta‐analysis , 2015 .

[8]  Andrew K Burroughs,et al.  Stratification of hepatocellular carcinoma risk in primary biliary cirrhosis: a multicentre international study , 2015, Gut.

[9]  A. Burroughs,et al.  Levels of alkaline phosphatase and bilirubin are surrogate end points of outcomes of patients with primary biliary cirrhosis: an international follow-up study. , 2014, Gastroenterology.

[10]  J. Kutner,et al.  Confusing Relative Risk with Absolute Risk Is Associated with More Enthusiastic Beliefs about the Value of Cancer Screening , 2014, Medical decision making : an international journal of the Society for Medical Decision Making.

[11]  K. Shirabe,et al.  Guidelines for the management of primary biliary cirrhosis , 2014, Hepatology research : the official journal of the Japan Society of Hepatology.

[12]  P. Austin.  The use of propensity score methods with survival or time-to-event outcomes: reporting measures of effect similar to those used in randomized experiments , 2013, Statistics in medicine.

[13]  G. Alexander,et al.  Sex and age are determinants of the clinical phenotype of primary biliary cirrhosis and response to ursodeoxycholic acid. , 2013, Gastroenterology.

[14]  J. Lefkowitch,et al.  Liver biopsy assessment in chronic hepatitis. , 2007, Archives of medical research.

[15]  B. Hansen,et al.  Prognosis of Ursodeoxycholic Acid-Treated Patients with Primary Biliary Cirrhosis. Results of a 10-Yr Cohort Study Involving 297 Patients , 2006, The American Journal of Gastroenterology.

[16]  J. Rodés,et al.  Excellent long-term survival in patients with primary biliary cirrhosis and biochemical response to ursodeoxycholic Acid. , 2006, Gastroenterology.

[17]  P. Heagerty,et al.  Survival Model Predictive Accuracy and ROC Curves , 2005, Biometrics.

[18]  K. Lindor,et al.  Primary biliary cirrhosis , 2003, The Lancet.

[19]  A. Chetwynd,et al.  Survival and symptom progression in a geographically based cohort of patients with primary biliary cirrhosis: follow-up for up to 28 years. , 2002, Gastroenterology.

[20]  J. Robins,et al.  Marginal Structural Models and Causal Inference in Epidemiology , 2000, Epidemiology.

[21]  D G Altman,et al.  Calculating the number needed to treat for trials where the outcome is time to an event , 1999, BMJ.

[22]  O. Chazouilleres,et al.  Primary biliary cirrhosis–autoimmune hepatitis overlap syndrome: Clinical features and response to therapy , 1998, Hepatology.

[23]  K. Gyr,et al.  Influence of method of reporting study results on decision of physicians to prescribe drugs to lower cholesterol concentration , 1994, BMJ.

[24]  B. Balkau,et al.  Ursodiol for the long-term treatment of primary biliary cirrhosis. The UDCA-PBC Study Group. , 1994, The New England journal of medicine.

[25]  C D Naylor,et al.  Measured Enthusiasm: Does the Method of Reporting Trial Results Alter Perceptions of Therapeutic Effectiveness? , 1992, Annals of Internal Medicine.

[26]  P. Grambsch,et al.  Prognosis in primary biliary cirrhosis: Model for decision making , 1989, Hepatology.

[27]  M. Kaplan,et al.  Primary Biliary Cirrhosis , 1987, The New England journal of medicine.

[28]  Reginald S. Lee,et al.  PROPENSITY SCORE ANALYSIS AND ASSESSMENT OF PROPENSITY SCORE APPROACHES USING SAS ® PROCEDURES , 2012 .

[29]  D. Studi,et al.  Università degli Studi di Milano , 2011 .

[30]  W. Kremers,et al.  Concordance for Survival Time Data: Fixed and Time-Dependent Covariates and Possible Ties in Predictor and Time , 2007 .

[31]  K. Lindor,et al.  Primary biliary cirrhosis , 1998, Springer Netherlands.

[32]  A. Burroughs,et al.  University of Birmingham Development and Validation of a Scoring System to Predict Outcomes of Patients With Primary Biliary Cirrhosis Receiving Ursodeoxycholic Acid Therapy , 2022 .