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Racial and ethnic disparities in rifaximin use and subspecialty referrals for patients with hepatic encephalopathy in the United States

Published:March 30, 2022DOI:https://doi.org/10.1016/j.jhep.2022.02.010

      Highlights

      • Hepatic encephalopathy is associated with frequent hospitalizations and morbidity.
      • Compared to White patients, Black patients incur a higher burden of hospitalizations.
      • Rifaximin is a medication approved for secondary prevention of hepatic encephalopathy.
      • Black and Hispanic patients are less likely to be prescribed or receive rifaximin and have less access to subspecialists.

      Background & Aims

      Rifaximin use in combination with lactulose is associated with a decreased risk of overt hepatic encephalopathy (HE). We sought to determine whether race and ethnicity were associated with rifaximin prescriptions.

      Methods

      We examined data for a 20% random sample of United States Medicare enrollees with cirrhosis and hepatic encephalopathy treated with outpatient lactulose and Part D prescription coverage from 2011-2019. Beginning at the time of first diagnosis, we evaluated time to first prescription of rifaximin accounting for competing risks (Fine-Gray, yielding subdistribution hazard ratios [sHRs]) and cumulative rifaximin exposure using a gamma hurdle model (yielding exposure length ratios). We aimed to determine the association of race and ethnicity with each outcome, adjusting for demographics, clinical factors, and other features of clinical management.

      Results

      Overall, 29,095 patients were diagnosed with HE and treated with lactulose, of whom 13,272 were prescribed rifaximin. Compared to White patients, Black patients were least likely to receive any prescription for rifaximin (sHR 0.70; 95% CI 0.65-0.76). Asian and Hispanic patients were also less likely to receive rifaximin compared to White patients. Black patients also received fewer doses of rifaximin (exposure length ratio 0.90; 95% CI 0.82-0.98). Hispanic patients also received fewer doses (0.88; 95% CI 0.80-0.98). Out-of-pocket spending on rifaximin per person-year was higher for Black and Hispanic than White patients. Out-of-pocket medication spending was associated with reduced odds of filling a rifaximin prescription. Black and Hispanic patients were least likely to be referred to a gastroenterologist.

      Conclusion

      In a national cohort of patients with HE, we observed stark racial and ethnic disparities in the use of rifaximin, an approved therapy for the improvement of HE-specific outcomes. Access to gastroenterologists and cost controls may reduce disparities.

      Lay summary

      Hepatic encephalopathy is a serious problem that can affect people with cirrhosis. When someone develops hepatic encephalopathy, there are 2 main treatments. The first-line treatment is called lactulose. If episodes of hepatic encephalopathy happen on lactulose, another treatment called rifaximin is recommended. In this study, we found that compared to White patients, Black and Hispanic patients are less likely to be prescribed rifaximin, receive fewer rifaximin refills, spend more on rifaximin, and have less access to subspecialists who are familiar with rifaximin. We conclude that efforts to address the cost of rifaximin and access to gastroenterologists could help improve these disparities.

      Graphical abstract

      Keywords

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      References

        • Tapper E.B.
        • Aberasturi D.
        • Zhao Z.
        • Hsu C.Y.
        • Parikh N.D.
        Outcomes after hepatic encephalopathy in population-based cohorts of patients with cirrhosis.
        Aliment Pharmacol Ther. 2020;
        • Tapper E.B.
        • Halbert B.
        • Mellinger J.
        Rates of and reasons for hospital readmissions in patients with cirrhosis: a multistate population-based cohort study.
        Clin Gastroenterol Hepatol. 2016;
        • Tapper E.
        • Kanwal F.
        • Asrani S.
        • Ho C.
        • Ovchinsky N.
        • Poterucha J.
        • et al.
        Patient reported outcomes in cirrhosis: a scoping review of the literature.
        Hepatology (Baltimore, Md). 2017;
        • Bass N.M.
        • Mullen K.D.
        • Sanyal A.
        • Poordad F.
        • Neff G.
        • Leevy C.B.
        • et al.
        Rifaximin treatment in hepatic encephalopathy.
        New Engl J Med. 2010; 362: 1071-1081
        • Tapper E.B.
        • Hao S.
        • Lin M.
        • Mafi J.N.
        • McCurdy H.
        • Parikh N.D.
        • et al.
        The quality and outcomes of care provided to patients with cirrhosis by advanced practice providers.
        Hepatology. 2019;
        • Bajaj J.S.
        • O’Leary J.G.
        • Tandon P.
        • Wong F.
        • Kamath P.S.
        • Biggins S.W.
        • et al.
        Targets to improve quality of care for patients with hepatic encephalopathy: data from a multi-centre cohort.
        Aliment Pharmacol Ther. 2019;
        • Chou C.
        • Zheng J.T.
        • Tapper E.B.
        Su1606 Why did it happen? A qualitative study of patients with a readmission for hepatic encephalopathy.
        Gastroenterology. 2020; 158: S-S1354
        • Essien U.R.
        • Dusetzina S.B.
        • Gellad W.F.
        A policy prescription for reducing health disparities—achieving pharmacoequity.
        JAMA. 2021 Nov 9; 326: 1793-1794
        • Tapper E.B.
        • Henderson J.B.
        • Parikh N.D.
        • Ioannou G.N.
        • Lok A.S.
        Incidence of and risk factors for hepatic encephalopathy in a population-based cohort of Americans with cirrhosis.
        Hepatol Commun. 2019;
        • Rakoski M.O.
        • McCammon R.J.
        • Piette J.D.
        • Iwashyna T.J.
        • Marrero J.A.
        • Lok A.S.
        • et al.
        Burden of cirrhosis on older Americans and their families: analysis of the health and retirement study.
        Hepatology. 2012; 55: 184-191
        • Tapper E.B.
        • Korovaichuk S.
        • Baki J.
        • Williams S.
        • Nikirk S.
        • Waljee A.K.
        • et al.
        Identifying patients with hepatic encephalopathy using administrative data in the ICD-10 era.
        Clin Gastroenterol Hepatol. 2019;
        • Jarrín O.F.
        • Nyandege A.N.
        • Grafova I.B.
        • Dong X.
        • Lin H.
        Validity of race and ethnicity codes in Medicare administrative data compared with gold-standard self-reported race collected during routine home health care visits.
        Med Care. 2020; 58
        • Deyo R.A.
        • Cherkin D.C.
        • Ciol M.A.
        Adapting a clinical comorbidity index for use with ICD-9-CM administrative databases.
        J Clin Epidemiol. 1992; 45: 613-619
        • Mellinger J.L.
        • Shedden K.
        • Winder G.S.
        • Tapper E.
        • Adams M.
        • Fontana R.J.
        • et al.
        The high burden of alcoholic cirrhosis in privately insured persons in the United States.
        Hepatology. 2018;
        • Allen A.M.
        • Therneau T.M.
        • Larson J.J.
        • Coward A.
        • Somers V.K.
        • Kamath P.S.
        Nonalcoholic fatty liver disease incidence and impact on metabolic burden and death: a 20 year-community study.
        Hepatology. 2018; 67: 1726-1736
        • Villanueva C.
        • Albillos A.
        • Genescà J.
        • Garcia-Pagan J.C.
        • Calleja J.L.
        • Aracil C.
        • et al.
        β blockers to prevent decompensation of cirrhosis in patients with clinically significant portal hypertension (PREDESCI): a randomised, double-blind, placebo-controlled, multicentre trial.
        Lancet. 2019; 393: 1597-1608
        • Tapper E.B.
        • Parikh N.D.
        • Sengupta N.
        • Mellinger J.
        • Ratz D.
        • Lok A.S.-F.
        • et al.
        A risk score to predict the development of hepatic encephalopathy in a population-based cohort of patients with cirrhosis.
        Hepatology. 2018; 68: 1498-1507
        • Zhou X.
        • Shrestha S.S.
        • Shao H.
        • Zhang P.
        Factors contributing to the rising national cost of glucose-lowering medicines for diabetes during 2005–2007 and 2015–2017.
        Diabetes Care. 2020; 43: 2396-2402
        • Baetschmann G.
        • Winkelmann R.
        A dynamic hurdle model for zero-inflated count data.
        Commun Stat.-Theory Methods. 2017; 46: 7174-7187
        • Tapper E.B.
        • Konerman M.
        • Murphy S.
        • Sonnenday C.J.
        Hepatic encephalopathy impacts the predictive value of the Fried Frailty Index.
        Am J Transplant. 2018; 18: 2566-2570
        • Rosenblatt R.
        • Yeh J.
        • Gaglio P.J.
        Long-term management: modern measures to prevent readmission in patients with hepatic encephalopathy.
        Clin Liver Dis. 2020; 24: 277-290
        • Cook N.L.
        • Ayanian J.Z.
        • Orav E.J.
        • Hicks L.S.
        Differences in specialist consultations for cardiovascular disease by race, ethnicity, gender, insurance status, and site of primary care.
        Circulation. 2009; 119: 2463-2470
        • Nguyen G.C.
        • LaVeist T.A.
        • Harris M.L.
        • Wang M.-H.
        • Datta L.W.
        • Brant S.R.
        Racial disparities in utilization of specialist care and medications in inflammatory bowel disease.
        Am J Gastroenterol. 2010; 105: 2202-2208
        • Essien U.R.
        • Kim N.
        • Hausmann L.R.
        • Mor M.K.
        • Good C.B.
        • Magnani J.W.
        • et al.
        Disparities in anticoagulant therapy initiation for incident atrial fibrillation by race/ethnicity among patients in the veterans health administration system.
        JAMA Netw Open. 2021; 4 (e2114234-e2114234)
        • Tapper E.B.
        • Parikh N.D.
        • Green P.K.
        • Berry K.
        • Waljee A.K.
        • Moon A.M.
        • et al.
        Reduced incidence of hepatic encephalopathy and higher odds of resolution associated with eradication of HCV infection.
        Clin Gastroenterol Hepatol. 2019;