Hospitalizations and healthcare costs associated with rifaximin versus lactulose treatment among commercially insured patients with hepatic encephalopathy in the United States

Figures & data

Table 1. Patient characteristics.

	Marketscan sample^a	Optum sample^a
	N = 7,675	N = 3,530
Duration of follow-up period^b, mean ± SD [median]	14.5 ± 12.6 [10.3]	13.9 ± 13.1 [9.6]
HE patient selection criteria, N (%)
Criterion 1: HE diagnosis	6,425 (83.7%)	3,277 (92.8%)
Criterion 2: HE-related treatment + cirrhosis/decompensated cirrhosis	866 (11.3%)	174 (4.9%)
Criterion 3: DRG + treatment at discharge	37 (0.5%)	8 (0.2%)
Criterion 4: Unspecified encephalopathy diagnosis	347 (4.5%)	71 (2.0%)
Demographics (as of the index date)
Age (years), mean ± SD [median]	54.0 ± 8.6 [56.0]	53.0 ± 8.8 [55.0]
Female, N (%)	3,163 (41.2%)	1,454 (41.2%)
Clinical characteristics during baseline period
Procedure during baseline period^c, N (%)
Paracentesis	2,104 (27.4%)	1,088 (30.8%)
Endoscopy/banding	743 (9.7%)	415 (11.8%)
TIPS	162 (2.1%)	91 (2.6%)
Dialysis	242 (3.2%)	111 (3.1%)
CCI, mean ± SD [median]	4.3 ± 2.0 [4.0]	4.7 ± 2.0 [4.0]
Physical comorbidities of interest^c, N (%)
Liver disease	6,999 (91.2%)	3,339 (94.6%)
Cirrhosis of liver without mention of alcohol	1,537 (20.0%)	469 (13.3%)
Unspecified cirrhosis of liver	3,796 (49.5%)	2,130 (60.3%)
Alcoholic cirrhosis of liver with/without ascites	3,108 (40.5%)	1,863 (52.8%)
Alcohol abuse	3,935 (51.3%)	2,214 (62.7%)
Treatment characteristics
Treatment episodes^d
Patient only had rifaximin treatment episodes	876 (11.4%)	316 (9.0%)
Patient only had lactulose treatment episodes	2,719 (35.4%)	1,596 (45.2%)
Patient had both rifaximin episodes and lactulose episodes	4,080 (53.2%)	1,618 (45.8%)

Abbreviations. CCI, Charlson comorbidity index; DRG, diagnosis-related group; HE, hepatic encephalopathy; IBS-D, irritable bowel syndrome with diarrhea; IP, inpatient; SD, standard deviation; TIPS, transvenous intrahepatic portosystemic shunt.

Notes: ^aThe MarketScan sample was the sample identified from the MarketScan database; the Optum sample was the sample identified from the Optum database. ^bThe follow-up period was defined as the period from the fill date of first prescription for HE-related treatment to the earliest of end of health care plan enrollment, liver transplant or end of data availability in Q2 2019 (MarketScan) or Q1 2020 (Optum). ^cCategories are not mutually exclusive. ^dOn average, at a given time point, 36% (MarketScan) and 43% (Optum) of patients were on lactulose only and 64% (MarketScan) and 57% (Optum) were on rifaximin (with or without lactulose).

Figure 1. IRR of HE-related and all-cause IP admissions and days during rifaximin versus lactulose episodes in the Marketscan database. Abbreviations. CCI, Charlson comorbidity index; CI, confidence interval; DRG, diagnosis-related group; HE, hepatic encephalopathy; IP, inpatient; IRR, incidence rate ratio; PDC, proportion of days covered; SD, standard deviation.

Notes: ^aHE-related hospitalizations were defined as hospitalizations with HE as primary diagnosis, as well as DRG 441, 442, or 443 (liver-related diseases).

^bFor the secondary scenario, HE-related hospitalizations were defined as hospitalizations with HE as primary or secondary diagnosis.

^cModels were adjusted for age, gender, region, health plan, baseline procedures (paracentesis, endoscopy, transvenous intrahepatic portosystemic shunt, and dialysis) and Charlson comorbidity index.

Figure 2. IRR of HE-related and all-cause IP admissions and days during rifaximin versus lactulose episodes in the Optum database. Abbreviations. CCI, Charlson comorbidity index; CI, confidence interval; DRG, diagnosis-related group; HE, hepatic encephalopathy; IP, inpatient; IRR, incidence rate ratio; PDC, proportion of days covered; SD, standard deviation.

Notes: ^aHE-related hospitalizations were defined as hospitalizations with HE as primary diagnosis, as well as DRG 441, 442, or 443 (liver-related diseases).

^bFor the secondary scenario, HE-related hospitalizations were defined as hospitalizations with HE as primary or secondary diagnosis.

^cModels were adjusted for age, gender, region, health plan, baseline procedures (paracentesis, endoscopy, transvenous intrahepatic portosystemic shunt, and dialysis) and Charlson comorbidity index.

Figure 3. Healthcare costs among patients during rifaximin versus lactulose episodes in the Marketscan database^a,b. Abbreviations. CI, confidence interval; DRG, diagnosis-related group; HE, hepatic encephalopathy; IP, inpatient; PPPM, per-patient-per-month; USD, United States dollar.

Notes: ^aMean costs presented are unadjusted, while cost differences were weighted using episode duration and adjusted for age, gender, region, health plan, Charlson comorbidity index during baseline, and procedures during baseline (i.e. paracentesis, dialysis, endoscopy, transvenous intrahepatic portosystemic shunt).

^bThe mean medical and pharmacy costs were estimated from separate unadjusted models and therefore do not sum to the total healthcare costs.

^cHE-related IP costs were defined as those from hospitalizations with HE as primary diagnosis, as well as DRG 441, 442, or 443 (liver-related diseases). For the secondary scenario (hospitalizations with HE as primary or secondary diagnosis), unadjusted HE-related IP costs were $2,219 in the rifaximin cohort and $3,108 in the lactulose cohort, with an adjusted cost difference (95% CI) of –$1,235 (–$1,655; –$814); p < .001. Unadjusted all-cause IP costs were $3,990 in the rifaximin cohort and $5,679 in the lactulose cohort, with an adjusted cost difference (95% CI) of –$2,054 (–$2,613; –$1,495); p < .001.

^dUnadjusted pharmacy costs were $2,760 in the rifaximin cohort and $921 in the lactulose cohort, with an adjusted cost difference (95% CI) of $1,878 ($1,742; $2,014); p < .001. Unadjusted outpatient costs were $2,283 in the rifaximin cohort and $2,255 in the lactulose cohort, with an adjusted cost difference (95% CI) of –$180 (–$343; –$17); p = .030.

Figure 4. Healthcare costs among patients during rifaximin versus lactulose episodes in the Optum database^a,b. Abbreviations. CI, confidence interval; HE, hepatic encephalopathy; IP, inpatient; PPPM, per-patient-per-month; USD, United States dollar.

Notes: ^aMean costs presented are unadjusted, while cost differences were weighted using episode duration and adjusted for age, gender, region, health plan, Charlson comorbidity index during baseline, and procedures during baseline (i.e. paracentesis, dialysis, endoscopy, transvenous intrahepatic portosystemic shunt).

^bThe mean medical and pharmacy costs were estimated from separate unadjusted models and therefore do not sum to the total healthcare costs.

^cHE-related IP costs were defined as those from hospitalizations with HE as primary diagnosis, as well as DRG 441, 442, or 443 (liver-related diseases). For the secondary scenario (hospitalizations with HE as primary or secondary diagnosis), unadjusted HE-related IP costs were $2,372 in the rifaximin cohort and $3,175 in the lactulose cohort, with an adjusted cost difference (95% CI) of –$1,693 (–$2,312; –$1,075); p < .001. Unadjusted all-cause IP costs were $3,497 in the rifaximin cohort and $4,901 in the lactulose cohort, with an adjusted cost difference (95% CI) of –$2,113 (–$2,765; –$1,462); p < .001.

^dUnadjusted pharmacy costs were $2,738 in the rifaximin cohort and $763 in the lactulose cohort, with an adjusted cost difference (95% CI) of $1,978 ($1,802; $2,155); p < .001. Unadjusted outpatient costs were $2,295 in the rifaximin cohort and $2,307 in the lactulose cohort, with an adjusted cost difference (95% CI) of –$35 (–$280; $211); p = .782.