Real-world cost-effectiveness associated with infliximab maintenance therapy for moderate to severe Crohn’s disease in China

Table 1 Patient characteristics associated with the included moderate to severe Crohn’s disease patients in real-world study

	IMT, n = 295		CMT, n = 130		P value
Patient characteristics	Mean/%	SD	Mean/%	SD
Demographics
Male proportion	72.2%		64.6%		0.125
Age in yr	34.1	10.9	37.2	11.2	0.004b
BMI range
< 18.5	32.8%		40.0%		0.162
18.5-23.9	56.0%		53.8%		0.689
≥ 24	10.4%		6.2%		0.165
Lifestyle
Non-smoker	85.7%		87.7%		0.592
Non-drinker	81.9%		88.5%		0.093
Marital status
Unmarried	43.2%		32.3%		0.037a
Married	56.0%		67.7%		0.026a
Employment status
Student	13.5%		7.7%		0.090
Full-time	59.1%		54.6%		0.401
Part-time	2.7%		2.3%		0.816
Unemployed	6.9%		1.5%		0.023a
Farmer	1.5%		1.5%		0.996
Retired	3.9%		4.6%		0.724
Unknown	5.8%		18.5%		< 0.001
Missing	6.6%		9.2%		0.345
Disease site at diagnosis
Distal colon	52.9%		34.1%		< 0.001
Terminal ileum	19.5%		48.8%		< 0.001
Colon	9.7%		10.9%		0.729
Upper gastrointestinal and back colon	4.3%		3.1%		0.572
Upper gastrointestinal and ileum end	4.7%		0.8%		0.045a
Upper gastrointestinal tract	0.0%		0.8%		0.158
Previous surgery	29.0%		30.0%		0.831
Previous complication
Perianal abscess	27.4%		13.8%		0.003b
Intestinal fistula	36.3%		14.6%		< 0.001
Intestinal obstruction	18.1%		13.1%		0.203
Extra-intestinal manifestation
Aphthous stomatitis	8.9%		3.8%		0.070
Joint pain	3.1%		3.1%		0.995
Comorbidities
Gallbladder diseases	3.9%		5.4%		0.488
Chronic hepatitis B	3.1%		8.5%		0.020a
Lung nodes	3.9%		2.3%		0.421
Gastroenteritis	1.5%		4.6%		0.071

^aP < 0.05.

^bP < 0.01. BMI: Body mass index; CMT: Conventional maintenance therapy; IMT: Infliximab maintenance therapy; SD: Standard deviation.

Table 2 Unadjusted comparisons of the measured clinical outcomes, health resources utilization, and direct medical costs associated with infliximab maintenance therapy and conventional maintenance therapy during 1-year observation time

	IMT, n = 295			CMT, n = 130			P value
Outcome measure	Mean/%	SD	Median	Mean/%	SD	Median
Clinical outcomes
Surgery rate	12.7%			25.4%			0.002b
Disease remission rate	94.6%			86.9%			0.008b
Utility for quality of life	0.890	0.080	0.900	0.757	0.093	0.748	< 0.001
Newly developed complications
Any complications	27.0%			42.3%			0.002b
Anus fistula	17.4%			14.6%			0.489
Intestinal fistula	3.5%			4.6%			0.582
Intestinal obstruction	4.2%			12.3%			0.003b
Perianal abscess	5.8%			6.2%			0.886
Bowel perforation	1.9%			3.8%			0.260
Health resource utilization
Outpatient clinic visits	1.9	3.3	1.0	3.7	5.2	2.0	< 0.001
Hospital admissions	5.3	2.2	6.0	1.4	1.0	1.0	< 0.001
Hospital admissions for infliximab administration	4.4	2.2	5.0	0.0	0.0	0.0	< 0.001
Hospital admissions for active disease management	0.9	1.0	1.0	1.4	1.0	1.0	< 0.001
Hospital stay days	15.2	11.1	14.0	14.8	12.4	9.5	0.207
Hospital stay days related to infliximab administration	5.7	3.8	6.0	0.0	0.0	0.0	< 0.001
Hospital stay days for active disease management	9.5	11.3	9.0	14.8	12.4	9.5	< 0.001
Direct medical costs for outpatient clinic visits
Outpatient costs for drugs	¥710	¥4,268	¥0	¥2,342	¥4698	¥644	< 0.001
Outpatient costs for others	¥232	¥589	¥0	¥130	¥446	¥0	0.008b
Total outpatient costs	¥942	¥4371	¥54	¥2473	¥4777	¥810	< 0.001
Direct medical costs for hospitalizations
Hospital costs related to infliximab administration	¥5,305	¥7650	¥3577	¥0	¥0	¥0	< 0.001
Drug acquisition costs of infliximab	¥39018	¥9610	¥39200	¥0	¥0	¥0	< 0.001
Hospital costs for active disease management	¥11041	¥17982	¥4090	¥24274	¥29285	¥9321	< 0.001
Total hospital costs	¥55365	¥22337	¥52155	¥24274	¥29285	¥9321	< 0.001
Total direct medical costs	¥56307	¥23866	¥52476	¥26747	¥30541	¥12503	< 0.001

^bP < 0.01. CMT: Conventional maintenance therapy; IMT: Infliximab maintenance therapy; SD: Standard deviation.

Table 3 Summary of the multivariable regression analyses for clinical outcomes in the included moderate to severe Crohn’s disease patients

Outcome type	Disease remission					CD-related surgery					CD-related complications					Utility, quality of life
Regression analysis method	Logistic regression analysis					Logistic regression analysis					Logistic regression analysis					Beta-binomial regression analysis
Independent variables	Sample size	OR	95%CI		P value	Sample size	OR	95%CI		P value	Sample size	OR	95%CI		P value	Sample size	Coefficient	95%CI		P value
			Lower	Upper				Lower	Upper				Lower	Upper				Lower	Upper
IMT vs CMT	389	4.060	1.643	10.753	0.003a	389	0.658	0.349	1.249	0.196	389	0.527	0.323	0.858	0.010a	389	0.822	0.218	1.426	0.008a
Demographics
Male gender											389	1.111	0.675	1.844	0.681	389	-0.008	-0.622	0.607	0.980
Age in yr	389	0.951	0.918	0.986	0.005	389	1.027	1.002	1.052	0.035a	389	0.990	0.968	1.011	0.351	389	-0.016	-0.041	0.010	0.223
BMI
< 18.5						389	1.936	0.682	6.535	0.244
18.5-23.9						389	0.826	0.292	2.755	0.733
Residence area
Urban city						389	0.521	0.246	1.035	0.073
Insurance plan
Farmar	389	0.384	0.098	1.634	0.178
Other plans						389	2.578	1.034	6.247	0.038a
Disease site at diagnosis
Terminal ileum						389	1.350	0.612	3.042	0.460	389	1.246	0.732	2.104	0.414	389	-0.227	-0.847	0.392	0.472
Colon						389	0.812	0.385	1.762	0.590	389	1.581	0.756	3.247	0.216
History of CD-related complications
Intestinal fistula	389	0.307	0.098	0.976	0.042a
Intestinal obstruction	389	0.831	0.322	2.293	0.709
Extraintestinal abscess						389	5.766	1.277	25.741	0.020a
Anal fistula						389	0.747	0.350	1.509	0.431						389	0.142	-0.546	0.829	0.687
Joint pain	389	0.318	0.059	1.866	0.187
History of CD-related surgery	389	0.158	0.056	0.407	0.000						389	0.488	0.282	0.824	0.009b	389	-0.304	-0.908	0.299	0.323
Comorbidities
Gallbladder disease											389	3.812	1.343	11.494	0.013a
Kidney disease						389	5.015	0.826	31.142	0.070

^aP < 0.05.

^bP < 0.01. BMI: Body mass index; CD: Crohn’s disease; CI: Confidence interval; CMT: Conventional maintenance therapy; IMT: Infliximab maintenance therapy; OR: Odds ratio; SD: Standard deviation.

Table 4 Summary of the multivariable regression analyses for health resources utilization in the included moderate to severe Crohn’s disease patients

Outcome type	Outpatient visits					Hospital admissions related to active disease					Hospital stay length related to active disease
Regression analysis method	Poisson regression analysis					Poisson regression analysis					Linear regression analysis
Independent variables	Sample size	Coefficient	95%CI		P value	Sample size	Coefficient	95%CI		P value	Sample size	Coefficient	95%CI		P value
			Lower	Upper				Lower	Upper				Lower	Upper
IMT vs CMT	238	-0.564	-0.703	-0.425	0.000	291	-0.074	-0.276	0.128	0.470	389	-4.725	-7.112	-2.337	0.000
BMI
< 18.5						291	0.244	-0.122	0.643	0.209	389	5.510	1.587	9.433	0.006b
18.5-23.9						291	-0.020	-0.382	0.375	0.917	389	-0.759	-4.449	2.932	0.686
Lifestyles
Smoker	238	0.073	-0.231	0.355	0.623
Residence area
Urban city	238	0.693	0.558	0.830	0.000
Insurance plan
Urban workers	238	-0.070	-0.230	0.092	0.392
Urban residents	238	-0.442	-0.696	-0.196	0.001b
Disease site at diagnosis
Terminal ileum	238	0.113	-0.086	0.314	0.268						389	-2.100	-5.085	0.884	0.167
Colon
Ileocolon	238	0.128	-0.057	0.317	0.179						389	-2.505	-5.099	0.089	0.058
End ileum + upper digestive tract						291	0.222	-0.359	0.731	0.421
Ileocolon + upper digestive tract	238	0.502	0.162	0.825	0.003b	291	0.253	-0.218	0.670	0.263
History of CD-related complications
Pyloric obstruction	238	-0.247	-1.698	0.815	0.690	291	0.819	0.080	1.450	0.018a
Intestinal fistula	238	0.028	-0.272	0.312	0.850
Intestinal obstruction	238	0.372	0.183	0.555	0.000
Extraintestinal abscess											389	11.363	4.696	18.030	0.001b
Anal fistula						291	0.241	0.007	0.468	0.040a	389	-0.316	-2.710	2.078	0.795
Perianal abscess						291	0.150	-0.091	0.383	0.214
Extraintestinal manifestations
Joint pain	238	-0.438	-0.919	-0.013	0.057
Mouth ulcers	238	-0.465	-0.936	-0.053	0.038a
History of CD-related surgery	238	-0.117	-0.291	0.054	0.184
Comorbidities
HP infection	238	1.168	0.588	1.672	0.000
Rhinitis	238	1.439	0.221	2.966	0.034a
Gallbladder disease	238	-0.233	-0.640	0.133	0.235
Tuberculosis											389	6.773	-2.555	16.100	0.154
Peritonitis	238	1.986	1.438	2.471	0.000	291	0.872	-0.321	1.759	0.091	389	53.048	32.426	73.671	0.000
Abdominal abscess	238	NA	NA	NA	NS	291	NA	NA	NA	NS	389	NA	NA	NA	NS
fracture						291	1.213	0.030	2.080	0.017a
Osteoporosis	238	-0.159	-1.626	0.945	0.802
Muscle atrophy											389	45.956	23.426	68.486	0.000
Arrhythmia	238	-1.109	-2.919	0.055	0.123
Hepatitis B virus carriers	238	-0.358	-1.062	0.235	0.275

^aP < 0.05.

^bP < 0.01. BMI: Body mass index; CD: Crohn’s disease; CI: Confidence interval; CMT: Conventional maintenance therapy; IMT: Infliximab maintenance therapy; NA: Not available; NS: Not significant.

Table 5 Summary of the multivariable regression analyses for direct medical costs in the included moderate to severe Crohn’s disease patients

Outcome type	Outpatient medical costs					Hospital costs related to active disease					Total medical costs
Regression analysis method	Generalized linear regression analysis					Generalized linear regression analysis					Generalized linear regression analysis
Independent variables	Sample size	Coefficient	95%CI		P value	Sample size	Coefficient	95%CI		P value	Sample size	Coefficient	95%CI		P value
			Lower	Upper				Lower	Upper				Lower	Upper
IMT vs CMT	237	-1.248	-1.651	-0.850	< 0.001	293	-0.117	-0.387	0.150	0.384	342	-0.378	-0.659	-0.101	0.008b
BMI
< 18.5						293	0.753	0.240	1.225	0.003b	342	0.513	0.013	0.972	0.035a
18.5-23.9						293	0.214	-0.276	0.657	0.367	342	-0.002	-0.486	0.435	0.992
Lifestyles
Smoker	237	0.563	-0.529	1.824	0.263
Heavy drinker						293	-1.519	-2.805	0.515	0.057	342	-1.714	-2.835	0.009	0.013a
Residence area
Urban city	237	0.741	0.365	1.127	< 0.001
Insurance plan
Urban residents	237	-0.562	-1.038	-0.030	0.028a
Other plans						293	0.395	-0.071	0.915	0.111	342	0.248	-0.235	0.784	0.325
Disease site at diagnosis
Terminal ileum											342	0.183	-0.204	0.564	0.343
Colon	237	-0.116	-0.728	0.569	0.707
Ileocolon	237	-0.279	-0.662	0.102	0.158	293	-0.252	-0.513	0.010	0.060	342	-0.163	-0.517	0.178	0.347
Ileocolon + upper digestive tract											342	0.600	-0.073	1.397	0.106
CD-related complications
Intestinal obstruction	237	1.270	0.680	1.901	< 0.001
Gastric fistula											342	-2.351	-4.061	1.308	0.049a
Intestinal abscess						293	-1.183	-2.224	0.372	0.064	342	-1.180	-2.174	0.261	0.050
Bowel perforation											342	0.570	-0.048	1.314	0.094
Perianal abscess	237	-0.058	-0.495	0.409	0.795
Intestinal-cutaneous fistula						293	-2.539	-4.153	0.711	0.022a
Extraintestinal manifestations
Psoriasis											342	NA	NA	NA	NS
Mouth ulcers	237	-0.089	-0.933	1.004	0.852	293	-0.781	-1.253	-0.241	0.002a	342	-0.680	-1.166	-0.121	0.010a
History of CD-related surgery	237	0.019	-0.407	0.466	0.929
Comorbidities
Intestinal ulcer	237	-4.250	-6.471	0.449	0.004b
Shingles						293	-2.464	-4.080	0.786	0.026a
Joint pain											342	-3.952	-5.675	-0.291	0.001a
Esophageal disease											342	-2.696	-4.467	0.976	0.026a
Diabetes											342	-2.147	-3.910	1.523	0.076
Asthma											342	-3.391	-5.092	0.265	0.005

^aP < 0.05.

^bP < 0.01. BMI: Body mass index; CD: Crohn’s disease; CI: Confidence interval; CMT: Conventional maintenance therapy; IMT: Infliximab maintenance therapy; NA: Not available; NS: Not significant.

Table 6 The summary of the main model variables in the decision analytic model assessing the cost-effectiveness of infliximab maintenance therapy relative to conventional maintenance therapy for moderate to severe Crohn’s disease in China

Model variable	Base line value	95%CI
		Lower limit	Upper limits
Treatment efficacies of induction therapy
Disease remission rate of steroids (reference)	0.347	0.247	0.447
Disease remission rate ratio for infliximab relative to reference	1.476	0.620	2.090
Disease remission rate ratio for infliximab plus immunosuppressant relative to reference	2.331	1.639	3.315
Disease remission rate ratio for infliximab plus enteral nutrition relative to reference	1.743	1.523	2.986
Treatment efficacies of maintenance therapy
Quarterly risk of disease relapse associated with no treatment	0.207	0.146	0.284
Relative risk of disease relapse associated with infliximab relative to no treatment	0.040	0.000	0.140
Relative risk of disease relapse associated with immunosuppressant relative to no treatment	0.360	0.170	0.630
Mortality
Perioperative mortality rate associated with surgery	0.014	0.007	0.030
Hazard ratio of mortality associated with active disease relative to age and gender-matched general population	3.047	2.195	4.230
Utility ratio between CD patients and general population
Disease remission	0.829	0.622	0.994
Active disease	0.743	0.565	0.926
Direct medical costs
Annual medical costs related to disease reemission management	¥9512
Annual medical costs related to active disease management	¥14436
Surgery costs per episode	¥16781
Annual drug acquisition costs of infliximab used as induction therapy	¥49000
Drug acquisition costs of infliximab used as MT in the first year	¥39200
Drug acquisition costs of infliximab used as MT beyond the first year	¥29400

CD: Crohn’s disease; CI: Confidence interval; MT: Maintenance therapy.

Table 7 Summary of the results of undiscounted and discounted point estimations of measured outcomes in base case analysis comparing infliximab maintenance therapy vs conventional maintenance therapy in the constructed decision analytic model

Model outputs	Results of base-case analysis without discounting			Results of base-case analysis with discounting
	IMT	CMT	Difference	IMT	CMT	Difference
Overall survival in yr	43.815	40.944	2.871	23.858	22.947	0.911
Disease remission before surgery	30.433	13.157	17.276	18.102	9.392	8.710
Active disease before surgery	1.398	2.540	-1.142	0.803	1.788	-0.985
Disease remission after surgery	11.407	20.893	-9.486	4.709	9.701	-4.993
Active disease after surgery	0.576	4.354	-3.777	0.244	2.066	-1.821
Total QALY	33.365	30.889	2.476	18.392	17.491	0.901
Disease remission before surgery	23.450	10.220	13.230	14.066	7.288	6.778
Active disease before surgery	0.973	1.803	-0.831	0.566	1.278	-0.711
Disease remission after surgery	8.553	15.889	-7.335	3.592	7.492	-3.900
Active disease after surgery	0.389	2.977	-2.588	0.168	1.433	-1.266
Total reimbursed medical costs	¥469958	¥373757	¥96201	¥242107	¥192336	¥49771
Drug costs	¥156606	¥48359	¥108246	¥84553	¥25062	¥59491
Surgery costs	¥8261	¥28346	-¥20085	¥4019	¥14511	-¥10492
Disease remission management	¥284675	¥226987	¥57687	¥143601	¥116897	¥26704
Active disease management	¥20417	¥70065	-¥49648	¥9934	¥35866	-¥25932
Total patient out-of-pocket costs	¥726433	¥163918	¥562515	¥431392	¥109111	¥322281
Drug costs	¥629970	¥27629	¥602340	¥374967	¥18346	¥356622
Surgery costs	¥2526	¥11736	-¥9210	¥1452	¥7840	-¥6387
Disease remission management	¥87695	¥95541	-¥7846	¥51383	¥63547	-¥12165
Active disease management	¥6243	¥29012	-¥22769	¥3590	¥19378	-¥15789
Total medical costs	¥1196392	¥537676	¥658716	¥673499	¥301447	¥372052

IMT: Infliximab maintenance therapy; CMT: Conventional maintenance therapy; QALY: Quality-adjusted life years.