Assessing the economics of biologic and small molecule therapies for the treatment of moderate to severe ulcerative colitis in Japan: a cost per responder analysis of upadacitinib

Figures & data

Figure 1. Model schematic.

This schematic represents treatment with advanced therapies as 8-week induction and 44-week maintenance phases. Duration of induction and maintenance phases varies according to differing specifications for each advanced therapy in the model (Table 1). Patients classified as non-responders were switched to either of the alternative treatment scenarios (i) 5-biologics-basket (weighted average of infliximab, adalimumab, vedolizumab, ustekinumab, and golimumab) or (ii) no treatment. Non-responder frequency of visits was once per month. Response rate was stable until the end of the maintenance phase (formula applied: 1-clinical response rate). Patients in the responder population, continued the advanced therapies they received in the induction phase once per two months. Clinical response was reduced in the same proportion every month.

Table 1. Comparators in the model.

Product	Induction		Maintenance		Treatment code
	Regimen	Duration (weeks)	Regimen	Duration (weeks)
Infliximab	5 mg/kg	6	5 mg/kg Q8W	46	INF5 × 5
Adalimumab	160/80 mg	4	40 mg Q2W	48	ADA160/80 × 40
Golimumab	200/100 mg	6	100 mg Q4W	46	GOL200/100 × 100
Ustekinumab	>55kg and ≦80kg 390 mg	8	90 mg Q12W	44	UST390 × 90
Vedolizumab	300 mg	6	300 mg Q8W	46	VED300 × 300
Tofacitinib	10 mg BID	8	5 mg BID	44	TOF10 × 5
Filgotinib	200 mg QD	10	200 mg QD	42	FIL200 × 200
Upadacitinib	45 mg QD	8	30 mg QD	44	UPA45 × 30
			15 mg QD	44	UPA45 × 15

Note: All dosing regimens are aligned with the Japanese label of the respective drugs; the induction dosing of ustekinumab was assumed to be 390 mg based on the average weight of Japanese patients was approximately 60 kg in a Phase III trial in Japan of golimumab for induction therapy to treat UC (Hibi et al. 2017).

Abbreviations for dosing regimens: BID, twice per day; QD, once per day; Q2W, every two weeks; Q4W, every four weeks; Q8W, every 8 weeks; Q12W, every 12 weeks.

Table 2. Median efficacy rates with median 95% credible intervals.

Treatment code:	INF5 × 5	ADA160/80 × 40	GOL200/100 × 100	UST390 × 90	VED300 × 300	TOF10 × 5	FIL200 × 200	UPA45 × 15	UPA45 × 30
Clinical response
Biologic-naïve induction	65.40% (53.28–76.04%)	54.57% (41.03–67.28%)	51.84% (35.78–67.66%)	66.78% (50.43–79.95%)	53.99% (38.60–68.81%)	63.39% (49.01–75.60%)	65.09% (47.25–79.47%)	79.32% (68.00–87.39%)	79.32% (68.00–87.39%)
Biologic-naïve end of maintenance	34.90% (14.14%, 56.01%)	NA	30.58% (14.70%, 48.56%)	41.25% (19.33%, 61.72%)	38.29% (20.77%, 55.23%)	42.98% (22.30%, 60.57%)	41.88% (20.42%, 61.83%)	56.57% (30.46%, 74.43%)	66.73% (44.88–79.66%)
Biologic-exposed induction	NA	28.08% (11.87–53.16%)	NA	49.21% (26.33–72.44%)	29.88% (13.98–52.55%)	50.92% (29.92–71.94%)	59.27% (34.66–80.07%)	78.63% (59.79–90.22%)	78.63% (59.79–90.22%)
Biologic-exposed end of maintenance	NA	12.10% (3.58%, 30.03%)	NA	17.46% (6.88%, 34.72%)	15.99% (6.26%, 32.71%)	28.72% (13.57%, 48.33%)	34.14% (16.44%, 54.77%)	52.20% (30.98%, 70.91%)	59.79% (39.04%, 76.27%)
Clinical remission
Biologic-naïve induction	29.03% (15.37–47.79%)	15.60% (7.11–30.56%)	25.31% (10.05–50.82%)	17.70% (6.39–40.86%)	25.63% (10.70–50.56%)	19.44% (8.07–40.96%)	19.56% (7.52–42.46%)	50.26% (25.22–76.68%)	50.26% (25.22–76.68%)
Biologic-naïve end of maintenance	17.15% (4.90–40.73%)	12.24% (3.48%, 30.92%)	21.91% (8.99%, 41.08%)	21.52% (7.07%, 45.05%)	25.05% (11.07%, 43.02%)	37.49% (16.45%, 57.57%)	35.58% (14.70%, 57.77%)	34.14% (11.94%, 61.45%)	40.60% (15.75–65.86%)
Biologic-exposed induction	NA	5.60% (1.33–19.28%)	NA	11.74% (3.50–35.14%)	6.59% (1.88–19.95%)	10.48% (3.44–29.42%)	6.75% (1.96–20.64%)	18.21% (6.34–45.24%)	18.21% (6.34–45.24%)
Biologic-exposed end of maintenance	NA	5.77% (1.15%, 21.20%)	NA	7.77% (2.54%, 19.72%)	13.18% (4.71%, 29.41%)	10.31% (3.48%, 24.84%)	17.68% (5.82%, 40.52%)	46.91% (22.28%, 71.23%)	51.04% (26.01–73.50%)
Endoscopic improvement
Biologic-naïve induction	NA	33.89% (25.00–44.20%)	37.04% (25.23–50.74%)	37.69% (23.83–54.39%)	44.98% (31.00–60.02%)	40.09% (27.28–55.60%)	39.35% (25.57–55.68%)	69.07% (54.48–81.22%)	69.07% (54.48–81.22%)
Biologic-naïve end of maintenance	NA	NA	25.18% (11.49%, 43.44%)	27.39% (10.41%, 50.23%)	30.48% (14.36%, 48.34%)	38.02% (17.74%, 57.32%)	37.19% (16.70%, 58.07%)	43.08% (18.26%, 66.55%)	55.04% (28.76%, 73.49%)
Biologic-exposed induction	NA	10.11% (3.51–25.67%)	NA	27.60% (10.57–55.98%)	11.21% (4.38–26.12%)	33.13% (13.90–61.88%)	20.87% (7.62–46.92%)	61.02% (32.75–85.02%)	61.02% (32.75–85.02%)
Biologic-exposed end of maintenance	NA	NA	NA	7.65% (2.45%, 19.54%)	15.44% (5.63%, 32.80%)	16.61% (6.22%, 34.74%)	17.97% (6.48%, 38.64%)	46.65% (23.50%, 69.14%)	54.11% (30.79%, 73.88%)

Note: Efficacy rates presented as percentages with 95% credible intervals (CrIs); NA denotes not applicable values.

Table 3. SAE rates.

Treatment code	SAE rate (median)
INF5 × 5	1.12%
ADA160/80 × 40	0.80%
GOL200/100 × 100	3.40%
UST390 × 90	2.94%
VED300 × 300	1.54%
TOF10 × 5	1.89%
FIL200 × 200	1.89%
UPA45 × 15	1.57%
UPA45 × 30	1.19%

Figure 2. Cost per responder for clinical remission (5-biologic-basket for non-responders). (A) Biologic-naïve cost per clinical remission; (B) biologic-exposed cost per clinical remission; in figure, dots represent the median cost per responder and the whiskers represent the 95% CrI.

Figure 3. Cost per responder for endoscopic improvement (5-biologic-basket for non-responders). (A) Biologic-naïve cost per endoscopic improvement; (B) biologic-exposed cost per endoscopic improvement; in figure, dots represent the median cost per responder and the whiskers represent the 95% CrI.

Figure 4. Cost per responder for clinical response (5-biologic-basket for non-responders). (A) Biologic-naïve cost per clinical response; (B) biologic-exposed cost per clinical response; in figure, dots represent the median cost per responder and the whiskers represent the 95% CrI.

Data availability statement

The data supporting the findings of this study are available within the article and its online supplementary materials.