Modeling the optimal sequence of biologic therapies in plaque psoriasis in Spain

Figures & data

Figure 1. Illustration of a treatment sequence. The figure presents the model outline. All patients are initiated on first-line therapy at the beginning of the mode. Afterwards, patients will discontinue gradually based on the discontinuation rates. After discontinuation, patients will start next-in-line therapy.

Table 1. Posology and treatment drug cost.

	Posology	Vial size (mg)	Pack size (no. of vials)	Pack price (€)	Calculated price/mg (€)	Treatment drug cost (€)
						First year	Second year
Adalimumab	Week 0: 40 mg	40	2	874.05	10.93	12,237	11,363
	Maintenance: 40 mg every 2 weeks
Ustekinumab	Weeks 0 and 4: 45 mg	45	1	2747.36	61.05	16,484	10,989
	Maintenance: 45 mg every 12 weeks
Secukinumab	Weeks 0–4: 300 mg every week	150	2	1143.11	3.81	19,433	14,860
	Maintenance: 300 mg monthly (every 4 weeks)
Ixekizumab	Week 0: 160 mg	80	2	2020.00	12.63	18,180	13,130
	Weeks 2–12: 80 mg every 2 weeks
	Maintenance: 80 mg every 4 weeks
Brodalumab	Weeks 0, 1 and 2: 210 mg	210	2	1050.16	2.50	14,702	13,652
	Maintenance: 210 mg every 2 weeks
Guselkumab	Weeks 0 and 4: 100 mg	100	1	2536.10	25.36	20,289	15,217
	Maintenance: 100 mg every 8 weeks
Risankizumab	Weeks 0 and 4: 150 mg	75	2	3833.49	25.55	22,998	15,332
	Maintenance: 150 mg every 12 weeks
Certolizumab pegol	Weeks 0, 2 and 4: 400 mg	200	2	948.00	2.37	14,220	12,324
	Maintenance: 400 mg every 2 weeks

Posology during the induction period and the maintenance period is based on product resumes. The pack size and the corresponding price were chosen to minimize the cost per treatment. Drug costs are Spanish ex-factory price levels, excluding VAT, accessed in May 2020.

Table 2. Discontinuation rates.

	Evaluation period (cycle)	Discontinuation rate per cycle	Share of patients leaving treatment after evaluation	Yearly discontinuation rate
Adalimumab	4	1.59%	6.19%	18.8%
Ustekinumab	7	1.00%	6.79%	12.3%
Secukinumab	4	1.00%	6.79%	12.3%
Ixekizumab	4	1.00%	6.79%	12.3%
Brodalumab	4	1.00%	6.79%	12.3%
Guselkumab	4	1.00%	6.79%	12.3%
Risankizumab	4	1.00%	6.79%	12.3%
Certolizumab pegol	4	1.59%	6.19%	18.8%

Discontinuation rates are based on drug survival reported in Yiu et al.⁷ for adalimumab, ustekinumab and secukinumab. Ixekizumab, brodalumab, guselkumab, risankizumab, and certolizumab pegol were not included in the study by Yiu et al. In the base case scenario, we therefore applied the discontinuation rate of adalimumab to all anti-TNF therapies, the discontinuation rate of ustekinumab to all IL-23 therapies, and the discontinuation rate of secukinumab to all IL-17 therapies. The length of the evaluation period is based on product resumes, if not specified, the induction period in the product resumes was used.

Table 3. PASI response rates.

Treatment	52-week NMA
	PASI75	PASI90	PASI100
Adalimumab	68.9%	49.7%	25.6%
Ustekinumab	76.3%	58.5%	33.2%
Secukinumab	81.9%	66.0%	40.6%
Ixekizumab	85.0%	70.5%	45.6%
Brodalumab	89.1%	76.8%	53.3%
Guselkumab	89.1%	76.8%	53.3%
Risankizumab	91.5%	80.9%	58.9%
Certolizumab pegol	71.1%	52.2%	27.6%

PASI scores are based on estimates published by Yasmeen et al.²¹ and represent the share of patients who as a minimum achieved the specific PASI score between weeks 40 and 64.

Table 4. Baseline results from the treatment sequence model: top five cost-effective treatment sequences (in €).

Rank	1st line	2nd line	3rd line	4th line	Cost 1st line	Cost 2nd line	Cost 3rd line	Cost 4th line	Total cost
1	Brodalumab	Risankizumab	Guselkumab	Ixekizumab	96,588	34,133	7,285	1,277	139,283
2	Brodalumab	Risankizumab	Ixekizumab	Guselkumab	96,588	34,133	7,504	1,226	139,451
3	Brodalumab	Risankizumab	Guselkumab	Ustekinumab	96,588	34,133	7,285	1,530	139,536
4	Brodalumab	Risankizumab	Guselkumab	Secukinumab	96,588	34,133	7,285	1,560	139,565
5	Brodalumab	Risankizumab	Guselkumab	Certolizumab pegol	96,588	34,133	7,285	1,724	139,730

The table presents the top five cost-effective treatment sequences among the 840 combinations of possible treatments. The cost represents the aggregated costs during the five-year time horizon. The cost of first-, second-, third- and fourth-line therapy represents the aggregated cost per responder associated with treatment with the therapy in the specific line of treatment.

Table 5. Cost-effective treatment sequences if brodalumab is not recommended as first-line therapy or any of the first four lines of therapy compared to rank 1 where brodalumab is allowed as first-line therapy (in €).

Rank	1st line	2nd line	3rd line	4th line	Cost 1st line	Cost 2nd line	Cost 3rd line	Cost 4th line	Total cost
1	Brodalumab	Risankizumab	Guselkumab	Ixekizumab	96,588	34,133	7,285	1,277	139,283
82	Risankizumab	Brodalumab	Guselkumab	Ixekizumab	112,931	28,124	7,285	1,277	149,616
171	Risankizumab	Ixekizumab	Guselkumab	Ustekinumab	112,931	35,784	7,285	1,530	157,529

The table presents the cost-effective treatment sequence from Table 4, along with the most cost-effective treatment sequence in a scenario where brodalumab is not recommended as first-line therapy, and in row 3, the most cost-effective treatment sequence if brodalumab is not recommended in any of the first four lines of treatment. The cost represents the aggregated costs during the five-year time horizon. The cost of first-, second-, third- and fourth-line therapy represents the aggregated cost per responder associated with treatment with the therapy in the specific line of treatment.

Table 6. Estimated cost per responder per year by line of therapy and treatment sequence (in €) for the most cost-effective sequence with and without brodalumab.

	1st line	2nd line	3rd line	4th line	Total cost
Year 1
BRO–RIS–GUS–IXE	26,219	2,401	70	1	28,691
RIS–IXE–GUS–UST	37,363	2,697	70	1	40,131
Year 2
BRO–RIS–GUS–IXE	21,175	5,550	548	37	27,310
RIS–IXE–GUS–UST	21,409	5,775	548	43	27,776
Year 3
BRO–RIS–GUS–IXE	18,581	7,391	1,305	155	27,432
RIS–IXE–GUS–UST	18,976	7,811	1,305	183	28,276
Year 4
BRO–RIS–GUS–IXE	16,305	8,835	2,200	376	27,716
RIS–IXE–GUS–UST	20,717	9,261	2,200	449	32,628
Year 5
BRO–RIS–GUS–IXE	14,308	9,957	3,161	709	28,134
RIS–IXE–GUS–UST	14,466	10,239	3,161	853	28,719

The table presents the total cost per year by line of therapy for the “BRO–RIS–GUS–IXE” treatment sequence (brodalumab–risankizumab–guselkumab–ixekizumab) and “RIS–IXE–GUS–UST” treatment sequence (risankizumab–ixekizumab–guselkumab–ustekinumab). The cost of first-, second-, third- and fourth-line therapy represents the yearly cost per responder associated with treatment of the therapy in the specific treatment line.

Figure 2. Estimated cost per responder per year by line of therapy and treatment sequence (in €). The figure presents the total cost per year by line of therapy for the “BRO–RIS–GUS–IXE” treatment sequence (brodalumab–risankizumab–guselkumab–ixekizumab) and the “RIS–IXE–GUS–UST” treatment sequence (risankizumab–ixekizumab–guselkumab–ustekinumab). The cost of first-, second-, third- and fourth-line therapy represents the yearly cost per responder associated with treatment with the therapy in the specific treatment line.

Figure 3. Estimated cost per responder per year by line of therapy for IL-17 treatment sequences (in €). The figure presents the total cost per year by line of therapy for the “BRO–RIS–GUS–IXE” treatment sequence (brodalumab–risankizumab–guselkumab–ixekizumab), the “IXE-BRO-RIS-GUS” treatment sequence (ixekizumab–brodalumab–risankizumab–guselkumab), and the “SEC-BRO-RIS-GUS” treatment sequence (secukinumab–brodalumab–risankizumab–guselkumab). The cost of first-, second-, third- and fourth-line therapy represents the yearly cost per responder associated with treatment with the therapy in the specific treatment line.

Table 7. Cost-effective treatment sequences where first-line therapy is an IL-17 (in €).

Rank	1st line	2nd line	3rd line	4th line	Cost 1st line	Cost 2nd line	Cost 3rd line	Cost 4th line	Total cost
1	Brodalumab	Risankizumab	Guselkumab	Ixekizumab	96,588	34,133	7,285	1,277	139,283
121	Ixekizumab	Brodalumab	Risankizumab	Guselkumab	117,440	28,124	7,093	1,226	153,883
497	Secukinumab	Brodalumab	Risankizumab	Guselkumab	146,472	28,124	7,093	1,226	182,914

The table presents the cost-effective treatment sequence from Table 4, along with the most cost-effective treatment sequence if other IL-17 therapies are recommended as first-line therapy. The cost represents the aggregated costs during the five-year time horizon. The cost of first-, second-, third- and fourth-line therapy represents the aggregated cost per responder associated with treatment with the therapy in the specific line of treatment.

Table 8. Sensitivity analyses.

	1st line	2nd line	3rd line	4th line	Total cost (€)
Cost per responder defined by PASI75	Brodalumab	Ustekinumab	Ixekizumab	Certolizumab pegol	81,367
Cost per responder defined by PASI90	Brodalumab	Ixekizumab	Guselkumab	Ustekinumab	96,102
Including adalimumab	Brodalumab	Risankizumab	Guselkumab	Ixekizumab	139,283
All discontinuation rates set to 1%	Brodalumab	Risankizumab	Guselkumab	Ixekizumab	139,281

The table presents the optimal treatment sequence as well as the total cost of the given treatment sequence for each listed sensitivity analysis.

Yiu Z, Mason K, Reynolds N, et al. Drug survival of adalimumab, ustekinumab and secukinumab in patients with psoriasis: a prospective cohort study from the British Association of Dermatologists Biologics and Immunomodulators Register (BADBIR). Br J Dermatol. 2020;183(2):294–302.

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Yasmeen N, Sawyer L, Malottki K, et al. Targeted therapies for patients with moderate-to-severe psoriasis: a systematic review and network meta-analysis of PASI response at 1 year. J Dermatolog Treat. 2020.

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