Matching-adjusted indirect comparison (MAIC) results confirmed by head-to-head trials: a case study in psoriasis

Figures & data

Table 1. Key characteristics of large-scale studies included in the 2017 unanchored MAIC (16–18,22).

Trial	VOYAGE 1	VOYAGE 2	FIXTURE	ERASURE	UNCOVER-3
	(GUS; n = 329)	(GUS, n = 496)	(SEC 300 mg, n = 327)	(SEC 300 mg, n = 245)	(IXE 80 mg Q2W, n = 385)
Design	Randomized, double-blind, placebo- and active-controlled, parallel-group trial (active control = adalimumab)	Randomized, double-blind, placebo- and active-controlled, parallel-group trial (active control = adalimumab)	Randomized, double-blind, placebo- and active-controlled, parallel-group trial (active control = etanercept)	Randomized, double-blind, placebo-controlled, parallel-group trial	Randomized, double-blind, placebo- and active-controlled, parallel-group trial (active control = etanercept)
Geographic regions	101 global sites	115 global sites	231 sites in N. America, S. America, Europe, India, Australia, Egypt, Philippines, Singapore, S. Korea	88 sites in N. America, S. America, Europe, Taiwan, Japan	N. America, S. America, Europe
Duration	Placebo-controlled Weeks 0–16; active controlled Weeks 0–48	Placebo-controlled Weeks 0–16; active controlled Weeks 0–28, randomized withdrawal and retreatment Weeks 28–72	12-week induction, 40-week maintenance periods	12-week induction, 40-week maintenance periods	Placebo-controlled Weeks 0–12; long-term extension Weeks 12–60
Inclusion criteria	Age ≥18 y	Age ≥18 y	Age ≥18 y	Age ≥18 y	Age ≥18 y
	PASI score ≥12	PASI score ≥12	PASI score ≥12	PASI score ≥12	PASI score ≥12
	IGA score ≥3	IGA score ≥3	mIGA score of 3 or 4	mIGA score of 3 or 4	sPGA score ≥3
	≥10% BSA involvement	≥10% BSA involvement	≥10% BSA involvement	≥10% BSA involvement	≥10% BSA involvement
Exclusion criteria	Significant medical conditions, active tuberculosis, previous systemic PsO therapy	Significant medical conditions, active tuberculosis, previous systemic PsO therapy	Forms of PsO other than chronic plaque-type PsO; drug-induced PsO	Forms of PsO other than chronic plaque-type PsO; drug-induced PsO	Forms of PsO other than chronic plaque-type PsO; drug-induced PsO
Handling of missing data	NRI	NRI	NRI	NRI	NRI

BSA: body surface area; GUS: guselkumab; IGA: Investigator’s Global Assessment; IXE: ixekizumab; MAIC: matching-adjusted indirect comparison; mIGA: modified Investigator’s Global Assessment; NRI: non-responder imputation; PASI: Psoriasis Area and Severity Index; PsO: psoriasis; Q2W: every 2 weeks; SEC: secukinumab; sPGA: static Physician’s Global Assessment.

Table 2. Summary of observed baseline characteristics from the large-scale studies included in the 2017 unanchored MAIC (16–18,22).

Characteristic	Pooled VOYAGE 1 and VOYAGE 2 (GUS, n = 825)	FIXTURE (SEC 300 mg, n = 327)	ERASURE (SEC 300 mg, n = 245)	UNCOVER-3 (IXE 80 mg Q4W, n = 385)
Previous biologic therapy, %	21	12	29	15
Mean age, y	44	44.5	45	46
Race, %
White	81	69	70	94
Black or African American	1	22	21	1
Asian	15	0	0	3
Other/mixed race	2	9	9	2
Mean duration of PsO, y	18	16	17	18
Male sex, %	71	69	69	66
Mean PASI score	22	24	22.5	21
Mean weight, kg	89	83	89	NR
Weight <100 kg, %	75	NR	NR	72
Mean BMI, kg/m^2	30	28	30	30
Mean DLQI score	14	13	14	12
BSA involvement, %	28	34	33	28
Previous non-biologic systemic therapy, %	66	60	52	44
Previous phototherapy, %	58	NR	NR	39

BMI: body mass index; BSA: body surface area; DLQI: Dermatology Life Quality Index; GUS: guselkumab; IXE: ixekizumab; MAIC: matching-adjusted indirect comparison; NR: not reported; PASI: Psoriasis Area and Severity Index; PsO: psoriasis; Q4W: every 4 weeks; SEC: secukinumab.

Figure 1. Comparisons of PASI 90 response rates for guselkumab vs. secukinumab based on (A) unanchored MAIC using pooled data from VOYAGE 1 and VOYAGE 2 vs. pooled data from ERASURE, FIXTURE, JUNCTURE, and FEATURE using NRI methods, and (B) head-to-head comparison in the ECLIPSE trial (15,26). Error bars represent 95% CI. CI: confidence interval; MAIC: matching-adjusted indirect comparison; NRI: non-responder imputation; PASI: Psoriasis Area and Severity Index.

Figure 2. Forest plot of the risk differences in PASI 90 response rates over time based on results from the MAIC and the head-to-head ECLIPSE trial (15,26). Error bars represent 95% CI. CI: confidence interval; GUS: guselkumab; MAIC: matching-adjusted indirect comparison; PASI: Psoriasis Area and Severity Index; SEC: secukinumab.

Figure 3. Comparison of guselkumab vs. ixekizumab based on PASI 90 response rates in (A) the unanchored MAIC using data from VOYAGE 1 and VOYAGE 2 vs. UNCOVER-3 through Week 156 using mNRI and NRI methods, and (B) from IXORA-R through Week 24. Error bars represent 95% CI. CI: confidence interval; MAIC: matching-adjusted indirect comparison; mNRI: modified non-responder imputation; NRI: non-responder imputation; PASI: Psoriasis Area and Severity Index.

Figure 4. Forest plot of the risk differences in PASI 90 response rates over time based on results from the head-to-head IXORA-R trial using NRI methods and the unanchored MAIC using mNRI methods (23,27). Error bars represent 95% CI. CI: confidence interval; GUS: guselkumab; IXE: ixekizumab; MAIC: matching-adjusted indirect comparison; mNRI: modified non-responder imputation; PASI: Psoriasis Area and Severity Index.

Figure 5. Schematic representation of appropriate circumstances for use of unanchored MAIC and other indirect comparison methods. H2H: head-to-head; MAIC: matching-adjusted indirect comparison; NMA: network meta-analysis; PLD: patient-level data; RW: real-world.

Griffiths CE, Reich K, Lebwohl M, et al. Comparison of ixekizumab with etanercept or placebo in moderate-to-severe psoriasis (UNCOVER-2 and UNCOVER-3): results from two phase 3 randomised trials. Lancet. 2015;386(9993):541–551.

 PubMed Web of Science ®Google Scholar

Diels J, Van Sanden S, Druchok C, et al. Novel evidence synthesis methods to assess comparative efficacy in ‘disconnected’ networks of evidence: a case study assessing comparative efficacy of guselkumab versus interleukin-17 inhibitors for maintenance treatment of moderate-to-severe psoriasis. Poster presented at the annual Fall Clinical Dermatology Conference®; Las Vegas, Nevada, USA; October 2017. p. 12–15.

 Google Scholar

Reich K, Armstrong AW, Langley RG, et al. Guselkumab versus secukinumab for the treatment of moderate-to-severe psoriasis (ECLIPSE): results from a phase 3, randomised controlled trial. Lancet. 2019;394(10201):831–839.

 PubMed Web of Science ®Google Scholar

Diels J, Thilakarathne P, Van Sanden S, et al. Three-year clinical efficacy of guselkumab and ixekizumab in moderate-to-severe plaque psoriasis: a matching-adjusted indirect comparison. Poster presented at the annual Fall Clinical Dermatology Conference®; 17–20 October 2019; Las Vegas, Nevada, USA; 2019.

 Google Scholar

Blauvelt A, Papp K, Gottlieb A, IXORA-R Study Group, et al. A head-to-head comparison of ixekizumab vs. guselkumab in patients with moderate-to-severe plaque psoriasis: 12-week efficacy, safety and speed of response from a randomized, double-blinded trial. Br J Dermatol. 2020;182(6):1348–1358.

 PubMed Web of Science ®Google Scholar

Data availability statement

Data available on request from the authors; The data that support the findings of this study are available from the corresponding author, FH, upon reasonable request.