Table 2.

Methods employed by each included network meta-analysis

NMA	Analysis and base-case model type		PASI outcome type (cut-offs); summary statistic	Timepoints	Treatment of doses	How was heterogeneity considered	How was inconsistency considered	Number of studies
Woolacott 2006 [35]	Bayesian, ordered probit, RE		Ordered categorical (50, 75, 90); RR	4–16 weeks	ETN doses analyzed separately, IFX combined 5 mg and 3 mg/ kga	Qualitative assessment of clinical characteristics and quantitative assessment based on χ2 for pair-wise analyses; RE model used	N/A; no loops of evidence in the network	16
Reich 2008 [32]	Bayesian, ordered probit, RE		Ordered categorical (50, 75, 90); RR	10–12 and 24 weeks	Analyzed separately	Assessed based on clinical characteristics and χ2 for pair-wise analysis; only considered significant for infliximab; explored by removing the smallest study from pairwise analyses; RE model used	N/A; no loops of evidence in the network	15
Bansback 2009 [31]	Bayesian, ordered probit, RE		Ordered categorical (50, 75, 90); RR	8–16 weeks	One dose per drug with lower or higher doses tested in sensitivity analysis	Qualitative assessment of baseline characteristics; meta-regression on baseline characteristics considered, but deemed unnecessary; sensitivity analyses performed using different trials and high or low evaluated dosages were run and compared with base case results; RE model used	NR	22
Reich 2012 [39]	Bayesian, ordered probit, RE		Ordered categorical (50, 75, 90); RR	10–16 weeks	Analyzed separately	Assessment NR; RE model used	NR	20
Lin 2012 [43]	Bayesian, binomial logit (assumed), RE		Dichotomous (50, 75, 90); OR	10–16 weeks	Analyzed separately	Three models assessed for best fit: FE, RE and RE with meta-regression on disease duration and BSA involvement; sensitivity analyses performed using high or low evaluated dosages and excluding studies with only treatment-naïve patients; RE model used	Compared results including and excluding head-to-head trials, but results inconclusive	17
Gupta 2014 [19]	Bayesian, binomial logit (assumed), RE		Dichotomous (75); OR	10–16 weeks	For ETN both licensed doses combined; for other one dose per drug	Qualitative assessment of study and patient characteristics, quantitative assessment based on Q and I2 statistics for pairwise analyses; RE model used	Node-splitting analysis for each loop of evidence in network; no inconsistency detected	21
Messori 2015 [18]	Bayesian; binomial logit (assumed), FE		N/A	12–24 weeks	Analyzed separately	Accounted for in a meta-regression (not described); RE and FE models compared for goodness of fit and FE model used	NR	Any SAE 10, any infectious AE 11
Signorovitch 2015 [42]	Bayesian, ordered probit, RE, included regression adjustment for placebo arm responses		Ordered categorical (50, 75, 90); RR	8–16 weeks	Analyzed separately	RE models with and without adjustment for placebo arm responses compared for goodness of fit and RE model with adjustment used; sensitivity analyses performed using WB dosing for ustekinumab and using binomial logit model at PASI 75 alone	NR	15
Gomez Garcia 2016 [23]	Frequentist multivariate, RE		Dichotomous (75, 90); OR	10–16 weeks	Analyzed separately	Quantitative assessment based on I2 in pairwise meta-analysis	Assessed using the ratio of ORs where a value ≥ 2 indicated potential inconsistency; some evidence of inconsistency identified	27
Jabbar-Lopez 2017 [17]	Frequentist multivariate, RE		Dichotomous (75, 90b); OR	> 12 weeks reported, but 10-week IFX trials included	All doses combined	Assessed by visual inspection of forest plots; RE model used; subgroup analysis included data on licensed biologic doses only	Assessed by visual inspection of forest plots, loop-specific inconsistency plots and calculation of an inconsistency factorb; some evidence of inconsistency identified	PASI 75: 40, Withdrawals due to AEs: 36
Sbidian 2017 [34]	Frequentist multivariate, choice of FE or RE NR		Dichotomous (75, 90); RR	12–16 weeks	All doses combined	Assessed by inspection of patient and study characteristics and estimation of between-study standard deviation followed by comparison with empirical distributions; subgroup analyses and meta-regression on key patient characteristics planned, but data insufficient to perform; sensitivity analyses at dose-level considering each drug dose a different intervention, excluding trials at high risk of bias or with total sample size of < 50 patients and analyzing outcomes on observed cases only	Assessed using loop-specific and side-splitting approaches (Bucher 1997 and Dias 2010) and by fitting a design by treatment interaction model; some evidence of inconsistency identified	PASI 90: 58; SAE: 60; PASI 75: 64; Any AE: 54
Geng 2018 [22]	Bayesian, binomial logit (assumed), RE		Dichotomous assumed (50, 75, 90); OR	NR	Analyzed separately	Assessment NR; RE model used	Assessed by node-splitting; because p > 0.05, the inconsistency model was used	33
Loos 2018 [24]	Bayesian, ordered probit, RE, included regression adjustment for placebo arm responses		Ordered categorical (50, 75, 90); RR	10–16 weeks	Only one dose per drug except UST, where doses were combined	Assessment NR; RE model with adjustment for placebo arm responses used	NR	34
Sawyer 2018 (i) [36]	Bayesian, ordered probit, RE, included regression adjustment for placebo arm responses		Ordered categorical (50, 75, 90, 100); RR	10–16 weeks	Analyzed separately	Qualitative assessment of study and patient characteristics; RE and FE models with and without adjustment for placebo arm responses compared for goodness of fit and RE model with adjustment used; sensitivity analyses performed including data from trial arms of unlicensed doses of systemic therapies	Assessed using RE unrelated mean effects model; no evidence of inconsistency detected	41
Sawyer 2018(m) [40]	Bayesian, ordered probit, FE		Ordered categorical (75, 90, 100); RR	40–64 weeks	Analyzed separately	Qualitative assessment of study design, patient characteristics and endpoints; FE and RE models assessed for goodness of fit and FE model used; sensitivity analysis performed excluding studies with < 5% of patients report prior biologic exposure	Assessed using loop-specific approach (Bucher 1997); no evidence of inconsistency detected	17
Cameron 2018c [38]	Base-case analysis	Bayesian, binomial logit, RE, included regression adjustment for placebo arm responses	Dichotomous (50, 75, 90, 100); RR	10–16 weeks	Analyzed separately	Qualitative assessment of study and patient characteristics; quantitative assessment based I2 statistics for pairwise analyses; FE and RE models combined with several meta-regressions to account for variation in placebo response, prior biologic use, body weight, disease duration, age, race, and baseline outcome scores were compared for goodness of fit; RE model with placebo adjustment used for PASI 50, 90 and 100 and RE model with disease duration adjustment used for PASI 75	Assessed by comparing the mean of the posterior residual deviance and DIC statistics in fitted consistency and inconsistency models; no evidence of inconsistency detected	45
	Supplementary analysisc	Bayesian, ordered probit, RE, included regression adjustment for placebo arm responses	Ordered categorical (50, 75, 90, 100); RR			RE model combined with meta-regression to account for variation in placebo response using covariate at each PASI cut-off; RE model with placebo adjustment used
Sawyer 2019 [37]	Bayesian, ordered probit, RE, included regression adjustment for placebo arm responses		Ordered categorical (50, 75, 90, 100); RR	10–16 weeks	Analyzed separately	Qualitative assessment of study and patient characteristics; RE models with and without adjustment for placebo arm responses compared for goodness of fit; sensitivity analyses performed to test impact of excluding trials reporting < 5% biologic exposed patients, using a different timepoint (12 weeks rather than 16 weeks) for secukinumab, and excluding studies with fewer than 50 patients per arm	Assessed using RE unrelated mean effects model; no evidence of inconsistency detected	77
Bai 2019 [21]	Frequentist, model type NR, choice of FE or RE NR		Dichotomous (75, 100); RR	12–16 weeks	Only one dose per drug except UST, where high dose and WB dose combined	NR	Assessed using loop-specific approach; some inconsistency detected	28
Xu 2019a [25]	Bayesian, binomial logit (assumed), RE		Dichotomous (50, 75, 90, 100); OR	12–16 weeks	Only one dose per drug except IXE, SEC, UST, where doses were combinedd	Assessment NR; RE model used	Node-splitting and net heat plots conducted; node-splitting showed some inconsistency; net heat plots showed no statistical inconsistency	54
Xu 2019b [26]	Bayesian, binomial logit (assumed), choice of FE or RE NR		Dichotomous (75); RR	12–24 weeks	All doses combined	Assessment NR; subgroup analyses stratified by drugs and time of follow-up. Meta-regression analysis was performed by publication year, drugs, number of patients, male ratio, white ratio, time of follow-up, biologic agents and PsA. Sensitivity analysis was conducted to find whether one or more studies deviated from the overall results	Method NR, but no significant inconsistency found	13
Warren 2019 [41]	Bayesian, model type NR, FE		Unclear; proportion of AUC (75, 90, 100)	12–16 weeks	Analyzed separately	Authors comment on similarity of inclusion/exclusion criteria of trials and similarity of baseline characteristics; FE and RE models assessed for goodness of fit and FE model used; estimated percentages of maximum AUC from NMA were placebo-adjusted, but no rationale provided for why	NR	28
Wu 2020 [44]	Frequentist, model type NR, RE		N/A	Up to 24 weeks	All doses combined	NR	Assessed using design-by-treatment model, loop inconsistency model and node-splitting model	BW change: 6 BMI change: 5
Sbidian 2020 [34]	Frequentist multivariate, choice of FE or RE NR		Dichotomous (75, 90); RR	8–24 weeks	All doses combined	Assessed by inspection of patient and study characteristics and estimation of between-study standard deviation followed by comparison with empirical distributions; subgroup analyses and meta-regression on key patient characteristics planned, but data insufficient to perform; sensitivity analyses at dose-level considering each drug dose a different intervention, excluding trials at high risk of bias or with total sample size of < 50 patients and analyzing outcomes on observed cases only	Assessed using loop-specific and side-splitting approaches (Bucher 1997and Dias 2010) and by fitting a design by treatment interaction model; some evidence of inconsistency identified	PASI 75: 107 PASI 90: 95
Warren 2020 [20]	Bayesian and frequentist, model type NR, FE		Dichotomous (75, 90); unclear	4, 8 and 12 weeks	Analyzed separately	Assessment NR; authors assumed studies to be generally similar and consistent	NR	33
Armstrong 2020 [30]	Bayesian, ordered probit, RE, included regression adjustment for placebo arm responses		Ordered categorical (50, 75, 90, 100); Response rates	10–16 weeks	Analyzed separately	Assessment NR; to account for heterogeneity across trials, a model that adjusted for reference-arm response was implemented	NR	60

ADA adalimumab, AE adverse events, AUC area under the curve, BMI body mass index, BSA body surface area, BW body weight, ETN etanercept, FE fixed-effect (model), IFX infliximab, IXE ixekizumab, kg kilogram, i induction, m maintenance, mg milligram, N/A not applicable, NMA network meta-analysis, NR not reported, OR odds ratio, PASI Psoriasis Area and Severity Index, PsA psoriatic arthritis, RE random-effects (model), RR risk ratio, SAE serious adverse events, SEC secukinumab, UST ustekinumab, WB weight-based

^aThe same outcome code was used in the model

^bInconsistency factor was defined as the logarithm of the ratio of two ORs from direct and indirect evidence in a loop, with values close to 1 suggesting agreement between direct and indirect evidence

^cThe only results available in the base-case analysis were for guselkumab versus each comparator; comparisons for all treatments versus placebo were available in a further analysis, supplied in the online supplement. These results are used for the comparisons in our analysis

^dThe labels in this study suggest that only licensed doses were included; however, closer inspection reveals that the study data relates to trial arms of unlicensed doses. It is assumed that these were combined with studies evaluating licensed doses