Anti-tumor necrosis factor (TNF) drugs for the treatment of psoriatic arthritis: an indirect comparison meta-analysis

Figures & data

Figure 1 Schematic of the publication selection process.

Table 1 Characteristics of the included trials

Trial	Intervention	Setting	Blinded period	No of patients randomized	Quality score	Outcomes of interest
Mease et al^Citation8	ETN (25 mg twice weekly)	NS	12 weeks	60	5/5	HAQ, PASI, PsARC
Mease et al^Citation25^–^Citation27	ETN (25 mg twice weekly)	17 sites in USA	24 weeks	205	4/5	PASI, PsARC
IMPACT^Citation10^–^Citation12	INF (5 mg/kg at weeks 0, 2, 6, 14)	9 sites in Europe, Canada, USA	16 weeks	104	4/5	HAQ, PsARC
IMPACT 2^Citation21^–^Citation24	INF (5 mg/kg at weeks 0, 2, 6, 14, 22)	36 sites in Europe, Canada, USA	16 weeks	200	4/5	HAQ, PASI, PsARC
ADEPT^Citation14^–^Citation18	ADA (40 mg every other week)	50 sites in Europe, Australia, Canada, USA	24 weeks	313	3/5	HAQ, PASI, PsARC
Genovese et al^Citation19	ADA (40 mg every other week)	16 sites in Canada, USA	24 weeks	100	5/5	HAQ, PsARC
GO-REVEAL^Citation20	GOL (50 mg or 100 mg every fourth week)	52 sites in Europe, Canada, USA	24 weeks	405	5/5	HAQ, PASI, PsARC

Abbreviations: ADA, adalimumab; ADEPT, Adalimumab Effectiveness in Psoriatic Arthritis Trial; ETN, etanercept; GOL, golimumab; GO-REVEAL, Golimumab-Randomized Evaluation of Safety and Efficacy in Subjects with Psoriatic Arthritis Using a Human Anti-TNF Monoclonal Antibody; HAQ, Health Assessment Questionnaire; IMPACT, Infliximab Multinational Psoriatic Arthritis Controlled Trial; INF, inflizimab; NS, not stated; PASI, Psoriasis Area and Severity Index; PsARC, Psoriatic Arthritis Response Criteria.

Figure 2 Forest plots of direct estimates for anti-TNFs versus placebo comparisons.

Abbreviations: anti-TNF, anti-tumor necrosis factor; HAQ, Health Assessment Questionnaire; PASI, Psoriasis Area and Severity Index; PsARC, Psoriatic Arthritis Response Criteria.

Table 2 Head-to-head indirect estimates of the anti-TNF drugs

Comparison	PsARC RR (95% CI)	HAQ MD (95% CI)		PASI MD (95% CI)
		Responders	Nonresponders
ADA versus ETN	0.75 (0.49, 1.24)	−0.23 (−0.51, 0.05)	−0.15 (−0.33, 0.03)	0.98 (−1.72, 3.68)
ADA versus INF	0.91 (0.53, 1.32)	−0.21 (−0.48, 0.06)	−0.11 (−0.27, 0.05)	−2.33 (−7.30, 2.64)
ADA versus GOL	0.69 (0.44, 1.26)	−0.03 (−0.33, 0.27)	−0.08 (−0.25, 0.09)	−0.79 (−3.27, 1.69)
ETN versus INF	1.21 (0.69, 1.34)	0.02 (−0.26, 0.30)	0.04 (−0.15, 0.23)	−3.31 (−8.44, 1.82)
ETN versus GOL	0.92 (0.57, 1.28)	0.20 (−0.10, 0.50)	0.07 (−0.13, 0.26)	−1.77 (−4.55, 1.01)
INF versus GOL	0.76 (0.42, 1.35)	0.18 (−0.11, 0.47)	0.03 (−0.15, 0.21)	1.54 (−3.48, 6.56)

Abbreviations: ADA, adalimumab; anti-TNF, anti-tumor necrosis factor; CI, confidence interval; ETN, etanercept; GOL, golimumab; HAQ, Health Assessment Questionnaire; INF, infliximab; MD, mean difference; PASI, Psoriasis Area and Severity Index; PsARC, Psoriatic Arthritis Response Criteria; RR, relative risk.

Table 3 Expected response rates and 95% confidence intervals for the three considered outcomes with the four anti-TNF drugs

Outcome	Placebo response	Anti-TNF treatment response
		ADA	ETN	INF	GOL
PsARC response (proportion)	0.25 (0.21, 0.28)	0.60 (0.50, 0.70)	0.80 (0.70, 0.88)	0.66 (0.48, 0.81)	0.86 (0.76, 0.93)
HAQ responders (mean response)	0.24 (0.18, 0.31)	0.44 (0.29, 0.51)	0.67 (0.47, 0.87)	0.65 (0.47, 0.83)	0.47 (0.24, 0.69)
HAQ nonresponders (mean response)	0.01 (−0.3, 0.04)	0.09 (−0.02, 0.18)	0.24 (0.10, 0.39)	0.19 (0.09, 0.32)	0.17 (0.04, 0.31)
PASI (mean response)	0.68 (0.31, 1.04)	4.79 (3.10, 6.48)	3.81 (1.71, 5.91)	7.12 (2.43, 11.78)	5.58 (3.76, 7.40)

Note: Confidence intervals are derived assuming a fixed placebo response.

Abbreviations: ADA, adalimumab; anti-TNF, anti-tumor necrosis factor; ETN, etanercept; GOL, golimumab; HAQ, Health Assessment Questionnaire; INF, infliximab; PASI, Psoriasis Area and Severity Index; PsARC, Psoriatic Arthritis Response Criteria.

Table S1 Outcomes included in the analysis

Outcome	Definition
Psoriatic arthritis response criteria (PsARC)	PsARC is defined as an improvement in at least two of the following four measures: patient self-assessment, physician assessment, joint pain/tenderness score, and joint swelling score. One of the two measures must be joint pain/tenderness score or joint swelling score. No worsening can occur in any of the four measures.
Psoriasis area and severity index (PASI)	PASI combines the assessment of the severity of lesions and the area affect into a score that spans from 0 (no disease) to 72 (maximal disease). At least 3% of the body surface area has to be affected by the psoriasis in order for the PASI measure to be used.
Health assessment questionnaire (HAQ)	The HAQ focuses on two dimensions of health status: physical disability and pain, generating a score of 0 (least disability) to 3 (most severe disability).

Table S2 Imputations solutions and assumptions employed to construct PASI mean changes

Trial	Data format	Imputation solutions and employed assumptions
Mease et al^Citation13	Baseline median and range (assumed range = 2 × 3 SEs) Percentage change from baseline	Assume similar percentage change SD as Mease 2004 Assume mean percentage change is normally distributed Simulate PASI mean change scores from available baseline and % change data
Mease et al^Citation25^–^Citation27	Baseline not reported Percentage change (SE)	Assume similar baseline score as Mease 2000 Assume mean percentage change is normally distributed Simulate PASI mean change scores from assumed baseline and available % change data
IMPACT^Citation10^–^Citation12	PASI (BSA > 3%) reported by PsARC responders and nonresponders	Take weighted average of PsARC responders and nonresponders
IMPACT 2^Citation21^–^Citation24	PASI (BSA > 3%) reported by PsARC responders and nonresponders	Same as IMPACT
ADEPT^Citation14^–^Citation18	Baseline PASI mean and SE Percentage achieving 50%, 75%, and 90% PASI improvement	Assume percentage change is normally distributed Approximate normal distribution mean and SE using available percentiles (PASI50, PASI75, and PASI90 transformed) Simulate PASI mean change scores from assumed baseline and available % change data
GO-REVEAL^Citation20	PASI (BSA > 3%) reported by PsARC responders and non-responders	Same as IMPACT

Abbreviations: ADEPT, Adalimumab Effectiveness in Psoriatic Arthritis Trial; BSA, body surface area; GO-REVEAL, Golimumab-Randomized Evaluation of Safety and Efficacy in Subjects with Psoriatic Arthritis Using a Human Anti-TNF Monoclonal Antibody; IMPACT, Infliximab Multinational Psoriatic Arthritis Controlled Trial; PASI, Psoriasis Area and Severity Index; PsARC, Psoriatic Arthritis Response Criteria; SD, standard deviation; SE, standard error.

Table S3 Demographic characteristics of participants in the included randomized controlled trials

	Mease^Citation8		Mease^Citation9,Citation25^–^Citation27		IMPACT^Citation10^–^Citation12		IMPACT 2^Citation21^–^Citation24		ADEPT^Citation14^–^Citation18		Genovese et al^Citation19		GO-REVEAL^Citation20
	ETN 25 mg twice weekly	Placebo	ETN 25 mg twice weekly	Placebo	INF 5 mg/kg at weeks 0, 2, 6, 14	Placebo	INF 5 mg/kg at weeks 0, 2, 6, 14, 22c	Placebo	ADA 40 mg every other week	Placebo	ADA 40 mg every other week	Placebo	GOL 50 mg every forth week	GOL 100 mg every forth week	Placebo
Patients randomized, no	30	30	101	104	52	52	100	100	151	162	51	49	146	146	113
Male sex, %	53	60	57	45	58	58	71	51	56	55	57	51	61	59	61
Caucasian, %	90	83	90	91	–	–	–	–	97	94	98	94	97	97	97
Age, years	46.0*	43.5*	47.6**	47.3**	45.7**	45.2**	47.1**	46.5**	48.6**	49.2**	50.4**	47.7**	45.7**	48.2**	47.0**
Psoriasis duration, years	19.0*	17.5*	18.3**	19.7**	16.9**	19.4**	NS	NS	17.2**	17.1**	18.0**	13.8**	NS	NS	NS
PsA duration, years	9.0*	9.5*	9.0**	9.2**	11.7**	11.0**	8.4**	7.5**	9.8**	9.2**	7.5**	7.2**	7.2**	7.7**	7.6**
PsA type, %
Distal interphalangeal joint arthritis	NS	NS	51	50	NS	NS	NS	NS	10	5	6	0	16	15	14
Arthritis mutilans	NS	NS	1	2	NS	NS	NS	NS	1	0	0	0	1	1	0
Asymmetric peripheral arthritis	NS	NS	41	38	NS	NS	NS	NS	25	25	10	14	30	34	24
Polyarticular arthritis	NS	NS	86	83	100	100	NS	NS	64	70	82	84	43	38	51
Ankylosing spondylitis	NS	NS	3	4	NS	NS	NS	NS	1	0	2	2	10	12	11
Swollen joint count	NS	NS	NS	NS	14.6**,†	14.7**,†	13.9**,†	14.4**,†	14.3**,††	14.3**,††	18.2**,††	18.4**,††	14.1**,†	12.0**,†	13.4**,†
Tender joint count	NS	NS	NS	NS	23.7**,†	20.4**,†	24.6**,†	25.1**,†	22.7**,††	19.1**,††	29.3**,††	25.3**,††	24.0**,†	22.5**,†	21.9**,†
Prior number of DMARDs	1.5*	2.0*	NS	NS	NS	NS	NS	NS	1.5**	1.5**	NS	NS	NS	NS	NS
Concomitant therapies during study, %
Corticosteroid	20	40	19	15	NS	NS	10	15	NS	NS	8	18	13	18	17
NSAID	67	77	88	83	NS	NS	73	71	NS	NS	73	86	75	75	78
MTX	47	47	42	41	NS	NS	45	47	51	50	47	47	49	47	48

Notes:

* Median;

** mean;

† 0–66 (swollen joints), 0–68 (tender joints);

†† 0–76 (swollen joints), 0–78 (tender joints).

Abbreviations: ADEPT, Adalimumab Effectiveness in Psoriatic Arthritis Trial; ADA, adalimumab; DMARDs, disease-modifying antirheumatic drugs; ETN, etanercept; GOL, golimumab; GO-REVEAL, Golimumab-Randomized Evaluation of Safety and Efficacy in Subjects with Psoriatic Arthritis Using a Human Anti-TNF Monoclonal Antibody; IMPACT, Infliximab Multinational Psoriatic Arthritis Controlled Trial; INF, inflizimab; MTX, methotrexate; NSAID, nonsteroidal anti-inflammatory drugs; PsA, psoriatic arthritis; NS, not stated.

Table S4 Publications excluded after detailed evaluation

Study	Reason for exclusion
Baranauskaite et al^Citation28	Included patients naïve to methotrexate
Kimball et al^Citation29	Does not exclusively include psoriatic arthritis patients; sub-analysis to randomized controlled trial
Mease et al^Citation30	Treatment not of interest; included inadequate responders to adalimumab, entanercept, or infliximab
Prinz et al^Citation31	Does not include a control arm; post hoc analysis to randomized controlled trial
Asahina et al^Citation32	Does not exclusively include psoriatic arthritis patients
Atteno et al^Citation33	Not a randomized controlled trial
Mease et al^Citation34	Pooled analyses of randomized controlled trials
Sterry et al^Citation35	Does not include a control arm
Torii et al^Citation36	Does not exclusively include psoriatic arthritis patients
Van Kuijk et al^Citation37	Does not include outcomes of interest
Bongiorno et al^Citation38	Not a randomized controlled trial
Brodszky et al^Citation39	Not a randomized controlled trial
Feldman et al^Citation40	Does not exclusively include psoriatic arthritis patients
Kristensen et al^Citation41	Not a randomized controlled trial
Ravindran et al^Citation42	Not a randomized controlled trial
Revicki et al^Citation43	Does not exclusively include psoriatic arthritis patients
Saad et al^Citation44	Not a randomized controlled trial
Spadaro et al^Citation45	Not a randomized controlled trial
Strober et al^Citation46	Does not include outcomes of interest
Frankel et al^Citation47	Not a randomized controlled trial
Kimball et al^Citation48	Not a randomized controlled trial
Romero-Maté et al^Citation49	Not a randomized controlled trial
Vander Cruyssen et al^Citation50	Not a randomized controlled trial
Fransen et al^Citation51	Not a randomized controlled trial
Gottlieb et al^Citation52	Not a randomized controlled trial
Mease et al^Citation25	Not a randomized controlled trial
Ritchlin^Citation53	Not a randomized controlled trial
Kvien et al^Citation54	Not a randomized controlled trial
Rinaldi et al^Citation55	Not a randomized controlled trial

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