Matching-adjusted indirect comparison of adalimumab vs etanercept and infliximab for the treatment of psoriatic arthritis

Figures & data

Table 1.  Baseline demographics and disease characteristics—adalimumab vs etanercept.

	Before matching			After matching
	ADEPT Pooled ADA and PBO arms	Mease et al.25 Pooled ETA and PBO arms	p-value	ADEPT Pooled ADA and PBO arms	Mease et al.25 Pooled ETA and PBO arms	p-value
Number of patients, n	296	205		296	205
Age (years), mean (SD)	47.8 (10.6)	47.4	–	47.4 (10.4)	47.4	1.000
Female, %	44.6	48.8	0.357	48.8	48.8	1.000
White, %	95.3	90.7	0.057	90.7	90.7	1.000
Duration of PsA (years), mean (SD)	9.5 (8.5)	9.1	–	9.1 (8.6)	9.1
Duration of Psoriasis (years), mean (SD)	17.1 (12.3)	19.0	–	19.0 (13.4)	19.0	1.000
Rheumatoid Factor Positive, %	9.8	6.5	0.172	6.5	6.5	1.000
Psoriasis Evaluation, %
Patients with ≥3% BSA affected  with Psoriasis	43.6	62.4	<0.001*	62.4	62.4	1.000
Radiographic Scores at Baseline, mean (SD)						1.000
Total Sharp Score	18.1 (33.4)	22.0	–	22.0 (41.6)	22.0	1.000
Erosion Score	9.4 (18.6)	10.7	–	10.7 (22.1)	10.7	1.000
Joint Space Narrowing Score	8.8 (16.1)	11.3	–	11.3 (20.7)	11.3	1.000
Concomitant Therapy During Study, %
Corticosteroids	12.5	17.1	0.161	17.1	17.1	1.000
Methotrexate	51.0	41.5	0.034*	41.5	41.5	1.000

ADA, adalimumab; ETA, etanercept; PBO, placebo; PsA, Psoriatic Arthritis; BSA, body surface area; SD, standard deviation.

p-values could not be calculated for continuous baseline characteristics because standard deviations were not reported in Mease et al.25

*p-value <0.05.

Table 2.  Baseline demographics and disease characteristics—adalimumab vs infliximab.

	Before matching			After matching
	ADEPT Pooled ADA and PBO arms	Antoni et al.26 Pooled INF and PBO arms	p-value	ADEPT Pooled ADA and PBO arms	Antoni et al.26 Pooled INF and PBO arms	p-value
Number of patients, n	234	200		234	200
Age (years), mean (SD)	48.8 (12.0)	46.8 (12.0)	0.084	46.8 (12.0)	46.8 (12.0)	1.000
Female, %	45.3	39.0	0.185	39.0	39.0	1.000
Duration of PsA (years), mean (SD)	9.0 (7.7)	8.0 (7.5)	0.137	8.0 (7.4)	8.0 (7.5)	1.000
ACR Component, mean (SD)
Number of Swollen Joints	14.9 (10.3)	14.2 (8.4)	0.424	14.2 (9.8)	14.2 (8.4)	1.000
Number of Tender Joints	24.7 (15.1)	24.9 (13.7)	0.900	24.9 (14.3)	24.9 (13.7)	1.000
CRP (mg/L)	14.0 (17.8)	21.0 (28.2)	0.003*	21.0 (29.6)	21.0 (28.2)	1.000
Physician’s Global Assessment of  Disease Activity	54.0 (15.0)	57.0 (17.5)	0.059	57.0 (14.5)	57.0 (17.5)	1.000
Patient’s Global Assessment of  Disease Activity	47.8 (21.9)	56.5 (21.5)	<0.001*	56.5 (21.1)	56.5 (21.5)	1.000
Patient’s Assessment of Pain	50.5 (21.3)	57.5 (22.0)	<0.001*	57.5 (21.5)	57.5 (22.0)	1.000
HAQ Disability Index	1.0 (0.6)	1.1 (0.6)	0.085	1.1 (0.6)	1.1 (0.6)	1.000
Patients with 1 or more Dactylitis Digits, %	39.3	40.5	0.802	40.5	40.5	1.000
Patients with Enthesopathy, %	37.2	38.5	0.778	38.5	38.5	1.000
Psoriasis Evaluation, %
Patients with ≥3% BSA affected  with Psoriasis	44.4	85.0	<0.001*	85.0	85.0	1.000
SF-36 Score (years), mean (SD)
Physical Component	32.9 (9.5)	32.0 (9.2)	0.314	32.0 (9.4)	32.0 (9.2)	1.000
Mental Component	47.7 (11.4)	46.3 (11.9)	0.213	46.3 (11.9)	46.3 (11.9)	1.000
Concomitant Therapy During Study, %
Corticosteroids	10.7	12.5	0.558	12.5	12.5	1.000
Methotrexate	51.7	46.0	0.236	46.0	46.0	1.000

ADA, adalimumab; INF, infliximab; PBO, placebo; PsA, Psoriatic Arthritis; BSA, body surface area; SD, standard deviation; ACR, American College of Rheumatology criteria; CRP, C-reactive protein; HAQ, Health Assessment Questionnaire.

*p-value <0.05.

Table 3.  Comparison of outcomes after matching—adalimumab vs etanercept.

	ADEPT			Mease et al.25			Difference in differences		Numbers needed to treat (NNT)
	ADA [A]	PBO [B]	Δ1 = [A] − [B]	ETA [C]	PBO [D]	Δ2 = [C] − [D]	Δ1 − Δ2	p-value
Number of patients, n	142	154		101	104
Week 12 outcomes
ACR20, %	62.0	13.8	48.2	59.4	15.4	44.0	4.2	0.609	–
ACR50, %	38.7	3.5	35.2	37.6	3.8	33.8	1.4	0.840	–
ACR70, %	21.1	0.5	20.6	10.9	0.0	10.9	9.7	0.055	10.3
PsARC, %	62.2	23.4	38.9	72.3	30.8	41.5	−2.7	0.761	–
Mean % change  in HAQ^a	49.0	−1.8	50.8	53.5	6.3	47.2	3.6	0.709	–
Week 24 outcomes
ACR20, %	59.3	12.0	47.3	49.5	13.5	36.0	11.3	0.161	–
ACR50, %	41.5	4.8	36.7	36.6	3.8	32.8	3.9	0.591	–
ACR70, %	24.6	0.6	23.9	8.9	1.0	7.9	16.0	0.002*	6.3
PASI50^b, %	71.2	10.7	60.5	47.0	17.7	29.2	31.3	0.001*	3.2
PASI75^b, %	55.6	0.5	55.0	22.7	3.2	19.5	35.5	<0.001*	2.8
PASI90^b, %	40.2	0.0	40.2	6.1	3.2	2.8	37.4	<0.001*	2.7
PsARC, %	60.2	19.2	41.0	70.3	23.1	47.2	−6.2	0.465	–
Mean change  in modified TSS^c	−0.20	1.57	−1.77	−0.03	0.53	−0.56	−1.21	0.080	–
Mean % change  in HAQ^a	49.1	−7.7	56.7	53.6	6.4	47.2	9.5	0.406	–

ADA, adalimumab; ETA, etanercept; PBO, placebo; Δ₁, ADA–PBO; Δ₂, ETA–PBO; ACR, American College of Rheumatology criteria; HAQ, Health Assessment Questionnaire; PASI, Psoriasis Area and Severity Index; PsARC, PsA Response Criteria; TSS, total sharp score.

*p-value <0.05.

^aPatients with HAQ disability index of zero at baseline were omitted.

^bOnly patients with psoriasis involving at least 3% of body surface area were evaluated for PASI responses.

^cModified TSS measured as mean change from baseline to 6 months. Mean change at 6 months was calculated for ADEPT patients by linear extrapolation from week 24 Modified TSS, to match the study design of Mease et al.25

Table 4.  Comparison of outcomes after matching—adalimumab vs infliximab.

	ADEPT			Antoni et al.26			Difference in differences		Numbers needed to treat (NNT)
	ADA [A]	PBO [B]	Δ1 = [A] − [B]	INF [C]	PBO [D]	Δ2 = [C] − [D]	Δ1 − Δ2	p-value
Number of patients, n	108	126		100	100
Week 14 outcomes
ACR20, %	56.1	14.6	41.5	58.0	11.0	47.0	−5.5	0.610	–
ACR50, %	38.7	1.2	37.5	36.0	3.0	33.0	4.5	0.635	–
ACR70, %	33.2	0.3	32.9	15.0	1.0	14.0	18.9	0.034*	5.3
PASI50^a, %	85.8	9.9	75.9	81.9	9.2	72.7	3.2	0.699	–
PASI75^a, %	70.0	0.6	69.4	63.9	2.3	61.6	7.8	0.368	–
PASI90^a, %	33.9	0.0	33.9	41.0	0.0	41.0	−7.1	0.481	–
PsARC, %	66.3	24.8	41.4	77.0	27.0	50.0	−8.6	0.447	–
Mean % change  in HAQ^b	50.5	−22.7	73.2	48.6	−18.4	67.0	6.2	0.751	–
Week 24 outcomes
ACR20, %	59.3	12.1	47.2	54.0	16.0	38.0	9.2	0.381	–
ACR50, %	44.4	3.7	40.7	41.0	4.0	37.0	3.7	0.704	–
ACR70, %	35.8	0.5	35.2	27.0	2.0	25.0	10.2	0.273	–
PASI50^a, %	83.2	11.7	71.6	74.7	8.0	66.7	4.9	0.576	–
PASI75^a, %	67.6	0.0	67.6	60.2	1.1	59.1	8.5	0.342	–
PASI90^a, %	44.3	0.0	44.3	38.6	0.0	38.6	5.8	0.578	–
PsARC, %	67.0	15.6	51.4	70.0	32.0	38.0	13.4	0.197	–
Mean % change  in HAQ^b	50.0	−15.6	65.7	46.0	−19.4	65.4	0.3	0.987	–

ADA, adalimumab; INF, infliximab; PBO, placebo; Δ₁, ADA – PBO; Δ₂, INF – PBO; ACR, American College of Rheumatology criteria; HAQ, Health Assessment Questionnaire; PASI, Psoriasis Area and Severity Index; PsARC, PsA Response Criteria.

*p-value <0.05.

^aOnly patients with psoriasis involving at least 3% of body surface area were evaluated for PASI responses.

^bPatients with HAQ disability index of zero at baseline were omitted.

Table 5.  Comparison of cost per responder after matching—adalimumab vs etanercept.

	Placebo- adjusted response rate	Number of doses	US				Germany
			Drug cost per dose (2011 USD)^a	Drug cost per patient (2011 USD)	Drug cost per incremental responder (2011 USD)	p-value^b	Drug cost per dose (2011 EUR)^a	Drug cost per patient (2011 EUR)	Drug cost per incremental responder (2011 EUR)	p-value^b
Week 12
ACR20
Adalimumab	48.2%	6	838	5031	10,441		766	4594	9535
Etanercept	44.0%	12	427	5127	11,646	0.539	383	4594	10,436	0.612
ACR50
Adalimumab	35.2%	6	838	5031	14,288		766	4594	13,048
Etanercept	33.8%	12	427	5127	15,178	0.770	383	4594	13,601	0.841
ACR70
Adalimumab	20.6%	6	838	5031	24,414		766	4594	22,295
Etanercept	10.9%	12	427	5127	47,073	0.060	383	4594	42,183	0.068
PsARC
Adalimumab	38.9%	6	838	5031	12,949		766	4594	11,825
Etanercept	41.5%	12	427	5127	12,351	0.828	383	4594	11,068	0.761
Week 24
ACR20
Adalimumab	47.3%	12	838	10,062	21,261		766	9189	19,416
Etanercept	36.0%	24	427	10,254	28,448	0.148	383	9188	25,493	0.176
ACR50
Adalimumab	36.7%	12	838	10,062	27,453		766	9189	25,070
Etanercept	32.8%	24	427	10,254	31,273	0.532	383	9188	28,024	0.593
ACR70
Adalimumab	23.9%	12	838	10,062	42,037		766	9189	38,388
Etanercept	7.9%	24	427	10,254	128,986	0.007	383	9188	115,587	0.008
PsARC
Adalimumab	41.0%	12	838	10,062	24,527		766	9189	22,398
Etanercept	47.2%	24	427	10,254	21,714	0.527	383	9188	19,459	0.465
PASI50
Adalimumab	60.5%	12	838	10,062	16,629		766	9189	15,185
Etanercept	29.2%	24	427	10,254	35,081	0.002	383	9188	31,437	0.003
PASI75
Adalimumab	55.0%	12	838	10,062	18,280		766	9189	16,693
Etanercept	19.5%	24	427	10,254	52,578	<0.001	383	9188	47,116	<0.001
PASI90
Adalimumab	40.2%	12	838	10,062	25,024		766	9189	22,851
Etanercept	2.8%	24	427	10,254	361,702	0.011	383	9188	324,129	0.011

ACR, American College of Rheumatology criteria; PASI, Psoriasis Area and Severity Index; PsARC, PsA Response Criteria.

^aWholesale Acquisition Costs were used for drug prices.

^bCost per responder was compared using weighted t-tests.

Table 6.  Comparison of cost per responder after matching—adalimumab vs infliximab.

	Placebo- adjusted response rate	Number of doses	US				Germany
			Drug cost per dose (2011 USD)^a	Drug cost per patient (2011 USD)^b	Drug cost per incremental responder (2011 USD)	p-value^c	Drug cost per dose (2011 EUR)^a	Drug cost per patient (2011 EUR)^b	Drug cost per incremental responder (2011 EUR)	p-value^c
Week 14
ACR20
Adalimumab	41.5%	7	838	5869	14,154		766	5360	12,925
Infliximab	47.0%	3	2971	8913	18,963	0.247	3659	10,977	23,355	0.019
ACR50
Adalimumab	37.5%	7	838	5869	15,647		766	5360	14,289
Infliximab	33.0%	3	2971	8913	27,008	0.038	3659	10,977	33,263	0.001
ACR70
Adalimumab	32.9%	7	838	5869	17,835		766	5360	16,287
Infliximab	14.0%	3	2971	8913	63,661	<0.001	3659	10,977	78,405	<0.001
PsARC
Adalimumab	41.4%	7	838	5869	14,172		766	5360	12,941
Infliximab	50.0%	3	2971	8913	17,825	0.377	3659	10,977	21,953	0.042
PASI50
Adalimumab	75.9%	7	838	5869	7731		766	5360	7060
Infliximab	72.7%	3	2971	8913	12,254	<0.001	3659	10,977	15,092	<0.001
PASI75
Adalimumab	69.4%	7	838	5869	8460		766	5360	7725
Infliximab	61.6%	3	2971	8913	14,479	<0.001	3659	10,977	17,832	<0.001
PASI90
Adalimumab	33.9%	7	838	5869	17,333		766	5360	15,828
Infliximab	41.0%	3	2971	8913	21,757	0.426	3659	10,977	26,796	0.066
Week 24
ACR20
Adalimumab	47.2%	12	838	10,062	21,306		766	9189	19,457
Infliximab	38.0%	5	2971	14,854	39,090	0.012	3659	18,295	48,144	<0.001
ACR50
Adalimumab	40.7%	12	838	10,062	24,726		766	9189	22,580
Infliximab	37.0%	5	2971	14,854	40,147	0.049	3659	18,295	49,445	0.001
ACR70
Adalimumab	35.2%	12	838	10,062	28,556		766	9189	26,077
Infliximab	25.0%	5	2971	14,854	59,417	0.013	3659	18,295	73,178	<0.001
PsARC
Adalimumab	51.4%	12	838	10,062	19,578		766	9189	17,879
Infliximab	38.0%	5	2971	14,854	39,090	0.003	3659	18,295	48,144	<0.001
PASI50
Adalimumab	71.6%	12	838	10,062	14,062		766	9189	12,842
Infliximab	66.7%	5	2971	14,854	22,286	<0.001	3659	18,295	27,448	<0.001
PASI75
Adalimumab	67.6%	12	838	10,062	14,888		766	9189	13,596
Infliximab	59.1%	5	2971	14,854	25,138	<0.001	3659	18,295	30,960	<0.001
PASI90
Adalimumab	44.3%	12	838	10,062	22,700		766	9189	20,730
Infliximab	38.6%	5	2971	14,854	38,528	0.029	3659	18,295	47,451	<0.001

ACR, American College of Rheumatology criteria; PASI, Psoriasis Area and Severity Index; PsARC, PsA Response Criteria.

^aWholesale Acquisition Costs were used for drug prices.

^bThe mean weight of infliximab patients was assumed to be identical to ADEPT patients mean weight after matching.

^cCost per responder was compared using weighted t-tests.

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