Efficacy and safety of ixekizumab in patients with plaque psoriasis across different degrees of disease severity: results from UNCOVER-2 and UNCOVER-3

Figures & data

Figure 1. PASI 75, PASI 90, and PASI 100 response at week 12 for patients administered IXEQ2W or ETN by baseline psoriasis severity (NRI). ETN: etanercept; IXEQ2W: ixekizumab 80 mg every 2 weeks; N: total number of patients; NRI: non-responder imputation; PASI: Psoriasis Area and Severity Index. *p < .001, IXEQ2W vs. ETN.

Table 1. Baseline patient demographics and clinical characteristics by baseline psoriasis severity.

	PASI <20 (N = 1590)	PASI ≥20 (N = 977)	Total (N = 2567)	p value
Gender				.002
Male, n (%)	1039 (65.3)	697 (71.3)	1736 (67.6)
Female, n (%)	551 (34.7)	280 (28.7)	831 (32.4)
Geographic region, n (%)				<.001
Europe	580 (36.5)	523 (53.5)	1103 (43.0)
North America	930 (58.5)	381 (39.0)	1311 (51.1)
Weight (kg), mean (SD)	89.9 (22.4)	93.7 (23.5)	91.4 (22.9)	<.001
Age at enrollment (years), mean (SD)	45.5 (13.2)	45.1 (12.9)	45.4 (13.1)	.393
Age at psoriasis onset (years), mean (SD)	27.3 (14.6)	27.6 (14.0)	27.4 (14.4)	.659
Duration of psoriasis (years), mean (SD)	18.7 (12.7)	17.9 (11.6)	18.4 (12.3)	.148
Previous use of non-biologic systemic therapy, n (%)	784 (49.3)	569 (58.2)	1353 (52.7)	<.001
Previous use of biologic systemic therapy, n (%)	328 (20.6)	169 (17.3)	497 (19.4)	.082
Nail psoriasis, n (%)	924 (58.1)	655 (67.0)	1579 (61.5)	<.001
Facial psoriasis, n (%)	634 (39.9)	499 (51.1)	1133 (44.2)	<.001
Palmoplantar psoriasis, n (%)	391 (24.6)	297 (30.4)	688 (26.8)	<.001
Medical history of psoriatic arthritis, n (%)	298 (18.7)	264 (27.0)	562 (21.9)	<.001
Baseline DLQI, mean (SD)	11.3 (6.5)	13.5 (7.4)	12.2 (6.9)	<.001

DLQI: Dermatology Quality of Life Index; N: total number of patients; PASI: Psoriasis Area and Severity Index; SD: standard deviation.

p values ≤.05 are bolded.

p values are based on Cochran–Mantel–Haenszel test stratified by study for categorical data and analysis of variance for continuous data with treatment and study as independent factors.

Figure 2. Absolute PASI ≤5, PASI ≤2, and PASI ≤1 by baseline psoriasis severity at Week 12 (NRI). ETN: etanercept; IXEQ2W: ixekizumab 80 mg every 2 weeks; N: total number of patients; NRI: non-responder imputation; PASI: Psoriasis Area and Severity Index. *p < .001, IXEQ2W vs. ETN.

Figure 3. PASI 75, PASI 90, and PASI 100 response by baseline psoriasis severity at Week 156 (mNRI and observed). (A) PASI 75 over 156 weeks of treatment. Some values are obscured where data overlap for the two observed groups. (B) PASI 90 over 156 weeks of treatment. (C) PASI 100 over 156 weeks of treatment. Abbreviations: IXEQ2W: ixekizumab 80 mg every 2 weeks; mNRI: modified non-responder imputation; N: total number of patients; PASI: Psoriasis Area and Severity Index; Q4W: every 4 weeks.

Figure 4. Absolute PASI ≤5, PASI ≤2, and PASI ≤1 by baseline psoriasis severity at Week 156 (mNRI and observed). (A) PASI ≤5 over 156 weeks of treatment. (B) PASI ≤2 over 156 weeks of treatment. (C) PASI ≤1 over 156 weeks of treatment. Abbreviations: IXEQ2W: ixekizumab 80 mg every 2 weeks; mNRI: modified non-responder imputation; N: total number of patients; PASI: Psoriasis Area and Severity Index; Q4W: every 4 weeks.

Table 2. Week 12 rates of treatment-emergent adverse events and serious adverse events by baseline psoriasis severity.

	PBO			ETN			IXEQ2W
	(N = 360)			(N = 739)			(N = 734)
	PASI <20(N = 210) n (%)	PASI ≥20(N = 150) n (%)	p value^b	PASI <20(N = 475) n (%)	PASI ≥20(N = 264) n (%)	p value^b	PASI <20(N = 473) n (%)	PASI ≥20(N = 261) n (%)	p value^b
Discontinuation due to AE	1 (0.5)	2 (1.3)	.389	6 (1.3)	3 (1.1)	.908	9 (1.9)	6 (2.3)	.767
Any serious AE	1 (0.5)	7 (4.7)	.009	9 (1.9)	6 (2.3)	.702	7 (1.5)	7 (2.7)	.300
Death	0	0	–	0	0	–	0	0	–
Any TEAE	100 (47.6)	62 (41.3)	.283	265 (55.8)	138 (52.3)	.475	281 (59.4)	143 (54.8)	.314
AEs of special interest
Allergic reaction/hypersensitivity	4 (1.9)	3 (2.0)	.955	13 (2.7)	6 (2.3)	.782	20 (4.2)	8 (3.1)	.469
Cytopenia – SOC	1 (0.5)	2 (1.3)	.362	5 (1.1)	6 (2.3)	.194	4 (0.8)	4 (1.5)	.334
Depression	0	2 (1.3)	.093	4 (0.8)	3 (1.1)	.614	2 (0.4)	1 (0.4)	.994
Hepatic event	0	1 (0.7)	.255	9 (1.9)	8 (3.0)	.349	10 (2.1)	4 (1.5)	.553
CCE	0	1 (0.7)	.255	1 (0.2)	1 (0.4)	.576	2 (0.4)	1 (0.4)	.892
IBD^a	0	0	–	0	0	–	1 (0.2)	1 (0.4)	.662
Infection	44 (21.0)	30 (20.0)	.922	110 (23.2)	51 (19.3)	.367	132 (27.9)	58 (22.2)	.158
Injection-site reactions	12 (5.7)	1 (0.7)	.012	94 (19.8)	28 (10.6)	.002	93 (19.7)	35 (13.4)	.050
Interstitial lung disease	0	0	–	0	0	–	1 (0.2)	0	.408
Malignancies	0	0	–	1 (0.2)	0	.496	3 (0.6)	0	.255

AE: adverse event; CCE: cerebro-cardiovascular events; ETN: etanercept; IBD: inflammatory bowel diseases; IXEQ2W: ixekizumab 80 mg every 2 weeks; N: total number of patients; PASI: Psoriasis Area and Severity Index; PBO: placebo; SOC: system organ class.

p values ≤.05 are bolded.

^aIncludes Crohn’s disease and ulcerative colitis.

^bComparison between psoriasis severity groups using Cochran–Mantel–Haenszel test stratified by study.

Table 3. Week 12–156 rates of treatment-emergent adverse events and serious adverse events by baseline psoriasis severity.

	IXEQ2W/IXEQ4W (N = 362)
	PASI <20 (N = 214) n (%)	PASI ≥20 (N = 148) n (%)
Discontinuation due to AE	15 (7.0)	8 (5.4)
Any serious AE	21 (9.8)	18 (12.2)
Death	1 (0.5)	1 (0.7)
Any TEAE	191 (89.3)	127 (85.8)
AEs of special interest
Allergic reaction/hypersensitivity	29 (13.6)	18 (12.2)
Cytopenia – SOC	6 (2.8)	5 (3.4)
Depression	5 (2.3)	3 (2.0)
Hepatic event	15 (7.0)	12 (8.1)
CCE	4 (1.9)	5 (3.4)
IBD^a	0	1 (0.7)
Infection	150 (70.1)	99 (66.9)
Injection-site reactions	20 (9.3)	11 (7.4)
Interstitial lung disease	0	0
Malignancies	4 (1.9)	1 (0.7)

AE: adverse event; CCE: cerebro-cardiovascular events; IBD: inflammatory bowel diseases; IXEQ2W: ixekizumab 80 mg every 2 weeks; IXEQ4W: ixekizumab 80 mg every 4 weeks; N: total number of patients; PASI: Psoriasis Area and Severity Index; SOC: system organ class.

^aIncludes Crohn’s disease and ulcerative colitis.