Predictors of PASI90 response in patients with psoriasis treated with ınterleukin ınhibitors: observational cohort study<sup/>

Engin, Burhan; Demir, Yusuf; Yucesoy, Sera Nur; Ak, Tumay

doi:10.1016/j.abd.2025.501132

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ORIGINAL ARTICLE • An. Bras. Dermatol. 100 (4) • 2025 • https://doi.org/10.1016/j.abd.2025.501132 linkcopy

Predictors of PASI90 response in patients with psoriasis treated with ınterleukin ınhibitors: observational cohort study^*

Authorship SCIMAGO INSTITUTIONS RANKINGS

Abstract

Background: Psoriasis is a chronic multisystem disorder, and the inhibition of different cytokine pathways has been associated with different treatment responses.

Objective: To demonstrate independent predictors of PASI90 response in patients with psoriasis under biologic therapy and compare the effectiveness of different biologic classes

Methods: This cross-sectional study was conducted in a single tertiary center between January 2023 and May 2024 and included 623 patients (M/F: 320/303). PASI90 response was the primary end-point of the study, and PASI100 was the secondary end-point. Univariate and multivariate cox-regression analyses were used to identify predictors of PASI90. The efficacy of different biologic classes for achieving PASI90 and PASI100 responses was assessed using the Kaplan-Meier method.

Results: The age of disease onset (HR = 1.037, 95% CI [1.029-1.044], p < 0.001) and being biologic-naïve (HR = 1.261, 95% CI [1.046-1.521], p = 0.015) were identified as significant predictors of PASI90 response. IL23 inhibitors showed considerably superior efficacy in achieving PASI90 response than both TNF inhibitors (p = 0.042) and ustekinumab (p = 0.027). Also, IL17 inhibitors exhibited near-significantly higher effectiveness than TNF inhibitors (p = 0.090) and ustekinumab (p = 0.050). The performance of biologic classes was not substantially different in reaching PASI100 overall.

Study limitations: The most important limitation of this study is the retrospective data collection.

Conclusion: Age of disease onset and being biologically naïve were positively associated with achieving PASI90 response, whereas ustekinumab use was negatively associated. Age of disease onset was the strongest predictor of PASI90. Also, IL23 and IL17 inhibition, especially IL23, appeared to provide a better therapeutic response.

KEYWORDS
Biological therapies; Psoriasis; Proportional hazards models; Treatment outcome

Medication	Dosing schedule
TNF inhibitors
Adalimumab	80 mg SC at week-0, 40 mg at week-1, then 40 mg SC q2w
Infliximab	5 mg/kg IV at weeks 0, 2 and 6 and thereafter every 8-weeks
Certolizumab Pegol	Patient weight >90 kg: 400 mg SC q2w
Etanercept	50 mg SC twice weekly for first 12-weeks, then 50 mg SC weekly
IL-17 inhibitors
Secukinumab	300 mg SC at weeks 0, 1, 2, 3, 4, then 300 mg SC q4w
Ixekizumab	160 mg SC at week-0, 80 mg at week 2, 4, 6, 8, 10, 12, then 80 mg SC q4w
IL-23 inhibitors
Guselkumab	100 mg SC at week 0 and 4, then 100 mg q8w
Risankizumab	150 mg SC at week 0 and 4, then 150 mg q12w
IL-12/23 inhibitor
Ustekinumab	Patient weight <100 kg: 45 mg SC at week 0 and 4, then 45 mg SC q12w
	Patient weight >100 kg, 90 mg SC at week 0 and 4, then 90 mg SC q12w

Features	Total (n = 623)
Sex (M/F)	320/303
Age, median (min-max)	40 (18-72)
BMI (kg/m²), median (min-max)	25.5 (14.2-49.2)
Smoking, n (%)	295 (47)
Age of disease onset, median (min-max)	23 (8-58)
Disease duration, years, median (min-max)	15 (0.1-68)
Family history of psoriasis: n(%)	264 (42)
Psoriasis morphology Plaque, n (%)	608 (97)
Pustular, n (%)	11 (2)
Erythrodermic, n (%)	4 (0.6)
Special areas of involvement Genital, n (%)	151 (24)
Scalp, n (%)	344 (55)
Nail, n (%)	231 (37)
Face, n (%)	232 (37)
Palmoplantar, n (%)	91 (15)
Trunk involvement, n (%)	456 (73)
Extremity involvement, n (%)	530 (85)
Psoriatic arthritis, n (%)	190 (30)
Biologic-naïve, n (%)	318 (51)
PASI score just before the last biologic therapy, median (min-max)	24 (5-70)
Last biological treatments of patients
Anti-TNFs Adalimumab, n (%)	46 (7)
Etanercept, n (%)	6 (1)
Certolizumab pegol, n (%)	8 (1)
Infliximab, n (%)	7 (1)
Anti-IL17 Secukinumab, n (%)	86 (13)
Ixekizumab, n (%)	84 (13)
Anti-IL23 Risankizumab, n (%)	169 (27)
Guselkumab, n (%)	163(26)
Anti-IL12/23 Ustekinumab, n (%)	54 (9)
Duration of treatment with the last biologic agent, months, median (min-max)	16 (1-72)
PASI 90 response, n (%)	519 (83)
PASI 100 response, n (%)	278 (45)
Comorbidities Diabetes mellitus, n (%)	63 (10)
Hypertension, n (%)	75 (12)
Dyslipidemia, n (%)	41 (7)
Obesity, n (%)	112 (18)
Ischemic heart disease, n (%)	27 (4)
Asthma/COPD, n (%)	26 (4)
Thyroid dysfunction, n (%)	46 (7)

Covariates	Univariate analysis, (95% CI)	HR	p	Multivariate analysis
Covariates	Univariate analysis, (95% CI)	HR	p	Model 1, HR (95% CI)	p	Model 2, HR (95% CI)	p	Model 3, HR (95% CI)	p
Female gender	1.021 (0.859-1.214)	0.814		-	-	-	-	-	-
Age of disease onset 1.034 (1.027-1.041)		<0.001 c		1.035	<0.001c	1.036	<0.001c	1.037	<0.001c
				(1.028-1.043)		(1.029-1.044)		(1.029-1.044)
Smoking	1.032 (0.868-1.227)	0.719		-	-	-	-	-	-
BMI (kg/m²)	0.998 (0.979-1.018)	0.869		-	-	-	-	-	-
Pustular/erythrodermic 0.965 (0.603-1.545)		0.884		-	-	-	-	-	-
morphology
Family history of	0.971 (0.819-1.151)	0.733		-	-	-	-	-	-
psoriasis
PASI score just	0.999 (0.992-1.006)	0.777		-	-	-	-	-	-
before the last
biologic therapy
Special areas of involvement
Genital	0.842 (0.689-1.029)	0.092		-	-	-	-	-	-
Scalp	0.996 (0.837-1.185)	0.964		-		-	-	-	-
Nail	0.860 (0.719-1.029)	0.100		-	-	-	-	-	-
Face	0.834 (0.695-1.001)	0.051		-	-	-	-	-	-
Palmoplantar	1.293 (1.010-1.657)	0.042 a		-	-	-	-	-	-
Trunk involvement 0.970 (0.797-1.181)		0.761		-	-	-	-	-	-
Extremity	0.765 (0.596-0.980)	0.034 a		-	-	-	-	-	-
involvement
Psoriatic arhtritis	0.892 (0.740-1.076)	0.232		-	-	-	-	-	-
Biologic-naïve	1.118 (0.941-1.329)	0.205		-	-	-	-	1.261	0.015 a
								(1.046-1.521)
Class of biologic treatment
Anti-TNF	Reference category
Anti-IL17	0.996 (0.721-1.376)	0.983		-	-	0.935	0.703	0.995	0.977
						(0.662-1.320)		(0.702-1.410)
Anti-IL23	1.173 (0.867-1.586)	0.300		-	-	1.112	0.505	1.238	0.197
						(0.813-1.521)		(0.895-1.712)
Anti-IL12/23	0.611 (0.394-0.946)	0.027 a		-	-	0.534	0.006 b	0.560	0.011 a
						(0.342-0.834)		(0.358-0.876)
Comorbidities				-	-	-	-	-	-
Diabetes mellitus	0.777 (0.578-1.044)	0.095		-	-	-	-	-	-
Hypertension	0.773 (0.584-1.022)	0.071		-	-	-	-	-	-
Dyslipidemia	0.901 (0.636-1.276)	0.556		-	-	-	-	-	-
Obesity	0.895 (0.716-1.118)	0.329		-	-	-	-	-	-
Coronary artery	0.803 (0.524-1.232)	0.315		-	-	-	-	-	-
disease
Asthma/COPD	0.850 (0.554-1.303)	0.455		-	-	-	-	-	-
Thyroid dysfunction 0.798 (0.571-1.116)		0.188		-	-	-	-	-	-

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[1] PASI, Psoriasis Area Severity Index; HR, Hazard Ratio; CI, Confidence Interval; BMI, Body Mass Index; TNF, Tumor Necrosis Factor; IL, Interleukin; COPD, Chronic Obstructive Pulmonary Disease. Model 1: -2 Log likelihood = 5137.3, Chi-Square = 88.6, p < 0.001. Model 2: -2 Log likelihood = 5117.8, Chi-Square = 106.4, p < 0.001. Model 3: -2 Log likelihood = 5111.9, Chi-Square = 112.9, p < 0.001.

[TFN1] ^a
p < 0.05,

[TFN2] ^b
p < 0.01,

[TFN3] ^c
p < 0.001. Note: Univariate analysis was performed using the enter method, and multivariate analysis was performed using the forward stepwise method.

Predictors of PASI90 response in patients with psoriasis treated with ınterleukin ınhibitors: observational cohort study*

Abstract

Predictors of PASI90 response in patients with psoriasis treated with ınterleukin ınhibitors: observational cohort study^*