
==== Front
Dermatol Ther (Heidelb)
Dermatol Ther (Heidelb)
Dermatology and Therapy
2193-8210
2190-9172
Springer Healthcare Cheshire

39153060
1245
10.1007/s13555-024-01245-6
Original Research
Progression of Quality of Life in Patients with Plaque Psoriasis Who Achieved Three or More Years of Complete Skin Clearance with Guselkumab Treatment: a Post hoc Analysis of the VOYAGE 1 Clinical Trial
http://orcid.org/0000-0001-6083-0952
Puig Luis LPuig@santpau.cat

1
Costanzo Antonio 23
de Jong Elke M. G. J. 4
Torres Tiago 56
Warren Richard B. 7
Wapenaar Robert 8
Wegner Sven 9
Gorecki Patricia 10
Gramiccia Talia 11
Jazra Maria 12
Buyze Jozefien 13
Conrad Curdin 14
1 grid.7080.f 0000 0001 2296 0625 Department of Dermatology, IIB Sant Pau, Hospital de Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain
2 https://ror.org/020dggs04 grid.452490.e 0000 0004 4908 9368 Dermatology, Department of Biomedical Sciences, Humanitas University, Milan, Italy
3 grid.417728.f 0000 0004 1756 8807 Humanitas Clinical and Research Center IRCCS, Milan, Italy
4 https://ror.org/05wg1m734 grid.10417.33 0000 0004 0444 9382 Department of Dermatology, Radboud University Medical Center, Nijmegen, The Netherlands
5 grid.5808.5 0000 0001 1503 7226 Centro Hospitalar Universitário do Porto, Porto, Portugal
6 https://ror.org/043pwc612 grid.5808.5 0000 0001 1503 7226 Institute of Biomedical Sciences Abel Salazar, University of Porto, Porto, Portugal
7 https://ror.org/027m9bs27 grid.5379.8 0000 0001 2166 2407 Dermatology Centre, Northern Care Alliance NHS Foundation Trust, National Institute for Health Research Manchester Biomedical Research Centre, The University of Manchester, Manchester, UK
8 grid.497529.4 0000 0004 0625 7026 Janssen-Cilag BV, Breda, The Netherlands
9 grid.497524.9 0000 0004 0629 4353 Janssen-Cilag GmbH, Neuss, Germany
10 grid.507827.f Janssen-Cilag Ltd, High Wycombe, UK
11 Janssen-Cilag SpA, Milan, Italy
12 Janssen-Cilag, Paris, France
13 https://ror.org/04yzcpd71 grid.419619.2 0000 0004 0623 0341 Janssen Pharmaceutica NV, Beerse, Belgium
14 https://ror.org/019whta54 grid.9851.5 0000 0001 2165 4204 Department of Dermatology, Lausanne University Hospital CHUV and University of Lausanne, Lausanne, Switzerland
17 8 2024
17 8 2024
9 2024
14 9 25392558
14 5 2024
25 7 2024
© The Author(s) 2024
2024
https://creativecommons.org/licenses/by-nc/4.0/ Open Access This article is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License, which permits any non-commercial use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc/4.0/.
Introduction

The interleukin-23p19 subunit inhibitor, guselkumab, has demonstrated improvements in clinical and patient-reported outcome (PRO) measures in patients with moderate-to-severe psoriasis. Understanding the relationship among clinical response, PRO measures and baseline characteristics could help clinicians individualize treatment plans. The objective of this analysis was to examine changes in signs, symptoms and quality-of-life (QoL) PRO measures in patients who maintained complete skin clearance through ≥ 3 years in the phase 3 VOYAGE 1 trial.

Methods

A descriptive post hoc analysis of data from VOYAGE 1 was conducted to compare baseline characteristics of patients who maintained complete skin clearance (Psoriasis Area and Severity Index [PASI] = 0 for ≥ 156 consecutive weeks) versus patients who did not. Mean scores for individual domains of the Dermatology Life Quality Index (DLQI) and Psoriasis Symptom and Sign Diary (PSSD) were evaluated in patients who maintained complete skin clearance, and baseline characteristics of patients who achieved PRO scores of DLQI = 0/1 and PSSD = 0 were compared with those who did not.

Results

Of the 329 patients included in this post hoc analysis, 73 (22.2%) maintained PASI = 0 for ≥ 156 weeks. This group had a numerically lower proportion of patients at baseline with obesity, depression or previous biologic treatment and a higher proportion who had never smoked. Patients who maintained PASI = 0 generally achieved positive DLQI and PSSD outcomes, though some impact of residual disease was observed, largely related to the DLQI “Symptoms and feelings” sub-scale and PSSD components “Dryness,” “Redness” and “Itch.” Patients reporting continued disease impact (despite sustaining PASI = 0) had greater disease severity at baseline versus those achieving DLQI = 0/1 and PSSD = 0.

Conclusion

Clinical measures alone do not capture the full patient experience. While both QoL and clinical symptoms are responsive to highly effective treatment, a subset of patients with complete clinical response is still impacted by their psoriasis. Further investigation into this population is warranted.

Trial registration

ClinicalTrials.gov, NCT02207231.

Keywords

Psoriasis
Quality of life
Biologics
Clinical evaluation and treatment
Janssenissue-copyright-statement© Springer Healthcare Ltd., part of Springer Nature 2024
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pmcKey Summary Points

Why carry out this study?	
Some patients with clear skin report residual symptoms and impact of their psoriasis on quality of life (QoL); it is therefore important to understand the relationship among clinical response, patient-reported outcomes and patient characteristics to help guide decision making for individualized care.	
This analysis examined changes in signs, symptoms and QoL measures among patients with moderate-to-severe plaque psoriasis treated with guselkumab who maintained skin clearance for ≥ 156 consecutive weeks in the VOYAGE 1 clinical trial.	
What was learned from the study?	
Patient-reported QoL measures typically paralleled clinical measures, but some patients who maintained clear skin experienced residual impact on QoL, which was largely related to individual Dermatology Life Quality Index (“Symptoms and feelings”) and Psoriasis Signs and Symptoms Diary components (“Dryness,” “Redness” and “Itch”).	
While both QoL and clinical signs and symptoms improved with guselkumab treatment, a subset of patients with complete skin clearance experienced residual impact of their plaque psoriasis, and further investigation into this patient population is warranted.	

Introduction

Psoriasis is a chronic, immune-mediated disease presenting with painful, red, scaly, raised skin plaques that can greatly affect a patient’s quality of life (QoL) in terms of both physical and mental wellbeing [1, 2]. Clinical assessments of psoriasis, such as the Psoriasis Area and Severity Index (PASI) [3], focus on visible signs and therefore do not account for the impact on a patient’s QoL. As such, they may fail to identify certain characteristics and traits indicative of a positive response to therapy, such as improvements in psychosocial well-being [4]. Similarly, the full burden of disease may be underestimated by failing to identify worsening QoL. Understanding how to effectively relieve disease burden, beyond just the clinical presentation, is of critical importance, as reflected in a recent consensus statement that included patients with psoriasis and healthcare professionals [5]. This paper highlighted “freedom from disease in psoriasis” as a multifaceted concept and demonstrated the importance of considering QoL measures in conjunction with clinical measures when assessing response to therapy.

Patient-reported outcome (PRO) measures more closely consider a patient’s QoL. The Dermatology Life Quality Index (DLQI) is a commonly used measure of health-related QoL for patients with skin disease [6] and has been shown to correlate closely with PASI [7]. Another frequently used PRO measure, the Psoriasis Signs and Symptoms Diary (PSSD), is a fully validated, nonproprietary tool for assessing patient-observable signs and symptoms specific to psoriasis [8]. Development of these tools and subsequent improvement in our capacity to assess health-related QoL has led to a greater emphasis on this aspect of treatment outcomes in clinical research [9].

Biologic therapies have improved the management of moderate-to-severe plaque psoriasis [2, 10, 11] and have demonstrated greater efficacy over traditional non-biologic treatments [12]. Several studies have shown long-term biologic treatment results in significant and sustained improvements in both clinical and QoL outcomes in patients with moderate-to-severe psoriasis [13–17]. The interleukin-23p19 subunit inhibitor guselkumab led to significant improvements in PASI, DLQI and PSSD scores over 5 years and showed greater improvements in these measures compared with adalimumab (a tumor necrosis factor α blocker) in the VOYAGE 1 and 2 clinical trials [17]. However, while clinical and PRO measures have been seen to improve with guselkumab treatment, there is still a gap in our understanding of how clinical symptoms and QoL relate to one another and how they in turn might be influenced by patient baseline demographics. Understanding these relationships could further aid clinicians in developing and managing individual patient treatment plans [18].

The objective of this analysis was to assess the patterns of signs, symptoms and QoL PRO measures in patients with moderate-to-severe plaque psoriasis who maintained complete skin clearance (PASI = 0) for ≥ 156 consecutive weeks with guselkumab treatment. We compared baseline characteristics of patients who maintained complete skin clearance versus patients who did not meet this stringent level of clinical response and also assessed DLQI and PSSD responses among patients who maintained a complete clinical response.

Methods

This post hoc descriptive analysis was performed using the full 5-year VOYAGE 1 clinical trial dataset (ClinicalTrials.gov Identifier: NCT02207231) [2].

Study Design

The study design and patient population of the VOYAGE 1 clinical trial have been described previously [2]. In brief, patients with moderate-to-severe plaque psoriasis (Investigator Global Assessment [IGA] ≥ 3 and PASI score ≥ 12) for at least 6 months who were candidates for systemic or phototherapy were enrolled. Patients with a current or previous severe, progressive or uncontrolled medical condition, malignancy within 5 years of screening (except nonmelanoma skin cancer) or with symptoms of active tuberculosis were excluded. Patients previously treated with guselkumab or adalimumab were excluded, as were patients treated with other inhibitors of tumor necrosis factor alpha (within 3 months), inhibitors of IL-12/23, IL-17, or IL-23 (within 6 months) or any immunosuppressant or phototherapy (within 4 weeks).

During the 48-week blinded period, patients were randomized to receive guselkumab (100 mg at Weeks 0, 4, 12 and every 8 weeks through Week 44), placebo (Weeks 0, 4 and 12) followed by guselkumab (100 mg at Weeks 16 and 20, and every 8 weeks through Week 44), or adalimumab (80 mg at Week 0, 40 mg at Week 1 and 40 mg every 2 weeks through Week 47). Upon completing the blinded treatment period, patients entered an open-label extension phase during which all patients received guselkumab (100 mg at Week 52 and every 8 weeks thereafter until Week 252) (Fig. 1).Fig. 1 VOYAGE 1 clinical trial design, including the open-label extension phase through Year 5. aThe last dose of guselkumab was administered at Week 252; efficacy was evaluated through Week 252. bSafety was evaluated through Week 264. ADA adalimumab, GUS guselkumab, q2/8w every 2/8 weeks, R randomization

Analysis Populations

In this post hoc analysis, we compared the baseline demographics and clinical characteristics of patients randomized to guselkumab who maintained PASI = 0 for ≥ 156 consecutive weeks versus those who did not. As the trial was completed at Week 252, to achieve 156 consecutive weeks of complete skin clearance, the initial PASI = 0 response would need to have been achieved within the first 96 weeks of treatment. The following patient baseline and disease characteristics were selected for inclusion in this analysis: age, sex, weight, body mass index (BMI), depression history, smoking history, alcohol consumption history, psoriasis duration, age at diagnosis, percentage of body surface area (BSA) with psoriasis, total PASI score, total DLQI score, total IGA score, prior biologic treatment history and PSSD scores.

PRO Measures

The DLQI and PSSD instruments were used to evaluate patient-reported changes in QoL and symptoms and signs, respectively. During the initial phase of the study, the DLQI was completed at baseline and at Weeks 8, 16, 24 and 48, and PSSD outcomes were recorded daily in an electronic diary. During the open-label extension phase, both instruments were completed during clinic visits at Weeks 76, 100, 124, 156, 172, 204, 228 and 252.

The DLQI comprises 10 questions, pertaining to 6 different domains or sub-scales: symptoms and feelings, daily activities, leisure, work and school performance, personal relationships and treatment. A score of 0 indicates no impact of psoriasis for a particular domain, while a score of 3 indicates the most severe impact. An overall DLQI score of 0/1 is considered to represent no effect on a patient’s health-related QoL [19]. When completing the PSSD, the patient rates five cutaneous symptoms (itching, tightness, burning, stinging and pain) and six signs (dryness, cracking, scaling, flaking, shedding, redness and bleeding) on a scale from 0–10. A score of 0 indicates the absence of a given symptom or sign, and a score of 10 indicates a symptom or sign is the worst imaginable [20].

Statistics

How the individual components of DLQI and PSSD scores and PASI changed over time was evaluated for patients who achieved and maintained PASI = 0 for ≥ 156 consecutive weeks. Mean scores for individual domains, as well as overall score distribution across the population, were assessed. Finally, a comparison of the baseline demographics and clinical characteristics of patients who scored DLQI = 0/1 and PSSD = 0 versus those who did not was conducted. All analyses were based on data as observed.

This was a post hoc analysis, and formal statistical testing was not performed. Baseline demographics and clinical characteristics are reported as mean (95% confidence interval). The analyses were conducted using SAS version 9.4 software.

Ethics

This study was conducted in accordance with the ethical principles that have their origin in the Declaration of Helsinki and that are consistent with Good Clinical Practices and applicable regulatory requirements. As a post hoc analysis of the VOYAGE 1 clinical trial, ethical approval was not needed.

Results

Baseline Characteristics of Patients Who Maintained PASI = 0 Versus Those Who Did Not

Baseline characteristics were compared among guselkumab-treated patients who maintained PASI = 0 for ≥ 156 weeks (n = 73) and those who did not (n = 256) (Table 1). The group that maintained PASI = 0 had numerically lower proportions of biologic-naïve patients (n = 15 [20.6%] versus n = 85 [33.2%]), obese patients (n = 26 [35.6%] versus n = 113 [44.1%]) and patients with depression (n = 1 [1.4%] versus n = 20 [7.8%]). Additionally, a higher proportion of patients who maintained PASI = 0 (n = 37 [50.7%]) had never smoked compared with those who did not maintain PASI = 0 (n = 106 [41.4%]). Baseline characteristics otherwise appeared similar between groups. Table 1 Baseline demographics and clinical characteristics of patients who maintained PASI = 0 at all visits for ≥ 156 consecutive weeks compared with patients who did not

	Total patients (N = 329)	
	PASI = 0 (n = 73)	PASI ≠ 0 (n = 256)	
Age, years	44.2 (41.2, 47.1)	43.8 (42.2, 45.4)	
Age category, % (95% CI)			
 < 45 years	53.4 (41.4, 65.2)	52.7 (46.4, 59.0)	
 ≥ 45 to < 65 years	39.7 (28.5, 51.9)	42.2 (36.1, 48.5)	
 ≥ 65 years	6.8 (2.3, 15.3)	5.1 (2.7, 8.5)	
Male, % (95% CI)	74.0 (62.4, 83.6)	72.7 (66.8, 78.0)	
Weight, kg	88.2 (83.2, 93.2)	89.9 (87.4, 92.3)	
BMI, kg/m2	28.9 (27.5, 30.3)	29.9 (29.2, 30.7)	
BMI category, % (95% CI)			
 Normal (< 25 kg/m2)	23.3 (14.2, 34.7)	20.3 (15.6, 25.8)	
 Overweight (≥ 25 to < 30 kg/m2)	41.1 (29.7, 53.2)	35.6 (29.7, 41.8)	
 Obese (≥ 30 kg/m2)	35.6 (24.8, 47.7)	44.1 (38.0, 50.5)	
Depression, % (95% CI)	1.4 (0.0, 0.1)	7.8 (0.0, 0.1)	
Never smoked, % (95% CI)	50.7 (38.7, 62.6)	41.4 (35.3, 47.7)	
Currently consumes alcohol, % (95% CI)	60.3 (48.1, 71.6)	62.9 (56.7, 68.8)	
Disease duration, years	18.1 (15.4, 20.7)	17.9 (16.3, 19.4)	
Age at diagnosis, years	26.3 (23.2, 29.3)	26.0 (24.3, 27.7)	
BSA involvement, %	26.5 (23.3, 29.6)	28.8 (26.6, 31.0)	
PASI score	21.1 (19.5, 22.7)	22.4 (21.1, 23.6)	
DLQI score	13.5 (11.8, 15.3)a	14.1 (13.1, 15.0)b	
IGA score	3.3 (3.2, 3.4)	3.2 (3.2, 3.3)	
Prior biologic therapies, n	0.30 (0.2, 0.4)	0.24 (0.2, 0.3)	
Biologic-naïve patients, % (95% CI)	20.6 (12.0, 31.6)	33.2 (27.5, 39.3)	
PSSD sign score	54.5 (48.9, 60.0)c	57.7 (54.6, 60.7)d	
PSSD symptom score	50.5 (44.5, 56.5)c	55.6 (52.0, 59.2)d	
Data are mean (95% CI) unless otherwise specified

BMI body mass index, BSA body surface area, CI confidence interval, DLQI Dermatology Life Quality Index, IGA Investigator Global Assessment, PASI Psoriasis Area and Severity Index, PSSD Psoriasis Signs and Symptoms Diary

aData were missing for one patient

bData were missing for six patients

cData were missing for 13 patients

dData were missing for 67 patients

DLQI Score Change in the PASI = 0 Population

Of the patients who maintained PASI = 0 for ≥ 156 weeks, > 50% had achieved completely clear skin by Week 24 of guselkumab treatment (Fig. 2). DLQI responses closely followed PASI improvements, with mean overall DLQI scores (baseline 13.5) improving rapidly through Week 16 (1.6) (Fig. 3). At Week 252, mean overall DLQI score was 0.6, corresponding to little or no effect of psoriasis on patients’ health-related QoL (Fig. 3a) [19]. The distribution of individual DLQI scores across the study population showed that the residual impact on QoL can be attributed to a relatively small proportion of patients, given that 75.7% achieved DLQI = 0 and 88.6% achieved DLQI = 0/1 at Week 252 (Fig. 3b).Fig. 2 Cumulative percentage of patients starting their period of ≥ 156 weeks of maintenance of PASI = 0. GUS guselkumab, PASI Psoriasis Area and Severity Index

Fig. 3 a Comparison of mean PASI and DLQI scores over time and b total DLQI score distribution in patients with PASI = 0 for ≥ 156 weeks over 252 weeks of guselkumab treatment. The overlayed PASI = 0 line shows the cumulative percentage of patients starting their period of ≥ 156 weeks of maintenance of PASI = 0. DLQI Dermatology Life Quality Index, PASI Psoriasis Area and Severity Index

Across the individual components of the DLQI for each of the two-item sub-scales “Daily activities,” “Leisure” and “Personal relationships,” > 50% of patients had scores > 1 at Week 0, and for each of the one-item sub-scales “Work and School” and “Treatment,” > 25% of patients had scores > 1 at Week 0. By Week 252, no patients had DLQI scores > 1 for either of the one-item sub scales, and < 3% of patients had scores > 1 for each of the aforementioned two-item sub-scales (Fig. 4). Most of the Week 252 DLQI score was, therefore, attributed to the two-item domain “Symptoms and feelings.” For this domain, 95.8% of patients had scores > 1 at Week 0, improving to just 8.6% at Week 252.Fig. 4 Frequency of patients achieving different DLQI scores for a two-itema domains of “Symptoms and feelings,” “Daily activities,” “Leisure” and “Personal relationships” and b one-itemb domains of “Treatment” and “Work or school.” aTwo-item domain scores each represent a combination of two items from the DLQI questionnaire (each score 0–3) and are, therefore, scores out of a maximum of 6. bOne-item domain scores are scores of 0–3. DLQI Dermatology Life Quality Index

PSSD Score Change in the PASI = 0 Population

Patients maintaining PASI = 0 for ≥ 156 weeks typically also experienced large improvements in both PSSD signs and symptoms scores. Mean overall PSSD scores were 54.5 and 50.5, respectively, at Week 0 and decreased sharply through Week 16 (8.1 and 7.5, respectively). Week 252 PSSD signs and symptoms scores ultimately reached 4.8 and 3.6, respectively, and were attributable to 52.9% of study patients still having PSSD sign scores > 0 and 37.1% still having PSSD symptom scores > 0 (Figs. 5, 6).Fig. 5 PSSD sign score categories in patients with ≥ 156 consecutive weeks of PASI = 0. The overlayed PASI = 0 line shows cumulative percentage of patients starting their period of ≥ 156 weeks of maintenance of PASI = 0. PASI Psoriasis Area and Severity Index, PSSD Psoriasis Signs and Symptoms Diary

Fig. 6 PSSD symptom score categories in patients with ≥ 156 consecutive weeks of PASI = 0. The overlayed PASI = 0 line shows cumulative percentage of patients starting their period of ≥ 156 weeks of maintenance of PASI = 0. PASI Psoriasis Area and Severity Index, PSSD Psoriasis Signs and Symptoms Diary

The sharp decline through Week 16 was consistent across all individual PSSD sign and symptom score components; however, greater variability in the Week 252 scores was observed for each category (Figs. 7, 8). The categories showing the most persistent scores > 0 were those of “Dryness” and “Redness” in the signs domain and “Itch” in the symptoms domain (mean scores of 6.1, 5.8 and 5.9 at Week 0, dropping to 0.9, 0.6 and 0.6 by Week 256, respectively).Fig. 7 PSSD sign scores in patients with ≥ 156 consecutive weeks of PASI = 0. PASI Psoriasis Area and Severity Index, PSSD Psoriasis Signs and Symptoms Diary

Fig. 8 PSSD symptom scores in patients with ≥ 156 consecutive weeks of PASI = 0. PASI Psoriasis Area and Severity Index, PSSD Psoriasis Signs and Symptoms Diary

Subgroup Analyses of the PASI = 0 Population

DLQI 0/1 Versus DLQI ≥ 2

Some differences in the baseline characteristics for the group of patients who maintained PASI = 0 and achieved DLQI = 0/1 (n = 62) at Week 252 and those who did not (n = 8) were noted (Table 2). The group of patients who achieved DLQI = 0/1 were generally younger at diagnosis (mean age 25.2 years, standard deviation [SD] = 13.4 versus 33.3 years, SD = 9.5) and had a numerically lower percentage of BSA affected (25.4%, SD = 13.4% versus 33.9%, SD = 12.0%), lower mean overall DLQI score (13.2, SD = 7.4 versus 17.6, SD = 6.5), PASI score (20.5, SD = 6.7 versus 25.3, SD = 6.3), PSSD sign score (52.4, SD = 21.8 versus 63.7, SD = 13.5) and PSSD symptom score (47.9, SD = 23.7 versus 64.0, SD = 15.5). Additionally, mean disease duration was numerically greater for the group achieving DLQI = 0 (19.1, SD = 11.3 versus 10.4, SD = 8.2). Table 2 Baseline characteristics of patients who maintained PASI = 0 for ≥ 156 consecutive weeks and achieved DLQI = 0/1 and DLQI ≥ 2 at Week 252

	DLQI = 0/1 (n = 62)	DLQI ≥ 2 (n = 8)	
Age, years	44.1 (40.7, 47.4)	43.5 (37.2, 49.8)	
Male, % (95% CI)	75.8 (63.3, 85.8)	75.0 (34.9, 96.8)	
Weight, kg	88.1 (82.7, 93.5)	88.2 (66.3, 110.1)	
BMI, kg/m2	28.7 (27.2, 30.2)	29.8 (22.8, 36.7)	
Psoriasis disease duration, years	19.1 (16.2, 21.9)	10.4 (3.5, 17.3)	
Age at diagnosis, years	25.2 (21.8, 28.5)	33.3 (25.3, 41.2)	
BSA affected by psoriasis, %	25.4 (22.0, 28.8)	33.9 (23.9, 43.9)	
PASI total score	20.5 (18.8, 22.2)	25.3 (20.1, 30.6)	
DLQI total score	13.2 (11.3, 15.1)a	17.6 (12.2, 23.0)	
IGA score	3.2 (3.1, 3.3)	3.6 (3.2, 4.1)	
Number of prior biologic therapies	0.3 (0.1, 0.4)	0.5 (0.1, 1.0)	
PSSD sign score	52.4 (46.3, 58.5)b	63.7 (49.5, 77.8)c	
PSSD symptom score	47.9 (41.3, 54.6)b	64.0 (47.7, 80.3)c	
Data are mean (95% CI) unless otherwise specified

BMI body mass index, BSA body surface area, CI confidence interval, DLQI Dermatology Life Quality Index, IGA Investigator Global Assessment, PASI Psoriasis Area and Severity Index, PSSD Psoriasis Signs and Symptoms Diary

aData were missing for one patient

bData were missing for 11 patients

cData were missing for two patients

PSSD Sign Score 0 Versus ≥ 1

Differences in baseline characteristics for the group of patients who maintained PASI = 0 and achieved PSSD sign score = 0 (n = 33) at Week 252 compared with those who did not (n = 37) were identified (Table 3). The group of patients who achieved a PSSD sign score = 0 had numerically lower mean baseline PSSD sign (49.7, SD = 23.4 versus 56.9, SD = 19.2) and PSSD symptom scores (43.4, SD = 26.6 versus 54.8, SD = 19.3) as well as lower baseline total DLQI score (12.3, SD = 8.0 versus 14.9, SD = 6.7) and were slightly younger at diagnosis (mean age 25.0 years, SD = 12.4 versus 27.1 years, SD = 13.9) compared with patients who did not achieve PSSD sign score = 0 at Week 252. Table 3 Baseline demographics and clinical characteristics of patients who maintained PASI = 0 for ≥ 156 consecutive weeks and achieved PSSD sign score = 0 and PSSD sign score ≥ 1 at Week 252

	PSSD sign score = 0 (n = 33)	PSSD sign score ≥ 1 (n = 37)	
Age, years	42.6 (37.6, 47.5)	45.3 (41.5, 49.1)	
Male, % (95% CI)	81.8 (64.5, 93.0)	70.3 (53.0, 84.1)	
Weight, kg	87.6 (80.2, 95.0)	88.5 (81.0, 96.1)	
BMI, kg/m2	28.2 (26.3, 30.2)	29.4 (27.2, 31.5)	
Psoriasis disease duration, years	17.7 (14.1, 21.3)	18.4 (14.3, 22.5)	
Age at diagnosis, years	25.0 (20.6, 29.4)	27.1 (22.4, 31.7)	
BSA affected by psoriasis,% (95% CI)	25.6 (21.2, 30.0)	27.1 (22.3, 31.9)	
PASI total score	21.2 (18.8, 23.5)	20.9 (18.6, 23.2)	
DLQI total score	12.3 (9.5, 15.2)	14.9 (12.7, 17.2)a	
IGA score	3.3 (3.1, 3.4)	3.2 (3.1, 3.4)	
Number of prior biologic therapies	0.2 (0.0, 0.3)	0.4 (0.2, 0.7)	
PSSD sign score	49.7 (40.2, 59.1)b	56.9 (49.8, 63.9)c	
PSSD symptom score	43.4 (32.7, 54.1)b	54.8 (47.8, 61.9)c	
Data are mean (95% CI) unless otherwise specified

BMI body mass index, BSA body surface area, CI confidence interval, DLQI Dermatology Life Quality Index, IGA Investigator Global Assessment, PASI Psoriasis Area and Severity Index, PSSD Psoriasis Signs and Symptoms Diary

aData were missing for one patient

bData were missing for seven patients

cData were missing for six patients

PSSD Symptom Score 0 Versus ≥ 1

Lastly, some differences in baseline characteristics of the group of patients with PASI = 0 who achieved PSSD symptom score = 0 (n = 44) at Week 252 were noted compared with those who did not (n = 26) (Table 4). The group achieving PSSD symptom score = 0 had a numerically lower mean percentage of BSA affected (24.0%, SD = 11.7% versus 30.3%, SD = 15.3%) and numerically lower mean baseline total DLQI (11.9, SD = 6.7 versus 16.7, SD = 7.7) and PSSD symptom scores (45.8, SD = 25.7 versus 55.2, SD = 18.7) compared with the group that did not achieve PSSD symptom score = 0 at Week 252. Table 4 Baseline demographics and clinical characteristics of patients who maintained PASI = 0 for ≥ 156 consecutive weeks and achieved PSSD symptom score = 0 and PSSD symptom score ≥ 1 at Week 252

	PSSD symptom score = 0 (n = 44)	PSSD symptom score ≥ 1 (n = 26)	
Age, years	43.2 (39.1, 47.3)	45.4 (41.0, 49.7)	
Male, % (95% CI)	79.6 (64.7, 90.2)	69.2 (48.2, 85.7)	
Weight, kg	90.4 (83.4, 97.4)	84.2 (76.6, 91.8)	
BMI, kg/m2	29.1 (27.2, 31.0)	28.4 (26.1, 30.7)	
Psoriasis disease duration, years	17.8 (14.6, 21.0)	18.6 (13.5, 23.7)	
Age at diagnosis, years	25.6 (21.4, 29.7)	27.0 (21.8, 32.1)	
BSA affected by psoriasis,% (95% CI)	24.0 (20.5, 27.6)	30.3 (24.1, 36.5)	
PASI total score	20.2 (18.4, 22.1)	22.4 (19.2, 25.6)	
DLQI total score	11.9 (9.8, 13.9)a	16.7 (13.6, 19.8)	
IGA score	3.2 (3.1, 3.4)	3.3 (3.1, 3.5)	
Number of prior biologic therapies	0.3 (0.1, 0.4)	0.4 (0.1, 0.7)	
PSSD sign score	52.5 (44.4, 60.6)b	55.2 (47.2, 63.2)c	
PSSD symptom score	45.8 (36.9, 54.8)b	55.2 (47.1, 63.3)c	
Data are mean (95% CI) unless otherwise specified

BMI body mass index, BSA body surface area, CI confidence interval, DLQI Dermatology Life Quality Index, IGA Investigator Global Assessment, PASI Psoriasis Area and Severity Index, PSSD Psoriasis Signs and Symptoms Diary

aData were missing for one patient

bData were missing for ten patients

cData were missing for three patients

Discussion

Previous research has explored the efficacy and safety of guselkumab in moderate-to-severe chronic plaque psoriasis for a period of up to 5 years in clinical trials [17]. This post hoc analysis expands on this research, assessing changes in both overall and individual-component PSSD and DLQI scores in guselkumab-treated patients who maintained PASI = 0 for ≥ 156 consecutive weeks. This approach was taken with the aim of further understanding the relationship between clinical signs and symptoms and QoL in people with moderate-to-severe plaque psoriasis. Real-world evidence suggests that these factors may be closely linked [21–23], and identifying characteristics and traits that may potentially be associated with achieving improvements in PRO measures would be important for better informing assessment of treatment responses.

Mean patient-reported PSSD and DLQI scores generally followed mean PASI scores over time, which is consistent with previous research demonstrating that guselkumab leads to high levels of improvements in PSSD, DLQI and PASI scores [17, 24]. Mean overall DLQI score improved from 13.5 at baseline to 0.6 by Week 252, suggesting very little or no impact of psoriasis on health-related QoL in most patients at the latter time point. Most of the Week 252 score was driven by a single component of the DLQI, namely the “Symptoms and feelings” sub-scale, for which the mean score was 0.3 at Week 252; mean scores for all other sub-scales were < 0.1. These findings are consistent with similar studies that also identified DLQI scores correlating with PASI scores [7, 25].

For both PSSD signs and symptoms measures, average individual component scores reached < 1 by Week 16 for all categories other than itch, redness and dryness, all of which were marginally > 1. The Week 252 scores for these components could be explained by the PASI failing to account for signs, such as dryness, or failing to consider disease of the fingernails; furthermore, patients and clinicians may have different interpretations of skin redness intensity. PRO measures may capture aspects of health-related QoL impairment experienced by patients that may not be addressed by PASI assessments. The highest Week 252 PSSD score was seen in the category of dryness, indicating that the subjective experience of skin dryness may be particularly disconnected from PASI measures of psoriasis.

Several studies have suggested residual health-related QoL impairment in a minority of patients with psoriasis who achieved total skin clearance following biologic therapy. Estimates suggest that 82–91% of patients with a PASI 100 response achieve a DLQI score of 0/1 [26–28], and up to 61–67% achieve a DLQI score of 0 [26, 29]. In an analysis of the ProLOGUE study, which assessed health-related QoL in patients with plaque psoriasis who achieved clear or almost clear skin following treatment with brodalumab, 24% and 18% of patients with an absolute PASI score of 0 (clear skin) at Weeks 12 and 48, respectively, had DLQI scores ≥ 2 [30]. Interestingly, itch was reported as a residual symptom by the majority of these patients [30], suggesting that, consistent with the current analysis, itch may contribute substantially to impaired QoL in patients who achieve clear or almost clear skin. Honma et al. reported that > 50% of patients who achieved PASI 100 response continued to report some level of itch (score of > 0 on an itch numerical rating scale) [27], and it has been suggested that patients who achieve clear or almost clear skin, but have a discordant DLQI response, should be monitored for persistence of itch [30]. These findings, which align with the observations reported herein, suggest that itch is likely to play a significant (or relevant) role in relation to persistent impact of psoriasis on QoL in patients with clear or almost clear skin.

A difference in the proportions of patients impacted by psoriasis when using different PRO measures was observed. Among patients achieving PASI = 0 for ≥ 156 weeks, 11.4% had a DLQI score ≥ 2 at Week 252. Meanwhile, 37.1% and 52.9% of patients had PSSD signs and symptoms scores ≥ 1, respectively, suggesting their disease may still have substantial impact on them. These results reinforce the perception that people with plaque psoriasis who have no visible signs of skin lesions as a consequence of highly effective treatment may still be affected by the disease. The difference in proportions is not surprising, since PSSD is a more sensitive measure overall; also, this difference may be explained by the PSSD measures having greater focus on patient signs and symptoms than DLQI. While PSSD places a high degree of emphasis on a patient's symptomatic experience, the “Symptoms and feelings” sub-scale of the DLQI accounts for just two items but nonetheless comprises most of the observed Week 252 score. In particular, item 1 of the DLQI concerning itch, soreness, pain and stinging may be highly correlated with PSSD measures and may explain most of the residual impact on a patient’s health-related QoL after achieving PASI = 0.

Among patients who maintained PASI = 0 over the long term and achieved DLQI = 0/1 at Week 252, the following differences were observed versus those who did not. First, patients achieving DLQI = 0/1 had lower baseline PSSD and DLQI scores, indicating that patients who started off reporting less impact of psoriasis remained less impacted over time. Additionally, patients with DLQI = 0/1 were generally younger at diagnosis and had longer mean disease duration. This could be explained by long-standing disease leading to increased coping skills, resulting in less impact of psoriasis based on DLQI assessments. Major differences in other criteria, such as age and sex, were not observed. Notably, other studies have found differing results; a survey in an Arab population of patients with psoriasis found no differences in DLQI scores between patients with differing duration of disease [31], and another study showed longer disease duration was associated with higher DLQI scores [32]. Collectively, these findings indicate the need for more research in this area in order to draw more definitive and well-informed conclusions.

Similarly, in comparing baseline characteristics of patients with PASI = 0 who achieved PSSD signs and symptoms scores = 0 at Week 252 versus those who did not, some potential differences were identified as well. Notably, patients who achieved PSSD sign scores = 0 at Week 252 had lower average baseline PSSD signs and symptoms scores as well as marginally lower baseline DLQI scores. This indicates that patients with more severe psoriasis symptoms at baseline may be more challenged to achieve complete freedom from disease after treatment, even as clinical signs improve. Similar findings were seen when comparing patients who achieved PSSD symptom scores = 0 to those who did not with the former having lower average baseline PSSD symptom and DLQI scores. Taken together, these findings suggest that more severe disease at baseline may be associated with cumulative life course impact, particularly with regard to “psychological scarring” related to self-esteem and self-confidence, highlighting the importance of early intervention.

When evaluating the overall cohort of patients who maintained PASI = 0 through ≥ 156 weeks versus those who did not, some numerical differences in the baseline demographics and clinical characteristics were also observed. For example, baseline disease severity did not seem to have as large of an impact on patients’ ability to achieve PASI = 0 as it did for their ability to achieve DLQI 0/1 or PSSD scores = 0, as patients who maintained PASI = 0 but did not achieve DLQI = 0/1 had higher mean baseline PSSD scores. Further exploration into differences between these groups was reported in a recent manuscript [33].

As highlighted in the recent freedom from disease in psoriasis consensus statement [5], it is important to address both QoL and clinical aspects of the disease. Our results suggest that, in most cases, guselkumab can support long-term effective treatment of patients with psoriasis, but there is a subset of patients who experience residual impairment of QoL, despite clearance of visible manifestations, who need to be considered. Our findings provide insight into the specific domains driving impairment of QoL in these patients. In addition, we identified multiple characteristics and traits that appeared to differ between patients who did and did not achieve PRO outcomes indicative of no impact on QoL; nonetheless, further work exploring these relationships would be valuable and could aid clinicians in planning treatment regimens.

There are several limitations to this study. Sample sizes were generally low, making meaningful comparisons challenging. For example, only eight patients who achieved PASI = 0 simultaneously failed to achieve DLQI = 0/1. Furthermore, due to the exploratory, post hoc nature of these analyses, formal statistical testing was not conducted, and the data should be viewed as hypothesis-generating. Additionally, several limitations applying to post hoc analyses in general should be considered when interpretating our results; specifically, due to the nature of the study, subgroups were not randomized and there was no control group.

Conclusion

This post hoc analysis of VOYAGE 1 data shows that for guselkumab-treated patients who achieved sustained skin clearance, overall DLQI and PSSD responses followed changes in PASI closely. Substantial improvements were seen across the overall PRO measures; however, mean scores for some demonstrated that meaningful impact of psoriasis on QoL persisted for a subset of patients. These were largely accounted for by the individual DLQI component “Symptoms and feelings” and the individual PSSD components “Dryness,” “Redness” and “Itch.”

This work highlights that analysis and reporting of clinical measures do not capture the full patient experience, and PRO measures ought to be used in conjunction with these to provide a more comprehensive assessment of an individual’s response to treatment. In addition, while both QoL and clinical signs and symptoms are responsive to highly effective treatment, some patients exhibit persistent impact of psoriasis on QoL despite complete skin clearance, warranting further investigation into these observations.

Acknowledgements

The authors gratefully acknowledge the participants of the VOYAGE 1 clinical trial.

Medical Writing Assistance

Medical writing support was provided by Patrick Callaghan of Lumanity under the direction of the authors and was funded by Janssen.

Author Contributions

Drs Luis Puig, Antonio Costanzo, Elke M.G.J. de Jong, Tiago Torres, Richard B. Warren, Robert Wapenaar, Sven Wegner, Patricia Gorecki, Talia Gramiccia, Maria Jazra, Jozefien Buyze, and Curdin Conrad made substantial contributions to study conception and design and to the analysis and interpretation of data. Robert Wapenaar and Jozefien Buyze also made substantial contributions to data acquisition and statistical analysis. Drs Luis Puig, Antonio Costanzo, Elke M.G.J. de Jong, Tiago Torres, Richard B. Warren, Robert Wapenaar, Sven Wegner, Patricia Gorecki, Talia Gramiccia, Maria Jazra, Jozefien Buyze, and Curdin Conrad contributed to drafting and/or revision of the article, provided final approval of the version of the article to be published, and agree to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Funding

The VOYAGE 1 clinical trial and the analyses presented in this article were sponsored by Janssen. The journal’s Rapid Service and Open Access Fees were also funded by Janssen.

Data Availability

The data sharing policy of Janssen Pharmaceutical Companies of Johnson & Johnson is available at https://www.janssen.com/clinical-trials/transparency. As noted on this site, requests for access to the study data can be submitted through the Yale Open Data Access (YODA) Project site at http://yoda.yale.edu.

Declarations

Conflict of interest

Luis Puig reports consulting fees from AbbVie, Almirall, Amgen, Biogen, Boehringer Ingelheim, Bristol Myers Squibb, Janssen, JS BIOCAD, Leo-Pharma, Lilly, Novartis, Pfizer, Sandoz, Samsung-Bioepis, and UCB; payment or honoraria from Janssen, Lilly, Novartis, and UCB; support for attending meetings and/or travel from Janssen and UCB; grants received from AbbVie, Almirall, Amgen, Boehringer Ingelheim, Janssen, Leo-Pharma, Lilly, Novartis, and UCB; and a non-financial relationship with the International Psoriasis Council. Luis Puig is an Editorial Board member of Dermatology and Therapy. Luis Puig was not involved in the selection of peer reviewers for the manuscript nor any of the subsequent editorial decisions. Antonio Costanzo reports consulting fees from AbbVie and UCB; payment or honoraria from AbbVie, Almirall, Amgen, Galderma, Janssen, Lilly, Novartis, and UCB; support for attending meetings and/or travel from AbbVie; and participation on a Data Safety Monitoring Board and/or Advisory Board for AbbVie, Almirall, Amgen, Boehringer Ingelheim, Janssen, Leo-Pharma, Lilly, Novartis, and UCB. Elke de Jong reports receiving research grants from AbbVie, BMS, Janssen Pharmaceutica, Leo Pharma, Lilly, Novartis, and UCB; and has acted as a consultant, paid speaker, and/or participated in research sponsored by companies that manufacture drugs used for the treatment of psoriasis or eczema, including AbbVie, Almirall, Amgen, Boehringer-Ingelheim, Celgene, Galapagos, Janssen Pharmaceutica, Leo Pharma, Lilly, Novartis, Sanofi, and UCB. Tiago Torres reports consulting fees from AbbVie, Almirall, Amgen, Arena Pharmaceuticals, Biocad, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly, Janssen, Leo Pharma, MSD, Novartis, Pfizer, Samsung-Bioepis, Sandoz, and Sanofi; payment or honoraria from AbbVie, Almirall, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Janssen, Leo Pharma, MSD, Novartis, Pfizer, Sandoz, and Sanofi; support for attending meetings and/or travel from AbbVie, Almirall, Janssen, Leo Pharma, MSD, Novartis, Pfizer, and Sanofi; and participation on a Data Safety Monitoring Board and/or Advisory Board for Samsung-Bioepis. Tiago Torres is an Editorial Board member of Dermatology and Therapy. Tiago Torres was not involved in the selection of peer reviewers for the manuscript nor any of the subsequent editorial decisions. Richard B. Warren reports consulting fees from AbbVie, Almirall, Amgen, Arena, Astellas, Avillion, Biogen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, DiCE, GSK, Janssen, Leo, Lilly, Novartis, Pfizer, Sanofi, Sun Pharma, UCB, and UNION; payment or honoraria from AbbVie, Almirall, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Janssen, Leo, Lilly, Novartis, Pfizer, Sanofi, Sun Pharma, and UCB; and grants received from AbbVie, Almirall, Janssen, Leo, Lilly, Novartis, Pfizer, and UCB, and is supported by the Manchester NIHR Biomedical Research Facility. Richard B. Warren is an Editor-in-Chief of Dermatology and Therapy. Richard B. Warren was not involved in the selection of peer reviewers for the manuscript nor any of the subsequent editorial decisions. Robert Wapenaar holds stock at Johnson & Johnson and was a full-time employee of Janssen at the time of the study. Sven Wegner is a full-time employee of and owns stock at Janssen. Patricia Gorecki is a former full-time employee of Janssen and current employee at Kenvue Inc. Talia Gramiccia is a full-time employee at Janssen. Maria Jazra holds stocks at Johnson & Johnson and is a full-time employee at Janssen. Jozefien Buyze is a full-time employee at Janssen. Curdin Conrad reports consulting fees from AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly, Galderma, Incyte, Janssen, LEO Pharma, MSD, Novartis, Pfizer, Samsung, Sanofi, and UCB; payment or honoraria from AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly, Galderma, Incyte, Janssen, LEO Pharma, Novartis, Pfizer, Sanofi, and UCB; participation on a Data Safety Monitoring Board and/or Advisory Board for AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly, Galderma, Janssen, LEO Pharma, MSD, Novartis, Pfizer, and UCB; grants received from AbbVie, Amgen, Boehringer Ingelheim, Celgene, Eli Lilly, Galderma, Janssen, LEO Pharma, Novartis, and Pfizer; and leadership and/or fiduciary roles for the European Society for Dermatological Research and the Swiss Society for Dermatology and Venereology.

Ethical approval

This study was conducted in accordance with the ethical principles that have their origin in the Declaration of Helsinki and that are consistent with Good Clinical Practices and applicable regulatory requirements. All participants provided written informed consent. As a post hoc analysis of the VOYAGE 1 clinical trial, ethical approval was not needed.
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