Front. Immunol. Frontiers in Immunology Front. Immunol. 1664-3224 Frontiers Media S.A. 10.3389/fimmu.2025.1639049 Original Research Impact of treatment interruption on the efficacy and safety of vunakizumab in patients with moderate-to-severe plaque psoriasis: a post-hoc analysis of a phase 3 trial LiQunyan 1 2 3 † Data curation Formal analysis Investigation Writing – original draft YaoWeifeng 2 † Data curation Formal analysis Methodology Resources Writing – original draft LeiDongyun 3 Data curation Formal analysis Investigation Methodology Writing – original draft XuYan 3 Data curation Formal analysis Resources Visualization Writing – original draft Writing – review & editing ZhangLitao 3 Data curation Investigation Methodology Writing – original draft ZhaoZuotao 3 Data curation Formal analysis Methodology Resources Visualization Writing – original draft HeJunchen 3 Data curation Formal analysis Investigation Validation Visualization Writing – review & editing GuoTao 2 * Data curation Formal analysis Investigation Methodology Resources Writing – original draft Writing – review & editing LiJunying 2 * Conceptualization Resources Supervision Validation Writing – review & editing Graduate School, Tianjin Medical University, Tianjin, China Department of Dermatology, Tianjin Academy of Traditional Chinese Medicine Affiliated Hospital, Tianjin, China Department of Dermatology, Tianjin lnstitute of lntegrative Dermatology, Tianjin Academy of Traditional Chinese Medicine Affiliated Hospital, Tianjin, China Correspondence: Junying Li, li_junying2016@163.com; Tao Guo, teqko93@163.com

These authors have contributed equally to this work

 16 01 2026 2025 16 1639049 01 06 2025 17 11 2025 16 11 2025 Copyright © 2026 Li, Yao, Lei, Xu, Zhang, Zhao, He, Guo and Li. 2026 Li, Yao, Lei, Xu, Zhang, Zhao, He, Guo and Li https://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. Objective

Vunakizumab, a novel IL-17A inhibitor, has demonstrated satisfactory efficacy and safety for the treatment of moderate-to-severe plaque psoriasis. This analysis aimed to assess the impact of treatment interruption on the efficacy and safety of vunakizumab in the treatment of this disease.

 Methods

This post-hoc analysis used data from a phase 3 trial of vunakizumab (NCT04839016) that enrolled patients with moderate-to-severe plaque psoriasis. A total of 460 patients received vunakizumab treatment and were included in this analysis.

 Results

Over the 52-week treatment, 223 patients had one or more treatment interruption, and 237 patients had no treatment interruption. At week 52, patients with treatment interruption had lower achievement rates for Psoriasis Area and Severity Index (PASI) 75 (77.1% vs. 97.9%), PASI 90 (67.3% vs. 94.1%), PASI 100 (49.8% vs. 75.9%), and static Physician’s Global Assessment of 0/1 (62.8% vs. 93.7%) than those without interruption (all P<0.001). Additionally, at week 52, patients with treatment interruption had lower improvements in patient-reported outcomes (PROs), including Dermatology Life Quality Index score, Itch Numerical Rating Scale score, EuroQol-5D and visual analogue scale score, and Short Form-36 Mental Component Score than those without interruption (all P<0.05). Further subgroup analysis indicated that the increased frequency of treatment interruption correlated with poorer PASI responses and PROs (all P<0.05). The incidence of overall adverse events was similar between the two groups.

 Conclusion

Interrupted vunakizumab treatment reduced the clinical response and quality of life in patients with moderate-to-severe plaque psoriasis.

 moderate-to-severe plaque psoriasis vunakizumab treatment interruption efficacy safety The author(s) declared financial support was received for this work and/or its publication. Vunakizumab PsO Phase III study (NCT04839016) was funded by Jiangsu Hengrui Pharmaceuticals Co., Ltd. This post-hoc analysis did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. section-at-acceptance Autoimmune and Autoinflammatory Disorders: Autoinflammatory Disorders Introduction

Plaque psoriasis is the most common form of psoriasis, accounting for more than 80% of psoriasis cases (1). Over the last 20 years, biologics have greatly revolutionized the treatment landscape of plaque psoriasis, leading to improved treatment response and quality of life in patients with plaque psoriasis (2–6). However, biological treatment interruption occurs in some patients with plaque psoriasis (7), and interrupting these treatments is responsible for reduced efficacy (8–10). Therefore, continuously administering biologics is crucial in improving the clinical outcomes of patients with plaque psoriasis.

Among the therapeutic targets of biological agents, interleukin (IL)-17A plays a pivotal role in the pathogenesis of plaque psoriasis (11–13). IL-17A interacts with its receptor to stimulate the production of cytokines and chemokines, which further promotes hyperproliferation and alters the differentiation of keratinocytes, thereby facilitating psoriasis (11, 14, 15). Thus, inhibition of IL-17A can ameliorate psoriasis.

Vunakizumab (SHR-1314), a novel IL-17A inhibitor, has been approved for the treatment of moderate-to-severe plaque psoriasis in China (16). According to the phase 3 trial (NCT04839016), vunakizumab treatment resulted in satisfactory efficacy during 52 weeks compared to placebo with good tolerability in patients with moderate-to-severe plaque psoriasis (17). However, the impact of treatment interruption on the efficacy and safety of vunakizumab in patients with moderate-to-severe plaque psoriasis is unclear.

This post-hoc analysis extracted data from the phase 3 trial (NCT04839016) and aimed to investigate the effect of vunakizumab treatment interruption on treatment responses, patient-reported outcomes (PROs), and adverse events in patients with moderate-to-severe plaque psoriasis.

 Methods Study design and population

This was a post-hoc analysis of a randomized, double-blind, parallel, placebo-controlled, multicenter phase 3 trial (NCT04839016). In brief, 460 patients with moderate-to-severe plaque psoriasis who were treated with 52-week vunakizumab were selected. The ‘moderate-to-severe’ was defined as a psoriasis area and severity index (PASI) score of 12 or higher, a static physician’s global assessment (sPGA) score of 3 or higher, and equal to or more than 10% body surface area (BSA) affected by psoriasis. The objective of this post-hoc analysis was to assess the impact of treatment interruption on the efficacy and safety of vunakizumab in patients with moderate-to-severe plaque psoriasis. The detailed inclusion and exclusion criteria for patients with moderate-to-severe plaque psoriasis were published in the previous phase 3 trial (17). This study received ethical approval from the institutional review boards at each center.

 Treatment interruption

Treatment interruption was defined as one or more times of vunakizumab discontinuation at any time point over the 52-week treatment period, regardless of the reason. Based on this definition, patients with moderate-to-severe plaque psoriasis who had one or more times of vunakizumab discontinuation were categorized into the treatment interruption group (N=223), while patients in the continuous treatment group were those without discontinuation of vunakizumab treatment (N=237).

 Outcomes

This post-hoc analysis contained the following outcomes: (1) long-term responses at the 52nd week after treatment initiation (W52), including PASI 75, PASI 90, PASI 100, and sPGA 0/1 responses; (2) PROs at W52, including the Dermatology Life Quality Index (DLQI) score (18), DLQI 0/1 response rate, Itch Numerical Rating Scale (I-NRS) (19), EuroQol-5D (EQ-5D) utility index, EQ-5D and visual analogic scale (VAS) (Available versions | EuroQol), and Short Form-36 (SF-36) Mental Component Score (MCS) and Physical Component Score (PCS) (20); (3) adverse events.

 Subgroup analysis

To investigate how different times of treatment interruption affect the efficacy and safety of vunakizumab, patients were categorized into four subgroups based on the times of treatment interruption: 0 (n=237), 1 (n=62), 2 (n=67), and ≥3 times (n=94). The outcomes involving long-term response, PROs, and adverse events were compared among four subgroups. Furthermore, the median duration of drug exposure was 364 days. Based on this, the long-term response was further compared between patients with short (<median duration) and lengthy (≥median duration) drug exposure.

 Statistical analysis

The analyzed data were collected from the phase 3 trial (NCT04839016) (17). This post-hoc analysis was performed from August to November 2024. SPSS 29.0 (IBM, USA) was used for statistical analysis with a P<0.05 indicating statistical significance. All analyses were post-hoc and not adjusted for multiplicity. The comparison of long-term response was conducted via the χ2 test between groups or among four subgroups. The comparison of continuous variables in PROs was analyzed via student t-test between groups and ANOVA among four subgroups, while the comparison of categorical variables in PROs was analyzed via χ2 test. The comparison of adverse events between groups and among four subgroups was performed via χ2 test or Fisher’s exact test. Following adjustment for baseline variables, outcomes between the treatment interruption and continuous treatment groups were compared using analysis of covariance (ANCOVA) or multivariate logistic regression analysis.

 Results Baseline characteristics of the patients in the treatment interruption and continuous treatment groups

Age (P=0.684) and sex (P=0.423) did not differ between the two groups. However, family history of psoriasis (P=0.003), hyperlipemia (P=0.035), type II diabetes mellitus (DM) (P=0.021), PASI score (P=0.028), sPGA score (P=0.036), and SF-36 PCS (P=0.008) were different between the two groups. Other clinical features were not different between the two groups, including race, body mass index, smoking status, drinking status, DM, hypertension, hyperuricemia, disease duration, BSA score, DLQI score, I-NRS score, EQ-5D utility index score, EQ-5D VAS score, and SF-36 MCS (all P>0.05) (Table 1).

Clinical characteristics of patients with moderate-to-severe plaque psoriasis.

Characteristics Continuous treatment (N=237) Treatment interruption (N=223) P value
Age, n (%) 0.684
 <65 years 221 (93.2) 210 (94.2)
 ≥65 years 16 (6.8) 13 (5.8)
Sex, n (%) 0.423
 Female 52 (21.9) 56 (25.1)
 Male 185 (78.1) 167 (74.9)
Race, n (%)
 Asian 237 (100.0) 223 (100.0) (-)
BMI (kg/m2), mean ± SD 25.1 ± 3.5 25.6 ± 4.3 0.146
Smoking, n (%) 0.677
 Never 130 (54.9) 118 (52.9)
 Former or current 107 (45.1) 105 (47.1)
Drinking, n (%)
 No 237 (100.0) 223 (100.0) (-)
Family history of PsO, n (%) 0.003
 No 202 (85.2) 165 (74.0)
 Yes 35 (14.8) 58 (26.0)
Hypertension, n (%) 0.325
 No 195 (82.3) 191 (85.7)
 Yes 42 (17.7) 32 (14.3)
Hyperlipemia, n (%) 0.035
 No 190 (80.2) 195 (87.4)
 Yes 47 (19.8) 28 (12.6)
DM, n (%) 0.061
 No 209 (88.2) 208 (93.3)
 Yes 28 (11.8) 15 (6.7)
Type II DM, n (%) 0.021
 No 213 (89.9) 213 (98.2)
 Yes 24 (10.1) 10 (4.5)
Hyperuricemia, n (%) 0.170
 No 205 (86.5) 202 (90.6)
 Yes 32 (13.5) 21 (9.4)
Disease duration (years), mean ± SD 11.6 ± 9.8 11.7 ± 9.1 0.912
PASI score, mean ± SD 23.1 ± 9.4 21.3 ± 8.3 0.028
sPGA score, n (%) 0.036
 3 108 (45.6) 80 (35.9)
 4 110 (46.4) 120 (53.8)
 5 19 (8.0) 23 (10.3)
BSA (%), mean ± SD 35.6 ± 17.4 33.3 ± 17.2 0.081
DLQI score, mean ± SD 10.7 ± 6.6 11.8 ± 7.3 0.102
I-NRS score, mean ± SD 5.6 ± 2.4 5.6 ± 2.8 0.737
EQ-5D utility index, mean ± SD 0.9 ± 0.1 0.9 ± 0.2 0.327
EQ-5D VAS score, mean ± SD 80.7 ± 16.1 80.0 ± 16.5 0.640
SF-36 MCS, mean ± SD 48.3 ± 10.0 47.3 ± 10.5 0.292
SF-36 PCS, mean ± SD 52.2 ± 5.7 50.6 ± 6.8 0.008

BMI, body mass index; SD, standard deviation; PsO, psoriasis; DM, diabetes mellitus; PASI, psoriasis area and severity index; sPGA, static physician’s global assessment; BSA, body surface area; DLQI, dermatology life quality index; I-NRS, itch numerical rating scale; EQ-5D VAS, EuroQol-5D and visual analogic scale; SF-36, short form-36; MCS, mental component score; PCS, physical component score.

 Comparison of treatment responses at W52 between treatment interruption and continuous treatment groups

At W52, achievement rates for PASI 75 (77.1% vs. 97.9%) (P<0.001) (Figure 1A), PASI 90 (67.3% vs. 94.1%) (P<0.001) (Figure 1B), PASI 100 (49.8% vs. 75.9%) (P<0.001) (Figure 1C), and sPGA 0/1 (62.8% vs. 93.7%) (P<0.001) (Figure 1D) responses were lower in the treatment interruption group than in the continuous treatment group.

Association between vunakizumab treatment interruption and treatment responses at W52 in patients with moderate-to-severe plaque psoriasis. Association of vunakizumab treatment interruption with PASI 75 (A), PASI 90 (B), PASI 100 (C), and sPGA 0/1 (D) responses at W52 in patients with moderate-to-severe plaque psoriasis.

Bar charts labeled A to D compare response rates for continuous treatment and treatment interruption across different measures. Each chart shows significantly higher response rates for continuous treatment with P < 0.001. Chart A shows PASI 75 rates of 97.9% vs. 77.1%, B shows PASI 90 rates of 94.1% vs. 67.3%, C shows PASI 100 rates of 75.9% vs. 49.8%, and D shows SPGA 0/1 rates of 93.7% vs. 62.8%. Subgroup analysis for treatment responses

At W52, achievement rates for PASI 75 (P<0.001), PASI 90 (P<0.001), PASI 100 (P<0.001), and sPGA 0/1 (P<0.001) responses were the highest in patients without treatment interruption, followed by patients with 1 time and 2 times of treatment interruption, and the lowest in patients with ≥3 times of treatment interruption (Table 2). Subgroup analysis based on drug exposure duration showed that achievement rates for PASI 75/90/100 and sPGA 0/1 responses were higher in patients with lengthy drug exposure than those with short drug exposure (all P<0.05) (Supplementary Table 1).

Comparison of long-term response among patients with different times of treatment interruption.

Items Times of treatment interruption P value
0 (n=237) 1 (n=62) 2 (n=67) ≥3 (n=94)
PASI 75 response, n (%) <0.001
 No 5 (2.1) 6 (9.7) 10 (14.9) 35 (37.2)
 Yes 232 (97.9) 56 (90.3) 57 (85.1) 59 (62.8)
PASI 90 response, n (%) <0.001
 No 14 (5.9) 9 (14.5) 20 (29.9) 44 (46.8)
 Yes 223 (94.1) 53 (85.5) 47 (70.1) 50 (53.2)
PASI 100 response, n (%) <0.001
 No 57 (24.1) 22 (35.5) 31 (46.3) 59 (62.8)
 Yes 180 (75.9) 40 (64.5) 36 (53.7) 35 (37.2)
sPGA 0/1 response, n (%) <0.001
 No 15 (6.3) 13 (21.0) 21 (31.3) 49 (52.1)
 Yes 222 (93.7) 49 (79.0) 46 (68.7) 45 (47.9)

PASI, psoriasis area and severity index; sPGA, static physician’s global assessment.

 Comparison of PROs at W52 between treatment interruption and continuous treatment groups

At W52, the mean DLQI score was higher in the treatment interruption group than in the continuous treatment group (2.0 ± 3.9 vs. 1.2 ± 2.2) (P=0.012) (Figure 2A). However, achievement rates for DLQI 0/1 did not differ between the two groups (73.3% vs. 79.4%) (P=0.140) (Figure 2B). Similarly, the mean I-NRS score was higher in the treatment interruption group than in the continuous treatment group (1.2 ± 1.7 vs. 0.8 ± 1.2) (P<0.001) (Figure 2C). The mean EQ-5D utility index score did not differ between the two groups (1.0 ± 0.1 vs. 1.0 ± 0.0) (P=0.121) (Figure 2D). Additionally, the mean EQ-5D VAS score (91.2 ± 9.2 vs. 93.4 ± 6.9) (P=0.008) (Figure 2E) and SF-36 MCS (53.5 ± 7.6 vs. 55.4 ± 6.2) (P=0.008) (Figure 2F) were lower in the treatment interruption group than in the continuous treatment group. Nevertheless, the mean SF-36 PCS was not different between the two groups (55.5 ± 5.7 vs. 55.9 ± 4.3) (P=0.444) (Figure 2G).

Association between vunakizumab treatment interruption and PROs at W52 in patients with moderate-to-severe plaque psoriasis. Association of vunakizumab treatment interruption with DLQI score (A), DLQI 0/1 response (B), I-NRS score (C), EQ-5D utility index score (D), EQ-5D VAS score (E), SF-36 MCS (F), and SF-36 PCS (G) in patients with moderate-to-severe plaque psoriasis.

Bar graphs comparing continuous treatment and treatment interruption groups across various scores. (A) DLQI score shows significant difference (P = 0.012). (B) DLQI response rate not significant (P = 0.140). (C) I-NRS score significant (P < 0.001). (D) EQ-5D utility index not significant (P = 0.121). (E) EQ-5D VAS score significant (P = 0.008). (F) SF-36 MCS significant (P = 0.008). (G) SF-36 PCS not significant (P = 0.444). Data includes mean and standard deviation. Continuous treatment is maroon, treatment interruption is teal. Subgroup analysis for PROs

At W52, the mean DLQI score showed an increasing trend with the increase in times of treatment interruption (P<0.001), and achievement rates for DLQI 0/1 showed a decreasing trend (P=0.007). The mean EQ-5D utility index score (P=0.037), EQ-5D VAS score (P<0.001), and SF-36 MCS (P=0.002) and PCS (P=0.003) at W52 gradually decreased with the increment in times of treatment interruption (Table 3).

Comparison of PROs among patients with different times of treatment interruption.

Items Times of treatment interruption P value
0 (n=237) 1 (n=62) 2 (n=67) ≥3 (n=94)
DLQI score, mean ± SD 1.2 ± 2.2 0.9 ± 1.6 1.5 ± 2.7 3.2 ± 5.4 <0.001
DLQI 0/1 response, n (%) 0.007
 No 48 (20.6) 8 (13.6) 16 (27.1) 27 (37.0)
 Yes 185 (79.4) 51 (86.4) 43 (72.9) 46 (63.0)
I-NRS score, mean ± SD 0.8 ± 1.2 0.7 ± 1.0 1.3 ± 1.8 1.6 ± 2.0 <0.001
EQ-5D utility index, mean ± SD 1.0 ± 0.0 1.0 ± 0.0 1.0 ± 0.1 1.0 ± 0.1 0.037
EQ-5D VAS score, mean ± SD 93.4 ± 6.9 93.1 ± 8.1 92.7 ± 7.5 88.5 ± 10.7 <0.001
SF-36 MCS, mean ± SD 55.4 ± 6.2 54.8 ± 6.2 54.3 ± 8.5 51.9 ± 7.7 0.002
SF-36 PCS, mean ± SD 55.9 ± 4.3 56.4 ± 5.0 56.6 ± 4.9 53.8 ± 6.5 0.003

PROs, patient-reported outcomes; DLQI, dermatology life quality index; I-NRS, itch numerical rating scale; EQ-5D VAS, EuroQol-5D and visual analogic scale; SF-36, short form-36; MCS, mental component score; PCS, physical component score.

 Comparison of adverse events between treatment interruption and continuous treatment groups

The incidence of any adverse events was not different between the two groups (88.2% vs. 87.4%) (P=0.808). However, the incidence of hyperuricemia (13.5% vs. 24.1%) (P=0.004) and hyperlipidemia (9.9% vs. 16.5%) (P=0.037) was lower in the treatment interruption group than in the continuous treatment group. The incidence of elevated blood glucose (14.3% vs. 3.4%) (P<0.001) was higher in the treatment interruption group than in the continuous treatment group (Table 4).

Adverse events.

Events, n (%) Continuous treatment (N=237) Treatment interruption (N=223) P value
Any 209 (88.2) 195 (87.4) 0.808
Hyperuricemia 57 (24.1) 30 (13.5) 0.004
URTI 47 (19.8) 54 (24.2) 0.256
Hyperlipidemia 39 (16.5) 22 (9.9) 0.037
Injection site reaction 23 (9.7) 27 (12.1) 0.408
Elevated ALT 20 (8.4) 31 (13.9) 0.062
Eczema 17 (7.2) 10 (4.5) 0.220
Elevated blood bilirubin 16 (6.8) 11 (4.9) 0.407
Pruritus 15 (6.3) 11 (4.9) 0.517
Urticaria 11 (4.6) 17 (7.6) 0.181
Elevated AST 10 (4.2) 14 (6.3) 0.321
Elevated blood glucose 8 (3.4) 32 (14.3) <0.001

URTI, upper respiratory tract infection; ALT, alanine aminotransferase; AST, aspartate aminotransferase.

 Subgroup analysis for adverse events

The incidence of any adverse events was not affected by different times of treatment interruption (P=0.376). The incidence of hyperuricemia, hyperlipidemia, elevated aspartate aminotransferase (AST), and elevated blood glucose differed by different times of treatment interruption (all P<0.05) (Supplementary Table 2).

 Comparisons of efficacy and safety between treatment interruption and continuous treatment groups after adjusting for baseline variables

Regarding treatment response, treatment interruption (vs. continuous treatment) was independently related to a lower probability of achieving PASI 75, PASI 90, PASI 100, and sPGA 0/1 responses at W52 (all P<0.001). Regarding PROs, treatment interruption (vs. continuous treatment) was independently related to a higher I-NRS score at W52 (P=0.026). Regarding adverse events, treatment interruption (vs. continuous treatment) was not related to any adverse events (P=0.197) (Supplementary Table 3).

 Factors contributing to treatment interruption

The Coronavirus Disease-19 (COVID-19) epidemic was the major reason for treatment interruption. Specifically, 90.3%, 94.0%, and 84.0% of patients experienced 1, 2, and ≥3 times of treatment interruption, respectively, due to the COVID-19 epidemic. Additionally, 6.5%, 10.4%, and 24.5% of patients experienced 1, 2, and ≥3 times of treatment interruption, respectively, due to adverse events. A total of 11.3%, 22.4%, and 16.0% of patients experienced 1, 2, and ≥3 times of treatment interruption, respectively, due to other reasons (Supplementary Table 4).

 Discussion

Recently, several studies have focused on the impact of biological treatment interruption on treatment response in patients with moderate-to-severe plaque psoriasis (8–10, 21, 22). As reported by a previous study, at W52, achievement rates for sPGA 0/1, PASI 75, PASI 90, and PASI 100 responses were lower in patients with moderate-to-severe plaque psoriasis with risankizumab treatment interruption than those without interruption (8). Another study reported that achievement rates for Investigator Global Assessment score of 0 (IGA 0), IGA 0/1, PASI 75, PASI 90, and PASI 100 responses were decreased in patients with moderate-to-severe plaque psoriasis with guselkumab treatment interruption compared to those without interruption (9). Moreover, achievement rates for PASI 90 response at W56 were lower in patients with moderate-to-severe plaque psoriasis with bimekizumab treatment interruption than those without interruption (10). In line with these previous studies (8–10), the current study discovered that achievement rates for PASI 75, PASI 90, PASI 100, and sPGA 0/1 responses at W52 were lower in patients with moderate-to-severe plaque psoriasis with vunakizumab treatment interruption than those without interruption. Our findings revealed that vunakizumab treatment interruption had an adverse impact on skin clearance in patients with moderate-to-severe plaque psoriasis.

PROs are essential in assessing the efficacy of treatments, which encompass various dimensions of patients’ perceptions, including quality of life, symptoms, physical function, and mental health (23–25). The effect of biological treatment interruption on PROs in patients with moderate-to-severe plaque psoriasis has been investigated in some previous studies (9, 26). For instance, a previous study reported that tofacitinib treatment interruption was related to worse quality of life and pruritus, as evidenced by increased Itch Severity Item scores and DLQI scores in patients with moderate-to-severe plaque psoriasis (26). Another study claimed that improvements in DLQI score and Psoriasis Symptoms and Signs Diary symptoms or sign scores were smaller in patients with moderate-to-severe plaque psoriasis with guselkumab treatment interruption than those without interruption (9). In accordance with the findings of these previous studies (9, 26), we also discovered that PROs were worse in patients with moderate-to-severe plaque psoriasis with vunakizumab treatment interruption compared to those without interruption, as evidenced by increased DLQI score and I-NRS score, as well as decreased EQ-5D VAS score and SF-36 MCS. Our findings indicated that vunakizumab treatment interruption might impair quality of life, worsen pruritus symptoms, and decrease mental health in patients with moderate-to-severe plaque psoriasis.

Biologics show tolerable safety profiles for the treatment of moderate-to-severe plaque psoriasis (27–29). However, rare studies explored the impact of treatment interruption on the safety profiles of biologics in patients with moderate-to-severe plaque psoriasis. In this study, we found that the incidence of any adverse events (88.2% vs. 87.4%) did not differ between patients with vunakizumab treatment interruption and those without interruption. Nevertheless, analysis of individual adverse events revealed that the incidence of some specific events was different between patients with and without vunakizumab interruption, including hyperuricemia, hyperlipidemia, and elevated blood glucose. The potential reason might be that, in this study, patients were interrupted vunakizumab due to the COVID-19 pandemic, adverse events, and others; the interruption of vunakizumab affected the drug exposure, leading to the different incidence of these specific adverse events.

Subgroup analyses for treatment responses, PROs, and adverse events based on the times of vunakizumab treatment interruption in patients with moderate-to-severe plaque psoriasis were further conducted. Regarding efficacy, the increased frequency of vunakizumab treatment interruption was related to poor treatment response and PROs in patients with moderate-to-severe plaque psoriasis. Regarding safety, the incidence of any adverse events was not affected, but the incidence of some detailed adverse events was influenced by different frequencies of vunakizumab treatment interruption in patients with moderate-to-severe plaque psoriasis. Therefore, patients with moderate-to-severe plaque psoriasis should decrease the frequency of vunakizumab treatment interruption.

We observed that COVID-19 was the major reason for treatment interruption in patients with moderate-to-severe plaque psoriasis receiving vunakizumab. This finding was in line with a previous study (30). Based on this information, we speculated that during the COVID-19 pandemic, due to the safety considerations regarding the use of biologics (i.e., patients’ ability to fight infection), vunakizumab was interrupted, which led to less drug exposure over time, ultimately impairing the efficacy of vunakizumab in patients with treatment interruption.

This study contained several limitations. (1) The follow-up period was 52 weeks in the phase 3 trial. Considering that patients with moderate-to-severe plaque psoriasis require lifelong treatment, studies with long-term follow-up duration should be performed to validate the effect of treatment interruption on the efficacy and safety of vunakizumab in patients with moderate-to-severe plaque psoriasis. (2) Baseline features, including family history of psoriasis, hyperlipemia, PASI score, sPGA score, and SF-36 PCS, were unbalanced between the two groups, which might affect the findings of this study. (3) The generalizability of our findings should be further validated due to various reasons, such as strict patient selection in the phase 3 trial and the study region. (4) Further study could consider applying another grouping method, such as categorizing patients into ≤2, 3, 4, and ≥5 interruptions, to provide a deeper understanding of the impact of drug interruption frequencies on the efficacy and safety of vunakizumab.

In conclusion, vunakizumab treatment interruption contributes to poor treatment responses and quality of life in patients with moderate-to-severe plaque psoriasis. In clinical practice, the decision to interrupt vunakizumab treatment should be carefully deliberated, and patients with moderate-to-severe plaque psoriasis should be encouraged to maintain vunakizumab treatment.

 Data availability statement

The original contributions presented in the study are included in the article/Supplementary Material, further inquiries can be directed to the corresponding author/s.

 Ethics statement

The studies involving humans were approved by institutional review boards at each center. The studies were conducted in accordance with the local legislation and institutional requirements. The participants provided their written informed consent to participate in this study.

 Author contributions

QL: Data curation, Formal Analysis, Investigation, Writing – original draft. WY: Data curation, Formal Analysis, Methodology, Resources, Writing – original draft. DL: Data curation, Formal Analysis, Investigation, Methodology, Writing – original draft. YX: Data curation, Formal Analysis, Resources, Visualization, Writing – original draft, Writing – review & editing. LZ: Data curation, Investigation, Methodology, Writing – original draft. ZZ: Data curation, Formal Analysis, Methodology, Resources, Visualization, Writing – original draft. JH: Data curation, Formal Analysis, Investigation, Validation, Visualization, Writing – review & editing. TG: Data curation, Formal Analysis, Investigation, Methodology, Resources, Writing – original draft, Writing – review & editing. JL: Conceptualization, Resources, Supervision, Validation, Writing – review & editing.

 Conflict of interest

The author(s) declared that the study was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

The authors declare that this study received funding from Jiangsu Hengrui Pharmaceuticals Co., Ltd. The funder was involved in the decision to submit this article for publication but was not involved in the study design, data collection, data analysis, or the writing of the manuscript.

 Generative AI statement

The author(s) declare that no Generative AI was used in the creation of this manuscript.

Any alternative text (alt text) provided alongside figures in this article has been generated by Frontiers with the support of artificial intelligence and reasonable efforts have been made to ensure accuracy, including review by the authors wherever possible. If you identify any issues, please contact us.

 Publisher’s note

All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.

 Supplementary material

The Supplementary Material for this article can be found online at: https://www.frontiersin.org/articles/10.3389/fimmu.2025.1639049/full#supplementary-material

 References Griffiths CEM Armstrong AW Gudjonsson JE Barker J . Psoriasis. Lancet. (2021) 397:1301–15. doi: 10.1016/S0140-6736(20)32549-6, PMID: 33812489 Armstrong AW Read C . Pathophysiology, clinical presentation, and treatment of psoriasis: A review. JAMA. (2020) 323:1945–60. doi: 10.1001/jama.2020.4006, PMID: 32427307 Coates LC Soriano ER Corp N Bertheussen H Callis Duffin K Campanholo CB . Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA): updated treatment recommendations for psoriatic arthritis 2021. Nat Rev Rheumatol. (2022) 18:465–79. doi: 10.1038/s41584-022-00798-0, PMID: 35761070 Wride AM Chen GF Spaulding SL Tkachenko E Cohen JM . Biologics for psoriasis. Dermatol Clin. (2024) 42:339–55. doi: 10.1016/j.det.2024.02.001, PMID: 38796266 Reid C Griffiths CEM . Psoriasis and treatment: past, present and future aspects. Acta Derm Venereol. (2020) 100:adv00032. doi: 10.2340/00015555-3386, PMID: 31971601 Lee HJ Kim M . Challenges and future trends in the treatment of psoriasis. Int J Mol Sci. (2023) 24:13313. doi: 10.3390/ijms241713313, PMID: 37686119 Wang CY Foley P Baker C Rademaker M . Biological therapy interruption and re-treatment in chronic plaque psoriasis. J Drugs Dermatol. (2021) 20:1063–71. doi: 10.36849/JDD.5716, PMID: 34636525 Blauvelt A Leonardi CL Gooderham M Papp KA Philipp S Wu JJ . Efficacy and safety of continuous risankizumab therapy vs treatment withdrawal in patients with moderate to severe plaque psoriasis: A phase 3 randomized clinical trial. JAMA Dermatol. (2020) 156:649–58. doi: 10.1001/jamadermatol.2020.0723, PMID: 32267471 Reich K Armstrong AW Foley P Song M Wasfi Y Randazzo B . Efficacy and safety of guselkumab, an anti-interleukin-23 monoclonal antibody, compared with adalimumab for the treatment of patients with moderate to severe psoriasis with randomized withdrawal and retreatment: Results from the phase III, double-blind, placebo- and active comparator-controlled VOYAGE 2 trial. J Am Acad Dermatol. (2017) 76:418–31. doi: 10.1016/j.jaad.2016.11.042, PMID: 28057361 Gordon KB Foley P Krueger JG Pinter A Reich K Vender R . Bimekizumab efficacy and safety in moderate to severe plaque psoriasis (BE READY): a multicentre, double-blind, placebo-controlled, randomised withdrawal phase 3 trial. Lancet. (2021) 397:475–86. doi: 10.1016/S0140-6736(21)00126-4, PMID: 33549192 Ghoreschi K Balato A Enerback C Sabat R . Therapeutics targeting the IL-23 and IL-17 pathway in psoriasis. Lancet. (2021) 397:754–66. doi: 10.1016/S0140-6736(21)00184-7, PMID: 33515492 Brembilla NC Senra L Boehncke WH . The IL-17 family of cytokines in psoriasis: IL-17A and beyond. Front Immunol. (2018) 9:1682. doi: 10.3389/fimmu.2018.01682, PMID: 30127781 Furue M Furue K Tsuji G Nakahara T . Interleukin-17A and keratinocytes in psoriasis. Int J Mol Sci. (2020) 21:1275. doi: 10.3390/ijms21041275, PMID: 32070069 Guo J Zhang H Lin W Lu L Su J Chen X . Signaling pathways and targeted therapies for psoriasis. Signal Transduct Target Ther. (2023) 8:437. doi: 10.1038/s41392-023-01655-6, PMID: 38008779 Man AM Orasan MS Hoteiuc OA Olanescu-Vaida-Voevod MC Mocan T . Inflammation and psoriasis: A comprehensive review. Int J Mol Sci. (2023) 24:16095. doi: 10.3390/ijms242216095, PMID: 38003284 Keam SJ . Vunakizumab: first approval. Drugs. (2024) 84:1481–5. doi: 10.1007/s40265-024-02110-8, PMID: 39497021 Yan K Li F Bi X Han L Zhang Z Chen R . Efficacy and safety of vunakizumab in moderate-to-severe chronic plaque psoriasis: A randomized, double-blind, placebo-controlled phase 3 trial. J Am Acad Dermatol. (2025) 92:92–9. doi: 10.1016/j.jaad.2024.09.031, PMID: 39332633 Finlay AY Khan GK . Dermatology Life Quality Index (DLQI)–a simple practical measure for routine clinical use. Clin Exp Dermatol. (1994) 19:210–6. doi: 10.1111/j.1365-2230.1994.tb01167.x, PMID: 8033378 Stander S Zeidler C Pereira M Szepietowski JC McLeod L Qin S . Worst itch numerical rating scale for prurigo nodularis: a psychometric evaluation. J Eur Acad Dermatol Venereol. (2022) 36:573–81. doi: 10.1111/jdv.17870, PMID: 34908192 Laucis NC Hays RD Bhattacharyya T . Scoring the SF-36 in orthopaedics: A brief guide. J Bone Joint Surg Am. (2015) 97:1628–34. doi: 10.2106/JBJS.O.00030, PMID: 26446970 Gao X Pan W Zheng M Li F Dong X Lv D . Efficacy and safety analysis in Chinese patients with moderate-to-severe psoriasis from a phase 3 trial: impact of treatment withdrawal and retreatment of ixekizumab. Adv Ther. (2025) 42:334–47. doi: 10.1007/s12325-024-03030-5, PMID: 39535685 Bissonnette R Iversen L Sofen H Griffiths CE Foley P Romiti R . Tofacitinib withdrawal and retreatment in moderate-to-severe chronic plaque psoriasis: a randomized controlled trial. Br J Dermatol. (2015) 172:1395–406. doi: 10.1111/bjd.13551, PMID: 25418186 Perez-Chada LM Hopkins ZH Balak DMW Rashid S Creadore A Chu B . Patient-reported outcome measures for health-related quality of life in patients with psoriasis: A systematic review. JAMA Dermatol. (2024) 160:550–63. doi: 10.1001/jamadermatol.2023.5439, PMID: 38265774 Otuki MF Reis RC Cabrini D Prudente AS Horinouchi CD Correr CJ . Patient-reported outcomes in psoriasis research and practice. Br J Dermatol. (2011) 165:1361–2. doi: 10.1111/j.1365-2133.2011.10469.x, PMID: 21692769 Kitchen H Cordingley L Young H Griffiths CE Bundy C . Patient-reported outcome measures in psoriasis: the good, the bad and the missing! Br J Dermatol. (2015) 172:1210–21. doi: 10.1111/bjd.13691, PMID: 25677764 Griffiths CE Vender R Sofen H Kircik L Tan H Rottinghaus ST . Effect of tofacitinib withdrawal and re-treatment on patient-reported outcomes: results from a Phase 3 study in patients with moderate to severe chronic plaque psoriasis. J Eur Acad Dermatol Venereol. (2017) 31:323–32. doi: 10.1111/jdv.13808, PMID: 27600367 Kamata M Tada Y . Efficacy and safety of biologics for psoriasis and psoriatic arthritis and their impact on comorbidities: A literature review. Int J Mol Sci. (2020) 21:1690. doi: 10.3390/ijms21051690, PMID: 32121574 Al-Janabi A Yiu ZZN . Biologics in psoriasis: updated perspectives on long-term safety and risk management. Psoriasis (Auckl). (2022) 12:1–14. doi: 10.2147/PTT.S328575, PMID: 35024352 Kamata M Tada Y . Safety of biologics in psoriasis. J Dermatol. (2018) 45:279–86. doi: 10.1111/1346-8138.14096, PMID: 29226369 Jiang J Zhang M Li M . Impact of treatment interruption on the effectiveness of interleukin (IL)-17A inhibitors in plaque psoriasis: A retrospective analysis. Int J Gen Med. (2025) 18:1681–90. doi: 10.2147/IJGM.S515389, PMID: 40161451

Edited by: Arturo Borzutzky, Pontificia Universidad Católica de Chile, Chile

Reviewed by: Kexiang Yan, Fudan University, China

Thierry Sornasse, AbbVie (United States), United States