Abstract
Background:
Guselkumab is effective in treating moderate-to-severe plaque psoriasis; however, data from randomized controlled trials in the Chinese population are limited. This study evaluated and verified the efficacy and safety profile of guselkumab in Chinese patients with moderate-to-severe plaque psoriasis.
Methods:
This was a randomized, double-blind, placebo-controlled, phase 4 study. Patients with moderate-to-severe plaque psoriasis were randomized 2:1 to the guselkumab group (guselkumab 100 mg by subcutaneous injection at weeks 0 and 4, then every 8 weeks thereafter through week 44) or the placebo-to-guselkumab group (placebo at weeks 0, 4, and 12, then guselkumab at weeks 16, 20, 28, 36, and 44). Coprimary efficacy endpoints were the proportion of patients achieving Psoriasis Area and Severity Index (PASI) 90 response and the proportion of patients achieving Investigator’s Global Assessment (IGA) 0/1 response at week 16.
Results:
Among the 419 patients screened for eligibility between August 25, 2021, and July 21, 2022, 327 patients were enrolled. All 327 randomized patients (mean age, 41.5 [standard deviation, 12.7] years; 259 [79.2%] men) were treated and included in the analyses. At week 16, 103/110 patients assigned to the placebo group at baseline started guselkumab treatment. Most patients completed the study (210 in guselkumab group and 101 in placebo-to-guselkumab group). Significantly higher proportions of patients with guselkumab achieved PASI 90 (82.4% vs. 2.0%; P <0.001) and IGA score 0/1 (88.8% vs. 7.1%; P <0.001) compared with placebo at week 16. At week 48, response rates were maintained in the guselkumab group (PASI 90: 79.2%; IGA 0/1: 82.4%) and increased in the placebo-to-guselkumab group (PASI 90: 80.2%; IGA 0/1: 86.3%). During the first 16 weeks, the incidence of adverse events was comparable between groups (41.9% guselkumab vs. 39.1% placebo) and the incidence of serious adverse events was low (0.9% vs. 5.5%), respectively.
Conclusion:
Guselkumab was highly effective and displayed a favorable safety profile for the treatment of moderate-to-severe plaque psoriasis in Chinese patients.
Clinical trial registration:
Keywords: Guselkumab, Moderate-to-severe plaque psoriasis, Psoriasis Area and Severity Index, Investigator’s Global Assessment, Chinese
Introduction
Psoriasis is a chronic, immune-mediated inflammatory skin disease,[1] with a prevalence that varies across geographic locations.[2–5] In China, the prevalence of psoriasis has increased from 0.16% in 1984 to 0.47% in 2008.[6,7] The age-standardized prevalence rate was estimated to be 474 per 100,000 people in 2021, and the prevalence rate of psoriasis was lower in women than in men.[8] Furthermore, the incidence and prevalence of psoriasis in China are expected to continue to increase in the next decades.[8] The most common subtype is plaque psoriasis, accounting for 80–90% of cases.[9] Although plaque psoriasis is not a life-threatening condition, psoriatic skin lesions can cause pain, itching, and bleeding, and have a markedly negative impact on patients’ overall health-related quality of life.[10] In addition, more than one-third of Chinese patients with psoriasis had severe disease according to the Psoriasis Area and Severity Index (PASI).[11]
Although topical therapy is typically the first-line treatment for mild psoriasis, conventional systemic therapies, including methotrexate, acitretin, and cyclosporine, can be effective for patients with moderate-to-severe psoriasis. However, long-term administration of these agents can be associated with significant toxicities.[12,13] Within the past few decades, substantial improvements in treatment options for moderate-to-severe psoriasis have been achieved through the development of biologic therapies. Four classes of biologics are currently recommended by treatment guidelines[14,15]: tumor necrosis factor-alpha inhibitors (infliximab, adalimumab, and etanercept); an interleukin (IL)-12/23 antagonist (ustekinumab); IL-17A inhibitors (secukinumab, ixekizumab, and brodalumab); and IL-23 inhibitors (guselkumab, tildrakizumab, and risankizumab).
Guselkumab is a human monoclonal antibody directed against the p19 subunit of IL-23[16] that was included in the clinically urgently needed new drugs list issued by the National Medical Products Administration in 2018 and received conditional approval for the treatment of plaque psoriasis in China in 2019 based on results from global studies.[17–19] At the time of approval, however, no data from randomized controlled trials conducted in a Chinese population with moderate-to-severe plaque psoriasis were available. Long-term data on the efficacy and safety of guselkumab from randomized controlled trials in Chinese patients with plaque psoriasis are limited. Therefore, a postapproval commitment phase 4 study is crucial to further evaluate and verify the treatment efficacy of guselkumab in a Chinese population. This manuscript presents efficacy, safety, pharmacokinetics, and immunogenicity data for guselkumab in Chinese patients with moderate-to-severe plaque psoriasis.
Methods
Study design and patients
This was a randomized, double-blind, placebo-controlled, parallel-group, phase 4 study (NCT04914429) conducted at 26 hospitals in China. Adults (≥18 years of age) diagnosed with moderate-to-severe plaque psoriasis for at least 6 months before screening and eligible for systemic therapy or phototherapy for psoriasis were enrolled. Key eligibility criteria included a PASI score of ≥12, an Investigator’s Global Assessment (IGA) score of ≥3, involved body surface area of ≥10% during screening and at baseline, and screening laboratory test results within the protocol-defined ranges. Patients were excluded if they had a nonplaque form of psoriasis (e.g., erythrodermic, guttate, or pustular); a history of malignancy within 5 years before screening; and a history of, or ongoing, chronic or recurrent infectious disease. A complete list of inclusion and exclusion criteria is provided in the Supplementary Material, http://links.lww.com/CM9/C576.
Patients were randomized to the guselkumab group or the placebo-to-guselkumab group at a 2:1 ratio with a permuted block randomization method. Central randomization was implemented using an interactive web response system. As shown in Figure 1A, patients assigned to the guselkumab group received guselkumab 100 mg by subcutaneous injection at weeks 0 and 4, and then every 8 weeks thereafter through week 44. At week 16, patients initially randomized to the guselkumab group received a placebo to maintain the blind and to not reveal their previous treatment. Patients assigned to the placebo-to-guselkumab group received placebo at weeks 0, 4, and 12, and then crossed over to receive guselkumab 100 mg at weeks 16 and 20, and then every 8 weeks thereafter through week 44. Patients, investigators, and the clinical study team remained blinded to group assignments until the final database lock.
Figure 1.
Study design (A) and trial profile (B) for guselkumab in Chinese patients with moderate-to-severe plaque psoriasis. CO: Placebo crossover; DBL: Database lock; D/C: Discontinued; PE: Primary endpoint; R: Randomization; SE: Secondary endpoint.
This study was conducted in accordance with the principles that originated in the Declaration of Helsinki and Good Clinical Practices. The protocol and all amendments were approved by an Independent Ethics Committee/Institutional Review Board before implementation (The protocol was approved by the Ethics Committee of The Second Affiliated Hospital, Zhejiang University School of Medicine [No. 2021-Lun-Shen-Yao-047), with the final amendment approved under Approval No. 2023-Yao-0665). All patients provided informed consent.
Endpoints and assessments
The coprimary efficacy endpoints were the proportion of patients who achieved PASI 90 at week 16 and the proportion of patients who achieved IGA 0/1 (clear/minimal) at week 16, as one of the treatment goals for psoriasis is to achieve clear/almost clear of skin symptoms.[20]
Key secondary endpoints included the proportions of patients who achieved PASI 100 and PASI 75 at week 16 and over time; the proportion of patients who achieved PASI 90 over time; the proportion of patients who maintained PASI 90 response at week 48 among those who were PASI 90 responders at week 16 in the guselkumab group; the proportions of patients who achieved IGA 0 and IGA ≤2 at week 16 and over time; the proportion of patients who achieved IGA 0/1 over time; the proportion of patients who maintained IGA score of 0/1 at week 48 among those who achieved IGA score 0/1 at week 16 in the guselkumab group; the percent improvement from baseline in the Nail PASI (NAPSI) score at week 16 and over time among patients with nail psoriasis at baseline; the proportions of patients with a scalp-specific IGA (ss-IGA) score of 0/1 at week 16 and over time among patients with scalp psoriasis and an ss-IGA score ≥2 at baseline; the change from baseline in Dermatology Life Quality Index (DLQI) score at week 16 and over time; the proportion of patients who achieved a DLQI score of 0/1 at week 16 and over time among patients with a baseline DLQI score >1; and the proportion of patients with a reduction of ≥5 points in DLQI score at week 16 and over time. Safety was monitored from screening to 12 weeks after the last administration of study treatment. The severity of adverse events (AEs) was graded using the Common Terminology Criteria for Adverse Events version 5.0. Serum guselkumab concentrations and incidence of antibodies to guselkumab were evaluated with validated methods for guselkumab-treated patients.
Statistical analysis
To compare the efficacy of guselkumab with placebo, a total of approximately 300 patients randomized at a 2:1 ratio to receive guselkumab or placebo would yield power exceeding 99% to detect significant differences for both coprimary endpoints at a two-tailed level significance of 0.05, assuming the response rates of PASI 90 and IGA 0/1 at week 16 were 5% and 10% in the placebo group and 69% and 84% in the guselkumab group, respectively. A sample size of 300 would provide sufficient probability (>95%) to detect at least one potentially important AE with an occurrence rate of ≥1%.
The full analysis set (FAS), which included all randomized patients according to their treatment assignment, was used for efficacy analyses. Safety analyses were performed according to the actual intervention received during the study in the safety analysis set, which included patients who had at least one dose of study treatment. The pharmacokinetics analysis set included guselkumab-treated patients who received at least one complete dose of guselkumab and had at least one valid post-dose blood sample drawn for pharmacokinetic analysis. The immunogenicity analysis set included guselkumab-treated patients who had appropriate samples for the detection of anti-drug antibodies. The coprimary endpoints were tested at a two-sided α level of 0.05 using Pearson’s chi-squared tests. If one of the comparisons had not been significant at the two-sided α level of 0.05, the coprimary endpoints would have been considered not significant. The analyses on secondary endpoints were performed using descriptive statistics. The results of binary endpoints were presented by the average proportion of subjects with response over the 200 multiple imputation datasets.
All statistical analyses were performed using SAS version 9.4 (SAS Institute Inc, Cary, NC, USA).
Results
Patients
Among the 419 patients screened for eligibility between August 25, 2021, and July 21, 2022, 327 patients were enrolled and randomized (FAS), all of whom received at least one dose of study drug (217 guselkumab and 110 placebo; safety analysis set) [Figure 1B]. At week 16, 103 of 110 (93.6%) patients randomized to the placebo group at week 0 crossed over to receive guselkumab. Most patients completed the 56-week study, including 210 patients in the guselkumab group and 101 patients in the placebo-to-guselkumab group. The data cutoff date was September 26, 2023. Demographic and disease characteristics at baseline were generally comparable between the groups and were representative of a population with moderate-to-severe psoriasis [Table 1].
Table 1.
Demographic and disease characteristics at baseline (FAS) in Chinese patients with moderate-to-severe plaque psoriasis.
| Items | Placebo (n = 110) | Guselkumab (n = 217) | Total (n = 327) |
|---|---|---|---|
| Age (years), mean (SD) | 41.4 (13.0) | 41.6 (12.6) | 41.5 (12.7) |
| Male | 89 (80.9) | 170 (78.3) | 259 (79.2) |
| BMI (kg/m2), mean (SD) | 25.8 (3.9) | 25.3 (4.1) | 25.4 (4.0) |
| Duration of psoriasis (years), mean (SD) | 10.6 (8.5) | 12.4 (9.8) | 11.8 (9.4) |
| Body surface area involvement (%), mean (SD) | 36.0 (19.6) | 35.0 (19.7) | 35.3 (19.6) |
| IGA score | |||
| Mild (2) | 1 (0.9) | 0 | 1 (0.3) |
| Moderate (3) | 78 (70.9) | 166 (76.5) | 244 (74.6) |
| Severe (4) | 31 (28.2) | 51 (23.5) | 82 (25.1) |
| PASI score, mean (SD) | 23.9 (9.4) | 23.9 (10.6) | 23.9 (10.2) |
| NAPSI score, mean (SD)* | 4.2 (2.2) | 4.1 (2.2) | 4.1 (2.2) |
| ss-IGA score | |||
| Absence of disease (0) | 2 (1.8) | 8 (3.7) | 10 (3.1) |
| Very mild disease (1) | 3 (2.7) | 10 (4.6) | 13 (4.0) |
| Mild disease (2) | 27 (24.5) | 42 (19.4) | 69 (21.1) |
| Moderate disease (3) | 56 (50.9) | 117 (53.9) | 173 (52.9) |
| Severe disease (4) | 22 (20.0) | 40 (18.4) | 62 (19.0) |
| Psoriatic arthritis | 12 (10.9) | 23 (10.6) | 35 (10.7) |
| Prior treatments | |||
| Topical agents | 92 (83.6) | 195 (89.9) | 287 (87.8) |
| Phototherapy | 20 (18.2) | 66 (30.4) | 86 (26.3) |
| Conventional systemic agents | 27 (24.5) | 90 (41.5) | 117 (35.8) |
| Biologic agents | 5 (4.5) | 14 (6.5) | 19 (5.8) |
| DLQI score, mean (SD) | 14.9 (7.3) | 15.4 (7.7) | 15.2 (7.5) |
Values are reported as n (%) unless otherwise indicated. *Among patients who had a NAPSI score of >0 at baseline (78 patients in the placebo group and 158 patients in the guselkumab group), the mean (SD) NAPSI score was 4.3 (2.1) and 4.2 (2.1), respectively. BMI: Body mass index; DLQI: Dermatology Life Quality Index; FAS: Full analysis set; IGA: Investigator Global Assessment; NAPSI: Nail Psoriasis Area and Severity Index; PASI: Psoriasis Area and Severity Index; SD: Standard deviation; ss-IGA: Scalp-specific Investigator’s Global Assessment.
Clinical response
Guselkumab was superior to placebo for the coprimary endpoints. Significantly higher proportions of patients in the guselkumab group achieved PASI 90 (82.4% vs. 2.0%; P <0.001) and IGA 0/1 (88.8% vs. 7.1%; P <0.001) responses compared with the placebo group at week 16 [Table 2 and Figure 2]. As shown in Figure 2, separation of the response curves for the treatment groups occurred as early as week 4 and the differences continued to increase through week 16. Consistent results were seen in the predefined subgroup analyses by baseline and disease characteristics, including sex and previous psoriasis medication history [Supplementary Figures 1 and 2, http://links.lww.com/CM9/C576].
Table 2.
Efficacy findings at weeks 16 and 48 (FAS) in Chinese patients with moderate-to-severe plaque psoriasis.
| Items | Week 16 | Week 48 | ||
|---|---|---|---|---|
| Placebo (n = 110) | Guselkumab (n = 217) | Placebo-to-guselkumab (n = 103) | Guselkumab (n = 217) | |
| PASI response | ||||
| PASI 100 (%)*,† | 0.1 | 47.9 | 45.9 | 60.1 |
| PASI 90 (%)*,‡ | 2.0 | 82.4 | 80.2 | 79.2 |
| PASI 75 (%)*,§ | 5.5 | 93.0 | 91.1 | 89.8 |
| IGA score (n) | 110 | 217 | 103 | 217 |
| IGA 0 (%) | 0.1 | 60.0 | 51.6 | 62.6 |
| IGA 0/1 (%) | 7.1 | 88.8 | 86.3 | 82.4 |
| IGA ≤2 (%) | 30.2 | 96.2 | 95.0 | 89.8 |
| DLQI (n) | 110 | 217 | 103 | 217 |
| Change from baseline, mean (SD) | –3.0 (6.4) | –11.3 (7.8) | –12.1 (7.3) | –13.2 (8.1) |
| ≥5-point reduction in DLQI (%) | 37.0 | 83.8 | 85.4 | 84.8 |
| DLQI >1 at baseline (%) | 109 | 216 | 102 | 216 |
| DLQI 0/1 (%) | 4.8 | 46.9 | 59.5 | 73.3 |
| NAPSI score ≥1 at baseline (n) | 76 | 149 | 69 | 150 |
| Percent improvement from baseline (%), median (IQR) | 0 | 25.0 (0, 50.0) | 80.0 (50.0, 100.0) | 100.0 (50.0, 100.0) |
| ss-IGA ≥2 at baseline (n) | 105 | 199 | 98 | 199 |
| ss-IGA 0/1 and ≥2-grade improvement (%) | 7.1 | 82.9 | 87.6 | 84.8 |
*Patients who achieved PASI 100 were also considered to have achieved PASI 90 and PASI 75. Likewise, patients who achieved PASI 90 were also considered to have achieved PASI 75. †PASI 100 was defined as 100% improvement in PASI score from baseline. ‡PASI 90 was defined as 90% improvement in PASI score from baseline. §PASI 75 was defined as 75% improvement in PASI score from baseline. DLQI: Dermatology Life Quality Index; FAS: Full analysis set; IGA: Investigator Global Assessment; IQR: Interquartile range; NAPSI: Nail Psoriasis Area and Severity Index; PASI: Psoriasis Area and Severity Index; SD: Standard deviation; ss-IGA: Scalp-specific Investigator’s Global Assessment.
Figure 2.
Proportion of patients with moderate-to-severe plaque psoriasis achieving (A) PASI 90 and (B) IGA 0/1 responses through week 48. The severity of psoriasis was assessed by PASI and IGA at baseline and weeks 4, 12, 16, 20, 28, 36, 44, and 48, and corresponding proportions of patients achieving PASI 90 and IGA 0/1 were calculated. The coprimary endpoints were the proportions of patients achieving PASI 90 and IGA 0/1 at week 16. IGA: Investigator Global Assessment; PASI: Psoriasis Area and Severity Index.
Greater proportions of patients in the guselkumab group achieved PASI 75 [Supplementary Figure 3A, http://links.lww.com/CM9/C576], and IGA ≤2 [Supplementary Figure 3B, http://links.lww.com/CM9/C576] responses compared with the placebo group starting from week 4. Response rates observed at week 16 were 93.0% vs. 5.5% for PASI 75 and 96.2% vs. 30.2% for IGA ≤2, respectively [Table 2].
Among patients in the guselkumab group, responses were maintained throughout the study treatment period, with rates for PASI 90 of 79.2%, PASI 75 of 89.8%, IGA 0/1 of 82.4%, and IGA ≤2 of 89.8% at week 48 [Table 2]. Among 165 patients with a PASI 90 response at week 16, 89.0% maintained a PASI 90 response at week 48 with continued guselkumab treatment. Among 179 patients with an IGA score of 0/1 at week 16, 89.4% maintained an IGA score of 0/1 at week 48 [Supplementary Table 1, http://links.lww.com/CM9/D74].
For patients in the placebo-to-guselkumab group, PASI and IGA response rates increased from week 16 and were comparable to those for the guselkumab group at week 48 (PASI 90: 80.2%; PASI 75: 91.1%; IGA 0/1: 86.3%; and IGA ≤2: 95.0%) [Table 2 and Figure 2].
Psoriasis in special areas
Among 236 patients with nail psoriasis (NAPSI score >0) at baseline, the median percent improvement in NAPSI score at week 16 was greater for those in the guselkumab group compared with those in the placebo group (25.0% vs. 0.0%). From week 16 to 48, nail psoriasis continued to improve in both the guselkumab group and placebo-to-guselkumab group, with median percent improvement in NAPSI score of 100.0% and 80.0% at week 48, respectively [Table 2].
Among 304 patients with ss-IGA score ≥2 at baseline, a higher proportion in the guselkumab group achieved ss-IGA 0/1 and ≥2-grade improvement at week 16 compared with the placebo group (82.9% vs. 7.1%). From week 16 to 48, the proportion of patients achieving ss-IGA 0/1 and ≥2-grade improvement was maintained in the guselkumab group (84.8% at week 48) and improved in the placebo-to-guselkumab group (87.6% at week 48) [Table 2].
Measure of health-related quality of life
A greater reduction in DLQI score (mean change [SD] from baseline: –11.3 [7.8] vs. –3.0 [6.4]), a higher proportion of patients with a ≥5-point reduction (83.8% vs. 37.0%), and a higher proportion of patients with DLQI score of >1 at baseline achieving DLQI 0/1 (46.9% vs. 4.8%) at week 16 were seen in the guselkumab group compared with the placebo group [Table 2].
From weeks 16 through 48, improvements in DLQI score were maintained in the guselkumab group (mean change [SD] from baseline: –13.2 [8.1] at week 48; proportion of patients with a ≥5-point reduction: 84.8% at week 48), and the placebo-to-guselkumab group reached comparable levels of improvement at week 48 (mean change [SD] from baseline: –12.1 [7.3], proportion of patients with a ≥5-point reduction: 85.4%) [Table 2]. Among patients who had a DLQI score of >1 at baseline, the proportion of patients who achieved DLQI 0/1 at week 48 was 73.3% in the guselkumab group and 59.5% in the placebo-to-guselkumab group.
Safety
During the placebo-controlled period (through week 16), the proportion of patients with at least one treatment-emergent AE (TEAE) was comparable between treatment groups (41.9% in guselkumab group vs. 39.1% in placebo group) and most TEAEs were mild. The most frequently reported TEAEs in the guselkumab group (vs. the placebo group) were hyperlipidemia (5.5% vs. 2.7%), upper respiratory tract infection (5.1% vs. 1.8%), and urticaria (3.2% vs. 0%) [Table 3].
Table 3.
Summary of TEAEs (safety analysis set) in patients with moderate-to-severe plaque psoriasis, n (%).
| Items | Week 0–16 | Through week 56 | |
|---|---|---|---|
| Placebo (n = 110) | Guselkumab (n = 217) | Guselkumab-treated* (n = 320) | |
| At least TEAE | 43 (39.1) | 91 (41.9) | 265 (82.8) |
| At least 1 serious TEAE | 6 (5.5) | 2 (0.9) | 11 (3.4) |
| TEAEs leading to treatment discontinuation | 2 (1.8) | 3 (1.4) | 3 (0.9) |
| TEAEs leading to death | 1 (0.9) | 0 | 1 (0.3) |
| TEAE with incidence ≥2% | |||
| Coronavirus disease 2019 | 1 (0.9) | 2 (0.9) | 112 (35.0) |
| Upper respiratory tract infection | 2 (1.8) | 11 (5.1) | 37 (11.6) |
| Hyperlipidemia | 3 (2.7) | 12 (5.5) | 37 (11.6) |
| Nasopharyngitis | 1 (0.9) | 3 (1.4) | 18 (5.6) |
| Hyperuricemia | 2 (1.8) | 4 (1.8) | 16 (5.0) |
| Pyrexia | 0 | 1 (0.5) | 16 (5.0) |
| Viral upper respiratory tract infection | 0 | 0 | 15 (4.7) |
| Alanine aminotransferase increased | 4 (3.6) | 3 (1.4) | 12 (3.8) |
| Reticulocyte count increased | 1 (0.9) | 5 (2.3) | 12 (3.8) |
| Gamma-glutamyltransferase increased | 1 (0.9) | 2 (0.9) | 11 (3.4) |
| Urticaria | 0 | 7 (3.2) | 11 (3.4) |
| Hyperglycemia | 3 (2.7) | 4 (1.8) | 10 (3.1) |
| Hypertriglyceridemia | 0 | 1 (0.5) | 10 (3.1) |
| Blood uric acid increased | 0 | 0 | 9 (2.8) |
| Folliculitis | 0 | 3 (1.4) | 9 (2.8) |
| Injection site erythema | 0 | 3 (1.4) | 9 (2.8) |
| Injection site pruritus | 0 | 4 (1.8) | 9 (2.8) |
| Injection site swelling | 0 | 2 (0.9) | 9 (2.8) |
| Hepatic function abnormal | 0 | 2 (0.9) | 9 (2.8) |
| Cough | 2 (1.8) | 3 (1.4) | 8 (2.5) |
| Hypertension | 1 (0.9) | 5 (2.3) | 8 (2.5) |
| Blood glucose increased | 3 (2.7) | 2 (0.9) | 6 (1.9) |
*Included 217 patients randomly assigned to the guselkumab group and 103 patients in the placebo-to-guselkumab group. TEAE: Treatment-emergent adverse event.
During the first 16 weeks of treatment, two (1.8%) patients in the placebo group (increased hepatic enzymes and metastatic rectal cancer) and three (1.4%) patients in the guselkumab group (herpes zoster, schizophrenia, and urticaria) discontinued treatment due to AEs. The proportion of patients experiencing at least one serious AE (SAE) was low (0.9% in the guselkumab group vs. 5.5% in the placebo group). All SAEs, including soft tissue injury and schizophrenia in the guselkumab group and femur fracture, fracture, hand fracture, hepatic cirrhosis, and metastatic rectal cancer in the placebo group, were single events. The patient who experienced an SAE of schizophrenia had a medical history of psychotic disorder. All SAEs were deemed not related to the study treatment by the investigators. No serious infections, major adverse cardiovascular events (MACEs), or occurrences of venous thromboembolism were reported; one death (hepatic cirrhosis in the placebo group) and one malignancy (metastatic rectal cancer in the placebo group) were reported.
Through week 56, among guselkumab-treated patients, the median number of guselkumab doses received was 7.0 for the guselkumab group and 5.0 for the placebo-to-guselkumab group. Most (82.8%) guselkumab-treated patients experienced at least one TEAE through week 56 and most were considered mild. The most common AEs reported were coronavirus disease 2019 (35.0%), upper respiratory tract infection (11.6%), and hyperlipidemia (11.6%).
From weeks 16 through 56, no patients discontinued guselkumab due to an AE. The proportions of patients experiencing at least one SAE were low (2.3% in guselkumab group, 5.8% in placebo-to-guselkumab group). There was one death (pulmonary embolism in the placebo-to-guselkumab group) and three MACEs (pulmonary embolism and cerebral infarction in the placebo-to-guselkumab group and cerebral ischemia in the guselkumab group); these events were confounded by relevant medical history and assessed as not related to study treatment. Two cases of serious infection were reported (one case of appendicitis in the placebo-to-guselkumab group and one case of vulvitis in the guselkumab group); both were assessed as not related to the study treatment.
No cases of active tuberculosis, AEs of psoriasis, or AEs of anaphylaxis or serum sickness were reported during the study. Laboratory results showed that guselkumab had no meaningful impact on clinical hematology and chemistry parameters; none of the laboratory test abnormalities were reported as serious TEAEs.
Pharmacokinetics
In the guselkumab group, the mean (SD) serum guselkumab concentration at week 16 was 2.97 (1.37) μg/mL. A steady state was achieved by week 20, with a mean (SD) steady state trough serum guselkumab concentration of 0.99 (0.54) μg/mL. Trough serum, guselkumab concentrations were maintained at a steady state through week 44 with no evidence of guselkumab accumulation over time.
In the placebo-to-guselkumab group, mean (SD) serum guselkumab concentrations at weeks 20 (2.44 [1.14]) and 36 (0.98 [0.62]) were generally similar to those observed in the guselkumab group at weeks 4 (2.39 [1.06]) and 20 (0.99 [0.54]), respectively.
Immunogenicity
Among 317 guselkumab-treated patients, 79 (24.9%) had antibodies against guselkumab through week 56 and approximately half of these (49.4% [39/79]) had low peak titers of 1:11.25. In the 78 patients who were evaluable for neutralizing antibodies, neutralizing antibodies were detected in 12 (15.4%) patients.
In the guselkumab group, IGA 0/1 (86.5% vs. 82.1%) and PASI 90 (86.5% vs. 77.8%) response rates at week 48 were similar between patients who were positive and negative for antibodies to guselkumab, respectively.
The incidence of injection site reactions (ISRs) was 15.2% (12/79) and 0.4% (1/238) for guselkumab-treated patients who were positive and negative for antibodies to guselkumab, respectively. Of note, four of the 12 patients who were positive for antibodies to guselkumab experienced ISRs only prior to when antibodies to guselkumab were first detected. All ISRs were mild or moderate in severity.
Discussion
This randomized, double-blind, placebo-controlled study confirmed that guselkumab is effective in Chinese patients with moderate-to-severe plaque psoriasis. Guselkumab was superior to placebo for achieving PASI 90 and IGA 0/1 responses at week 16, and treatment benefits were consistent across subgroups defined by baseline and disease characteristics. Furthermore, clinical responses were sustained throughout the treatment period with guselkumab treatment. Guselkumab also led to improvements in nail and scalp psoriasis, as well as in patients’ quality of life. During the placebo-controlled period, the incidence of AEs was comparable between groups. The safety outcomes with guselkumab treatment were consistent with the known safety profile in its approved indications without the detection of any new safety signals.
Although genetic and environmental factors play important roles in the pathogenesis of psoriasis and the prevalence of psoriasis varies among regions, some genetic and environmental factors are shared by Chinese and global populations.[21–23] The efficacy of guselkumab in this Chinese population was generally comparable with that in global populations. Superior PASI 100, PASI 90, PASI 75, IGA 0, and IGA 0/1 responses were achieved with guselkumab compared with placebo at week 16 in this study and previous phase 3 trials.[17,18,24,25] The onset of response to guselkumab was rapid (as early as week 4), similar to previous phase 3 studies in which significant differences in treatment response between placebo and guselkumab were seen at week 4.[17,24,25] In addition, the clinical benefits of guselkumab treatment were durable, as demonstrated by the observation that approximately 90% of PASI 90 or IGA 0/1 responders at week 16 maintained response at week 48, similar to response rates maintained through week 48 in previous phase 3 trials.[17,18,24] Furthermore, improvements in psoriasis among patients in the placebo-to-guselkumab group were comparable to responses for patients in the guselkumab group at week 48.
Guselkumab also led to meaningful improvements in regional psoriasis that are considered difficult to treat. Scalp and nail psoriasis commonly occur in patients with psoriasis and can significantly impact patients’ quality of life.[9,26] Percent improvement in the NAPSI score from baseline and the proportion of patients achieving ss-IGA 0/1 and ≥2-grade improvement in the current study suggest that continuous guselkumab treatment can lead to clearance of scalp and nail psoriasis.
Consistent with previous studies, the incidence of safety events of interest, including malignancy, tuberculosis, infection, and MACEs,[27–30] was low in this study. One case of malignancy was reported in the placebo group after the patient received two doses of study treatment; the event was assessed as not related to study treatment and the outcome was unknown. There were three cases of MACE in patients with a predisposing medical history and two serious infections during guselkumab treatment over 1 year; however, each of these events was assessed as not related to the study treatment by the investigators.
Steady-state serum guselkumab concentrations in this cohort of Chinese patients were generally comparable to those measured in global study populations.[31] Consistent with previous observations, this study showed similar response rates among patients regardless of the presence of antibodies to guselkumab. The incidence of ISRs was higher in Chinese patients positive for antibodies to guselkumab than those without guselkumab antibodies. However, due to the limited number of patients who experienced ISRs and were positive for antibodies to guselkumab, these results should be interpreted with caution.
The study was powered to evaluate the efficacy of guselkumab vs. placebo in the controlled period and demonstrate the long-term efficacy of guselkumab in Chinese patients. Furthermore, the study had sufficient probability (>95%) to detect AEs with an occurrence rate of ≥1%. Nonetheless, this study had some limitations due to the study design that should be acknowledged. First, the comparisons between the guselkumab and placebo groups were limited to 16 weeks. In addition, overall treatment duration and data collection were limited to 56 weeks. Therefore, this study could not provide supportive data for long-term efficacy and safety beyond 56 weeks of guselkumab treatment. Furthermore, maintenance of guselkumab response after treatment withdrawal was evaluated in a global population[18] and treatment withdrawal effects of guselkumab have not been characterized in Chinese patients with psoriasis; however, relapse after treatment withdrawal is a crucial issue for this patient population.[32]
In conclusion, guselkumab treatment led to significant improvement in IGA and PASI measures compared with placebo in Chinese patients with moderate-to-severe plaque psoriasis. Guselkumab also improved patient-reported outcomes and measures for nail and scalp psoriasis. Furthermore, the efficacy of guselkumab was sustained through the treatment period up to week 56. The safety profile of guselkumab in Chinese patients was consistent with the known safety profile in global populations. Taken together, these findings support that guselkumab represents an attractive treatment option for Chinese patients with moderate-to-severe plaque psoriasis. Long-term studies are warranted to evaluate the efficacy and safety of guselkumab beyond 56 weeks.
Data sharing statement
Although these data are not currently publicly available for sharing, requests for sharing can be sent to the Corresponding Author and will be evaluated on an individual basis.
Acknowledgments
The authors thank the patients and their families who participated in the study, as well as the investigators and site staff who supported data collection and patient care. We are also grateful to the study team staff from Johnson & Johnson; Chaohui Yuan, and Shu Lyu for statistics methodology; Lina Yang, Mauricio Rosas Ballina, and Hewei Li, for pharmacovigilance; and Fabio Nunes, and Qingquan Chen, for study design and data interpretation. Medical writing support was provided by Shao-Hua Chin, and Molly Yu, of Parexel, funded by Johnson & Johnson.
Conflicts of interest
This study was supported by Janssen Research & Development, LLC. Wang L, Wang R, Zhang T, Zhao WL, Huang YH, Chen M, Dong ZQ, and Lyu S are current employees of Janssen Research & Development. All other authors declared no competing interests in this work.
Supplementary Material
Footnotes
Kun Huang and Songmei Geng contributed equally to this work.
How to cite this article: Huang K, Geng SM, Tao XH, Sun LD, Ji C, Yang B, Lu Y, Xiao R, Zhang CL, Zhang FR, Lu QJ, Zheng J, Wang HP, Shi YL, Li ZM, Yan W, Zhang LT, Tao J, Zhang SM, Yang XM, Cheng H, Xu JH, Su J, Zhang ZY, Song ZQ, Wang L, Wang R, Zhang T, Zhao WL, Huang YH, Chen M, Dong ZQ, Lyu S, Zheng M. Efficacy and safety of guselkumab in Chinese patients with moderate-to-severe plaque psoriasis: A randomized, double-blind, placebo-controlled trial. Chin Med J 2026;139:2587–2596. doi: 10.1097/CM9.0000000000003771
References
- 1.Campanati A, Marani A, Martina E, Diotallevi F, Radi G, Offidani A. Psoriasis as an immune-mediated and inflammatory systemic disease: From pathophysiology to novel therapeutic approaches. Biomedicines 2021;9:1511. doi: 10.3390/biomedicines9111511. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2.Damiani G Bragazzi NL Karimkhani Aksut C Wu D Alicandro G McGonagle D, et al. The global, regional, and national burden of psoriasis: Results and insights from the Global Burden of Disease 2019 study. Front Med (Lausanne) 2021;8:743180. doi: 10.3389/fmed.2021.743180. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3.Parisi R, Symmons DP, Griffiths CE, Ashcroft DM. Global epidemiology of psoriasis: A systematic review of incidence and prevalence. J Invest Dermatol 2013;133:377–385. doi: 10.1038/jid.2012.339. [DOI] [PubMed] [Google Scholar]
- 4.Wang X. Investigation on the epidemiology of psoriasis in 4 provinces and cities in Southwest China (in Chinese). Harbin Med 2017;37:426–427. [Google Scholar]
- 5.Ding X Wang T Shen Y Wang X Zhou C Tian S, et al. An epidemiological survey of psoriasis in six provinces and cities of China (in Chinese). Chin J Dermatol Venereol 2010;24:598–601. [Google Scholar]
- 6.Shao CG, Zhang GW, Wang GC. Distribution of psoriasis in China: A nationwide screening. Proc Chin Acad Med Sci Peking Union Med Coll 1987;2:59–65. [PubMed] [Google Scholar]
- 7.Ding X Wang T Shen Y Wang X Zhou C Tian S, et al. Prevalence of psoriasis in China: A population-based study in six cities. Eur J Dermatol 2012;22:663–667. doi: 10.1684/ejd.2012.1802. [DOI] [PubMed] [Google Scholar]
- 8.Yu K, Cao C, An F, Xu A, Wu X. Analysis and contrast of psoriasis disease burden trends in China and globally from 1990 to 2021. Front Public Health 2025;13:1541292. doi: 10.3389/fpubh.2025.1541292. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 9.Mosca M, Hong J, Hadeler E, Brownstone N, Bhutani T, Liao W. Scalp psoriasis: A literature review of effective therapies and updated recommendations for practical management. Dermatol Ther (Heidelb) 2021;11:769–797. doi: 10.1007/s13555-021-00521-z. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 10.Langley RG, Krueger GG, Griffiths CE. Psoriasis: Epidemiology, clinical features, and quality of life. Ann Rheum Dis 2005;64 Suppl 2:ii18–23; discussion ii24-15. doi: 10.1136/ard.2004.033217. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 11.Yang Z, Yao X, Wang M, Li H, Li R. Updates in psoriasis diagnosis and treatment status in China: Results from the National Psoriasis Center Registry. Chin Med J 2023;136:2874–2876. doi: 10.1097/cm9.0000000000002563. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 12.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. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 13.Elmets CA Korman NJ Prater EF Wong EB Rupani RN Kivelevitch D, et al. Joint AAD-NPF Guidelines of care for the management and treatment of psoriasis with topical therapy and alternative medicine modalities for psoriasis severity measures. J Am Acad Dermatol 2021;84:432–470. doi: 10.1016/j.jaad.2020.07.087. [DOI] [PubMed] [Google Scholar]
- 14.Chinese Society of Dermatology, China Dermatologist Association, Dermatology & Venereology Specialized Committee of Chinese Association of Integrative Medicine . Guidelines for the treatment of psoriasis with biologic agents in China. Chin J Dermatol 2021;54:1033–1047. doi: 10.35541/cjd.20210643. [Google Scholar]
- 15.Menter A Strober BE Kaplan DH Kivelevitch D Prater EF Stoff B, et al. Joint AAD-NPF guidelines of care for the management and treatment of psoriasis with biologics. J Am Acad Dermatol 2019;80:1029–1072. doi: 10.1016/j.jaad.2018.11.057. [DOI] [PubMed] [Google Scholar]
- 16.Kerut CK Wagner MJ Daniel CP Fisher C Henderson EJ Burroughs CR, et al. Guselkumab, a novel monoclonal antibody inhibitor of the p19 subunit of IL-23, for psoriatic arthritis and plaque psoriasis: A review of its mechanism, use, and clinical effectiveness. Cureus 2023;15:e51405. doi: 10.7759/cureus.51405. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 17.Blauvelt A Papp KA Griffiths CE Randazzo B Wasfi Y Shen YK, et al. Efficacy and safety of guselkumab, an anti-interleukin-23 monoclonal antibody, compared with adalimumab for the continuous treatment of patients with moderate to severe psoriasis: Results from the phase III, double-blinded, placebo- and active comparator-controlled VOYAGE 1 trial. J Am Acad Dermatol 2017;76:405–417. doi: 10.1016/j.jaad.2016.11.041. [DOI] [PubMed] [Google Scholar]
- 18.Reich K Armstrong AW Foley P Song M Wasfi Y Randazzo B, et al. 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;76:418–431. doi: 10.1016/j.jaad.2016.11.042. [DOI] [PubMed] [Google Scholar]
- 19.Janssen Research & Development . A study of guselkumab in participants with moderate to severe plaque-type psoriasis and an inadequate response to ustekinumab (NAVIGATE). Available from: https://clinicaltrials.gov/study/NCT02203032?term=CNTO1959PSO3003&rank=1. [Last accessed on June 04, 2024].
- 20.Rasmussen MK Enger M Dahlborn AK Juvik S Fagerhed L Dodge R, et al. The importance of achieving clear or almost clear skin for patients: Results from the Nordic Countries of the Global. Acta Derm Venereol 2019;99:158–163. doi: 10.2340/00015555-3048. [DOI] [PubMed] [Google Scholar]
- 21.Chandran V, Raychaudhuri SP. Geoepidemiology and environmental factors of psoriasis and psoriatic arthritis. J Autoimmun 2010;34:J314–J321. doi: 10.1016/j.jaut.2009.12.001. [DOI] [PubMed] [Google Scholar]
- 22.Chen K Wang G Jin H Xu J Zhu X Zheng M, et al. Clinic characteristics of psoriasis in China: A nationwide survey in over 12000 patients. Oncotarget 2017;8:46381–46389. doi: 10.18632/oncotarget.18453. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 23.Pan R, Zhang J. Epidemiology and treatment of psoriasis: A Chinese perspective. Psoriasis (Auckl) 2014;4:37–47. doi: 10.2147/PTT.S51717. [Google Scholar]
- 24.Ohtsuki M, Kubo H, Morishima H, Goto R, Zheng R, Nakagawa H. Guselkumab, an anti-interleukin-23 monoclonal antibody, for the treatment of moderate to severe plaque-type psoriasis in Japanese patients: Efficacy and safety results from a phase 3, randomized, double-blind, placebo-controlled study. J Dermatol 2018;45:1053–1062. doi: 10.1111/1346-8138.14504. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 25.Ferris LK Ott E Jiang J Hong HC Li S Han C, et al. Efficacy and safety of guselkumab, administered with a novel patient-controlled injector (One-Press), for moderate-to-severe psoriasis: results from the phase 3 ORION study. J Dermatolog Treat 2020;31:152–159. doi: 10.1080/09546634.2019.1587145. [DOI] [PubMed] [Google Scholar]
- 26.Hadeler E, Mosca M, Hong J, Brownstone N, Bhutani T, Liao W. Nail psoriasis: A review of effective therapies and recommendations for management. Dermatol Ther (Heidelb) 2021;11:799–831. doi: 10.1007/s13555-021-00523-x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 27.Blauvelt A, Chiricozzi A, Ehst BD, Lebwohl MG. Safety of IL-23 p19 inhibitors for the treatment of patients with moderate-to-severe plaque psoriasis: A narrative review. Adv Ther 2023;40:3410–3433. doi: 10.1007/s12325-023-02568-0. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 28.de Brito M, Yiu ZZN. Cardiovascular safety of biologics targeting interleukin (IL)-12 and/or IL-23: What does the evidence say? Am J Clin Dermatol 2021;22:587–601. doi: 10.1007/s40257-021-00612-9. [DOI] [PubMed] [Google Scholar]
- 29.Ru Y Ding X Luo Y Li H Sun X Zhou M, et al. Adverse events associated with anti-IL-23 agents: Clinical evidence and possible mechanisms. Front Immunol 2021;12:670398. doi: 10.3389/fimmu.2021.670398. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 30.Strober B Coates LC Lebwohl MG Deodhar A Leibowitz E Rowland K, et al. Long-term safety of guselkumab in patients with psoriatic disease: An integrated analysis of eleven phase II/III clinical studies in psoriasis and psoriatic arthritis. Drug Saf 2024;47:39–57. doi: 10.1007/s40264-023-01361-w. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 31.FDA Center for Drug Evaluation and Research . Multi-discipline review of guselkumab. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/761061Orig1s000MultidisciplineR.pdf. [Last accessed on July 23, 2024].
- 32.Wang XY, Zhang CL, Wang WH. Time to relapse after treatment withdrawal for different biologics used to treat plaque psoriasis. Chin Med J 2020;133:2998–3000. doi: 10.1097/cm9.0000000000001232. [DOI] [PMC free article] [PubMed] [Google Scholar]