Evaluation of Short-to-medium Term Efficacy of Guselkumab and Secukinumab in Overweight and Obese Patients with Moderate to Severe Plaque Psoriasis: A 24-Week Single-center Retrospective Study

Abstract

Background:

Overweight and obesity are common in patients with psoriasis and are associated with increased disease severity and declined treatment response.

Aims:

To evaluate the short-to-medium term (24w) efficacy and safety of two biologics, including Guselkumab and Secukinumab, in overweight and obese patients (body mass index [BMI] ≥25 kg/m²) with moderate to severe psoriasis.

Materials and Methods:

We retrospectively analyzed the data of patients with moderate to severe plaque psoriasis treated with Guselkumab or Secukinumab in Dermatology Hospital of Southern Medical University in 2020. Totally 34 and 67 patients were treated with Guselkumab and Secukinumab, respectively; the patient groups with BMI ≥25 kg/m² comprised 16 and 33 cases, respectively. Baseline demographics and clinical characteristics were recorded, and Psoriasis Area and Severity Index (PASI) scores, adverse events, and biochemical parameters were assessed at weeks 12, 16, and 24.

Results:

Both Guselkumab and Secukinumab demonstrated good clinical efficacy. In patients with BMI ≥25 kg/m², there was a higher percentage of cases achieving PASI 100 at week 16 in the Secukinumab group; however, at week 24, the proportion of patients treated with Guselkumab achieving PASI 100 was significantly higher than that of cases treated with Secukinumab (P = 0.037 and P < 0.001, respectively).

Conclusions:

Guselkumab and Secukinumab demonstrated good short-to-medium-term efficacy in Chinese patients with moderate to severe plaque psoriasis. In patients with a BMI ≥25 kg/m², Secukinumab demonstrated a faster onset of efficacy, while Guselkumab demonstrated significantly higher efficacy at week 24.

Introduction

Psoriasis is an immune-mediated chronic inflammatory skin disease with incidence rates of approximately 0.14%–3.6%[1] globally and 0.47%[2] in the Chinese population. The etiology of psoriasis remains unclear. It is thought to be related to the interactions of genetic, immune, and environmental factors. As a risk factor for many common diseases, obesity is a risk factor for psoriasis, and the severity of psoriasis lesions is positively correlated with BMI.[3,4]

In recent years, the wide application of biologics has provided better treatment options for psoriasis patients. However, because of personal differences, especially weight differences, not all biological agents work best in all populations.[4,5] When selecting biologics for patients with moderate to severe plaque psoriasis, BMI is a key factor to be considered. Guselkumab is an all-human IgG1/λmonoclonal antibody that selectively binds to the P19 subunit of IL-23, and Secukinumab is a high-affinity, complete human IgG1κmonoclonal antibody that selectively binds to IL-17A and neutralizes the bioactivity of cytokines, both of which are approved for the treatment of moderate-severe plaque psoriasis.[6] We aimed to retrospectively compare the short-to-medium-term therapeutic effects of Guselkumab and Secukinumab in patients with moderate-to-severe plaque psoriasis, especially in overweight and obese cases, in the Dermatology Hospital of Southern Medical University (Guangzhou, China) between 2020 and 2021.

Materials and Methods

Patients

Patients diagnosed with moderate to severe plaque psoriasis in our hospital in 2020 were included, inclusion criteria being: age ≥18 years, regardless of gender; stable condition for more than half a year; no biological agents used in the past 3 months; no use of traditional medicines within a month; no major underlying diseases such as heart disease, active tuberculosis, infection or tumor. Patients with autoimmune diseases other than psoriasis and psoriatic arthritis, those simultaneously taking traditional medicines, and those with no recorded baseline data were excluded. A total of 101 individuals met the inclusion/exclusion criteria, as shown in Figure 1. This study was approved by the Indtitutional Review Board (IRB) of Dermatology Hospital of Southern Medical University, Approval number GDDHLS-20190304 Date of approval: March 4^th, 2019.

Figure 1.

Flowchart of patient enrollment

Research protocol

The patients included in this study were treated according to the recommended treatment regimens and doses of the biologics’ instructions (Guselkumab administered at 100 mg subcutaneously in weeks 0 and 4, then every 8 weeks later; Secukinumab administered at 300 mg subcutaneously per week for the first 1 month, then 300 mg per month). Baseline data, including gender, age, disease course, height, weight, comorbidities, and PASI, were recorded. Follow-up was performed at 12, 16, and 24 weeks, recording PASI scores, adverse events, and biochemical indicators.

Data analysis

The R (Version 4.1.2) software was used for statistical analysis. The Shapiro-Wilk test was used to assess the normality of measurement data. Those with normal distribution were expressed as mean ± standard deviation (SD) and compared by the t-test; non-normally distributed measurement data were expressed as median and upper and lower quartiles (P₂₅, P₇₅), and compared by the Mann–Whitney U test. Enumeration data were expressed as frequency (percentage) and compared by the Chi-Square test or Fisher’s exact test. In addition, the 12w PASI 90 outcomes were used to determine associated factors. The missing data were filled by the Last Observation Carries Forward method, and the secondary analysis of efficacy, subgroup analysis, and association between certain factors and efficacy were performed. All statistical tests were two-sided, and P < 0.05 was considered statistically significant.

Results

Baseline characteristics

A total of 101 patients were included in this study, with 34 in the Guselkumab group and 67 in the Secukinumab group. The patient enrollment process is shown in Figure 1, and baseline data are summarized in Table 1. Patients in the Guselkumab group had a median age of 38 (28.25, 50.50) years and a median age of disease onset of 28.50 (21.00, 38.75) years; the median disease course was 9 (5, 13.75) years. Patients in the Secukinumab group had a median age of 38 (32, 49.50) years and a median disease course of 10 (5.50, 12.80) years. Most patients had one or more comorbidities, and the most common comorbidities in both groups were overweight and obesity (47.1% and 49.3%, respectively). In this study, age, gender, obesity, and other factors were included for univariate analysis, and overweight and obesity had negative impacts on the outcome of PASI 90 at week 12 (OR = 0.110, 95%CI: 0.040–0.307, P < 0.001); no other factors were found to promote or hinder the curative effect. In week 24, the mean weights of patients with BMI ≥25 kg/m² treated with Guselkumab and Secukinumab decreased from 86.65 to 80.18 kg and from 86.17 to 83.32 kg, respectively; mean BMI values decreased from 28.26 to 26.18 kg/m² and 29.43 to 28.47 kg/m², respectively. After treatment, the body weights and BMI values of overweight and obese cases administered Secukinumab were lower than before (P < 0.0004), and those administered Guselkumab had lower body weights (P < 0.001) and lower BMI values (P < 0.002).

Table 1.

Baseline demographic characteristics

Variable	Guselkumab (n=34)	Secukinumab (n=67)	P
Gender			0.629
Male	26 (76.5%)	54 (80.6%)
Female	8 (23.5%)	13 (19.4%)
Age (years)	38.00 (28.25, 50.50)	38.00 (32.00, 49.50)	0.793
Age of onset (years)	28.50 (21.00, 38.75)	28.50 (22.25, 40.25)	0.647
Duration of psoriasis (years)	9.00 (5.00, 13.75)	10.00 (5.50, 12.80)	0.706
BMI (kg/m2)			0.835
<25	18 (52.9%)	34 (50.7%)
≥25	16 (47.1%)	33 (49.3%)
Comorbidity
overweight and obese	16 (47.1%)	33 (49.3%)	0.835
Hyperlipidemia	13 (38.2%)	15 (22.4%)	0.093
Hypertension	2 (5.9%)	7 (10.4%)	0.714*
Diabetes or hyperglycemia	4 (11.8%)	3 (4.5%)	0.221*
Hyperuricemia	17 (50.0%)	30 (44.8%)	0.619
Tuberculosis or latent tuberculosis	5 (14.7%)	7 (10.4%)	0.532*
HBVAg	4 (11.8%)	4 (6.0%)	0.437*

*Fisher’s exact test

Adverse events

There were 5 cases of adverse events (14.7%) in the Guselkumab group during the treatment, including 3 cases of local itching, and 1 of transient muscle soreness and fatigue, and 1 of herpes zoster that lacked evidence for direct correlation to studied drugs. There were 25 cases of adverse events (37.3%) in the Secukinumab group, including 18 cases of local or systemic pruritus, 5 of increased skin-pigmented moles in a short period, and 2 of aggravated alopecia. No obvious abnormalities were found in liver and kidney functions, infection and tumor-related indicators, etc.

Efficacy (0–24 weeks)

During the follow-up period, both Guselkumab and Secukinumab had significant efficacy in moderate to severe plaque psoriasis. Skin lesions clearance in both groups almost reached 75% at week 12, and 90% at week 16; however, a few cases in the Secukinumab group relapsed at week 24. At week 24, the percentages of skin lesion aggravation or relapse were 14.9% and 3.4% in the Secukinumab and Guselkumab groups, respectively. At week 24, the proportions of complete clearance with Guselkumab and Secukinumab were 91.2% and 55.2%, respectively, which demonstrated significantly better efficacy in the Guselkumab group than in the Secukinumab group (P < 0.05) [Figure 2].

Figure 2.

Efficacy analysis of all enrolled patients

Subgroup analysis according to BMI found that efficacy in patients with BMI <25 kg/m² was generally better than that of overweight and obese cases, but no difference was found between the Guselkumab and Secukinumab groups [Table 2]. In patients with a BMI ≥25 kg/m², Guselkumab was comparable to Secukinumab in achieving a rate of 90% clearance [Figure 3]. However, at week 16, the proportion of patients administered Secukinumab with complete clearance was significantly higher than that of the Guselkumab group (P = 0.037); at week 24, the ratio of patients administered Guselkumab with complete clearance was higher than that of the Secukinumab group (P < 0.001) [Figure 3].

Table 2.

Subgroup efficacy analysis

	BMI ≥25 kg/m2 (n=49)			BMI <25 kg/m2 (n=52)
	Guselkumab	Secukinumab	P	Guselkumab	Secukinumab	P
n	16 (32.7%)	33 (67.3%)		18 (34.6%)	34 (65.4%)
Weeks 12
PASI 75	11 (68.8%)	26 (78.8%)	0.492*	18 (100.0%)	34 (100.0%)	—
PASI 90	7 (43.8%)	15 (45.5%)	0.910	18 (100.0%)	28 (82.4%)	0.081*
PASI 100	0 (0.0%)	0 (0.0%)	—	3 (16.7%)	2 (5.9%)	0.327*
Weeks 16
PASI 75	14 (87.5%)	30 (90.9%)	>0.999*	18 (100.0%)	34 (100.0%)	—
PASI 90	12 (75.0%)	22 (66.7%)	0.743*	18 (100.0%)	33 (97.1%)	>0.999*
PASI 100	1 (6.2%)	12 (36.4%)	0.037*	10 (55.6%)	20 (58.8%)	0.821
Weeks 24
PASI 75	15 (93.8%)	30 (90.9%)	>0.999*	18 (100.0%)	34 (100.0%)	—
PASI 90	15 (93.8%)	28 (84.8%)	0.649*	18 (100.0%)	33 (97.1%)	>0.999*
PASI 100	14 (87.5%)	10 (30.3%)	<0.001	17 (94.4%)	27 (79.4%)	0.236*

*Fisher’s exact test

Figure 3.

Therapeutic effects of Guselkumab and Secukinumab in subgroups (BMI ≥ 25 kg/m²)

Discussion

In this study, regardless of weight, comorbidities and other factors, the use of Guselkumab and Secukinumab according to respective recommended regimens in the treatment of moderate-to-severe plaque psoriasis had significant efficacy and no serious adverse reactions in the short-to-medium term, corroborating previous studies.[7,8,9] Recent studies have also shown that the risk of psoriasis is higher in overweight and obese individuals than in normal-weight individuals, and obesity hurts the severity and therapeutic effects of psoriasis.[5,10] In this study, by univariate regression analysis we also found that influencing factors, including overweight and obesity, negatively affected PASI 90 at week 12, and no other factors promoted or hindered the efficacy.

A subgroup analysis of BMI was performed to compare the efficacy of these two biologics in individuals with BMI <25 kg/m² versus BMI ≥25 kg/m². We found that in overweight and obese patients, Secukinumab had better efficacy compared with Guselkumab at week 16, while the efficacy of Guselkumab was significantly better compared with that of Secukinumab at week 24. This may be due to the faster onset of Secukinumab, more durable action of Guselkumab efficacy, and the relapse of some cases with Secukinumab.[11,12] However, both Guselkumab and Secukinumab have significant efficacy in normal-weight patients, with generally better efficacy in normal-weight patients compared with overweight and obese patients. This study analyzed the application of Guselkumab and Secukinumab in the Chinese population, and limitations included efficacy data availability for only 24 weeks and a small sample size. A phase-3 randomized controlled trial conducted in several European and American countries also found that at week 48, the proportion of patients treated with Guselkumab at PASI 90 was significantly higher than that obtained with Secukinumab, and the difference was even greater in overweight and obese patients in a subgroup analysis.[7,9] Therefore, we considered that comorbid overweight and obesity may affect the short-to-medium-term treatment effect in psoriasis. In our study, the short-term efficacy of Secukinumab was better, while Guselkumab had a longer duration of efficacy and was less affected by weight factors, which is beneficial for the treatment of overweight and obese patients with moderate to severe plaque psoriasis.

IL-17A and IL-23 are key inflammatory factors involved in the pathogenesis of psoriasis; in addition, IL-23 is a major driver of Th17 cell differentiation and an upstream regulator of IL-17A.[11,12] Research found that pro-inflammatory cytokines of the IL-17 family play a role in the pathogenesis of obesity and obesity-related sequelae.[13] Abnormal secretion of cytokines and adipokines in cutaneous tissues may be involved in the induction, differentiation, and proliferation of keratinocytes and immune cells leading to the development of psoriatic skin lesions.[14] Adipokines may also interfere with the IL-17 pathway, thereby affecting the efficacy of IL-17A inhibitors. Therefore, selectively blocking the IL-23/IL-17 axis can not only treat psoriasis, but also possibly combat the progression of obesity.[5] In this study, the weights and BMI values of overweight and obese patients treated with Secukinumab and Guselkumab were lower than before treatment, which may further affect the treatment effect; however, there is no large-scale evidence to prove that these two biological agents are directly related to weight loss. Tiberio et al.[15] found that Secukinumab is effective in patients with different weights, but its efficacy shows a downward trend in obese patients. Takamura et al.[16] found that the use of IL-23 or IL-17 inhibitors does not affect efficacy by increasing body weight. In contrast, other studies have found that IL-23 inhibitors may cause weight gain but do not influence efficacy.[5,17] Data on the association between body weight and IL-17 or IL-23 inhibitors were insufficient to draw clear conclusions.

No serious adverse events were observed in this study. Some patients reported local or systemic allergies during the treatment, but the onset was not related to body weight and could be relieved by oral antihistamines. In addition, 1 case of muscle soreness that was relieved after a few days and 1 case of herpes zoster that was considered not directly related to Guselkumab were observed in the Guselkumab group. In the Secukinumab group, 5 cases had increased moles with no specific reasons. Some patients were diagnosed with cell moles and black spots after pathological biopsy, and long-term follow-up was required. Studies have shown that IL-17A can significantly induce the production of IL-1β, IL-6, and TNF-α in skin cells such as keratinocytes and fibroblasts, and inhibit the production of melanin.[18] However, there is currently no conclusive evidence that the use of biologics in patients with psoriasis independently increases the risk of melanoma. Therefore, this study considered both biologics to be relatively safe and effective.

Conclusions

This study revealed significant short-to-medium-term efficacy for both Guselkumab and Secukinumab in patients with moderate to severe plaque psoriasis. Being overweight and obesity had a negative impact on therapeutic effects, but less influence for Guselkumab. These findings may guide clinicians in selecting appropriate biologic agents for patients. However, due to the small sample size and a highly subjective evaluation of efficacy indicators, a greater number of patients and more effective evaluation tools are still needed for future studies.

Conflicts of interest

There are no conflicts of interest.

Funding Statement

Nil.