Real‐life data over 36 weeks of guselkumab treatment in psoriasis patients: A single‐center study from Turkey

Psoriasis is an important health problem responsible for morbidity and workforce loss. In recent years, anti‐IL‐23 drugs have become essential in psoriasis treatment.


| INTRODUC TI ON
Psoriasis, a chronic inflammatory disease that can include skin and joint involvement, affects approximately 2%-3% of the population. 1 Plaque-type psoriasis is characterized by erythematous scaly papules and plaques located on the extensor surfaces. 2oriatic plaques can limit physical and social life, 3 affecting patients' physical and mental capacities.When the long-lasting chronic course of the illness and its psychosocial effects are considered, the extent of the problem becomes apparent.With these factors in mind, early recognition of the disease and adequate effective treatment are essential.
Although psoriasis is classically accepted as a keratinization disorder, as its pathogenic background is clarified, it has been shown to mostly occur due to changes in the interaction mechanisms between immune cells and keratinocytes. 4,5In addition, Since the 2008 approval of adalimumab, a TNFα inhibitor, several new targeted biologic agents have been approved for treating moderate-to-severe plaque psoriasis. 6Guselkumab, a humanized monoclonal antibody in the IgG1 structure binds to and inactivates the p19 subunit of IL-23, is one such agent. 7selkumab, approved by the United States Food and Drug Administration in 2017 for treating adults with moderate-tosevere plaque psoriasis and later in 2020 for treating active psoriatic arthritis, 8,9 has been used in the treatment of psoriasis patients in Turkey since December 2021.
Although clinical studies provide insight into therapeutic agents, real-life data are invaluable, and the combination of both sources of information can contribute to the safety and efficacy profile of drugs in daily administration. 10This study aimed to investigate the efficacy and safety of guselkumab therapy, recently used in Turkey, by examining real-life data over 36 weeks.

| MATERIAL SANDME THODS
Approval for the study was obtained from the local ethics committee.
Patients over 18 who received guselkumab treatment for psoriasis between December 2021 and December 2022 in the dermatology department of Erciyes University were included in the study.Patients' ages, sexes, body mass index (BMI), comorbidities, duration of illness, drugs used before guselkumab treatment, clinical response to guselkumab treatment, and side effects, if any, were recorded.Previous biological agent use was classified as IL-17 or other agents.The patients' Psoriasis Area Severity Index (PASI) values at Weeks 4, 12, 24, and 36 were examined for clinical response.In addition, the patients' Dermatology Life Quality Index (DLQI) values at the beginning of the treatment and at Week 36 were recorded.

| Statisticalmethods
The descriptive statistics of the data were indicated as mean, standard deviation, median, minimum, maximum, frequency, and ratio.

| RE SULTS
Patients who received guselkumab treatment in the dermatology clinic of the hospital between December 2021 and December 2022 were retrospectively screened.Of the 50 patients assessed, those who reached the 36th week of treatment, whose dose was not interrupted, and who could come for follow-up at least every 3 months were included in the data analysis.A total of 39 patients met these criteria and were included in the study.The mean age of the patients was 44.2 (15.8) years: 27 (69.2%)were male and 12 (30.8%)were female.The patients' BMI was 28.   1).
At the end of Week 56, patients were reevaluated, and the treatment of seven patients (17.9%) who did not achieve a PASI of 90 was changed due to ineffectiveness at week 36.Additionally, six patients (15.3%) discontinued the treatment on their own accord by not attending their follow-up appointments.Twenty-six patients (66.6%) continued their treatment, and all of them had a PASI score of 0.
The PASI score at baseline and Weeks 4, 24, and 36 did not differ based on IL-17 use (p > 0.05).In the group with IL-17 use, the PASI score at Week 12 was higher (p < 0.05) than in the non-use group.In both groups, the PASI scores at Weeks 4, 12, 24, and 36 decreased (p < 0.05) from baseline (Figure 2).3).

| DISCUSS ION
As the importance of IL-23 in the pathogenesis of psoriasis is understood, the suppression of this cytokine has become essential in treatment. 5Guselkumab was the first agent approved with this goal. 8[13] It was compared with adalimumab in VOYAGE studies, and its effectiveness was shown in the NAVIGATE study in patients who did not respond to ustekinumab. 13In the VOYAGE 1 study, the PASI 100% value at Week 4 was 37.4%, and in VOYAGE 2, it was 34.1%.
This rate was 38.4% in the present study, similar to these reports.
In addition, the percentage of patients who reached PASI 100% at the end of the 16th week was 47.4% in the VOYAGE 1 study.In the present study, Week 16 data were unavailable; however, considering Week 12, the PASI 100% rate was 64.1% and was higher.
Clinical studies and real-life data on guselkumab have been recently reported (Table 4).with these studies, the effectiveness of guselkumab was found to be quite high in the present study.In this study, the PASI 100 response was preserved in 66.6% of the patients at Week 52.Seven patients (17.9%) discontinued the drug due to ineffectiveness, and six patients (15.3%) were lost to follow up.Based on these findings, the treatment was more effective at Week 52 than other studies.
In the study by Van Muiyen et al., the drug survival rate of patients at 1 year was 85.5%, with a discontinuation rate of 92.8% due to ineffectiveness. 14In the present study, medication was discontinued in 33.3% of patients, with 53.8% of them discontinuing due to ineffectiveness.Six patients did not attend follow-up visits, and we believe this may be due to the earthquake occurring recently in the region where the study was conducted, as the hospital admitted a significant number of patients from surrounding cities, and there may have been difficulties in monitoring these patients after the earthquake.
The importance of the IL23-Th17 axis in the pathogenesis of psoriasis has led to the idea that an agent targeting this region may be ineffective after using another agent affecting the same pathway.In the study of Rodrigez et al., although 27 of 55 psoriasis patients had used an IL-17 inhibitor previously, guselkumab was found to be effective.Studies have reported biological agents may have a lower effect in patients with a high BMI. 18,19No association was found between body weight and efficacy at Weeks 16 and 24 in patients treated with guselkumab in the VOYAGE 1 and VOYAGE 2 studies.In the study of Galluzzo et al., although obese patients had higher baseline PASIs than non-obese patients (24.6 ± 14.3 vs. 17.9 ± 12.6), PASI levels were similar in both groups at Week 12. 20 In a recently published study by Galluzo et al., the decrease in the mean PASI score was found to be similar in obese and non-obese patients with psoriasis.
However, during long follow-up periods, while there was no significant difference in PASI 75, a significant difference was detected in PASI 90 and PASI 100 in favor of the non-obese patient group. 21The present study found no relationship between BMI and PASI changes.
In recently published real-life studies, the rate of adverse events reported during guselkumab treatment varies from 0% to 30.4%. 20ported side effects are generally arthro-myalgia, asthenia, infections (upper respiratory tract, dental, and pharyngitis), headache, syncope, and anxiety. 20,22,23This study's adverse event rate was 0%, as none of the patients described any side effects.

| Limitations
The retrospective design and limited number of patients were important limitations of this study.

| CON CLUS IONS
Guselkumab has been used frequently in treating psoriasis in recent years.Based on the findings of this study, using guselkumab in psoriasis patients is believed to be a very effective and safe treatment approach.

CO N FLI C TO FI NTE R E S TS TATE M E NT
No conflict of interest.

DATAAVA I L A B I L I T YS TAT E M E N T
The data that support the findings of this study are available from the corresponding author upon reasonable request.

E TH I C SS TATEM ENT
This study was approved by the Erciyes University Clinical Research Ethics Committee.

R E FE R E N C E S
autoinflammation caused by immunological responses is seen in the pathogenesis of the disease in genetically susceptible individuals.T-cell interaction with epidermal and dermal inflammatory type dendritic cells and cytokines, such as tumor necrosis factor-alpha (TNFα) and IL-23, play a role in this interaction.Cell differentiation and induction of keratocyte proliferation by cytokines such as IL-17 and IL-23 are the clearest and most notable contributors to the pathogenesis.Therefore, in the treatment of psoriasis, in addition to the classical medicines suppressing general inflammation, therapies targeting TNFα, IL-23, and IL-17 come to the forefront, especially in severe chronic cases.
The distribution of variables was measured with the Kolmogorov-Smirnov test.The Mann-Whitney U test was used in the analysis of independent quantitative data.The Wilcoxon test was used in the analysis of dependent quantitative data.A chi-squared test was used to analyze independent qualitative data, and a Fischer's test was used when chi-squared test conditions were not met.Spearman's correlation and SPSS software version 28.0 (IBM, NY, USA) were used in the analyses.
3 (5.3),and the mean disease duration was 13.7 (11.0) years.Considering the disease area, nine (23.1%) patients had palmoplantar and anogenital lesions, and 21 (53.8) had hair involvement.Another biologic agent was used by 26 (66.6%) patients before guselkumab treatment, of which 12 (30.7%)had previously used an IL-17 inhibitor.Psoriatic arthritis was present in 12 (30.8%)patients.Comorbidities in 11 patients included asthma (n = 3), hypertension (n = 3), benign prostatic hyperplasia (n = 1), hypothyroidism (n = 2), coronary artery disease (n = 3), steatohepatitis (n = 2) diabetes mellitus (n = 2), and familial Mediterranean fever (n = 1).No side effects were observed in any of the patients during the 36 weeks of treatment ( No significant correlation was observed between BMI values and PASI scores at baseline and Weeks 4, 12, 24, and 36.No significant correlation was observed between BMI value and percent of PASI change at Weeks 4, 12, 24, and 36 compared with baseline.No significant correlation was observed between disease duration and TA B L E 1 Demographic characteristics.

F I G U R E 1 2
Psoriasis Area and Severity Index (PASI) scores during treatment.Psoriasis Area and Severity Index (PASI) change based on IL-17 use.PASI score at baseline and Weeks 4, 12, 24, and 36.No significant correlation was observed between the duration of the disease and the percentage of PASI change at Weeks 4, 12, 24, and 36 compared with baseline (Table When patients who used and did not use another IL-17 before guselkumab treatment were compared in the present study, the PASI scores at Weeks 4, 12, 24, and 36 in both groups decreased compared with baseline, but only at the 12th week was the percentage of PASI score reduction significantly lower in the group with IL-17 use than the group without IL-17 use.
NTR I B UTI O N S E.Ö.S. and F.C.A., performed the research.E.Ö.S., D.K., S.L.Ç., and M.B. designed the research study.E.Ö.S. and D.K contributed essential reagents or tools.S.L.Ç., M.B., and E.Ö.S. analyzed the data.E.Ö.S wrote the paper.All authors have read and approved the final manuscript.

Table 1 )
.Considering the clinical response, PASI scores at Weeks 4, 12, 24, and 36 decreased (p < 0.05) from baseline, and there was a decrease in DLQI at Week 36 (Table2). 15 17earman's correlation between BMI and disease duration and PASI week.Some clinical studies about real-life data on guselkumab.Megna et al. found guselkumab effective in 44 patients who had previously used IL-17.16Hungetal. reported PASI improvements were lower in patients who had previously used biological agents, especially in those using anti-TNFα and IL-12/23 than those using anti-IL-1, compared with biologically naive patients.17 TA B L E 3