Received: 7 June 2021 Revised: 22 October 2021 Accepted: 22 November 2021 DOI: 10.1111/dth.15231 ORIGINAL ARTICLE Effectiveness and safety of guselkumab for the treatment of psoriasis in real-world settings at 24 weeks: A retrospective, observational, multicentre study by the Spanish Psoriasis Group Elena del Alcázar1 | Anna Lo   pez-Ferrer2 | Alvaro Martínez-Doménech3 | 4 5 Ricardo Ruiz-Villaverde | Mª. del Mar Llamas-Velasco | Vicenç Rocamora6 | 7 8 9 Marc Julià | Jaime Notario | Lourdes Rodríguez Fernández-Freire | Antonio Sahuquillo-Torralba10 | David Vidal11 | Raquel Rivera12 | Gregorio Carretero13 | Almudena Mateu14 | Pablo de la Cueva15 | José Manuel Carrascosa1 1 Department of Dermatology, Hospital Universitari Germans Trias i Pujol, Universitat Autònoma de Barcelona (UAB), Badalona, Spain 2 Department of Dermatology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain 3 Department of Dermatology, Hospital General Universitario de Valencia, Valencia, Spain 4 Department of Dermatology, Hospital Clínico Universitario San Cecilio, Granada, Spain 5 Department of Dermatology, Hospital Universitario de la Princesa, Madrid, Spain 6 Department of Dermatology, Hospital de Manacor (Illes Balears), Manacor, Spain 7 Department of Dermatology, Hospital Universitario de Basurto, Bilbao, Spain 8 Department of Dermatology, Hospital Universitari de Bellvitge, L'Hospitalet de Llobregat, Barcelona, Spain 9 Department of Dermatology, Hospital Universitario Virgen del Rocío, Sevilla, Spain 10 n Sanitaria La Fe, Valencia, Spain Department of Dermatology, Hospital Universitario y Politécnico La Fe Valencia, Instituto de Investigacio 11 Department of Dermatology, Complex Hospitalari Moisès Broggi, Sant Joan Despí (Barcelona), Barcelona, Spain 12 Department of Dermatology, Hospital Universitario 12 de Octubre, Madrid, Spain 13 Department of Dermatology, Hospital Universitario de Gran Canaria Dr. Negrín, Las Palmas de Gran Canaria, Las Palmas, Spain 14 Department of Dermatology, Hospital Universitario Dr. Peset, Valencia, Spain 15 Department of Dermatology, Hospital Infanta Leonor, Madrid, Spain Correspondence Elena del Alcázar, Department of Dermatology, Abstract Hospital Universitari Germans Trias i Pujol, Data on the effectiveness and safety of a drug in real-world clinical practice comple- Universitat Autònoma de Barcelona (UAB). Badalona, Spain. ment the evidence from clinical trials, which are carried out in a different setting. Lit- Email: elenadelalcazarviladomiu@gmail.com tle has been published on the effectiveness and safety of guselkumab in the treatment of psoriasis in clinical practice. The ojective of this study was to assess the effectiveness and safety of guselkumab at 24 weeks in patients with moderate to severe plaque psoriasis in routine clinical practice. A retrospective, multicentre study This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. © 2021 The Authors. Dermatologic Therapy published by Wiley Periodicals LLC. Dermatologic Therapy. 2022;35:e15231. wileyonlinelibrary.com/journal/dth 1 of 10 https://doi.org/10.1111/dth.15231 2 of 10  del ALCAZAR ET AL. of adult patients with moderate to severe plaque psoriasis treated with guselkumab for at least 24 weeks was carried out in Spain. We studied 343 patients, 249 of whom were followed for 24 weeks. By week 24, the mean (SD) psoriasis area severity index (PASI) had decreased from 11.1 (7.3) to 1.7 (2.8) ( 9.3; [ 10.2;-8.4]), 85.9% of the patients had achieved PASI score of 4 or less and 77.9% a PASI score of 2 or less. In terms of relative PASI response, 59.4% of the patients achieved a PASI-90 response and 49.0% a PASI-100 response. On multivariate analysis, two factors reduced the probability of a PASI of 2 or less at 24 weeks: a BMI ≥30 (OR, 0.44; 95% CI, 0.22– 0.88) and a greater previous exposure to biologic therapy (OR, 0.69; 95% CI, [0.56– 0.84]). Adverse events were rare (9.9%) and led to withdrawal from treatment in only nine patients (2.6%) by the end of the follow-up period. The results of this study con- firm the high efficacy and safety of guselkumab indicated by the clinical trial data. In clinical practice, the absolute PASI score appears to be a better marker of response to treatment than the relative value. KEYWORDS guselkumab, psoriasis, real-world 1 | I N T RO DU CT I O N Clinical trial data are obtained under conditions distinct from those found in routine clinical practice. Authors studying the real- Guselkumab is a fully human immunoglobulin G1 lambda monoclonal world use of various drugs have observed that the patient population antibody to the interleukin (IL)-23 protein, which it inhibits by binding in clinical practice has different characteristics to that of clinical tri- 1 selectively to the p19 subunit with high specificity and affinity. als8,9 and, in some cases, the outcomes observed in registry data are The immune response of the IL-23/T17 axis is currently thought different from those reported in clinical trials.10 For this reason, data to be the main pathogenic pathway in psoriasis, which would explain on the use of a drug in a real-world setting help clinicians to predict why agents targeting this pathway achieve the best clinical response how it will work in the patients they attend in their practice. The 2,3 and are currently the drugs most often used to treat these patients. objective of this study was to assess the effectiveness and safety of The Phase III clinical trials (VOYAGE 1 and 2) demonstrated the guselkumab at 24 weeks in patients with moderate to severe plaque superiority of guselkumab over adalimumab in the treatment of mod- psoriasis. erate to severe plaque psoriasis.4,5 In VOYAGE 1 and 2, respectively, 80.2% and 75.2% of patients treated with guselkumab achieved a psoriasis area and severity index (PASI)-90 response at week 24 as 2 | MATERIAL AND METHODS compared to 53.0% and 54.8% of those treated with adalimumab (p < 0.001). The results of the Phase III trials also showed that 2.1 | Study design, patients, and data collected 4,5 guselkumab has a good safety profile, similar to that of adalimumab and ustekinumab,6 with upper respiratory tract infections being the The Spanish Psoriasis Group of the Spanish Academy of Dermatology most commonly reported adverse event. Guselkumab also showed and Venereology carried out a retrospective, observational, multi- superior efficacy over secukinumab in the ECLIPSE study. In that centre study with the participation of 35 Spanish hospitals. The study, a PASI 90 response at week 48 was achieved by 84% of the patients included were adults (≥18 years) with a diagnosis of moder- patients treated with guselkumab compared to 70% of those treated ate to severe plaque psoriasis who had been treated with guselkumab with secukinumab (p < 0.0001).7 between February 1, 2019 and June 30, 2020. Patients who com- In November 2017, guselkumab became the first IL-23 inhibitor pleted at least 16 weeks of follow-up were deemed not to have with- to be approved by the EMA. Since February 2019, it has been avail- drawn from treatment. able in Spain for the treatment of moderate to severe plaque psoriasis The following patient data were extracted from anonymized elec- in patients who have had an inadequate response or a contraindica- tronic medical records: age, sex, weight, height, body mass index tion or intolerance to conventional systemic treatments and PUVA.1 (BMI; categorized as normal or overweight <30 or obesity ≥30), com- In accordance with the criteria of the treatment appraisal report issued orbidities, personal history of cancer, and previous treatment for pso- by the Spanish Ministry of Health, guselkumab is only prescribed to riasis, including systemic and biologic therapies. Patients received patients who have previously received a biologic TNF inhibitor. guselkumab 100 mg at weeks 0 and 4 followed by a maintenance  del ALCAZAR ET AL. 3 of 10 dose every 8 weeks as indicated in the Summary of Product Charac- ratios (OR) and 95% CI. The statistical analysis was performed using teristics, except in the case of 10.2% of the patients (35/343), who the SPSS software package (version 22.0 for Windows). A p value of did not receive an induction dose. less than 0.05 was considered significant. The as observed method The present study was conducted in accordance with the Decla- was used in the case of missing data as this is the most common ration of Helsinki on Ethical Principles for Medical Research Involving method used in this type of study. We also performed a modified Human Subjects and was approved by the local clinical research ethics non-responder imputation (NRI) analysis of the data. A non-responder committee at Hospital Universitari Germans Trias i Pujol (reference was defined as any patient in whom treatment was discontinued, number: EDA-GUS-2019-01). whether due to treatment-related factors (lack of efficacy, adverse events) or other reasons (i.e., patient decision). 2.2 | Response assessment 3 | RE SU LT S The 35 dermatologists who took part in the study are all members of the Spanish Psoriasis Group. Data on the following variables were 3.1 | Demographic and clinical characteristics obtained from the patients' medical records: PASI, body surface area (BSA), physician global assessment (PGA) and dermatology life quality The study included 343 patients with plaque psoriasis who received index (DLQI) at baseline and at weeks 16 and 24. The PGA was guselkumab in the 35 participating hospitals. The clinical and demo- assessed on a 6-point scale (0 = clear, 1 = almost clear, 2 = mild, graphic characteristics of the study population are shown in Table 1. 3 = moderate, 4 = severe, and 5 = very severe). The primary endpoints were improvement in mean PASI score TABLE 1 Baseline characteristics of study patientsa and the percentage of patients who had achieved a PASI score of Characteristic n = 343 2 or less (PASI ≤2) or of 4 or less (PASI ≤4) at week 24. The second- Male 198 (57.7) ary endpoints were the percentage of patients who achieved a PASI ≤2 or PASI ≤4 at week 16 and a PASI-90, or PASI-100 at weeks Age, mean (SD) years 48.3 (14.1) 16 and 24. Other effectiveness variables analyzed were the mean Weight, mean (SD) kg 85.5 (20.7) reduction in BSA, PGA, and DLQI scores at weeks 16 and 24. Other Height, mean (SD) cm 169.5 (10.1) objectives included describing the clinical characteristics of the Body mass index, mean (SD) kg/m (n = 331) 2 29.7 (6.5) patients, identifying variables that might condition the clinical <30 192 (58.0) response, and evaluating the clinical response according to prior ≥30 139 (42.0) treatments received. Duration of psoriasis, mean (SD) years (n = 338) 22.4 (12.0) Baseline PASI, mean (SD) (n = 343) 11.1 (7.3) Baseline BSA, mean (SD) (n = 316) 13.7(13.8) 2.3 | Safety Baseline PGA, mean (SD) (n = 202) 3.2 (0.8) Baseline DLQI, mean (SD) (n = 226) 11.9 (7.3) Data were collected on the frequency of adverse events and the per- Previous conventional systemic therapy centage of patients who discontinued treatment due to such events. Methotrexate 261(76.1) Reasons for discontinuation were also recorded and classified as fol- lows: lack or loss of efficacy, serious adverse events, and others (lack Ciclosporin 187 (54.5) of compliance, patient's decision, etc.). Acitretin 129 (37.6) Mean (SD) number prior to guselkumab 1.7 (0.9) Phototherapy 191 (55.7) 2.4 | Statistical analysis Apremilast 28(8.2) Number of prior biologic therapies Qualitative variables were expressed in absolute (n) and relative (per- 0 28 (8.2) centages) values and quantitative variables as mean and standard 1 105 (30.6) deviation (SD). Pearson's chi-square test was used to compare qualita- 2 80 (23.3) tive variables. For quantitative variables, Student's t test was used 3 54 (15.7) once the normality hypothesis had been tested. To compare the same ≥4 76 (22.2) variable over time at different time points, we used statistical tests for Mean (SD) number prior to guselkumab 2.4 (1.7) pairwise comparison and expressed the results as the difference in Previous biologic therapies the mean and 95% confidence interval (difference; 95% CI). The clini- cal characteristics associated with the achievement of PASI-90 and Adalimumab 184 (53.6) PASI ≤2 were analyzed using simple and multiple logistic regression Etanercept 134 (39.1) models and the forward method. The results were expressed as odds (Continues) 4 of 10  del ALCAZAR ET AL. TABLE 1 (Continued) The mean (SD) values for the physical characteristics of the population Characteristic n = 343 (198 men and 145 women) were as follows: age, 48.3 (14.1) years; weight, 85.5 (20.7) kg; and BMI, 29.7 (6.5). At baseline, mean PASI Infliximab 63 (18.4) was 11.1 (7.3), mean BSA was 13.7 (13.8), and mean DLQI was 11.9 Certolizumab 6 (1.7) (7.3). In total, 90.1% (309) of the patients had received conventional Ustekinumab 186 (54.2) systemic therapy (ciclosporin, methotrexate, or acitretin), 55.7% (191) Secukinumab 128 (37.3) had undergone phototherapy, and 8.2% (28) had received apremilast. Ixekizumab 75 (21.9) In all, 91.8% (315) had received biologic therapy and the mean num- Brodalumab 6 (1.7) ber of biologic agents received was 2.4 (1.7). Of the patients included, Efalizumab 16 (4.7) 16% (55) had psoriatic arthritis, 5.2% (18) had a history of cancer, Comorbidities 4.4% (15) a history of hepatitis (four with hepatitis C, three of whom Psoriatic arthritis 55 (16) had been treated and cured prior to the administration of guselkumab, Hypertension 105 (30.6) and 11 with hepatitis B), and 2.2% (7) a history of inflammatory bowel Dyslipidaemia 126 (36.7) disease. Diabetes mellitus 51 (14.9) Cardiovascular events 22 (6.4) 3.2 | Patient distribution over time NAFLD 70 (20.4) Bowel disease 7 (2.2) (Figure 1) Of the 343 patients included in the study, 249 completed Hepatitis 15 (4.4) 24-weeks follow-up. At week 16, eight patients had discontinued HIV 2 (0.6) treatment (four due to adverse events and four for other reasons) and Cancer in personal history 18 (5.2) by week 24 a further 10 patients had discontinued (five due to Mental disorders 51 (14.9) adverse events, three due to lack of efficacy, and two for two lack of Abbreviations: BSA, body surface area; DLQI, dermatology life quality efficacy for joint symptoms). In addition, no data on effectiveness index; HIV, human immunodeficiency virus; NAFLD, non-alcoholic fatty were collected at 24 weeks for 36 patients who were still receiving liver disease; PASI, psoriasis area severity index; PGA, physician global treatment but could not be assessed due to the COVID-19 pandemic, assessment. a nor for 40 others, who were between weeks 16 and 24 of treatment. Data expressed as number (%) of patients unless otherwise specified. F I G U R E 1 Distribution of patients over time (flow-chart)  del ALCAZAR ET AL. 5 of 10 3.3 | Effectiveness 24 weeks was achieved by 92.4% (61/66) of the patients treated with guselkumab after treatment with a TNF inhibitor, 84.9% (62/73) of Mean PASI, which was 11.1 (7.3) at baseline, decreased to 2.4 (3.2) those who switched from ustekinumab, and 60.8% (45/74) of those ( 8.8; [9.6; 8.0]) by week 16 and to 1.7 (2.8) ( 9.3; [ 10.2; 8.4]) previously treated with an IL-17 inhibitor, with significant differences at week 24, with statistically significant differences observed at both (p < 0.001). points (Figure 2). This represents a decline in mean PASI of 78.4% at week 16 and 84.7% at week 24. After 6 months of treatment, 85.9% (214/249) of the patients still receiving treatment had achieved PASI 3.4 | Safety ≤4 and 77.9% (194/249) PASI ≤2 (Figure 3A). In terms of relative response, 59.4% (148/249) achieved a PASI-90 and 49.0% (122/249) Adverse events were reported by 9.9% (34/343) of patients, with a PASI-100 (Figure 4A). The analysis carried out using the modified infections being the most common (Table 4). Only nine patients (2.6%) NRI method produced slightly lower results: 80.1% (214/267) of the discontinued treatment owing to adverse events: two headache, two patients achieved PASI ≤4, 72.7% (194/267) achieved PASI ≤2, 55.4% joint pain, two COVID-19 pneumonia, one flu-like symptoms, one (148/267) a PASI 90 response and 45.7% (122/267) a PASI respiratory infection, and one acute myocardial infarction. Other rea- 100 response (Figures 3B and 4B). Reductions at weeks 16 and sons for stopping treatment were as follows: patient decision (2), poor 24 were also observed for the other variables studied (BSA, PGA, and adherence (2), primary treatment failure (3), and lack of efficacy on DLQI) and significant differences were observed. The mean baseline joint disease (2). BSA of 13.7 (13.8) decreased to 3.8 (7.0) ( 9.8; [ 11.1; 8.4]) by week 16 and to 2.3 (4.7) ( 11.3; [ 12.9; 9.7]) by week 24. The baseline PGA of 3.2 (0.8) fell to 1.1 (0.9) ( 2.1; [ 2.2; 1.9]) by the 4 | DI SCU SSION end of the fourth month and to 0.9 (0.9) ( 2.2; [ 2.5; 2.1]) by the end of the study. With respect to quality of life, the baseline mean We present a series of 343 patients with plaque psoriasis treated with DLQI of 11.9 (7.3) decreased to 2.7 (4.1) ( 9.3; [ 10.2; 8.4]) at guselkumab in clinical practice, the largest series reported in the litera- week 16 and to 2.4 (4.3) ( 9.9; [ 11.1; 8.9]) by the end of the ture to date. study. To identify variables that might interfere with the PASI-90 and PASI ≤2 responses, we performed a bivariant analysis to observe the direct effect between variables complemented by a multivariate analysis to adjust for confounding variables (Table 2). On multivariate analysis the fol- lowing factors decreased the probability of a PASI ≤2 at 24 weeks: BMI ≥30 (OR, 0.44; 95% CI, 0.22–0.88) and greater exposure to prior biologic therapy (OR, 0.69; 95% CI, 0.56–0.84). No significant differences were observed in the other variables analyzed: age, sex, psoriatic arthritis, initial severity of psoriasis (PASI >10 and PASI <10), and duration of disease. Analysis of the clinical response according to the drug patients had received before guselkumab (Table 3) showed that PASI ≤2 at F I G U R E 3 (A) Proportion of patients with PASI ≤4 and PASI ≤2 at weeks 16 and 24 according to the as observed analysis and F I G U R E 2 Mean (SD) PASI at weeks 16 and 24 according to as (B) modified non-responder imputation analysis. PASI, psoriasis area observed analysis. PASI, psoriasis area severity index severity index 6 of 10  del ALCAZAR ET AL. Our clinical practice data reflect the effectiveness of guselkumab biologic therapy as compared to 20%–22% of the patients included in in a context different from that of clinical trials. It is well known that VOYAGE 1 and 2.4,5 Furthermore, patients treated in real-world prac- the profile of patients treated in a clinical practice is more complex tice usually have a lower PASI score when they start treatment than than that of patients included in trials, with real-world patients having participants in pivotal trials, mainly due to the absence of a washout more comorbid conditions and greater exposure to previous biologic period. In our study, the mean baseline PASI was 11, half that of the therapy.11 In our study, over 90% of patients had received prior VOYAGE trials in which baseline PASI was around 22.4,5 For this rea- son, the absolute PASI value is a better measure of the success of treatment than the relative values expressed as a 75% (PASI-75) or 90% (PASI-90) reduction over the baseline score. The advantage of using absolute PASI scores is that they are not dependent on baseline values, which are not thought to be clinically relevant 6 months after the start of treatment.12 The British BADBIR group recently reported that an absolute PASI ≤2 corresponds to a PASI-90 response and that PASI ≤4 corresponds to a PASI-75 response.13 These were the two absolute values used as primary endpoints in our study. At week 24, nearly 80% of our patients had a PASI ≤2, a percentage similar to that achieved for PASI-90 in VOYAGE 1 (80.2%) and VOYAGE 2 (75.2%). In addition, our results for complete clearing (PASI-100) at week 24 were slightly higher than those reported in the pivotal trials: 49% versus 44%. Little evidence is available on the effectiveness of guselkumab in real-world clinical practice, with only nine series published in the liter- ature14–22 (Table 5). Analysis of the baseline values in all of those series reveals that— in line with our findings—a higher proportion of the patients in clinical practice had received prior biologic therapy (59%–75.3%) than in the VOYAGE trials and that the mean baseline PASI was lower (12.7– 15.1) in clinical practice than in the pivotal trials, with the exception of the series by Galluzzo et al.19 with a mean baseline PASI of 20. In most of those series, effectiveness was expressed in relative PASI F I G U R E 4 (A) Proportion of patients with PASI-90 and PASI-100 values and the response rates achieved for PASI-90 and PASI-100 in at weeks 16 and 24 according to the as observed analysis and the two largest series are similar to those found in our study.14,15 The (B) modified non-responder imputation analysis. PASI, psoriasis area only earlier study that assessed treatment response in terms of severity index TABLE 2 Factors associated with PASI-90 and PASI ≤2 at week 24 (bivariant and multivariant analysis). As observed analysis Bivariant analysis odds ratio (95% CI) Multivariant analysis odds ratio (95% CI) Week 24 PASI-90 PASI ≤2 PASI-90 PASI ≤2 Age 0.99 (0.97–1.01) 0.99 (0.98–1.02) 0.99 (0.97–1.02) 1.00 (0.97–1.03) Sex Female 1 1 1 1 Male 0.55 (0.33–0.93) 0.49 (0.26–0.92) 0.60 (0.35–1.06) 0.61 (0.30–1.24) Obesity BMI < 30 1 1 1 1 BMI ≥ 30 0.58 (0.34–0.99) 0.34 (0.18–0.64) 0.73 (0.41–1.29) 0.44 (0.22–0.88) Psoriatic arthritis No 1 1 1 1 Yes 0.81(0.41–1.59) 0.60 (0.28–1.29) 1.08 (0.50–2.32) 1.16 (0.46–2.92) Severity psoriasis PASI < 10 1 1 1 1 PASI ≥ 10 1.07 (0.65–1.78) 0.45 (0.25–0.84) 1.16 (0.66–2.02) 0.50 (0.25–1.01) Duration of psoriasis 1.0 (0.99–1.03) 1.01 (0.98–1.03) 1.02 (0.99–1.04) 1.01 (0.98–1.05) Mean no. of prior biologic drugs 0.77 (0.66–0.90) 0.66 (0.55–0.79) 0.78 (0.65–0.92) 0.69 (0.56–0.85) Note: The bold numbers mean these results show statistically significant difference. Abbreviations: BMI, body mass index; PASI, psoriasis area severity index.  del ALCAZAR ET AL. 7 of 10 TABLE 3 Response to guselkumab at week 24 by prior biologic therapies. As observed analysis Mean (SD) N of Week 24 prior biologic treatments Mean (SD) baseline PASI Mean (SD) PASI PASI-90 PASI ≤2 TNF inhibitors (n = 92) 2.0 (1.5) 10.6 (6.3) 0.8 (2.2) 77.3% (51/66) 92.4% (61/66) IL-12/23 inhibitors (n = 105) 2.4 (1.4) 9.0 (5.5)a 1.4 (2.8) 58.9% (43/73) 84.9% (62/73) IL-17 inhibitors (n = 101) 3.2 (1.7) 12.5 (9.1)a 2.7 (3.3) 43.2% (32/74) 60.8% (45/74) p value <0.001 0.003a <0.001 <0.001 <0.001 Abbreviations: IL, interleukin; PASI, psoriasis area severity index. a Statistically significant difference. TABLE 4 Adverse events of pooled data from the head-to-head Phase III trials that compared guselkumab, adalimumab and placebo showed that guselkumab pro- Type of adverse event No. Description vided superior sustained efficacy compared to adalimumab and pla- Mild infections 8 Upper respiratory infection (3), flu-like cebo across all bodyweight classes.27 The impact of prior biologic syndrome (1), sty (1), boils (1), cystitis therapy has also been studied in other clinical practice series.15,19 (1), herpes zoster affecting the first Galluzzo et al.19 reported that lower prior exposure to biologic ther- branch of the trigeminal nerve (1) apy was associated with a higher probability of achieving PASI-90, a Serious infections 7 COVID-19 pneumonia (3), influenza A finding similar to that of our study. Benhadou et al., by contrast, found (1), acute bronchitis (1), viral no statistically significant differences in PASI-75, PASI-90, or PASI- pericarditis (1), salmonellosis (1) 100 response between biologic-naive patients and biologic- Injection-site 2 reactions experienced patients, although those authors do not specify what the differences were.15 Headache 2 Our study reviewed the effectiveness of guselkumab as a Joint pain 6 function of prior biologic treatment. It is particularly interesting Major adverse 1 Acute myocardial infarction cardiac events to evaluate the efficacy of guselkumab in patients who have (MACE) failed to respond to treatment with ustekinumab because of the Laboratory test 2 Hyperuricemia (1), proteinuria (1), similar mechanism of action in the pathogenicity of psoriasis. In anomalies leukocytosis with neutrophilia (1) patients who have received IL-17 inhibitors, it is interesting Others 6 Mesenteric paniculitis (1), rosaceiform because of the role of IL-23 in the positive regulation of IL-17 in dermatitis (1), hypertension (1), hip the IL-23/IL-17 axis. In our study, almost 60% of the patients fracture (1), airborne eczema (1), who switched from ustekinumab to guselkumab achieved PASI-90 anxiety (1) at week 24, a result similar to that reported in the NAVIGATE trial,6 reflecting that guselkumab may be an effective option for patients who do not achieve an optimal response with absolute PASI reported that 74.4% of the patients achieved a PASI ustekinumab in clinical practice. In the group of patients who ≤3 at week 20.19 It appears, therefore, that guselkumab achieves switched to guselkumab following failure with an IL-17 inhibitor, high-efficacy rates in patients who have previously been treated with 43.2% achieved a PASI- 90 response by week 24. It should, how- other biologic drugs. ever, be noted that the mean number of prior biologic treatments It is known that certain variables or factors can negatively influ- was higher in the IL-17 inhibitor group (3.2 [1.7]) than in the ence the efficacy of a drug: duration of the disease, obesity, a history groups that received ustekinumab (2.4 [1.4]) or tumor necrosis of psoriatic arthritis, and prior treatment with multiple biologic factor inhibitors (2.0 [1.5]), and that this difference probably agents. 23,24 In our series, the probability of achieving PASI ≤2 at influenced the lower therapeutic response obtained. 24 weeks decreased in the presence of obesity (BMI ≥30) and greater With respect to safety, there were no serious adverse events dur- prior exposure to biologic therapy. Obesity has, in general, been asso- ing the follow-up period. Almost 10% (34/343) of the patients experi- ciated with lower efficacy in biologic therapy, particularly in the case enced some adverse effects, with infections being the most common. 25 of drugs for which the dose is not weight adjusted. There are a However, only 2.7% (9/343) discontinued treatment for this reason, a number of possible explanations for this effect, including the fact that percentage similar to that observed in the VOYAGE 1 and 2 trials4,5 body mass modifies the pharmacokinetics and clearance of biologic and the series reported by Fougerousse et al.14 drugs, and that visceral fat triggers proinflammatory effects mediated Our study has some limitations. Due to its retrospective design, by the release of adipokines. Although the dose of guselkumab is not some of the data or variables were missing or incomplete and the as adjusted to body weight, fat may interfere with pharmacokinetics observed assessment may have overestimated the effectiveness find- (apparent clearance and volume of distribution).26 Subgroup analyses ings. However, the experience of the Spanish Psoriasis Group in 8 of 10 TABLE 5 Demographic characteristics of patients, effectiveness, and safety outcomes of guselkumab in real-world settings Maliyar Snast Megna Fougerousse Benhadou et al.18 Rodriguez Fernandez Galluzzo M et al.22 et al.16 Our series (n = 343) et al.14 (n = 180) et al.15 (n = 112) (n = 89) Freire et al.17 (n = 55) et al.19 (n = 52) (n = 33) (n = 23) Age, mean (SD) years 48.3 (14.1) 45.2 (14.05) 48.9 (14.1) 54.0 49.8 (15.2) 51.3 (14.1) 60 (13) 49.7 (17.9) Male, n (%) 198 (57.7%) 107 (59%) 63 (56.3%) 43 (48.3%) 37 (67.3%) 30 (57.7) 22 (67) 15 (65.2%) Mean (SD) PASI 11.1 (7.3) 12.7 (8.95) 14.8 (6.5) NA 13.7 (7.7) 20 (13.3) 14 (11) 15.1 (6.1) Previous biologic 315 (91.8%) 128 (71.1%) 66 (59%) 67 (75.3%) NA 30 (57.7%) 33 (100%) 15 (65.2%) therapy, n (%) PASI 90 week 12–16 43.9% (week 16) 50.6% (week 16) 55.4% (week 16) NA 69.1% (week 12) 36% (week 12) NA 43.5% (week (%) 12) PASI 90 week 24 (%) 59.4% NA NA NA 66.7% 62.8% (week 20) 62% (week 69.6% (week 24) 28) PASI ≤2 or 3 week 20– 77.9% PASI ≤2 (week 24) NA NA NA NA 74.4% PASI ≤3 NA NA 24 (%) (week 20) Mean (SD) reduction in 2.4 (3.2) (week 16) 2.3 (3.62) (week 2.03 (2.5) (week NA 1.5 (1.8) (week 12) 4.4 (4.7) (week NA 3.2 (1.9) PASI week 12–16 16) 16) 12) (week12) Mean (SD) reduction in 1.7 (2.8) (week 24) NA NA NA 1.7 (3.3) (week 24) 1.9 (week 28) 2.9 (3.3)c 1.1 (0.9) PASI week 24–28 (week 24) (week 28) Adverse event, n (%) 34 (9.9%) 15 (8.3%) 3 (2.6%) 24 (30.4%)a 0 0b 0 6 (26%) 4 (17.4%)d Withdrawal due to 9 (2.6%) 5 (2.7%) 0 4 (5.1%)a 0 0 0 0 adverse event, n (%) Withdrawal due to lack 3 (0.9%) 0 0 3 (3.8%)a 1 (1.8%) 0 2 (6.1%) 0 of efficacy, n (%) Abbreviations: NA, not available; PASI, psoriasis area severity index. a Only 79 patients were included for efficacy and safety analyses. b No evidence of cumulative or organ toxicity. c Not including four patients with palmoplantar psoriasis. d Mild blood alterations.  del ALCAZAR ET AL.  del ALCAZAR ET AL. 9 of 10 collaborative studies and the use of systematic data collection including AbbVie, Amgen, Janssen-Cilag, LEO Pharma, Lilly, Novartis, methods favor more homogeneous data collection in clinical practice and Pfizer. Jaime Notario has served as a consultant or paid speaker than generally found in multicentre studies. Another limitation is that for and/or participated in clinical trials sponsored by AbbVie, Almirall, the COVID-19 pandemic may have led to a higher percentage of Celgene, Gebro, Janssen, Leo Pharma, Lilly, MSD, Novartis, and Pfizer. patients for whom data was missing at 24 weeks. Nonetheless, one of Lourdes Rodríguez Fernández-Freire has served as a consultant and the strengths of the study is the large sample size (343 patients speaker for AbbVie Laboratories, Janssen Pharmaceuticals Inc, MSD, included and 249 with data collected up to 24 weeks) for a study of Pfizer-Wyeth, Novartis, Celgene, Almirall SA, Lilly, and Leo-Pharma. routine clinical practice. Antonio Sahuquillo-Torralba has served as a consultant or paid speaker for or participated in clinical trials sponsored by companies that manufacture drugs used for the treatment of psoriasis, including 5 | C O N CL U S I O N AbbVie, Celgene, Janssen-Cilag, LEO Pharma, Lilly, Novartis, and Pfizer. Raquel Rivera-Diaz acted as a consultant and/or speaker for We present the largest series to date of patients treated with and/or participated in clinical trials sponsored by companies that man- guselkumab in a clinical practice setting with data on effectiveness ufacture drugs used for the treatment of psoriasis, including AbbVie/ and safety at 24 weeks. Guselkumab achieved high response rates Abbott, Almirall, Amgen, Celgene, Janssen-Cilag, Leo Pharma, Lilly, measured in terms of absolute PASI ≤2 and PASI ≤4 in a popula- MSD-Schering-Plow, Novartis, Pfizer, and UCB. David Vidal has par- tion with a more complex profile than that of the patients included ticipated in clinical trials and/or received honoraria as a consultant, in clinical trials. The drug also has a good safety profile and a very investigator, speaker from AbbVie, Celgene, Janssen, Lilly, LeoPharma, low withdrawal rate due to adverse effects. This is the first study and Novartis. Gregorio Carretero has participated as PI/SI and/or in which response to treatment was evaluated using the absolute member of steering committee, and/or advisor and/or invited speaker PASI score, which, in the authors' opinion, may be a more useful for Celgene, Amgen, AbbVie, Almirall, Novartis, Leo-Pharma, Lilly, measure in clinical practice than relative response (PASI-75 or Sandoz, Mylan, Janssen. Almudena Mateu has potential conflict of PASI-90). We therefore highlight the usefulness of using absolute interests (advisory board member, consultant, research support, par- PASI scores to assess response to treatment in real-world clinical ticipation in clinical trials, and honorary for speaking) with the follow- practice. ing pharmaceutical companies AbbVie, Almirall SA, Celgene, Jansen- Cilag, Leo-Pharma, Lilly, Novartis y Pfizer. Pablo de la Cueva has ACKNOWLEDGMENTS served as a consultant or paid speaker for or participated in clinical tri- We would like to thank all the members of the Spanish Psoriasis als sponsored by companies that manufacture drugs used for the Group who contributed patients to this series of patients treated in treatment of psoriasis, including AbbVie, Almirall, Astellas, Biogen, real-world clinical practice. Boehringer, Celgene, Janssen, LEO Pharma, Lilly, MSD, Novartis, Pfizer, Roche, Sanofi, UCB. José Manuel Carrascosa has participated CONF LICT OF IN TE RE ST as PI/SI, and/or member of steering committees and/or advisor Elena del Alcázar has served as a consultant or paid speaker for or par- and/or invited speaker for Celgene, Amgen, AbbVie, Almirall, Novartis, ticipated in clinical trials sponsored by companies, including AbbVie, Leo-Pharma, Lilly, Sandoz, Mylan, and Janssen. PI/SI clinical trials Der- Amgen, Leo Pharma, Almirall, Janssen-Cilag, Lilly, Novartis, Sanofi, and matology IGTP. None of the aforementioned has any relation to the  pez- Ferrer has perceived consultancy/educational sup- UCB. Anna Lo present work. port/speakers honoraria and/or participated in clinical trials sponsored by AbbVie, Almirall, Amgen, Boehringer Ingelheim, Celgene, Janssen, AUTHOR CONTRIBU TIONS  Leo Pharma, Lilly, MSD, Novartis, Pfizer, and UCB. Alvaro Martínez- All authors contributed to the design and implementation of the Doménech has participated in clinical trials sponsored by companies research. Elena del Alcázar contributed to collect data from the differ- that manufacture drugs used for the treatment of psoriasis, including ent centers, the analysis of the results and to the writing of the manu- Almirall and Janssen-Cilag. Ricardo Ruiz-Villaverde has received grants script. José Manuel Carrascosa contributed to the supervision of the and research support, served as a consultant or received honoraria final manuscript. from Pfizer, Novartis, Lilly, Celgene, Almirall, and AbbVie. M. Llamas- Velasco has potential conflict of interests (advisory board member, DATA AVAILABILITY STAT EMEN T consultant, research support, participation in clinical trials, and honor- The data that support the findings of this study are available from the ary for speaking) with the following pharmaceutical companies: corresponding author upon reasonable request. AbbVie, Amgen, Janssen-Cilag, Leo Pharma, Novartis, Lilly and Celgene. Vinveç Rocamora has received grants and research support, OR CID served as a consultant or received honoraria from Novartis, Janssen- Elena del Alcázar https://orcid.org/0000-0002-5935-356X Cilag, AbbVie, Celgene, UCB i MSD. Marc Julià has served as a consul-  Alvaro Martínez-Doménech https://orcid.org/0000-0002-1252- tant or paid speaker for or participated in clinical trials sponsored by 1001 companies that manufacture drugs used for the treatment of psoriasis, Ricardo Ruiz-Villaverde https://orcid.org/0000-0002-0381-6174 10 of 10  del ALCAZAR ET AL. 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