Secukinumab Treatment Research Articles

Secukinumab May Be an Effective Treatment Option for Axial Spondyloarthritis and Psoriatic Arthritis Patients with a History of Malignancy: Multicenter Real-Life Experience from Turkey.

Background: Secukinumab is a monoclonal antibody against interleukin 17 approved for patients with axial spondyloarthritis (axSpA), psoriatic arthritis (PsA), and psoriasis. Treating axSpA and PsA patients with a history of malignancy is a challenge. While initial results on the applicability of secukinumab in this patient group are positive, the number of studies on this topic remains limited. This study aimed to investigate the drug's survival time and the efficacy and safety of secukinumab treatment in this specific patient group. Methods: This retrospective study included 30 patients with a history of malignancy who were followed up in rheumatology outpatient clinics in 12 centers throughout Turkey and treated with secukinumab between May 2018 and March 2024 with a diagnosis of axSpA and PsA. Results: The mean follow-up time was 29.8 ± 19.3 months. The drug retention rate was 89.7% after 12 months and 80.6% after 24 months. The most common tumor in our study was papillary thyroid carcinoma (n = 5, 16.7%). During follow-up, local tumor recurrence was observed in a patient with urothelial carcinoma of the bladder. Conclusions: In the largest cohort reported to date, treatment with secukinumab in axSpA and PsA patients with a history of malignancy was not shown to cause oncologic recurrence except for one local tumor recurrence. Drug retention rates were also high, and disease activation and function improved compared to baseline. Therefore, secukinumab could be a safe and effective option for this patient group.

Enhanced Type 1 Interferon Signature in Axial Spondyloarthritis Patients Unresponsive to Secukinumab Treatment.

Axial spondyloarthritis (axSpA) is an inflammatory disease in which overactive interleukin (IL)-17A-producing cells are implicated in a central role. Therapeutically, biologics that target IL-17A, such as secukinumab, have demonstrated improved clinical outcomes. Despite this translational success, there is a gap in understanding why some patients with axSpA do not respond to IL-17A-blocking therapy. Our study aims to discriminate immune profiles between secukinumab responders (SEC-R) and nonresponders (SEC-NR). Peripheral blood mononuclear cells were collected from 30 patients with axSpA before and 24 weeks after secukinumab treatment. Frequency of CD4+ subsets were compared between SEC-R and SEC-NR using flow cytometry. Mature CD45RO+CD45RA-CD4+ T cells were fluorescent-activated cell sorting sorted, and RNA was measured using NanoString analysis. SEC-NR had an increased frequency of IL-17A-producing RORγt+CD4+ T cells compared to healthy controls before secukinumab treatment (P < 0.01). SEC-NR had a significant increase of CXCR3+ CD4+ T cells before secukinumab treatment compared to SEC-R (P < 0.01). Differentially expressed gene analysis revealed up-regulation of type 1 interferon (IFN)-regulated genes in SEC-NR patients compared to SEC-R patients after receiving the biologic. SEC-R patients had an up-regulated cytotoxic CD4+ T cell gene signature before receiving secukinumab treatment compared to SEC-NR patients. The increased frequency of IL-17A-producing cells in SEC-NR patients suggests a larger inflammatory burden than SEC-R patients. With treatment, SEC-NR patients have a more pronounced type 1 IFN signature than SEC-R patients, suggesting a mechanism contributing to this larger inflammatory burden. The results point toward more immune heterogeneity in axSpA than has been recognized and highlights the need for precision therapeutics in this disease.

Residual metabolic burden in young psoriasis patients successfully treated with biologics

Metabolic disorders are common in patients with psoriasis and contribute significantly to an increased cardiovascular risk. While biologic therapy is very successful in clearing skin lesions, its impact on metabolic parameters is uncertain. Our aim was to investigate the residual metabolic burden in psoriasis patients successfully treated with biologic therapy. We conducted a cross-sectional study of 80 young patients (54 men, 26 women, aged 30–45 years) successfully treated with either adalimumab, secukinumab or guselkumab and topical therapy or methotrexate, and 20 healthy controls. Anthropometric parameters, lipid levels and metabolic indices (HOMA-IR, TyG index and FIB-4 index) were measured. Patients did not receive any other treatments to exclude confounding effects. After analysis, we found that patients treated with three different biologics had similar metabolic status, only the FIB-4 index was higher in the adalimumab group than in the secukinumab and guselkumab treatment groups. There were no significant differences between the patients treated with biologics and the control group. The comparison with patients treated topically or with methotrexate showed that only triglyceride levels, HOMA-IR, TyG index, and FIB-4 index were elevated in patients treated with adalimumab compared to patients treated with topical therapy. Finally, metabolic status was also similar in patients treated with methotrexate or topical therapy. In conclusion, this study suggests that psoriasis patients successfully treated with biologics have similar metabolic parameters to the control group and patients treated with topical therapy or methotrexate. This indicates that there is no significant residual metabolic burden in young patients successfully treated with biologics. These results are clinically relevant and should be considered in the treatment of psoriasis patients.The study is registered at http://clinicaltrials.gov (identifier: NCT05957120). Date of registration: 24th of July 2023.

New insights on hidradenitis suppurativa phenotypes and treatment response: An exploratory automated analysis of the SUNSHINE and SUNRISE trials.

Defining hidradenitis suppurativa (HS) subtypes was previously limited by small sample sizes and poor interrater reliability; no study has investigated subtype treatment responses. The objective of this analysis was to characterize HS clusters in adult patients with moderate to severe HS and evaluate secukinumab treatment responses between clusters. Clusters were identified via an unsupervised machine learning clustering analysis using baseline data from the randomized, placebo-controlled SUNSHINE (NCT03713619) and SUNRISE (NCT03713632) phase 3 trials. To assess treatment responses, patients received secukinumab every 2 (SECQ2W) or 4 weeks (SECQ4W) or placebo, for 16 weeks, after which, placebo patients randomly switched to SECQ2W/SECQ4W, and SECQ2W/SECQ4W patients maintained their original treatment, until week 52. Baseline outcomes included patient characteristics, disease characteristics and severity, HS-associated comorbidities and previous treatment exposures. Treatment response was assessed via the HS clinical response (HiSCR), abscess and inflammatory nodule (AN) count, flares and NRS30 (skin pain). Based on baseline data, three clusters were identified from 1084 patients (Cluster 1: 54.1%, Cluster 2: 17.8%, Cluster 3: 28.1%). Cluster 1 was predominantly female (65.4%) and was characterized by milder HS. Cluster 2 had more patients from the Asia Pacific, Middle East and Africa region (58.5%) and was characterized by moderate HS. Cluster 3 had the highest rates of previous exposure to biologics (45.9%) and prior HS-related surgeries (47.5%) and was characterized by severe HS. SECQ2W and SECQ4W demonstrated efficacy versus placebo in all clusters at week 16; SECQ2W and SECQ4W efficacy was maintained to week 52. SECQ2W treatment showed a trend for greater efficacy versus SECQ4W in Cluster 3 through week 52. Three HS clusters were identified. Secukinumab demonstrated benefit over placebo in all clusters. However, patients with more severe disease may take longer to respond and more frequent secukinumab dosing may be required for these patients. SUNSHINE (NCT03713619) and SUNRISE (NCT03713632).

Reflectance confocal microscopy for plaque psoriasis therapeutic follow-up during an anti-interleukin-17A monoclonal antibody: an observational study

Interleukin-17A therapeutic inhibitors are among the most effective treatment methods for moderate-to-severe plaque psoriasis (PP). Reflectance confocal microscopy is a non-invasive imaging technique already documented to be beneficial in evaluating the follow-up of PP under treatment with topical actives and phototherapy. This study aimed to assess the epidermal and dermal changes associated with psoriasis and its treatment with RCM during systemic secukinumab treatment in patients with moderate-to-severe PP. A pilot study was conducted to evaluate RCM as a non-invasive tool for monitoring secukinumab treatment in patients with PP. For patients receiving secukinumab treatment, lesional skin was selected for RCM imaging, which were recorded at all scheduled times. The RCM evaluation criteria were established based on the histopathological diagnostic criteria for psoriasis. The clinical severity of psoriasis was assessed utilizing the psoriasis area severity index. A total of 23 patients with PP were included in the study. Each patient received 300 mg of subcutaneous secukinumab as induction therapy at baseline and weeks 1–4, followed by maintenance therapy every four weeks. Microscopic confocal changes were observed during the treatment. The results identified early microscopic evidence of the anti-inflammatory activity of secukinumab, which was not detected during the clinical examination. RCM findings correlating with the PASI were used to observe the patient’s response to treatment and were identified as follows: acanthosis and parakeratosis, presence of epidermal and dermal inflammatory cells, presence of non-edge dermal papillae, and vascularization in the papillary dermis. This study is the first to demonstrate the use of RCM as an effective tool for non-invasive monitoring of secukinumab therapeutic response at a cellular level in a clinical or research setting. Early detection of RCM parameters associated with secukinumab activity may facilitate the identification of an early treatment response. RCM appears to be capable of providing practical and helpful information regarding follow-up in patients with PP undergoing secukinumab treatment. RCM may also provide novel perspectives on the subclinical evaluation of PP’s response to biological therapy.

Effectiveness of secukinumab in radiographic and non-radiographic axial spondyloarthritis: a European routine-care observational study

ObjectivesTo compare the treatment effectiveness of secukinumab in radiographic (r) versus non-radiographic (nr) axial spondyloarthritis (axSpA) patients treated in routine care across Europe.MethodsProspectively collected data on secukinumab-treated axSpA patients with...

Long-Term Persistence Rate of Secukinumab in Psoriatic Patients: A Six-Year Multicenter, Real-World Experience, Retrospective Study.

Background: Psoriatic disease, a chronic immune-mediated systemic inflammatory condition, significantly impairs patients' quality of life. The advent of highly targeted biological therapies has transformed treatment strategies, emphasizing the importance of selecting the most effective and cost-efficient option. Secukinumab, an IL-17A inhibitor, has demonstrated efficacy and safety in treating moderate-to-severe plaque psoriasis (PsO). However, long-term real-world data on its effectiveness and persistence rate are limited. Methods: This retrospective study, conducted across eight Italian dermatology centers, aimed to evaluate the 6-year persistence rate and effectiveness of secukinumab in patients with PsO. Additionally, the study investigated the onset of psoriatic arthritis during treatment. Results: Overall, 166 adult patients were analyzed. Their median age was 53.9 years. The mean BMI was 26.5. Of the 166 patients, 64 were bio-experienced while 102 were bio-naïve. A progressive reduction in PsO severity measured by PASI scores over 6 years of treatment was revealed: the PASI score decreased from a baseline value of 18.1 (±9.1) to 0.7 (±1.6) after 6 years of follow-up. Adverse events, including mucocutaneous fungal infections and cardiovascular disturbances, were reported in 19.9% of patients. The persistence rate was 86.8% at 24 months, decreasing to 66.4% at 72 months. Psoriatic arthritis onset during treatment was observed in 15 (9.0%) of patients. Conclusions: This study highlights the sustained effectiveness and favorable safety profile of secukinumab over 6 years, providing valuable real-world evidence. Understanding the long-term persistence rate and predictors of discontinuation could help clinicians optimize treatment decisions and improve patient outcomes in PsO management. We found that the absence of scalp PsO, no involvement of the genital area and normal weight were the best factors of persistence in secukinumab treatment in the long term.

Differential Pharmacodynamic Effects on Psoriatic Biomarkers by Guselkumab Versus Secukinumab Correlate with Long-Term Efficacy: An ECLIPSE Substudy

IL-23 is a cytokine produced by myeloid cells that drives the T helper 17 pathway and plays an essential role in the pathophysiology of plaque psoriasis. IL-23 activation initiates a cascade of cytokines subsequently inducing the expression of many psoriasis-related proteins. This study aimed to better understand the underlying mechanisms driving the differences between IL-23 and IL-17A blockade in patients with psoriasis and their implications for durability of clinical responses. Serum and/or skin biopsies were isolated from patients treated with guselkumab or secukinumab for evaluation of potential biomarkers of pharmacodynamic response to treatment. Guselkumab treatment led to significantly greater reductions of IL-17F and IL-22 serum levels than treatment with secukinumab at weeks 24 and 48, demonstrating sustained regulation of the IL-23/T helper 17 pathway. Analyses of proteomic and transcriptomic profiles of patient sera and skin biopsies demonstrated differential regulation of proteins involved in chemokine, TNF, and relevant immune signaling pathways to a greater degree with guselkumab than with secukinumab treatment. These data provide insights into the differences between the mechanisms and impact of IL-23 and IL-17A blockade in psoriasis, with implications for efficacy observations and treatment paradigms. Trial Registration: The original study was registered at ClinicalTrials.gov (NCT03090100).

Insights into the Window of Opportunity and Outcome Measures in Patients with Moderate to Severe Hidradenitis Suppurativa Treated with Secukinumab: A Real-World Study.

The concept of a window of opportunity in hidradenitis suppurativa (HS) management suggests that early initiation of biological therapy leads to better outcomes, though its timing remains uncertain. We conducted a retrospective observational multicenter study, including consecutive patients with moderate to severe HS who initiated secukinumab treatment following prior failure with systemic antibiotics or adalimumab. Therapeutic burden was defined as the sum of previous systemic treatment cycles and previous major surgical interventions for HS. Patients were followed up for 24weeks. Main outcomes were safety and effectiveness, assessed through the proportion of patients achieving HS Clinical Response (HiSCR) and a 55% reduction in International HS Severity Score System (IHS4-55). Additionally, potential predictors of response to secukinumab were studied. Analysis was performed on an intention-to-treat basis. A total of 67 patients (33 men, 34 women) were included, with a mean age of 41.55 (11.94) years and a mean baseline IHS4 of 17.88 (11.13). The mean therapeutic burden was 6.06 (3.49). At week24, 10.45% (7/67) of patients experienced adverse events, with three leading to treatment discontinuation. At week24, 41.79% (28/67) of patients achieved HiSCR, and 44.78% (30/67) of patients achieved IHS4-55. HiSCR could not be calculated in 12 patients with a baseline AN count < 3. A lower therapeutic burden was significantly associated with a higher likelihood of achieving HiSCR and IHS4-55 at week24. Secukinumab showed safety and efficacy in real-world patients with HS, and the inverse correlation found between therapeutic burden and treatment response supports the concept of a window of opportunity, offering insights into its timing.

Effectiveness and Drug Survival of Ixekizumab and Secukinumab in Patients with Moderate to Severe Plaque Psoriasis: Real-World Data from Bucharest, Romania.

Multiple biological therapies have been developed for the treatment of inflammatory diseases, including moderate to severe plaque psoriasis. Choosing the optimal treatment for psoriasis can depend on several factors and is strongly influenced by a drug's efficacy and safety profile. Continuous treatment with biological therapies is recommended to achieve effective disease management in patients with psoriasis. However, in real-world, patients often discontinue biologic therapy within the first year of treatment. Therefore, in this study, we aimed to investigate the effectiveness and drug survival of two anti-interleukin 17 agents (ixekizumab and secukinumab) in a group of adult patients with moderate to severe psoriasis from Bucharest, Romania. We designed an observational, non-interventional, retrospective study of 255 adult patients with moderate to severe psoriasis receiving ixekizumab and secukinumab. We performed descriptive statistics and inferential methods, such as z-test, median test and Kaplan Meier curve comparison, to characterize the groups with two biological treatments. Patients treated with ixekizumab had a longer drug survival compared to those treated with secukinumab with lower risks of non-persistence, discontinuation and switching therapy. Patients age-groups and psoriasis durations found to be significant factors in drug survival. This study contributes to the understanding of the drug survival profile and the factors that may influence it in ixekizumab and secukinumab treatment in a real-world setting.

Secukinumab and Dead Sea Climatotherapy Impact Resolved Psoriasis Skin Differently Potentially Affecting Disease Memory.

Secukinumab and Dead Sea treatment result in clear skin for many psoriasis patients, through distinct mechanisms. However, recurrence in the same areas after treatments suggests the existence of a molecular scar. We aimed to compare the molecular and genetic differences in psoriasis patients who achieved complete response from secukinumab and Dead Sea climatotherapy treatments. We performed quantitative immunohistochemical and transcriptomic analysis, in addition to digital spatial profiling of skin punch biopsies. Histologically, both treatments resulted in a normalization of the lesional skin to a level resembling nonlesional skin. Interestingly, the transcriptome was not normalized by either treatments. We revealed 479 differentially expressed genes between secukinumab and Dead Sea climatotherapy at the end of treatment, with a psoriasis panel identifying SERPINB4, SERPINB13, IL36G, IL36RN, and AKR1B10 as upregulated in Dead Sea climatotherapy compared with secukinumab. Using digital spatial profiling, pan-RAS was observed to be differentially expressed in the microenvironment surrounding CD103+ cells, and IDO1 was differentially expressed in the dermis when comparing the two treatments. The differences observed between secukinumab and Dead Sea climatotherapy suggest the presence of a molecular scar, which may stem from mechanistically different pathways and potentially contribute to disease recurrence. This may be important for determining treatment response duration and disease memory.

Comparative analysis of persistence and remission with guselkumab versus secukinumab and ixekizumab in the United States

Purpose: Real-world data comparing long-term performance of interleukin (IL)-23 and IL-17 inhibitors in psoriasis are limited. This study compared treatment persistence and remission among patients initiating guselkumab versus IL-17 inhibitors. Methods: Adults with psoriasis initiating guselkumab, secukinumab, or ixekizumab treatment (index date) were identified from Merative™ MarketScan® Research Databases (01/01/2016–10/31/2021). Persistence was defined as no index biologic supply gaps of twice the labeled maintenance dosing interval. Remission was defined using an exploratory approach as index biologic discontinuation for ≥6 months without psoriasis-related inpatient admissions and treatments. Results: There were 3516 and 6066 patients in the guselkumab versus secukinumab comparison, and 3805 and 4674 patients in guselkumab versus ixekizumab comparison. At 18 months, the guselkumab cohort demonstrated about twice the persistence rate as secukinumab (hazard ratio [HR] = 2.15; p < 0.001) and ixekizumab cohorts (HR = 1.77; p < 0.001). At 6 months after index biologic discontinuation, the guselkumab cohort was 31% and 40% more likely to achieve remission than secukinumab (rate ratio [RR] = 1.31; p < 0.001) and ixekizumab cohorts (RR = 1.40; p < 0.001). Conclusions: Guselkumab was associated with greater persistence and likelihood of remission than IL-17 inhibitors, indicating greater disease control and modification potential.

ERAP1 and ERAP2 gene variants as potential clinical biomarkers of anti-interleukin-17A response in psoriasisvulgaris.

Interleukin (IL)-17A is a proinflammatory cytokine that plays an essential role in the development of psoriasis. Although treatment with anti-IL-17A monoclonal antibodies has demonstrated high efficacy in patients with psoriasis, not all patients respond equally well, highlighting the need for biomarkers to predict treatment response. Specific single-nucleotide polymorphisms (SNPs) in the genes encoding endoplasmic reticulum aminopeptidases 1 and 2 (ERAP1 and ERAP2) have been associated with psoriasis and other immune-mediated diseases. To investigate the association between the ERAP1 and ERAP2 genotypes and response to secukinumab treatment in patients with psoriasis. In total, 75 patients with plaque psoriasis were included. All patients were genotyped for the ERAP1 rs27524, rs27044, rs30187, rs2287987 and rs26653 SNPs, the ERAP2 rs2248374 SNP, and the status of the human leucocyte antigen HLA-C*06:02 gene. Our results demonstrated that individuals with specific ERAP1 and ERAP2 genotypes had a considerably lower response rate to secukinumab treatment. Patients with the ERAP2 rs2248374 GG genotype had a more than sixfold increased risk of treatment failure compared with patients with the rs2248374 AG or AA genotypes. Stratifying for HLA-C*06:02 status, the ERAP2 GG genotype pointed towards an increased risk of treatment failure among HLA-C*06:02-positive patients, although this was not statistically significant. Taken together, this unique study breaks new ground by identifying distinct ERAP1 and ERAP2 gene variants that may serve as potential biomarkers for predicting the treatment response to secukinumab in patients with psoriasis. Notably, our data extend existing knowledge by linking specific ERAP1 and ERAP2 gene variants to treatment outcome.

Is the use of secukinumab after anti-TNF therapy greater than expected for the risk of developing inflammatory bowel disease?

ObjectiveIn this study, our objective was to present real-life data on the incidence of inflammatory bowel disease (IBD) among patients receiving secukinumab treatment. MethodsThe study consisted of 209 patients who had prior exposure to anti-tumor necrosis factor (TNF) or were biologically naive. Patients with a pre-existing history of IBD were excluded from the study. ResultsOf the 209 patients in the study, 176 (84.3%) had ankylosing spondylitis, while 33 (15.7%) had psoriatic arthritis. 112 (53.6%) patients had prior exposure to at least one anti-TNF treatment before initiating secukinumab. IBD developed in 10 (4.8%) of the 209 patients. The incidence of IBD among patients who initiated secukinumab as their first biologic agent was 1%. For patients who had previously received any anti-TNF treatment and subsequently transitioned to secukinumab, the incidence of IBD was 8% (p=0.018, odds ratio (OR): 8.38, 95% CI: 1.04–67.45). A mean of 3.67 months (±4.3) after anti-TNF use, whereas IBD symptoms developed in the biologically naive patient after 15 months. ConclusionOur study observed IBD incidence in 4.8% of patients using secukinumab. Patients who initiated secukinumab after previous anti-TNF treatment exhibited a significantly higher rate and risk of developing IBD. The onset of IBD occurred earlier in these patients (mean 3.67 months), whereas a single case of IBD showed a longer duration (15 months). Further studies with larger patient numbers are warranted to provide a more comprehensive understanding of our findings.

Risk of multiple sclerosis in patients with psoriasis receiving anti-IL-17 agents: A case-based review.

Biologics approved for psoriasis exhibit favorable safety profiles, and serious adverse events have rarely been reported. In this report, we present the case of a patient treated with ixekizumab, an anti-interleukin (IL)-17 agent, who 8 months later developed multiple sclerosis (MS). We also review the available literature regarding the use of anti-IL-17 agents in the context of psoriasis and pre-existing or new-onset demyelination. Eight case reports were evaluated as relevant and are presented in our report. In most of the cases secukinumab or ixekizumab administration adequately controlled both skin and pre-existing neurological clinical manifestations. However, there has been a report of MS exacerbation under secukinumab treatment and the occurrence of myelitis in a patient receiving ixekizumab. While the anti-IL-17-biologic-mediated induction of inflammatory events in the central nervous system has not been proven and a causal relationship is lacking, such a probability should be considered in extremely rare cases.

Secukinumab after first-line tumor necrosis factor-alpha inhibitor therapy in psoriatic arthritis: A real-world retrospective cohort study.

This study compared the secukinumab treatment responses and adverse effects in psoriatic arthritis patients who received secukinumab as second-line with those that received secukinumab after two or more tumor necrosis factor-alpha (TNF-α) inhibitors. The retrospective study included 68 psoriatic arthritis patients followed up between October 2018 and October 2021. The patients were divided into two groups according to their anti-TNF-α treatment history. Group 1 consisted of 29 patients (11 males, 18 females; mean age: 45.3±13.3 years; range, 21 to 69 years) who had previously received one anti-TNF-α agent, while Group 2 included 39 patients (18 males, 21 females; mean age: 46.4±13.0 years; range, 24 to 70 years) who had been treated with two or more anti-TNF-α agents. Treatment responses of the groups were measured and compared using the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and Visual Analog Scale (VAS). A posttreatment BASDAI score ≤4 was used as a criterion for remission. The mean duration of secukinumab treatment was 16.6±12.7 months for Group 1 and 16.0±11.6 months for Group 2 (p=0.84). Both groups responded significantly to secukinumab in terms of BASDAI and VAS scores (p<0.001 and p<0.001, respectively). Group 1 had a greater decline in BASDAI and VAS scores than Group 2 (p=0.045 and p=0.032, respectively). Furthermore, the remission rate was greater in Group 1 compared to Group 2 (58% vs. 34%, p=0.03). The adverse effects of secukinumab treatment were an allergic reaction in Group 1 and one case of ulcerative colitis in Group 2. Second-line secukinumab treatment resulted in a greater decline in BASDAI and VAS scores. Moreover, secukinumab achieved a significantly higher rate of remission when it was used as second-line therapy after one anti-TNF-α agent.

A novel online calculator based on clinical features and hematological parameters to predict total skin clearance in patients with moderate to severe psoriasis

BackgroundTreatment responses to biologic agents vary between patients with moderate to severe psoriasis; while some patients achieve total skin clearance (TSC), a proportion of patients may only experience partial improvement.ObjectiveThis study was designed to identify potential predictors for achieving TSC in psoriasis patients treated with IL-17 inhibitors. It also aimed to develop an easy-to-use calculator incorporating these factors by the nomogram to predict TSC response.MethodsA total of 381 patients with psoriasis receiving ixekizumab were included in the development cohort and 229 psoriasis patients who initiated secukinumab treatment were included in the validation cohort. The study endpoint was achieving TSC after 12 weeks of IL-17 inhibitors treatment, defined as the 100% improvement in Psoriasis Area and Severity Index (PASI 100). Multivariate Cox regression analyses and LASSO analysis were performed to identify clinical predictors and blood predictors respectively.ResultsThe following parameters were identified as predictive factors associated with TSC: previous biologic treatment, joint involvement, genital area affected, early response (PASI 60 at week 4), neutrophil counts and uric acid levels. The nomogram model incorporating these factors achieved good discrimination in the development cohort (AUC, 0.721; 95% CI 0.670–0.773) and validation cohort (AUC, 0.715; 95% CI 0.665–0.760). The calibration curves exhibited a satisfactory fit, indicating the accuracy of the model. Furthermore, the decision curve analysis confirmed the clinical utility of the nomogram, highlighting its favorable value for practical application. Web-based online calculator has been developed to enhance the efficiency of clinical applications.ConclusionsThis study developed a practical and clinically applicable nomogram model for the prediction of TSC in patients with moderate to severe psoriasis. The nomogram model demonstrated robust predictive performance and exhibited significant clinical utility.Trial registration A multi-center clinical study of systemic treatment strategies for psoriasis in Chinese population;ChiCTR2000036186; Registered 31 August 2020; https://www.chictr.org.cn/showproj.html?proj=58256.

Rapid response of nail psoriasis to secukinumab in patients with moderate to severe psoriasis after 12 weeks of treatment with a total of 24 weeks of follow-up.

Nail psoriasis, a subtype of psoriasis, can cause significant pain, disability, and reduced quality of life. Despite the established efficacy of anti-IL17 secukinumab in improving skin psoriasis, there is a lack of clinical trials focusing on nail psoriasis as primary endpoint. This study aims to investigate the efficacy of secukinumab in treating nail psoriasis in patients with moderate to severe psoriasis. We prospectively recruited patients newly diagnosed with moderate to severe psoriasis in single centre from January 2021 to January 2022 who were treated with secukinumab. A total of 16 patients consisting of 9 males and 7 females were included. Their mean age was 38.88 ± 10.29 years. They had an average initial Nail Psoriasis Severity Index (NAPSI) score of 45.06 ± 20.39 and an average NAPSI score at 12 weeks of 8.94 ± 13.50, showing a significant (p < 0.05) decrease of NAPSI score after 12 weeks of secukinumab treatment. After 24 weeks of treatment, NAPSI score was decreased to 5.12 ± 8.52. Secukinumab rapidly improved nail psoriasis after 12 weeks of treatment, with further enhancement at 24 weeks, suggesting its potential as a potent therapeutic option for nail psoriasis.

Deep resolution of clinical, cellular and transcriptomic inflammatory markers of psoriasis over 52 weeks of interleukin-17A inhibition by secukinumab.

Secukinumab, an anti-interleukin (IL)-17A monoclonal antibody, induces histological and molecular resolution of psoriatic plaques by 12 weeks. However, the long-term effects of secukinumab on the molecular resolution of psoriatic inflammation remain unknown. To investigate the molecular resolution of psoriasis following 52 weeks of secukinumab treatment. This was a two-part phase II randomized double-blinded placebo-controlled 52-week study of patients with moderate-to-severe psoriasis receiving secukinumab 300 mg (NCT01537432). Psoriatic lesional and nonlesional skin biopsies were obtained at baseline and at weeks 12 and 52, and the composition of the residual disease genomic profile (RDGP; i.e. 'molecular scar') of biopsies from secukinumab responders analysed. After 52 weeks of treatment, 14 of 24 enrolled patients were considered to be clinical responders [≥ 75% improvement in Psoriasis Area and Severity Index (PASI 75)], 4 of 24 were considered to be nonresponders (< PASI 75) and 6 of 24 patients were lost to follow-up; both the histological and transcriptomic profiles of PASI 75 responders improved from week 12 to week 52. RDGP transcripts of histological responders only partially overlapped between weeks 12 and 52, despite a similar number of transcripts in each RDGP; specifically, four novel transcript subsets showed distinct expression dynamics between weeks 12 and 52 ('slow-resolving', 'recurring', 'persistent' and 'resolved'), with anti-inflammatory and immunomodulatory genes (e.g. SOCS1, CD207 and IL37) notably restored at week 52. Shorter disease duration prior to secukinumab treatment coincided with greater transcript improvements at weeks 12 and 52. Secukinumab improves the histological and molecular phenotype of psoriatic lesional skin up to 52 weeks of treatment; these results suggest possible mechanisms that drive long-term control of psoriasis.

Real‐World Experience of Secukinumab Treatment in Patients with Moderate‐to‐Severe Plaque Psoriasis in Greece: 3‐Year Interim Results of the SERENA Study

SERENA is an ongoing European noninterventional longitudinal study evaluating retention, effectiveness, safety, and quality of life (QoL) in secukinumab‐treated patients with active moderate‐to‐severe plaque psoriasis, psoriatic arthritis, and ankylosing spondylitis. Herein, 3‐year interim results among patients with psoriasis enrolled in Greece are presented. Consented adults receiving secukinumab according to the approved label for ≥16 weeks were included. Of 292 patients enrolled, 290 eligible patients (mean age 48.4 years, 71.7% male) were analyzed. At treatment initiation, 65.9% of patients were biologic‐naïve and mean total Psoriasis Area Severity Index (PASI) score was 29.0. At enrolment, mean treatment duration was approximately 1.0 year. The treatment retention rate at 1/2/3 years after enrolment was 94.4/87.3/85.9%; main reasons for discontinuation were lack of effectiveness and adverse events (AEs) (43.6% and 28.2% of discontinuations, respectively). At enrolment, the mean PASI score was 4.0, 61.3% of patients had PASI ≤ 3, 71.7% had Physician’s Global Assessment (PGA) score 0/1, 59.5% had Dermatology Life Quality Index (DLQI) score 0/1, while the mean EuroQoL Visual Analogue Scale (EQ‐VAS) score was 82.0. At 1/2/3 years postenrolment, the mean PASI score was 1.9/1.6/1.0, 86.6/89.4/90.0% had PASI ≤ 3, 89.5/94.8/97.5% had PGA 0/1, 71.1/75.9/81.8% had DLQI 0/1, and mean EQ‐VAS score was 85.7/90.0/92.0. Of enrolled patients, 7.2% experienced secukinumab‐related AEs, while special interest AEs (candida infections, malignancy, and major adverse cardiovascular events) were reported in ≤2 patients, each. These results demonstrate high secukinumab persistence in the Greek population up to three years after study enrolment, accompanied by sustained improvements in both clinical and QoL parameters and a favorable safety profile.