The Cytokine IL-17A Limits Th17 Pathogenicity via a Negative Feedback Loop Driven by Autocrine Induction of IL-24.

Dysregulated Th17 cell responses underlie multiple inflammatory and autoimmune diseases, including autoimmune uveitis and its animal model, EAU. However, clinical trials targeting IL-17A in uveitis were not successful. Here, we report that Th17 cells were regulated by their own signature cytokine, IL-17A. Loss of IL-17A in autopathogenic Th17 cells did not reduce their pathogenicity and instead elevated their expression of the Th17 cytokines GM-CSF and IL-17F. Mechanistic in vitro studies revealed a Th17 cell-intrinsic autocrine loop triggered by binding of IL-17A to its receptor, leading to activation of the transcription factor NF-κB and induction of IL-24, which repressed the Th17 cytokine program. In vivo, IL-24 treatment ameliorated Th17-induced EAU, whereas silencing of IL-24 in Th17 cells enhanced disease. This regulatory pathway also operated in human Th17 cells. Thus, IL-17A limits pathogenicity of Th17 cells by inducing IL-24. These findings may explain the disappointing therapeutic effect of targeting IL-17A in uveitis.

Better efficacy, lower recurrence rate and decreased CD8+TRM with guselkumab treatment for generalized pustular psoriasis: A prospective cohort study from China.

Generalized pustular psoriasis (GPP) is a severe and uncommon form of psoriasis, for which treatment options are limited. There is an urgent need to expand the treatment options for GPP. Currently, adalimumab, secukinumab, and guselkumab are considered effective for GPP, but there is a lack of prospective direct comparative studies on their efficacy for GPP. We conducted a prospective, single-center, observational study on 50 GPP patients to compare the efficacy, safety, and recurrence rates of these three biologics. Adalimumab, secukinumab, and guselkumab resulted in varying degrees of improvement in patients with GPP, but guselkumab exhibited superior efficacy and a lower recurrence rate than the other two drugs. This enhanced response may be attributed to the significant reduction in CD8+ tissue-resident memory T cells within GPP lesions caused by guselkumab.

Enthesitis in patients with psoriatic arthritis treated with secukinumab or adalimumab: a post hoc analysis of the EXCEED study.

OBJECTIVES: To evaluate enthesitis treatment response, including time to resolution and data from multiple enthesitis instruments, in patients with PsA treated with secukinumab or adalimumab for 52 weeks. METHODS: In this post hoc analysis of the EXCEED study, patients receiving secukinumab 300 mg or adalimumab 40 mg per the label were grouped by presence or absence of baseline enthesitis based on the Leeds Enthesitis Index (LEI) and the Spondyloarthritis Research Consortium of Canada Enthesitis Index (SPARCC). Efficacy was assessed according to several enthesitis-related instruments using non-responder imputation for the achievement of enthesitis resolution (LEI/SPARCC = 0), Kaplan-Meier analysis for time to resolution, and as-observed data for other outcomes. RESULTS: Enthesitis was present at baseline in 498 of 851 patients (58.5%) as assessed by LEI and in 632 of 853 patients (74.1%) as assessed by SPARCC. Patients with baseline enthesitis generally presented with greater disease activity. Similar proportions of patients receiving secukinumab or adalimumab achieved resolution of LEI and SPARCC at weeks 24 (secukinumab: LEI/SPARCC, 49.6%/45.8%; adalimumab: LEI/SPARCC, 43.6%/43.5%) and 52 (secukinumab: LEI/SPARCC, 60.7%/53.2%; adalimumab: LEI/SPARCC, 55.3%/51.4%), with comparable mean time to enthesitis resolution. Improvements were similar for both drugs at individual enthesitis sites. Resolution of enthesitis with secukinumab or adalimumab was associated with improvements in quality of life at week 52. CONCLUSION: Secukinumab and adalimumab showed similar efficacy, including time to resolution, with respect to resolution of enthesitis. Inhibition of IL-17 with secukinumab reduced clinical enthesitis similarly to TNF-α inhibition. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02745080.

Effectiveness and safety of secukinumab in Chinese patients with moderate to severe plaque psoriasis in real-world practice.

A number of randomized controlled trials and real-world studies have demonstrated the effectiveness and safety of secukinumab in the treatment of moderate to severe psoriasis, whereas data on a large cohort of Chinese patients in long-term real-world practice are limited. This was a single-centre, uncontrolled, single-arm, prospective, observational cohort study that included 254 psoriatic patients treated with secukinumab between September 2019 and December 2022. Demographic and clinical characteristics of patients, clinical response and adverse events were evaluated. The 75% improvement in Psoriasis Area and Severity Index score (PASI 75), PASI 90, and PASI 100 in the 300 mg secukinumab group at 12 weeks were 91.7%, 74.0% and 39.7% respectively, increasing to 94.5%, 74.5% and 47.6% at 52 weeks. High body mass index (BMI), previous exposure to biologic therapies and history of previous conventional systemic therapies were associated with lower rates of PASI response. During the study period, 68 patients reported 83 adverse events (AEs) and the most frequent AEs were eczematous lesions. Up to 14.5% patients withdrew treatment due to disease remission combined with inconvenient transportation during the COVID-19 pandemic at 52 weeks. The rate of psoriasis exacerbation after COVID-19 infection in patients treated with secukinumab was 24.3% (17/70). This real-world study confirmed the high effectiveness of secukinumab in Chinese patients with moderate to severe plaque psoriasis, with an acceptable safety profile.

Development of IL-17A inhibitor-induced atopic dermatitis-like rash in psoriasis patients: Insights into immune shift.

Cases of atopic dermatitis (AD)-like rash induced by IL-17A inhibitor secukinumab treatment (SI-AD) have been recently reported in psoriasis patients. To identify immune and inflammatory factors expression in SI-AD. A panel of 15 immune and inflammatory factors in peripheral blood samples from various groups, including patients with patients with SI-AD, psoriasis with secukinumab (S-stable), advanced psoriasis patients (Advanced) and healthy controls (HC). Interleukin-10 (IL-10), IL-4 and IL-17A were detected in skin tissue biopsy samples by immunohistochemistry and real-time quantitative polymerase chain reaction. The immunoglobulin E levels in the SI-AD patients exceeded normal values. The IL-10 levels in SI-AD patients were higher than those in S-stable patients, advanced patients and HC. The IL-4 levels in SI-AD patients were higher than that in S-stable patients and HC. The IL-17A levels in SI-AD patients were higher than those in advanced psoriasis patients and HC, but no significant differences were observed between SI-AD patients and S-stable patients. IL-10 and IL-4 levels were higher in AD-like rashes than in healthy skin, while IL-17A did not differ significantly between the two. Upon discontinuing secukinumab, and switching to oral cyclosporine, antihistamines, Janus kinase 1 inhibitor and topical glucocorticoids, SI-AD patients experienced significant improvement in their skin lesions. Upon reexamination, all 15 immune and inflammatory factors returned to normal levels. Immune shift from Th17 towards Th2 may occur in SI-AD, as indicated by abnormal expression of multiple immune and inflammatory factors observed in peripheral blood and skin tissues.

Predicting and Preventing Immune Checkpoint Inhibitor Toxicity: Targeting Cytokines.

Cancer immunotherapies can successfully activate immune responses towards certain tumors. However, this can also result in the development of treatment-induced immune-related adverse events (irAEs) in multiple tissues. Growing evidence suggests that cytokine production in response to these therapeutics potentiates the development of irAEs and may have predictive value as biomarkers for irAE occurrence. In addition, therapeutic agents that inhibit cytokine activity can limit the severity of irAEs, and their use is being tested in the clinical setting. This review provides an in-depth analysis of strategies to uncouple the cytokine response, that precipitates irAEs following cancer immunotherapies, from the benefit gained in promoting antitumor immunity.

Effect of Secukinumab and Tumor Necrosis Factor Inhibitors on Humoral Response to BNT162b2 mRNA Vaccine in Patients With Spondyloarthritis Compared to Immunocompetent Controls.

OBJECTIVE: To assess the humoral response to the BNT162b2 mRNA vaccine among patients with spondyloarthritis (SpA) receiving secukinumab (SEC) compared to those receiving tumor necrosis factor inhibitors (TNFi) and immunocompetent controls. METHODS: Consecutive patients with psoriatic arthritis or axial SpA receiving SEC (n = 37) or TNFi (monotherapy, n = 109; + methotrexate [MTX], n = 16), immunocompetent controls (n = 122), and patients with rheumatoid arthritis (RA) receiving TNFi therapy (controls, n = 50) were vaccinated with 2 or 3 doses of the BNT162b2 vaccine. We evaluated humoral response, adverse events, and disease activity, and monitored for breakthrough coronavirus disease 2019 (COVID-19) postvaccination. RESULTS: The 2-dose vaccine regimen induced a comparable seropositive response in all study groups. S1/S2 antibody titers (in binding antibody units/mL; mean [SD]) were higher in the SEC group vs the TNFi + MTX-SpA and TNFi-RA groups (192.5 [68.4] vs 104.6 [46.9], P < 0.001, and 143.1 [81.9], P = 0.004). After 6 months, 96.3%, 96.6%, and 80.9% of the SEC, immunocompetent, and TNFi monotherapy-SpA groups (P = 0.10), respectively; 66.7% of the TNFi + MTX-SpA group (P = 0.03); and 63% of the TNFi-RA group (P = 0.004) remained seropositive. S1/S2 antibody titer decline was steeper in the TNFi groups than the SEC group. After the third dose, 100% of the SpA and immunocompetent and 88.9% of the TNFi-RA (P = 0.25) groups were seropositive. Rate of breakthrough COVID-19 infection was higher in the TNFi groups than in the SEC group (36-37.5% vs 10.8%). No significant between-group differences were observed for postvaccination disease activity and adverse events. CONCLUSION: SEC did not interfere with the immunogenic response to BNT162b2 vaccine in patients with SpA; however, TNFi therapy was associated with lower S1/S2-antibody titers, faster decline, and higher rate of breakthrough infections.

Membranous lupus nephritis secondary to secukinumab therapy: A case report and literature review.

The interleukin (IL)-17 axis is involved in many inflammatory and autoimmune diseases. Secukinumab, an IL-17 inhibitor, has been approved for psoriasis treatment. There are accumulating cases of lupus erythematosus induced by IL-17 inhibition. Lupus nephritis after IL-17 inhibition has not been reported. We report the case of a 57-year-old man who developed membranous lupus nephritis after secukinumab treatment for psoriasis. Anti-SSA and PM-Scl antibodies were positive. dsDNA, anti-Smith, and anti-histone antibodies were negative, and serum complement was low. Secukinumab was discontinued, while tacrolimus was initiated, subsequently switched to cyclosporin, belimumab, glucocorticosteroid, and hydroxychloroquine with a good response. The relationship between lupus erythematosus and IL-17 inhibition requires further research.

Vaccination recommendations for adults receiving biologics and oral therapies for psoriasis and psoriatic arthritis: Delphi consensus from the medical board of the National Psoriasis Foundation.

BACKGROUND: For psoriatic patients who need to receive nonlive or live vaccines, evidence-based recommendations are needed regarding whether to pause or continue systemic therapies for psoriasis and/or psoriatic arthritis. OBJECTIVE: To evaluate literature regarding vaccine efficacy and safety and to generate consensus-based recommendations for adults receiving systemic therapies for psoriasis and/or psoriatic arthritis receiving nonlive or live vaccines. METHODS: Using a modified Delphi process, 22 consensus statements were developed by the National Psoriasis Foundation Medical Board and COVID-19 Task Force, and infectious disease experts. RESULTS: Key recommendations include continuing most oral and biologic therapies without modification for patients receiving nonlive vaccines; consider interruption of methotrexate for nonlive vaccines. For patients receiving live vaccines, discontinue most oral and biologic medications before and after administration of live vaccine. Specific recommendations include discontinuing most biologic therapies, except for abatacept, for 2-3 half-lives before live vaccine administration and deferring next dose 2-4 weeks after live vaccination. LIMITATIONS: Studies regarding infection rates after vaccination are lacking. CONCLUSION: Interruption of antipsoriatic oral and biologic therapies is generally not necessary for patients receiving nonlive vaccines. Temporary interruption of oral and biologic therapies before and after administration of live vaccines is recommended in most cases.

Synergizing pharmacometrics and pharmacovigilance for medication error management: the case of secukinumab.

PURPOSE: To demonstrate the effective integration of pharmacometrics and pharmacovigilance in managing medication errors, highlighted by a case involving secukinumab in a patient with hidradenitis suppurativa. METHODS: We present the case of a 41-year-old male with progressive hidradenitis suppurativa, unresponsive to multiple antibiotic regimens and infliximab treatment. Due to a medication error, the patient received 300 mg of secukinumab daily for 4 days instead of weekly, totaling 1200 mg. The regional pharmacovigilance center assessed potential toxicity, and a pharmacometric analysis using a population pharmacokinetic model was performed to inform dosing adjustments. RESULTS: Clinical data indicated that the received doses were within a non-toxic range. No adverse effects were observed. Pharmacometric simulations revealed a risk of underexposure due to the dosing error. Based on these simulations, it was recommended to restart monthly secukinumab injections on day 35 after the initial dose. Measured plasma concentrations before re-administration confirmed the model's accuracy. CONCLUSION: This case highlights the crucial collaboration between clinical services, pharmacovigilance, and pharmacometrics in managing medication errors. Such interdisciplinary efforts ensure therapeutic efficacy and patient safety by maintaining appropriate drug exposure levels.

Efficacy and Safety of Secukinumab for the Treatment of Psoriasis: A Meta-Analysis of Pivotal Phase III Trials.

BACKGROUND: Secukinumab, a fully humanized monoclonal antibody against IL-17A, was approved for the treatment of moderate-to-severe plaque psoriasis in the USA and European Union in 2015. OBJECTIVES: Secukinumab, a fully humanized monoclonal antibody against IL-17A, was approved for the treatment of moderate-to-severe plaque psoriasis in the USA and European Union in 2015. The aim of this study was to systematically evaluate the efficacy and safety of secukinumab for the treatment of moderate and severe plaque psoriasis and provide an evidence-based reference for clinical practice. METHODS: PubMed, Google Scholar, Cochrane Library, and Clinical Trials databases were searched. Pivotal phase III clinical trials were analysed. RevMan was used for the statistical analysis of the data. RESULTS: Seven pivotal phase III clinical trials were analysed. All trials evaluated secukinumab in moderate-to-severe plaque psoriasis and had two common primary end points: the proportion of respondents to the Psoriasis Area and Severity Index (PASI) and the proportion of respondents to the Investigator's Global Assessment (IGA). The total response ratios of PASI and IGA respondents in the secukinumab group were 82.8 and 71.3%, respectively, compared to placebo. Secukinumab was superior to etanercept, with risk ratios of 1.7 and 2.1, respectively. Secukinumab was generally well tolerated during the 1-year trial period. However, adverse events also occurred. CONCLUSION: Secukinumab was found to be more effective than etanercept and had an acceptable safety profile. Since psoriasis is an autoimmune disease that requires lifelong treatment, attention should be paid to its adverse effects.

Use of biologics in patients with psoriasis - A retrospective analysis based on real-world data.

OBJECTIVE: To summarize and analysis the application of biologic agents in patients with psoriasis in the real world. METHODS: Relying on collected data from June 2020 to September 2021 in the database of China Psoriasis Standardized Diagnosis and Treatment Center, 2529 cases of psoriasis patients treated with biologic agents in 188 different tertiary hospitals across China were retrospective analyzed. The collected information mainly includes demographic data (age, gender, psoriasis history), curative effectiveness of used biologics drug withdrawal and its reason. According to the collected information, condition of the usage for each category of biologics and influencing factor of biologics replacement were analyzed. RESULT: A total of 2529 patients were analyzed, which included 1626 male (64.29%) and 903 female (35.71%) with an average age of 42.12 ± 14.70 (17 âˆ¼ 85) years old; 2336 (92.37%) patients were aged from 19 to 60 years old. Within these patients, 2362 of them (93.40%) had a psoriasis area and severity index (PASI) score, and 1776 of these patients had moderate to severe cases (75.19%). According to the patient's self-evaluation of the past efficacy of biological agents, secukinumab was chosen by the most people to have the highest efficacy (1140 cases, 93.60%). The main reason for the withdrawal of secukinumab is that the disease is already well controlled at the time of withdrawal (67 cases, 38.95%); for TNF- α inhibitor is the poor curative effect; for ustekinumab and ixekizumab were the non-affordable price. CONCLUSIONS: In the current biotherapy of psoriasis in China, the efficacy of secukinumab is thought by most people to be the highest. Secukinumab is the first choice when the needs of changing biologics appear.

Secukinumab is not associated with cancer recurrence or progression in patients with spondyloarthritis and history of neoplastic disease.

Secukinumab is a monoclonal antibody directed against interleukin-17 approved for the treatment of psoriasis and spondyloarthritis. The favorable oncological profile of secukinumab in patients with a history of malignancy has been shown in patients with psoriasis. However, systematic data to this regard have not been published yet for patients with spondyloarthritis. The objective of the present study was to evaluate the oncological safety of secukinumab in patients affected by this group of diseases. We performed a retrospective study in which we identified from our cohort patients with spondyloarthritis treated with secukinumab and with a history of malignancy. These patients' baseline demographic, treatment, rheumatological, and oncological data were collected. The neoplastic outcome (i.e., cancer recurrence or progression) after secukinumab start was then analyzed. Our study included 22 patients with spondyloarthritis. The most frequently reported oncological diagnosis was breast cancer (9 [41%] patients). Secukinumab was started after a median of 24 months following cancer diagnosis. At this time point, all but three patients were in oncological remission. No case of cancer relapse or progression was recorded over a median follow-up of 30 months. In the largest cohort reported to date to this regard, secukinumab was not associated with oncological recurrence or progression in patients with spondyloarthritis with a history of malignancy. Secukinumab may, therefore, represent a safe option in this clinical scenario.

Paradoxical psoriasis induced by IL-17 inhibitors: a case series of patients with axial spondyloarthritis and a systematic literature review.

Following the market authorization of interleukin (IL)-17 inhibitors, a growing number of cases of IL-17 inhibitor-induced paradoxical psoriasis (PsO) have been reported. Our objectives were to present two cases of IL-17 inhibitor-induced paradoxical PsO and to systematically review the literature for similar cases, summarizing and presenting the relevant data. A systematic literature review of previously presented cases of paradoxical PsO induced by IL-17 inhibitors was conducted. We presented two patients with axial spondyloarthritis (axSpA) and paradoxical PsO induced by secukinumab (SEC). One patient's psoriatic lesions responded well to adjuvant topical treatment, while the other patient required a combination of topical treatment and cyclosporine Α for successful treatment. SEC was continued in both cases. We also identified 35 patients with IL-17 inhibitor-induced paradoxical PsO in the literature review. The most frequent types of paradoxical PsO were palmoplantar pustular and plaque PsO, while the median latency period was 11 weeks. Approximately one-third of patients continued IL-17 inhibitor treatment with adjunctive therapy, primarily topical, which produced satisfactory results in most patients. Almost two-thirds of the patients discontinued the IL-17 inhibitor, with the majority of patients switching to another biological agent with a different mechanism of action or initiating other systemic antipsoriatic treatments, resulting in mainly satisfactory outcomes. Therefore, paradoxical PsO induced by IL-17 inhibitors appears to respond well in both patients who continue IL-17 inhibitors with adjunctive treatment and those who discontinue IL-17 inhibitors while switching to a different class of biological agent or initiating other systemic antipsoriatic treatments.

Evaluation of serial QuantiFERON-TB Gold in tube test results and tuberculosis infection status in patients with psoriasis receiving anti-IL-17 treatment (secukinumab and ixekizumab): Real-world data from a tuberculosis-endemic country.

BACKGROUND: In comparison with TNF-α inhibitors, anti-IL-17A agents are considered to have a lower risk of active tuberculosis (TB) or latent TB infection (LTBI) reactivation. METHODS: In this study, we aimed to evaluate the TB infection status and serial QuantiFERON-TB-Gold in tube test (QFT) results of psoriasis patients using IL-17 inhibitors (secukinumab [SEC] and ixekizumab [IXE]) in a real-world setting from a tuberculosis-endemic country. Patients who used an anti-IL-17 agent for at least 3 months in our follow-up were included in the study. Patients' clinical and demographic features, baseline QFT results and latest QFT results (if any), and TB infection status were noted from the past medical records. RESULTS: A total of 717 patients, of whom 333 (46.4%) were female, were included in the study. The cumulative exposure time to an anti-IL-17 agent was 14,147 patient-months, 9743 patient-months for SEC and 4404 patient-months for IXE. Also, 459 (SEC = 305/IXE = 154) patients used an anti-IL-17 agent for ≥ 12 months. Of these, 125 had positive baseline QFT results. In all, 334 had negative baseline QFT results. The latest QFT result of 309 was also negative (persistent seronegative group). During follow-up, the QFT results of 10 patients changed from negative to positive (positive seroconversion group). Seven of them were using SEC and three were using IXE, respectively. No case of active TB infection was detected. CONCLUSION: In our study, the positive seroconversion rate of 10/334 seems high, but this did not translate to active disease. However, closer monitoring may be required, especially in patients with advanced age, the presence of PsA, long disease duration and long anti-IL-17 treatment duration.

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.

BACKGROUND/OBJECTIVES: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

An Update on Current Clinical Management and Emerging Treatments in Hidradenitis Suppurativa.

Hidradenitis suppurativa (HS) is a severe, debilitating, chronic inflammatory skin disease characterized by recurrent painful nodules, abscesses and draining sinus tracts in intertriginous areas. While this condition appears to stem from follicular unit dysfunction, its cause is multifactorial and the exact pathogenesis has yet to be fully elucidated. These factors make treatment selection challenging and contribute to variable therapeutic response among affected patients. Typical regimens consist of a combination of medical and surgical modalities, tailored to individual responses. However, HS is often refractory to traditional treatments, prompting the need for newer and more effective therapies. Herein, we review current and emerging HS therapies.

Does obesity affect treatment response to secukinumab and survival in ankylosing spondylitis? Real-life data from the TURKBIO Registry.

OBJECTIVES: The aim of this study was to evaluate the impact of obesity on the treatment response to secukinumab and drug survival rate in patients with ankylosing spondylitis (AS). METHODS: We performed an observational cohort study that included AS patients based on the biological drug database in Turkey (TURKBIO) Registry between 2018 and 2021. The patients were divided into three groups: normal [body mass index (BMI) < 25 kg/m2], overweight (BMI: 25-30 kg/m2), and obese (BMI ≥ 30 kg/m2). Disease activity was evaluated at baseline, 3, 6, and 12 months. Drug retention rates at 12 months were also investigated. RESULTS: There were 166 AS patients using secukinumab (56.6% male, mean age: 44.9 ± 11.6 years). The median follow-up time was 17.2 (3-33.2) months. Forty-eight (28.9%) patients were obese. The mean age was higher in the obese group than in others (P = .003). There was no statistically significant difference in Bath Ankylosing Spondylitis Disease Activity Index 50, Assessment of SpondyloArthritis international Society 20 (ASAS20), ASAS40, Ankylosing Spondylitis Disease Activity Score (ASDAS) low disease activity, and ASDAS clinically important improvement responses between the three groups at 3, 6, and 12 months, although they were numerically lower in obese patients. Drug retention rates at 12 months were similar in all groups (P > .05). CONCLUSIONS: This study suggested that obesity did not affect secukinumab treatment response and drug retention in AS patients.

Long-term efficacy, safety, and drug survival of secukinumab in patients with psoriasis in Turkey: a retrospective analysis of real-world experience.

Introduction: Secukinumab (SEC) has been shown to be highly effective and safe in the treatment of moderate to severe plaque psoriasis (PsO), but data on SEC's long-term drug survival are limited. Aim: To analyse the survival rate of SEC and its predictive factors of survival, together with the drug safety and efficacy. Material and methods: Data of 268 patients who received SEC between May 2018 and April 2022 with moderate to severe psoriasis and/or psoriatic arthritis were analysed retrospectively. Psoriasis Area Severity Index (PASI) was used to define effectiveness. Drug survival was examined using the Kaplan-Meier analysis and Cox regression analysis was used to analyse predictive factors. Results: PASI 75/90/100 responses achieved at week 16 (89.5%, 78%, and 16.2%, respectively) were well maintained at week 52 (96.3%, 90.7%, and 15.4%, respectively). The drug survival probability rates for SEC were 94.4% at 12 months, 88.4% at 24 months, 78.6% after 3 years, 52.7% after 4 years. Concomitant treatments, dose escalation and family history of psoriasis were associated with a higher risk for SEC withdrawal. Conclusions: Close monitoring may improve SEC survival in psoriasis patients who require dose escalation and concomitant drugs.

Effects of secukinumab combined with tretinoin on metabolism, liver enzymes, and inflammatory factors in patients with moderate to severe psoriasis vulgaris.

Introduction: Psoriasis is a T cell-mediated polygenic chronic inflammatory disease. Interleukin (IL)-17A plays a major role in psoriasis pathogenesis. Secukinumab is a high-affinity human monoclonal antibody against IL-17A. Aim: This article explored efficacy and safety of secukinumab plus tretinoin in moderate to severe psoriasis (MSP) vulgaris, and assessed metabolism, liver function, and inflammation. Material and methods: A total of 135 patients diagnosed with moderate or severe psoriasis vulgaris were enrolled and randomized into three groups at a 1 : 1 : 1 ratio, receiving treatment with rretinoin, secukinumab, or combination therapy for a duration of 16 weeks. Psoriasis area and severity index (PASI) scores, serum T lymphocyte subsets, glucose, lipid, and uric acid (UA) metabolism, liver enzymes, and inflammatory factors (IFs) were measured. Results: Following the therapy, subjects had decreased PASI scores, increased serum CD3+, CD4+, and CD4+/CD8+, decreased serum CD8+, and decreased serum UA and IL-2, IL-6, IL-23, interferon-γ (IFN-γ), and tumor necrosis factor (TNF)-α (p < 0.05). Total cholesterol, triglycerides, low-density lipoprotein, high-density lipoprotein, apolipoproteins A1, B, fasting blood glucose, alanine transaminase, aspartate transaminase, and alkaline phosphatase had no obvious differences among the subjects (p > 0.05). As against the Tretinoin and the Secukinumab groups, the PASI score was visiblysmaller, the changes in serum T lymphocyte subsets were more obvious, and serum UA and IFs were lower in the Combination group following the therapy (p < 0.05). Conclusions: Secukinumab combined with tretinoin is more effective in MSP vulgaris, which can visibly reduce inflammatory response without affecting glucose and lipid metabolism and liver function.