Secukinumab Therapy Research Articles

Psoriatic arthritis, biologic therapy experience, body mass index, and onset age of psoriasis were independent factors of secukinumab discontinuation in patients with psoriasis

ABSTRACT Introduction Despite the availability of several treatments for psoriasis (PsO), factors influencing the persistence of secukinumab (SEC) therapy remain inadequately understood. This study aimed to identify predictors of SEC persistence in PsO. Methods A retrospective analysis was conducted on 109 PsO patients who received SEC treatment at least 1 year. Patients were categorized based on continued or discontinued SEC therapy. Results Among the 109 patients, 64 continued SEC treatment while 45 discontinued. Univariate analysis demonstrated that PsA presence and previous biologic therapy use increased the risk of SEC discontinuation 3.56- and 2.33-fold (p = 0.001, %95 CI: 1.66–7.65 and p = 0.032, %95 CI: 1.08–5.04, respectively). Additionally, the risk of SEC discontinuation is 57% higher in patients with a body mass index (BMI) above 26.5 compared to those with a BMI below 26.5 (p = 0.016, %95 CI: 0.22–0.85). Additionally, patients with PsO onset age below 26.5 years were found to have a 2.93-times higher risk of discontinuing SEC compared to those with PsO onset age above 26.5 years (p = 0.004, %95 CI: 1.40–6.13). Conclusion PsA presence, previous biologic therapy experience, BMI, and PsO onset age were identified as independent predictors of SEC discontinuation. These findings underscore the importance of personalized treatment strategies for PsO patients receiving SEC therapy.

Combined analysis of metabolomics and 16S rRNA sequencing for ankylosing spondylitis patients before and after secukinumab therapy.

Alterations in gut microbiota have been implicated in the pathogenesis of ankylosing spondylitis (AS), but the underlying mechanisms remain elusive. This study aims to investigate changes in gut microbiota and metabolites in individuals with AS before and after treatment with secukinumab, to identify the biological characteristics specific to AS patients and investigate the potential biomarkers, for optimizing therapeutic strategies more effectively. Fecal microbiome data were collected from 30 AS patients before and after secukinumab therapy and compared with data from 40 healthy controls (HC). Additionally, we analyzed the metabolic profile of both groups from plasma. Findings indicated that the treatment-induced changes in the composition of several crucial bacterial groups, including Megamonas, Prevotella_9, Faecalibacterium, Roseburia, Bacteroides, and Agathobacter. Post-treatment, these groups exhibited a distribution more akin to that of the healthy populations compared with their pretreatment status. We identified three gut microbial taxa, namely Prevotellaceae_bacterium_Marseille_P2831, Prevotella_buccae, and Elusimicrobiota, as potential biomarkers for diagnosing individuals at a higher risk of developing AS and assessing disease outcomes. Plasma metabolomics analysis revealed 479 distinct metabolites and highlighted three disrupted metabolic pathways. Integration of microbiome and metabolomics datasets demonstrated a significant degree of correlation, underscoring the impact of the microbiome on metabolic activity. Secukinumab can restore the balance of the gut microbiome and metabolites in AS patients, rendering them more similar to those found in the healthy population. The analysis of microbiome and metabolomics data have unveiled some candidate biomarkers capable of evaluating treatment efficacy.

Rapid and sustained resolution in generalized pustular psoriasis with IL-17A inhibitors required high adherence: a 96-week analysis in a real-life setting.

Generalized pustular psoriasis (GPP) is a rare, potentially life-threatening skin disease often requiring long-term therapy. We aimed to evaluate the use of Interleukin (IL)-17A inhibitors (secukinumab and ixekizumab) in GPP patients over 96 weeks. We retrospectively analyzed a case series of 18 patients with GPP who received secukinumab (n = 13) and ixekizumab (n = 5) therapy with a 96-week follow-up period. The primary effectiveness analysis included determining the percentage of patients who achieved ≥90% or 100% improvement in the Generalized Pustular Psoriasis Area and Severity Index (GPPASI) score. Adherence was captured using the medication possession ratio (MPR). Using the as-observed (AO) method, 87% and 67% of patients treated with secukinumab or ixekizumab achieved GPPASI 90and 100responses, respectively. At Week 96, the mean GPPASI improvements from baseline GPPASI were 96.3% (95% CI: 0.91-1.01) using the AO method. After Week 48, 14 patients tapered (n = 8) or terminated (n = 6) the treatment. High-adherence therapy (MPR ≥ 80%) was significantly superior to the low-adherence group in the rate of patients achieving a GPPASI 100 response (AO, 100% vs. 38%, P < 0.05). By Week 96, 5 (27.8%) patients had new GPP flares, and 4 (80%) were in the low-adherence group. No new safety signals occurred. IL-17A inhibitors led to effective and sustained improvement in GPP patients, and high-adherence therapy had long-term positive effects on skin clearance. Given its relapsing nature, improving compliance is beneficial for long-term clinical management.

Blood Monocyte Count Can Predict Early Response to Secukinumab Therapy in Patients With Psoriasis.

Early response to treatment with biologics, defined as Psoriasis Area and Severity Index (PASI) of 2 or less six months after initiation of therapy, seems to be associated with more stable psoriasis and a lower risk of flares and treatment discontinuation. This study aimed to identify markers that can predict early response to treatment with secukinumab in patients with plaque psoriasis. Treatment with secukinumab was initiated in 29 biologic-naive patients with plaque psoriasis (75.9% males). After six months, the patients were stratified as (1) PASI 2 or less responders or (2) PASI greater than 2 responders. Patients who achieved PASI 2 or less six months after initiation of secukinumab therapy already had significantly greater PASI reductions after the first month of therapy compared to those with PASI greater than 2 six months after treatment. Baseline blood monocyte counts significantly correlated with PASI, both before and six months after initiating secukinumab therapy. A lower monocyte count with a cutoff value set at less than 0.69 &times; 103/microL (based on ROC curve analysis) was found in multivariate analysis to be an independent factor for achieving PASI 2 or less six months after initiation of therapy with secukinumab (R2 = 0.7; beta = -0.67; P = 0.03). We showed that baseline monocyte count may be useful for predicting early response to secukinumab therapy in plaque psoriasis patients. Identifying such a marker may help clinicians choose the most appropriate biologics for patients with plaque psoriasis and help avoid the expense of switching from one biologic to another. J Drugs Dermatol. 2024;23(2):74-77.&nbsp; &nbsp;&nbsp; doi:10.36849/JDD.7525.

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

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. This article explored efficacy and safety of secukinumab plus tretinoin in moderate to severe psoriasis (MSP) vulgaris, and assessed metabolism, liver function, and inflammation. 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. 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). 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.

Case report: Interleukin-17 targeted biological therapy in netherton syndrome

Netherton syndrome (NS) is rare and multisystemic congenital skin disorder classically distinguied as a triad of congenital ichthyosiform erythroderma, trichorrhexis invaginata (TI), and an atopic diathesis. Recent advances in pathogenesis have explored the role of IL-23/Th17 pathway in NS. Herein, we present a 17 years old girl harbouring homozygous four base pair deletion in exon 26 of the SPINK5 gene, presented with pruritus, scaling, dry skin and generalized eczematous lesions. She was administered anti IL17A (subcutaneous secukinumab) therapy. The treatment was well tolerated and resulted in a favourable clinical response, reduction of the IL17A gene expression and CD4 + Th17 cell population after 6 months which revealed an abrogation of Th17-skewing during therapy.

Profile of psoriasis vulgaris patients receiving secukinumab therapy in 2019-2021

Introduction: Psoriasis vulgaris can affect patients' quality of life due to its clinical appearance, expensive treatment costs, and side effects of therapy. Effective long-term treatment with secukinumab injection can help improve this condition. This study aims to identify psoriasis vulgaris conditions with secukinumab injection based on disease severity and quality of life. Methods: This study is a cross-sectional descriptive study. Data were taken from patients' medical records at the Dermatology and Venerology Polyclinic of Prof. dr. I G. N. G. Ngoerah Hospital, Denpasar, Bali, from January 2019-December 2021. Demographic characteristics variables were age, gender and history of comorbidities. Variables that reflect disease severity and quality of life were body surface area (BSA), Psoriasis Area Severity Index (PASI) and Dermatology Life Quality Index (DLQI). The distribution of BSA, PASI and DLQI scores is shown in a box plot. In comparison, the distribution of the number of cases based on each category of BSA, PASI and DLQI is presented in a proportion table. Results: There were 17 patients, mostly men, with a mean age of 38. Patients' Diagnoses were divided into psoriasis vulgaris (52.9%) and psoriasis vulgaris with psoriatic arthritis (47.1%). Based on BSA, clinical improvement was seen two weeks after initiation of therapy, while the BSA grade category improved when entering the maintenance phase. Based on the PASI score, were decreased after an average of 1 week since initiation, and the PASI grade category improved after an average of 2 weeks. Finally, based on the DLQI score, the patient's quality of life improved after an average of 4 weeks since initiation. Conclusions: There was an improvement in the severity of psoriasis vulgaris according to BSA, PASI score and overall DLQI after two cycles of initial dosing of secukinumab injection.

Successful secukinumab therapy in plaque psoriasis is associated with altered gut microbiota and related functional changes.

The role of gut microbiome dysbiosis in the pathogenesis of psoriasis has gained increasing attention in recent years. Secukinumab, targeting interleukin (IL)-17, has a promising efficacy in psoriasis treatment. However, it remains unclear the gut microbiota alteration and related functional changes caused by successful secukinumab therapy in psoriatic patients. In our study, we compared the fecal microbiome profile between psoriatic patients after secukinumab successful treatment (AT) and the other two groups, psoriatic patients without therapy (BT) and healthy people (H), respectively, by using next-generation sequencing targeting 16S ribosomal RNA. Then, shotgun metagenomic sequencing was first used to characterize bacterial gut microbial communities and related functional changes in the AT group. We found that the diversity and structure of the microbial community in the AT group were significantly changed compared to those in the BT group and the H group. The AT group showed a microbiota profile characterized by increased proportions of the phylum Firmicute, families Ruminococcaceae, and a reduction in the phylum Bacteroidota (elevated F/B ratio). To detect functional alteration, we discovered that secukinumab treatment may construct a more stable homeostasis of the gut microbiome with functional alteration. There were different KEGG pathways, such as the downregulated cardiovascular diseases pathway and the upregulated infectious diseases in the AT group. By metagenomic analysis, the metabolic functional pathway was changed after secukinumab therapy. It seems that gut microbiota investigation during biologic drug treatment is useful for predicting the efficacy and risks of drug treatment in disease.

Secukinumab plays a synergistic role with starvation therapy in promoting autophagic cell death of hepatocellular carcinoma via inhibiting IL-17A-increased BCL2 level.

It is known that IL-17A inhibits autophagy of hepatocellular carcinoma (HCC) cells, thus contributing to the carcinogenesis of HCC. Starvation therapy can promote the autophagic death of HCC cells by blocking the nutrition supply. The purpose of this study was to explore whether the pharmacological antagonist of IL-17A, secukinumab, and starvation therapy have a synergistic effect on the autophagic cell death of HCC. Here, it could be observed that compared with serum-free condition, the combination of secukinumab and serum-free status better promoted autophagy (observed by LC3 conversion rate, p62 protein expression and the formation of autophagosomes), and more significantly inhibited the survival and function (observed by Trypan blue staining, CCK-8, Transwell, and scratch assays) in HCC HepG2 cells. Moreover, secukinumab significantly decreased BCL2 protein expression under serum-normal and serum-free conditions. However, both the addition of recombinant IL-17A and overexpression of BCL2 blocked the regulation of secukinumab on the survival and autophagy in HepG2 cells. Nude mice experiments demonstrated that compared to the lenvatinib-alone group, the combination group of lenvatinib and secukinumab better inhibited the in vivo tumorigenesis of HepG2 cells and enhanced autophagy in xenotumor tissues. Furthermore, secukinumab significantly decreased BCL2 protein expression in xenotumor tissues without or with lenvatinib application. In conclusion, the antagonism of IL-17A with secukinumab, due to the upregulation on BCL2-related autophagic cell death, can cooperate with starvation therapy in inhibiting HCC carcinogenesis. Our data suggested that secukinumab can become an effective adjuvant for the treatment of HCC.

When to start secukinumab treatment in patients with axial spondyloarthropathy: Before or after anti-TNFα treatment?

Introduction and objectivesThis study aimed to evaluate the efficacy of secukinumab (SEC) in axial spondyloarthropathy (axSpA) in anti-TNFα naïve and anti-TNFα experienced patients. It also focused on the duration of SEC treatment and its side effects. Patients and methodsThe patients with axSpA treated with SEC and followed up in our outpatient clinic from May 2018 through October 2021 were included in this study. All patients in the study also fulfilled the ASAS classification criteria for axSpA. Patients were separated into two groups according to whether they received prior anti-TNFα therapy. While anti-TNFα naïve patients comprised group 1, anti-TNFα experienced patients were included in group 2. Pre- and post-treatment BASDAI scores were reported and compared. ResultsEighty-four axSpA patients (42 men; duration of the disease: 86.86±65.35 months in group 1 and 160.65±97.4 months in group 2) were treated with SEC. 45.5% of anti-TNFα naïve patients and 56.5% of anti-TNFα experienced patients were still on SEC therapy in October 2021. Duration of SEC treatment was 12.5±7.9 months in group 1 and 17.19±12 months in group 2 (p=0.098). The differences between pre-and post-treatment BASDAI scores were statistically significant in both groups (p<0.001). While patients in group 1 did not develop any adverse effects, three patients in group 2 experienced alopecia, uveitis, and recurrent pneumonia after SEC treatment. ConclusionOur study's efficacy and safety data on the use of SEC were reassuring in both anti-TNFα naïve and anti-TNFα experienced patients. However, further studies are still needed to determine the appropriate timing to begin SEC treatment.

Impact of biological and non-biological treatment on hematological indices in patients with ankylosing spondylitis and psoriatic arthritis

BackgroundBlood dyscrasias are common in patients with rheumatic diseases, as bone marrow and blood cells can be targets for autoimmune processes. This in addition to the potentially adverse effect of the disease-modifying anti-rheumatic drugs used for the treatment of inflammatory arthritis as in psoriatic arthritis (PsA) and ankylosing spondylitis (AS) on blood counts.Aim of this studyThe aim of this study is to analyze the effect of biologic therapy on complete blood cell parameters, derived ratios, and cell volume indices in Egyptian patients with ankylosing spondylitis and psoriatic arthritis.ResultsOne hundred and twenty Egyptian patients had been included, 60 have ankylosing spondylitis (AS) and 60 have psoriatic arthritis (PSA). On comparing the blood indices between the biologics and non-biologics groups of PSA patients, there was a statistically highly significant reduction in red cell distribution width (RDW%) at the biologics group than non-biologics (p < 0.006), where there was a statistically highly significant increase in Hb (hemoglobin)/RDW ratio and Hb/platelets ratio at the biologics group than non-biologics (p < 0.005).ConclusionAs a result, biologic drugs used in rheumatology practice may have some effects on hematological parameters. In our study, no major negative effects on hematological parameters were observed in patients with AS and PsA who received Secukinumab, Adalimumab-atto, or Golimumab biologic therapy. However, the changes in the hematological indices correlates with their potent anti-inflammatory action in rheumatic patients.

Successful long‐term treatment of pyoderma gangrenosum with secukinumab

AbstractPyoderma gangrenosum (PG) belongs to the group of classical neutrophilic dermatoses and is characterised by painful ulcerations. While the clinical features have been well described, the underlying pathological mechanisms are incompletely understood and adequate treatment remains challenging. A 63‐year‐old male patient had suffered from recalcitrant ulcerations on the back, groins and legs for over 20 years. Due to suspicion of PG, a skin biopsy of the flank was obtained, which was confirming the suspected diagnosis. Following several frustrating attempts to treat, another skin biopsy was carried out and a cytokine profile by quantitative reverse transcription polymerase chain reaction was performed. Compared to healthy skin, a notable upregulation of interleukin (IL)‐17A and IL‐8 was detected. Subsequently, treatment with the anti‐IL17 antibody secukinumab was started. After 3 months of treatment, the PG area was 0 cm2. Due to the discontinuation of the drug by the patient typical PG lesions reappeared, all of which disappeared again within a few weeks of restarting secukinumab therapy. At month 23, the PG area was again 0 cm2 and this complete response was maintained under secukinumab therapy to this day (76 months after the onset of secukinumab therapy). This case of a patient with therapy‐resistant PG and subsequent long‐term responsiveness to anti‐IL‐17 therapy supports the potential importance of the Th17 axis in PG. Collectively, treatment of PG using IL‐17 antagonists seems to be very promising.

The effect of IL-17 blockage on the neutrophil to lymphocyte ratio in patients with axial spondylarthritis: a comparative study with anti-TNF

Objectives: This study aims to evaluate the neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) in patients with axial spondyloarthritis receiving different biologic treatments. Methods: The study included 33 axial spondyloarthritis patients (20 males, 13 females) receiving anti-TNF or secukinumab therapy. Patients’ age, disease duration, ongoing therapy duration, serum C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR), neutrophil, lymphocyte and platelet counts, Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) scores, NLR, and PLR were recorded retrospectively. Results: The patients' mean age was 44 years, and the disease's mean duration was 121.55 months. Fourteen (42.4%) patients were receiving secukinumab, 57.6% of the patients were receiving anti-TNF agents. The male/female ratio was 6/8 in the secukinumab group and 14/5 in the anti-TNF group. The ongoing therapy duration was 8 ± 5.1 months for the secukinumab group and 27 ± 27.6 months for the anti-TNF group. Only NLR was significantly higher in the secukinumab group, and there was no other statistical difference between groups. There was no correlation between NLR, PLR, and CRP, ESR, BASDAI. Conclusions: The results of our study show that only NLR is significantly higher in the secukinumab group compared to the anti-TNF group. Hence NLR may be a useful and sensitive parameter in terms of monitoring disease activity.

Secukinumab Therapy in Refractory Juvenile Idiopathic Arthritis.

Juvenile idiopathic arthritis (JIA), the most common chronic rheumatologic condition in childhood, remains a cause of significant morbidity, particularly in those with spondyloarthropathy, including psoriatic arthritis (PsA) and enthesitis-related arthritis (ERA). While secukinumab was recently approved for the treatment of children and adolescents with ERA and PsA, there is limited published data on its use in JIA, particularly in refractory cases, despite its efficacy in the treatment of adult arthritis. We aim to examine the use of this therapy in JIA in a single pediatric rheumatology center. A retrospective chart review was performed and 10 JIA patients who received treatment with secukinumab were identified. Data extracted included disease activity, patient demographics, comorbidities, medications, and laboratory data. Seven ERA, 2 PsA, and 1 poly JIA patient were treated with secukinumab at our center between April 2011 and July 2021. These patients had notably resistant disease, with a mean disease-modifying antirheumatic drug (DMARD) failure rate of 3.8. One hundred percent of patients who underwent magnetic resonance imaging (MRI) after being on at least 3 months of secukinumab therapy demonstrated improvement in their MRI findings. One patient developed a flare of uveitis while on secukinumab therapy, with no other adverse events recorded in our patients. Secukinumab therapy was recently approved for children and adolescents with ERA and PsA, and may offer an efficacious option given its demonstrated improvement in imaging and joint examination, as well as qualitative reports of pain, even in those who have failed other therapies. However, caution may be warranted in those with a history of uveitis and warrants further study.

Quantification of pre-existing radiographic damage and its relationship with joint activity and long-term clinical outcomes with secukinumab therapy in patients with psoriatic arthritis

BackgroundPsoriatic arthritis (PsA) patient data from two phase 3 secukinumab trials (FUTURE 1, 5) were analysed to quantify the prevalence and extent of pre-existing radiographic damage (RD) at baseline; investigate the association of RD with swollen/tender joint counts (SJC/TJC) at baseline; and investigate the extent to which RD at baseline correlated with response to secukinumab.MethodsPooled data (N = 1554) provided baseline radiographic bone erosion and joint space narrowing (JSN) scores at pre-specified locations per the van der Heijde-modified total Sharp score (vdH-mTSS) for PsA and swollen and tender joint scores in the same joints at multiple visits. Overall patient RD and individual joints RD bone erosion and JSN scores were assessed. The association between joint activity (tenderness, swelling) and vdH-mTSS was assessed at the overall patient-level and individual joint tender, swollen scores (yes/no) and RD joint JSN and bone erosion scores at the individual joint-level. Treatment response was assessed using SJC/TJC at weeks 16 and 52 and the proportion of patients achieving minimal disease activity (MDA) over all assessments within 1 year from FUTURE 5 alone.ResultsA substantial prevalence of pre-existing RD with higher prevalence of erosion than JSN was observed (86% and 60% of patients had positive erosion and JSN scores, respectively); higher RD prevalence was associated with longer time since PsA diagnosis. Joint activity was weakly associated with RD at baseline at the patient-level (Pearson’s coefficients: range 0.12–0.18), but strongly associated at the individual joint-level, with a higher probability of tender/swollen joints to associate with higher JSN/erosion scores: all 42 analysed joints showed statistical significance at the 0.05 level (unadjusted) for the relationship between joint tenderness (yes/no) and its JSN score, all but one for tenderness and bone erosion scores, and all but 2 for swollen and JSN scores and for swollen and bone erosion score. Secukinumab (150/300 mg), reduced TJC and SJC across all values of baseline erosion and JSN scores at weeks 16 and 52. Patients with higher levels of RD were less likely to achieve zero tender/zero swollen joint status and had lower chance of achieving MDA.ConclusionsPsA patients showed substantial prevalence of RD at baseline that correlated with time since diagnosis, but patient’s individual joint activity was strongly associated with pre-existing RD at those joints. Patients with the highest RD at baseline had a reduced likelihood of achieving zero joint count status.

A Review of the Safety of Interleukin-17A Inhibitor Secukinumab.

Secukinumab is an anti-interleukin (IL)-17A IgG1-κ monoclonal antibody approved for psoriasis, psoriatic arthritis, and ankylosing spondylitis. Its efficacy is well documented, but the complete safety profile of secukinumab, especially on long-term use, needs to be studied. IL-17 inhibitors increase the risk of infections, especially respiratory tract infections and candidiasis, and inflammatory bowel disease; the causal relationships are well described. However, evidence regarding the other adverse events is scarce, and causal associations between the adverse events and the biologic remain unresolved. This review aims to present a narrative perspective on the safety of secukinumab and identify some key areas where the safety of secukinumab may potentially be useful in understanding the scope of secukinumab therapy and making informed clinical decisions.

S2755 New-Onset Crohn’s Disease Unmasked by Secukinumab

Introduction: Psoriasis is an autoimmune disease that affects 1% to 2% of the population. Patients with this condition showed high expression of proinflammatory cytokines including interleukin (IL)-17. Secukinumab, an IL-17 inhibitor, is indicated for the treatment of psoriasis and psoriatic arthritis. IL-17 inhibition in patients with Crohn’s disease may be associated with worsening of the disease. We present the case of a 38-year-old female who received secukinumab therapy for psoriatic arthritis with subsequent unmasking of Crohn’s disease. Case Description/Methods: A 38-year-old female with psoriatic arthritis, presented with generalized abdominal pain, and diarrhea. She had no prior history or family history of inflammatory bowel disease (IBD). She started treatment with secukinumab one month prior to her presentation. After receiving 4 doses of secukinumab, she developed fecal urgency, watery diarrhea with intermittent hematochezia. Laboratory evaluation showed elevated inflammatory markers. Computed tomography of the abdomen showed colitis. Secukinumab was stopped and the patient was scheduled for esophagogastroduodenoscopy and colonoscopy which revealed ulcers in the antrum, terminal ileum, and throughout the colon. Biopsies showed acute and chronic colitis consistent with Crohn’s disease. Secukinumab was changed to infliximab which led to resolution of her symptoms. Six months later, colonoscopy showed no active inflammation (Figure). Discussion: IL-17 is a proinflammatory cytokine that has a significant role in autoimmune disorders including psoriasis and psoriatic arthritis. IL-17 may play a protective role in IBD. A few case reports describing new-onset IBD in patients treated with secukinumab, IL-17 inhibitor, have been reported. The incidence rate of IBD in patients treated with secukinumab in 21 pooled studies was 0.56%. In our case, IBD was unmasked one month after starting secukinumab. This rare occurrence can happen anytime from one week up to one year or longer after starting secukinumab. Although studies have shown very low incidence of new onset or exacerbation of preexisting IBD with IL-17 inhibitors, this association is not negligible. Clinicians should perform thorough risk stratification and screening for IBD prior to therapy and close monitoring for new-onset or worsening IBD following IL-17 inhibitor therapy initiation. Other agents that target IL-23 (ustekinumab) instead of IL-17 have shown promise in treating both psoriasis and IBD.Figure 1.: Colonoscopy from 5/2021 shows terminal ileum with aphthous ulcerations (A) and scattered ulcerations in the rectosigmoid (B). Colonoscopy from 1/2022 shows normal ileum (C).

Global circRNA expression changes predate clinical and histological improvements of psoriasis patients upon secukinumab treatment.

Psoriasis is a common chronic inflammatory skin disease accompanied by heterogenous clinical and histological features, including a characteristic keratinocyte hyperproliferation and dermal immunogenic profile. In addition, psoriasis is associated with widespread transcriptomic alterations including changes in microRNA (miRNA) and circular RNA (circRNA) abundance, which constitute non-coding RNA (ncRNA) classes with specific regulatory capacities in diverse physiological and pathological processes. However, the knowledge about the expression dynamics of ncRNA during psoriasis treatment is sparse. To elucidate the dynamics of miRNA and circRNA abundance during secukinumab (anti-IL-17A) treatment, we studied their expression patterns in skin biopsies from 14 patients with severe plaque-type psoriasis before and during an 84-day secukinumab therapy at day 0, 4, 14, 42, and 84 using NanoString nCounter technology. We found a comprehensive downregulation of the majority of investigated circRNAs and specific alterations in the miRNA profile, including an upregulation of miR-203a-3p, miR-93-5p, and miR-378i in lesional compared to non-lesional skin before treatment. During treatment, the circRNAs progressively returned to the expression levels observed in non-lesional skin and already four days after treatment initiation most circRNAs were significantly upregulated. In comparison, for miRNAs, the normalization to baseline during treatment was delayed and limited to a subset of miRNAs. Moreover, we observed a strong correlation between multiple circRNAs, including ciRS-7 and circPTPRA, and the psoriasis area and severity index (PASI). Similar pronounced correlations could, however, not be found for miRNAs. Finally, we did not observe any significant changes in circRNA expression in peripheral blood mononuclear cells during treatment. In conclusion, we uncovered a rapid shift in global circRNA abundance upon anti-IL-17A treatment, which predated clinical and histological improvements, and a strong correlation with PASI, indicating a biomarker potential of individual circRNAs.

Successful treatment of secukinumab in severe plaque psoriasis

Psoriasis is a persistent, chronic condition that manifests on the skin, joints, and other visible places that compromises the quality of life. The vast understanding of the pathophysiology of psoriasis has led to a rise in the use of biological therapy in treating psoriasis in recent years. A 48-year-old woman with severe plaque psoriasis was previously treated with methotrexate and phototherapy for 3 months, however, the treatment showed no significant improvement. The patient was then treated with a biological agent, namely secukinumab, with a dose of 150 mg weekly for 5 weeks followed by one dose a month later. The symptoms were improved considerably after 10 weeks of observation, which indicated by the decrease in Psoriasis Area Severity Index (PASI) score and the Dermatology Life Quality Index (DLQI) score. There was no significant side effect during the observation. This case showed that secukinumab therapy at a dose of 150 mg can successfully treat severe plaque psoriasis patient.

Should we be concerned about gastrointestinal-related adverse events in patients with plaque psoriasis receiving secukinumab therapy? A retrospective, real-life study.

Real-world secukinumab gastrointestinal-related adverse events (GIRAE) data in psoriatic patients treated with secukinumab are lacking. A descriptive, retrospective study was performed by reviewing the medical records of patients who received secukinumab for plaque psoriasis for at least 1 year and who made a follow-up visit to the dermatology clinic of "Ospedali Riuniti Umberto I" in Ancona between December 1, 2021, and March 31, 2022. The patients' medical history and clinical data were collected at T0, before treatment, and at T1, corresponding to the last follow-up visit. Special attention was given to gastrointestinal adverse events (GIRAE). A total of 108 patients were included in the study. At baseline median PASI was 14.8 (range 2.2-27, SD 6.1), and median DLQI was 9.3 (5-16, SD 2.6). The median PASI for treated patients was 0.7 (0-3, SD 0.8; p< 0.00) 1and median DLQI was 0.3 (0-1, SD 0.5; p< 0.001). At T1 54/114 patients (50%) reached PASI100, of the other 54, 48 (88.9%) reached PASI 90 while the other six discontinued for secondary ineffectiveness. Only three patients reported a GIRAE (diarrhea), however, when screened, no IBD was found. Consistent with data in the literature, secukinumab is an effective and safe drug for the treatment of plaque psoriasis also in a real-life experience context. There should be no concern in choosing the drug for fear of possible IBDs-related GIRAE if there is no personal history or familiarity for IBDs.