anti-IL-6 Research Articles

Peli1 Deficiency in Macrophages Attenuates Pulmonary Hypertension by Enhancing Foxp1-Mediated Transcriptional Inhibition of IL-6.

The infiltration of macrophages into the lungs is a common characteristic of perivascular inflammation, contributing to vascular remodeling in pulmonary hypertension (PH). Peli1 (pellino E3 ubiquitin-protein ligase 1) plays a critical role in regulating the production of proinflammatory cytokines and the polarization of macrophages in various diseases. However, the role of Peli1 in PH remains to be investigated. The expression and biological function of Peli1 were investigated in both human and experimental models of PH. Peli1-deficient mice and bone marrow transplant mice were utilized to explore the roles of Peli1 in macrophages in vivo. Proteomic analysis and molecular biology techniques were used to uncover the underlying mechanisms. The upregulation of Peli1 in the lungs and alveolar macrophages was observed in hypoxia-treated mice. Peli1 knockout mice and myeloid Peli1-deficient mice significantly ameliorated hypoxia-induced right ventricular systolic pressure, right ventricular hypertrophy, and pulmonary vascular remodeling. Mechanistically, Peli1 facilitated the ubiquitination and subsequent proteasomal degradation of Foxp1 (forkhead box p1), thereby alleviating its suppression of IL (interleukin)-6 transcription and contributing to macrophage activation. Furthermore, myeloid Foxp1 deficiency partially eliminates the protective effect of myeloid Peli1 deficiency in hypoxia-induced PH mice. Our findings demonstrate that the Peli1-Foxp1-IL-6 pathway plays a crucial role in macrophage activation and recruitment during the development of PH, underscoring the potential of Peli1 as a therapeutic target for PH.

Interleukin-6 Inhibitors for Neuromyelitis Optica Spectrum Disorder (NMOSD): a Systematic Review and Meta-analysis

BackgroundInterleukin-6 (IL-6) inhibitors recently emerged as a promising therapy for neuromyelitis optica spectrum disorder (NMOSD). ObjectiveWe performed a systematic review and meta-analysis comparing IL-6 inhibitors to placebo or traditional immunosuppressants in NMOSD. MethodsWe searched PubMed, Embase, and Cochrane Central for eligible studies. Efficacy endpoints included hazard ratio (HR) for relapse, annualized relapse ratio (ARR) and Expanded Disability Status Scale (EDSS) change over time. Safety outcomes comprised any adverse event, serious adverse events and infections. Statistical analysis was performed using RevMan Web and R studio package meta. Heterogeneity was assessed with I² statistics. ResultsFour studies involving 361 patients (228 treated with IL-6 inhibitors) were included. IL-6 inhibitors significantly reduced HR for relapse (HR 0.35; 95% CI 0.23, 0.55); p<0.00001; I²=0%) and ARR (mean difference -0.79 relapses/year; 95% CI -1.54, -0.03; p=0.04; I²=96%) compared to placebo or traditional immunosuppressants. No significant differences were observed in EDSS change over 24 weeks of follow-up (mean difference -0.18; 95% CI 0.41, 0.05; p=0.93; I²=0%), adverse events (odds ratio (OR) 1.59; 95% CI 0.45, 5.63; p=0.48; I²=48%), serious adverse events (OR 0.76; 95% CI 0.40, 1.44; p=0.50; I²=0%) and infection rates (OR 1.10; 95% CI 0.67, 1.79; p=0.71; I²=0%). ConclusionIL-6 inhibitors demonstrate superior efficacy in preventing relapses in NMOSD compared to placebo or traditional immunosuppressants, without a notable increase in safety risks.

Post-Marketing Safety of Ustekinumab Based on 14-Year Follow-Up in Danish National Patient Data.

Psoriasis (PsO), a chronic inflammatory skin disorder affecting a substantial proportion of populations globally, often necessitates systemic treatment including biologics. This 14-year cohort study, based on Danish national register data, aimed to investigate the enduring safety profile of ustekinumab compared to other systemic psoriasis treatments. Using comprehensive Danish national register data, this study scrutinized patients diagnosed with psoriasis or psoriatic arthritis (PsA) who received ustekinumab. The treatment group comparators were non-biological systemic treatment (non-biologic), tumor necrosis factor α inhibitor medicine groups (TNF-α), interleukin (IL)-17 inhibitors (IL-17), and IL-23 inhibitors (IL-23). The study periods for comparisons were 2009-2022 for non-biologic and TNF-α, 2015-2022 for IL-17, and 2018-2022 for IL-23. Outcomes were malignancies, cardiovascular events, serious infections, and serious hypersensitivity reactions. Cox proportional hazards regression models were employed to analyze two estimands: a standard intention-to-treat (ITT) estimand and a continuous-index-treatment (CIT) estimand, which considered switch and re-initiation of treatments within individuals. Users of ustekinumab were found to be younger on average, with an average age of 45.1 years compared to 51.6, 47.2, 49.0, and 48.4 years in the non-biologic, TNF-α, IL-17, and IL-23 groups, respectively. Also, 57.3% of the ustekinumab users were male, compared to 46.7%, 48.9%, 50.9%, and 58.3% for the non-biologic, TNF-α, IL-17, and IL-23 groups, respectively. Although the hazard ratio estimates varied across comparators, ustekinumab was found to be safe: regardless of PsA status, no discernible safety signals in terms of malignancy, MACE, severe infections, or severe hypersensitivity reactions were observed for ustekinumab when compared to the treatment comparators. The present study corroborated the enduring safety of ustekinumab in the context of PsO treatment.

Current Concepts and Medical Management for Patients with Radiographic Axial Spondyloarthritis.

Radiographic axial spondyloarthritis (r-axSpA), a chronic inflammatory disease, can cause significant radiographic damage to the axial skeleton. Regarding the pathogenic mechanism, association of r-axSpA with tumor necrosis factor (TNF) and the interleukin-23/17 (IL23/ IL17) pathway has been reported. Development of extraarticular manifestations, including uveitis, inflammatory bowel disease, and psoriasis, has been reported in some patients. The pivotal role of human leukocyte antigen-B27 in the pathogenesis of r-axSpA remains to be clarified. Symptoms usually start in late adolescence or early adulthood, and disease progression can vary in each patient, with clinical manifestations ranging from mild joint stiffness without radiographic changes to advanced manifestations including complete fusion of the spine, and severe arthritis of the hip, and could include peripheral arthritis and extraarticular manifestations. The modified New York criteria was used previously in diagnosis of r-axSpA. However, early diagnosis of the disease prior to development of bone deformity was required due to development of biological agents. As a result of Assessment of SpondyloArthritis international Society (ASAS), the classification was improved in part for diagnosis of spondyloarthritis prior to development of bone deformity. The diagnosis is based on comprehensive laboratory findings, physical examinations, and radiologic findings. Medical treatment for r-axSpA involves the use of a stepwise strategy, starting with administration of nonsteroidal anti-inflammatory drugs and physiotherapy, and progressing to sulfasalazine or methotrexate and biologics including TNF-α inhibitors or IL-17 inhibitors as needed. Use of Janus kinase inhibitors has been recently reported.

Pickering high internal phase emulsions stabilized by soy protein isolate/κ-carrageenan complex for enhanced stability, bioavailability, and absorption mechanisms of nobiletin

Nobiletin (NOB), a lipid-soluble polymethoxyflavone with potent antioxidant, antimicrobial, and anti-inflammatory properties, suffers from poor stability and pH sensitivity, limiting its bioavailability. In this study, Pickering high internal phase emulsions (HIPEs) stabilized by soy protein isolate (SPI) and κ-carrageenan (KC) were developed to encapsulate and protect NOB. The emulsions, containing a 75 % medium-chain triglyceride (MCT) volume fraction, were optimized by investigating the effects of pH and KC concentration on the key properties such as the creaming index, particle size, zeta potential, microstructure, and rheology. Results showed that under optimal conditions (pH 7 and 1.0 % KC), the SPI/KC HIPEs exhibited improved physicochemical properties. Furthermore, encapsulation of NOB in HIPEs significantly improved its stability against UV exposure, heat, and storage conditions. Additionally, simulated gastrointestinal digestion studies revealed that the SPI/KC HIPEs improved the digestion stability and bioaccessibility of NOB, with controlled release in the intestinal phase. Moreover, the SPI/KC HIPEs facilitated increased cellular uptake and bioavailability of NOB, with clathrin-mediated endocytosis and macropinocytosis as primary absorption pathways. The encapsulated NOB also showed enhanced inhibition of inflammatory markers, including NO, IL-6, and TNF-α. These findings suggested that SPI/KC HIPEs provided a promising delivery system for improving the bioavailability and bioactivity of hydrophobic compounds.

The Role of Panax Notoginseng Saponins on Neuronal Oxidative Stress and Autophagy Response in Craniocerebral Injury Model Rats

This study assessed how IL-6 affects the body’s autophagy status by regulating JAK-STAT3 and explored the mechanism by which IL-6 inhibits JAK-STAT3 signaling pathway-mediated autophagy, and how Panax notoginseng total saponins promote neuronal cell regeneration in rats. A model of neuronal oxidative stress in craniocerebral injury model rats was established, and IL-6 levels were detected by ELISA. Rat neuronal cells were isolated and cultured, while dual-luciferase gene reporter experiments analyzed the targeting relationship between IL-6 and JAK. qRT-PCR detected expression of neuronal autophagy-related genes (JAK, STAT3, ULK1, OsATG7, FAM176A, and Beclin 1). The level of IL-6 in the craniocerebral injury model was significantly higher than that in the control group. IL-6 binds to 3′-UTR of JAK, and transfection with IL-6 inhibitor increases the relative luciferase activity. pMIR-JAK-mut group has no significant effect. There is a targeted regulatory relationship between IL-6 and JAK. Adding total saponins of Panax notoginseng combined with nursing intervention can promote reduction genetic expression related to neuronal autophagy damage. IL-6 can target and regulate JAK gene. IL-6 can promote neuronal development by regulating JAK-STAT3. Autophagy repairs damage and inhibits the autophagy state of cells. Panax notoginseng total saponins are effective medicinal components extracted from high quality panax notoginseng according to extraction and separation technology. The results from this study provide a better understanding of pathogenesis of neuronal oxidative stress in craniocerebral injury model rats and find potential intervention targets, which will provide more treatment methods for neuronal oxidative stress damage in craniocerebral injury model rats.

Hidradenitis Suppurativa: A Review of the Biologic and Small Molecule Immunomodulatory Treatments.

Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease that presents as painful, deep-seated nodules, sinus tracts, and abscesses in about 1% of the population. Although the pathogenesis of HS is not perfectly understood, it is generally recognized to be caused by a combination of genetic, endocrine, environmental, and microbiological factors. The treatment principles of HS focus on decreasing the microbial load with antibiotics and/or modulating the host immune response to reduce inflammation. The treatment of adults with moderate-to-severe HS has significantly changed recently with the development of new biological medications and immunomodulators. While previously the mainstay of treatment of moderate-to-severe HS was adalimumab, a biologic tumour necrosis factor α inhibitor, the evidence for the use of other treatment classes such as interleukin (IL)-17 inhibitors, IL-1 inhibitors, and Janus kinase inhibitors has been growing. The goal of this review article is to review the available evidence that supports the efficacy and safety of biologics and small molecule immunomodulator treatments to treat adults with moderate-to-severe HS.

Comment on: "Hepatitis B reactivation in PsA patients: an SLR and meta-analysis for IL-17, IL-23 and JAK inhibitors": reply.

Comment on: "Hepatitis B reactivation in PsA patients: an SLR and meta-analysis for IL-17, IL-23 and JAK inhibitors": reply.

Efficacy and persistence comparison of TNF-alpha inhibitors and IL-17 inhibitors in patients with axial spondyloarthritis: experience of a tertiary centre

Efficacy and persistence comparison of TNF-alpha inhibitors and IL-17 inhibitors in patients with axial spondyloarthritis: experience of a tertiary centre

Real-World Switch Rates of Risankizumab and Other Biologics in Psoriasis Patients With Psoriatic Arthritis

Background: Psoriatic patients often experience issues with lack of therapeutic efficacy and intolerance, which may result in high levels of treatment switching. This study examined real-world, 12-month switch rates and patient characteristics associated with treatment switching in patients with both PsO and PsA treated with risankizumab and other biologics. Methods: This analysis used the Merative MarketScan® Databases (2016–2024) to identify adults from the US who had ≥2 medical claims for PsO, 1 claim for PsA and did not have any other autoimmune condition in the 6 months pre- and post-index period. Patients must have initiated a PsO-approved biologic and have continuous insurance benefits for ≥6 months before and ≥12 months after the biologic initiation date. Switch rates were defined as the proportion of patients who switched to a new biologic or advanced oral in the 12-month follow-up after treatment initiation. Discontinuation and non-adherence were not included in the switch definition. Switch rates were compared between biologics with sufficient sample size (n 100). Univariate logistic regression analyses were conducted to compare switch rates for risankizumab versus other biologics. Multivariate logistic regression analyses were performed to examine the impact of baseline demographic and treatment characteristics on switch rates and determine predictors of switching. Results: Among 3032 patients, mean age at baseline was 47.4 (SD 10.78) years and 55.4% were female. Overall treatment switch rate at 12-month follow-up was 24.9% (756/3032). Of those treatments with sufficient sample size, patients receiving risankizumab had the lowest switch rate (7.3%; 15/206) compared to all other biologics, including other IL-23 inhibitors (guselkumab 16.7%, P=0.0029), IL-17 inhibitors (ixekizumab 22.4%, P&lt;0.0001; secukinumab 23.7%, P&lt;0.0001), TNF inhibitors (adalimumab 28.3%, P&lt;0.0001; etanercept 35.8%, P&lt;0.0001), and IL-12/23 inhibitors (ustekinumab 22.4%, P&lt;0.0001). Results were similar in multivariate logistic regression analyses after adjusting for variations in baseline characteristics. Predictors of switching at 12 months included female sex (adjusted odds ratio [aOR] [95% CI]: 1.63 [1.36, 1.94]; P&lt;0.0001), baseline anxiety or depression (aOR [95% CI]: 1.47 [1.21, 1.80]; P=0.0001), baseline major adverse cardiovascular event (aOR [95% CI]: 1.47 [1.15, 1.88]; P=0.0023), and prior targeted immunomodulator (TIM) use (aOR [95% CI]: 1.45 [1.20, 1.74]; P=0.0001). Conclusion: In a real-world setting, switching was common among psoriasis patients with PsA. Risankizumab showed the lowest rate of treatment switching at 12 months, compared with all other biologics. Sex, comorbidities, and prior TIM use were predictors of higher switch rates.

Treatments Used Among Patients with Psoriasis: A First Look at a New Patient-Centered Psoriasis Registry

Introduction: Psoriasis management in the US has changed substantially, with increasing treatment options including new topical, oral, and biologic medications. The objective of this study was to examine the demographics, disease characteristics, and treatment usage in the first patients enrolled in the new patient-centered psoriasis registry, the FORWARD Psoriasis Registry. Methods: Adult patients with psoriasis were recruited from dermatology offices as part of a national practice group, through a patient support program for deucravacitinib, and online from the FORWARD registry website between August and December 2023. Patients were not required to be on therapy for psoriasis. We descriptively report demographics, disease characteristics, and current treatments at enrollment. Results: A total of 702 patients met inclusion criteria and completed the full enrollment questionnaire. Mean age was 53 years and 66% were female; mean BMI was 30 (SD 7); 88% self-reported as White and 6% as Hispanic. A diagnosis of psoriatic arthritis was reported by 28%. Most (75%) had private insurance. Median psoriasis duration was 10 (IQR 3–23) years. 85% had plaque psoriasis, 19% guttate, 14% inverse, 6% generalized pustular, and 3% erythrodermic. Body surface area as assessed by the PREPI questionnaire was minimal (&lt;1% BSA) in 21%, mild (1%–2%) in 39%, moderate (3%–10%) in 34%, and severe (&gt;10%) in 6%. The most commonly used therapies included IL-23 inhibitors (11%), IL-17 inhibitors (8%), apremilast (7%), and TNF inhibitors (5%). Additionally, 14% of the cohort were using deucravacitinib; 62% reported using topicals, and 48% reported use of any systemic agent.Conclusion: The FORWARD psoriasis registry represents a new patient-centered approach and proof of concept for studies seeking to understand the natural history of the disease, treatment outcomes, and treatment needs relevant for individuals with psoriasis, and long-term outcomes related to comorbidities.

Effect of Biological Therapy for Psoriasis on the Development of Psoriatic Arthritis: A Population-Based Cohort Study.

Evidence comparing the impact of various biologics for psoriasis on the progression to psoriatic arthritis (PsA) is limited. We therefore assessed the risk of PsA associated with interleukin (IL)-23 inhibitor, IL-17 inhibitor, or IL-12/23 inhibitor use compared with tumor necrosis factor (TNF) inhibitor use among patients with psoriasis. This population-based cohort study used the nationwide claims database from South Korea (2007-2023). New users of IL or TNF inhibitors with psoriasis who did not have PsA or other inflammatory arthritis were categorized into each class of the IL inhibitors for comparison with TNF inhibitor users. The outcome measured was the development of incident PsA. We calculated multinomial overlap weights to balance predefined covariates. Hazard ratio (HR) and 95% confidence intervals (CIs) were calculated using Cox proportional hazards models. We identified 9499 patients with psoriasis (mean age 45.1 years; 33.6% female), of whom 3913 (41.2%), 2126 (22.4%), 2773 (28.8%), and 727 (7.7%) were exposed to IL-23 inhibitor, IL-17 inhibitor, IL-12/23 inhibitor, and TNF inhibitor, respectively. PsA developed in 281 (3.0%) patients during 23,275 person-years. The weighted HR for any IL inhibitors was 0.40 (95% CI 0.25-0.62), with specific HRs of 0.22 (95% CI 0.13-0.37), 0.47 (95% CI 0.28-0.80), and 0.46 (95% CI0.29-0.74) for IL-23 inhibitor, IL-17 inhibitor, and IL-12/23 inhibitor, respectively. IL-23 inhibitors exhibited the greatest rate difference of - 2.61 (95% CI - 3.67 to - 1.55) cases of PsA per 100 person-years. The use of IL inhibitors, particularly IL-23 inhibitors, compared with TNF inhibitors, was associated with a lower risk of developing PsA.

Case report: VEXAS syndrome with excellent response to treatment with azacitidine.

Vacuoles, E1 enzyme, X-linked, auto inflammatory, somatic (VEXAS) syndrome is an inflammatory disorder caused by somatic UBA1 variants and is characterized by late-onset systemic autoimmune inflammation and blood abnormalities. Glucocorticoids ameliorate symptoms effectively. However, other treatment options have limited efficacy and a transient effect. Herein, we describe a case of a 69-year-old male patient with VEXAS syndrome with skin, lung and hematologic involvement. He was treated with glucocorticoids and after the failure with anti IL-1 he began treatment with azacitidine with excellent hematological and clinical response. Azacitidine may be a suitable option for treating VEXAS syndrome, especially due to the relationship between inflammatory symptoms and response to azacitidine.

Discovery of New Immunomodulatory Anticancer Thalidomide Analogs: Design, Synthesis, Biological Evaluation and In Silico Studies.

New thalidomide analogs have been designed and synthesized by hybridizing the immunomodulatory gutarimide moiety with three antiproliferative nuclei: quinazolinedione, phthalazinedione, and quinoxalinone. The biological results revealed the strong impact of quinazoline derivatives 7a and 28, and phthalazine based 20a against HepG-2, MCF-7, PC3, and HCT-116 cell lines, compared to thalidomide. In particular, compound 20a was the most promising as it had far better biological activity than thalidomide with regard to inhibition of TNF-α, IL-6, caspase 3, COX-I/II, and VEGFR-2, as well as cell cycle arrest, and apoptosis rate enhancement in MCF-7 cells, the most sensitive cell line to the current new molecules. Compound 20a caused reduction in levels of TNF-α and IL-6 by 75.22% and 82.51%, respectively. It elevated the caspase-3 level by 7.21-fold. Furthermore, IC50 against COX-I, COX-II, and VEGFR-2 were 0.65 μM, 0.33 μM, and 232 nM, respectively. In addition, it raised the apoptosis rate from 65.65% to 99.89%. Moreover, 20a was further examined through a docking study and a 200 ns molecular dynamics simulation for its complex with VEGFR-2, along with computational ADME properties. This work suggests the high significance of compounds 20a, 7a and 28, as lead compounds for development of new effective immunomodulatory antitumor drugs.

Abstract PR008: Genome-wide analyses of cfDNA fragmentomes for therapeutic monitoring of patients with pancreatic cancer

Abstract Determining response to therapy for patients with pancreatic cancer can be challenging using imaging alone, and there is an unmet need for noninvasive assessment of tumor burden. We developed a method for assessing response to therapy using circulating cell-free DNA (cfDNA) and tested it using 217 plasma samples from 40 patients with metastatic pancreatic cancer treated with immune checkpoint inhibition and radiation as part of the CheckPAC trial (NCT02866383). Samples were evaluated before and after initiation of therapy using a mutation-independent and tumor-independent approach (ARTEMIS-DELFI), combining genome-wide cfDNA fragmentation profiles and repeat landscapes. Patients with below median scores (n=16) at the time of the first follow up CT scan at 8 weeks had a longer median progression free survival (PFS) and longer median overall survival (OS) than patients with above median scores (n=17) (PFS: 153 days versus 50 days; HR=0.26, 95% CI=0.11-0.64, p=0.0013) (OS: 375 days versus 121 days; HR=0.12, 95% CI=0.045-0.30, p&amp;lt;0.0001). Additionally, a “fast fail” analysis of patients with scores above the 75th percentile evaluated at 2 weeks after initiation of therapy (n=9) resulted in shorter median PFS and shorter median OS than patients with lower scores (n=27) (PFS: 46 days versus 110 days; HR=0.29 95% CI=0.13-0.66, p=0.0027), (OS: 88 days versus 230 days; HR=0.35 95% CI=0.16-0.78, p=0.00011). We validated the approach in a separate cohort of 205 samples from 40 patients with pancreatic cancer treated with first line chemotherapy, with and without IL-6 inhibition, as part of the PACTO trial (NCT02767557). Patients with below median scores at the 8-week first follow up CT scan (n=16) had a longer median OS than patients with above median scores (n=16) (OS: 288 days vs 199 days, HR=0.488, 95% CI=0.24–1.01, p=0.048). Similar results were observed at 2 weeks after initiation of therapy when considering patients with scores above the 75th percentile (n=9) compared to patients with lower scores (n=27) (OS: 196 days versus 280 days) (HR=0.17, 95% CI=0.06-0.46, p=0.0074). These analyses suggest that non-invasive fragmentation-based cfDNA approaches can identify individuals with pancreatic cancer who are not responding to therapy as early as two weeks after treatment initiation. Incorporation of these molecular methods to evaluate tumor burden may provide timely information for patient-physician decision making to improve patient care. Citation Format: Carolyn A Hruban, Daniel C. Bruhm, Inna M Chen, Shashikant Koul, Akshaya V Annapragada, Nicholas A Vulpescu, Sarah Short, Susann Theile, Kavya Boyapati, Stephen Cristiano, Vilmos Adleff, Julia S Johannsen, Robert B Scharpf, Zachariah H Foda, Jillian A Phallen, Victor E Velculescu. Genome-wide analyses of cfDNA fragmentomes for therapeutic monitoring of patients with pancreatic cancer [abstract]. In: Proceedings of the AACR Special Conference: Liquid Biopsy: From Discovery to Clinical Implementation; 2024 Nov 13-16; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(21_Suppl):Abstract nr PR008.

Safety and efficacy of IL-17 inhibitors in hidradenitis suppurativa: an updated systematic review and meta-analysis including the BE-HEARD trials.

Safety and efficacy of IL-17 inhibitors in hidradenitis suppurativa: an updated systematic review and meta-analysis including the BE-HEARD trials.

Intra-class switch among interleukin-17 inhibitors for the treatment of plaque psoriasis: a single-center experience

Psoriasis is a chronic immune-mediated disease primarily affecting the skin. The most common subtype is plaque psoriasis, which can affect any body area, with a predilection for the knees, elbows, scalp, lumbosacral region, and genitalia. The European guidelines adopted in Italy recommend systemic therapies for moderate-to-severe psoriasis, defined by a Psoriasis Area and Severity Index (PASI) ≥ 10, Dermatology Life Quality Index (DLQI) ≥ 10, and/or Body Surface Area (BSA) ≥ 10. Over the past two decades, the development of biological agents has revolutionized psoriasis management, targeting specific cytokines such as TNF-α, IL-23, and IL-17. Among these, ixekizumab, secukinumab, brodalumab, and bimekizumab are approved for the treatment of moderate-to-severe plaque psoriasis. However, some patients require switching therapy because of primary/secondary ineffectiveness or side effects. We retrospectively analyzed 20 patients who had switched from one anti-IL-17 drug to another, assessing both safety and effectiveness. 70% of patients was represented by males, with a median age of 49.5 years. The most frequent comorbidities were arterial hypertension and hypercholesterolemia. Effectiveness was evaluated in terms of a 90% (PASI90) and 100% (PASI100) reduction in PASI compared to baseline at 16 and 52 weeks. Before switching to the current IL-17 inhibitor, seven patients had failed at least two biologics. Thirteen patients experienced a loss of effectiveness after more than 6 months (secondary ineffectiveness), whereas the other seven never showed improvement with the previous drug (primary ineffectiveness). Fourteen patients completed at least one year of follow-up. Two patients were lost during the follow-up, while four more are currently still under treatment without having completed the established temporal cut-off. Two patients switched to bimekizumab, nine to brodalumab, and nine to ixekizumab. At baseline, the median PASI was 10 (IQR 4.5). After 16 weeks, the median PASI decreased to 2 (IQR 5.5), and after one year, it was 1 (IQR 2). Eight patients (40%) and six patients (30%) achieved PASI 90 and PASI 100 at 16 weeks, respectively. After one year, sustained effectiveness was observed with PASI 90 (57.1%), PASI 100 (35.7%), and PASI ≤ 2 (78.6%). No serious adverse events or discontinuations due to adverse events were observed during the study period. Our study confirms the safety and effectiveness of intraclass switching among IL-17 antagonists, highlighting that an inter-class switch can be a valid option when patients fail to respond or lose effectiveness with an IL-17 inhibitor. However, further larger and longer studies are needed for a deeper understanding.

The holistic management of peripheral spondyloarthritis: focus on articular involvement in patients with inflammatory bowel disease.

To provide a comprehensive overview of peripheral spondyloarthritis (pSpA), focusing specifically on its occurrence and management in patients with inflammatory bowel disease (IBD). An exhaustive literature search was conducted in PubMed, Embase, Cochrane Database of Systematic Reviews, and Google Scholar to identify relevant studies on pSpA in IBD patients. Titles, abstracts, and full-text articles were screened for relevance. Data on study design, patient characteristics, diagnostic criteria, main findings, and conclusions were extracted from selected articles. Study quality was assessed using appropriate checklists. Information was synthesized narratively to summarize current understanding. pSpA is the most common extraintestinal manifestation in IBD, with a median prevalence of 16%. It worsens quality of life and requires collaboration between gastroenterologists and rheumatologists for optimal diagnosis and treatment. Several "red flags" guide appropriate specialist referral of IBD patients with suspected pSpA. Once the diagnosis is confirmed, the choice of therapy depends on IBD phenotype and patterns of articular/axial involvement. Anti-tumor necrosis factor (TNF) drugs are first-line biologics, with interleukin (IL)-12/23 and IL-23 inhibitors as alternatives for anti-TNF failure. Small molecules like apremilast and Janus kinase inhibitors also have utility. Recommended treatment algorithms exist, but more randomized controlled trials are needed. Early identification of pSpA is crucial in IBD patients to enable timely intervention, prevent structural damage, and minimize disability. A multidisciplinary, holistic approach addressing musculoskeletal and extra-musculoskeletal manifestations is key to optimal patient outcomes.

The Persistence of Biologic Therapies for Psoriatic Arthritis: A Narrative Review.

Drug persistence is a crucial measure of long-term efficacy, safety, and patient satisfaction. Lack of persistence can increase healthcare costs and morbidity and mortality rates. This review aimed to consolidate available data on drug persistence for various biological treatments used as the primary intervention for psoriatic arthritis and identify factors associated with nonpersistence. Reports indicate variable 1-year persistence rates for biologic therapies, ranging from 37% to 73%. Specifically, tumor necrosis factor inhibitors have shown fluctuating 1-year persistence rates ranging from 32% to 85%. IL-12/23 and IL-23 inhibitors demonstrate persistence rates of 25% to 89%, whereas data for IL-17 and JAK inhibitors are more limited, ranging from 51% to 77%. Factors such as female sex and a higher burden of comorbidities have been associated with an increased risk of nonpersistence, although evidence regarding other factors remains scarce. The significant variability in reported persistence rates may be attributed to differences in treatment gaps and methodologies across studies. Addressing and mitigating the factors leading to nonpersistence is essential for improving treatment outcomes in psoriatic arthritis.

Efficacy and Safety of Risankizumab in Patients with Psoriasis Showing Suboptimal Response to Secukinumab or Ixekizumab: Results from a Phase 3b, Open-Label, Single-Arm (aIMM) Study.

Risankizumab has demonstrated superior efficacy compared to other psoriasis treatments, including secukinumab, adalimumab, and ustekinumab; switching to risankizumab from other psoriasis treatments has shown superior clinical and quality of life (QoL) outcomes. We evaluated the efficacy and safety of directly switching patients with moderate-to-severe plaque psoriasis and a suboptimal response to interleukin (IL)-17 inhibitors (secukinumab or ixekizumab) to risankizumab. This 52-week, phase 3b study enrolled patients (≥ 18years) with moderate-to-severe plaque psoriasis who had previously been treated with the recommended dose of secukinumab or ixekizumab for ≥ 6months but did not achieve an optimal response (static Physician's Global Assessment [sPGA] 2/3; body surface are [BSA] 3- < 10%). Patients received subcutaneous risankizumab (150mg) without washout. The primary endpoint was the proportion of patients achieving sPGA of 0/1 at week 16. Secondary endpoints included sPGA 0/1 at week 52, sPGA 0, Dermatology Life Quality Index (DLQI) 0/1, and Psoriasis Symptoms Scale (PSS) 0 at weeks 16 and 52. Safety was monitored throughout the study. The study included 244 patients. sPGA 0/1 was achieved by 57.4% and 62.3% at week 16 and 52. At week 16, sPGA 0, DLQI 0/1, and PSS 0 were achieved by 20.5%, 40.2%, and 20.9%, respectively. At week 52, these proportions increased to 27.1% for sPGA 0, 47.2% for DLQI 0/1, and 27.5% for PSS 0. Most frequently reported adverse events (reported in ≥ 5% of patients) in risankizumab-treated patients were COVID-19 infection (8.6%) and nasopharyngitis (5.7%). No new safety signals were observed. Directly switching to risankizumab improved outcomes and QoL in patients with moderate-to-severe psoriasis who had suboptimal responses to anti-IL-17 inhibitors (secukinumab or ixekizumab). The safety results are consistent with previously reported safety of risankizumab. This study supports the efficacy of risankizumab in patients previously treated with biologics, including IL-17 inhibitors, and suggests a direct switch to risankizumab for improved clinical outcomes and QoL. ClinicalTrials.gov identifier: NCT04102007.