interleukin-17A Inhibitor Research Articles

Improvement in spinal pain at night and its impact on long-term outcomes in radiographic axial spondyloarthritis: Results from Ixekizumab COAST-V randomised trial

IntroductionSpinal pain at night is a major contributor to the patient burden of radiographic axial spondyloarthritis (r-axSpA), resulting in substantial functional limitations and impairment of health-related quality of life (QoL). Ixekizumab (IXE), an interleukin-17A inhibitor, has shown efficacy in patients with r-axSpA. ObjectiveTo assess spinal pain at night improvement up to week (W) 52 in COAST-V and to determine if clinically important improvement in spinal pain at night at W16 is associated with improvement in disease activity and other patient-reported outcomes (PROs) at W16 and W52. MethodsThe 52 W phase 3 COAST-V trial investigated the efficacy of IXE in patients with r-axSpA that were naïve to biological disease-modifying anti-rheumatic drug (bDMARD). Patients were randomised to IXE every two weeks (Q2W), IXE every four weeks (Q4W), adalimumab (ADA) Q2W, or placebo up to W16. Patients were categorised as achieving or not achieving a ≥3-point improvement, considered a clinically important improvement (CII), in spinal pain at night at W16. Associations between achieving CII in spinal pain at night at W16 and change from baseline in disease activity (ASDAS, ASAS40), Fatigue severity NRS, JSEQ, WPAI and the SF-36 survey, were tested using analysis of covariance (continuous variables) and logistic regression (binary variables). ResultsAt W16, 63.0 % (n=51), 46.7 % (n=42), and 32.2 % (n=28) of patients treated with IXE Q4W, ADA Q2W, and placebo, respectively, had reached a CII in spinal pain at night. Of those who were treated with IXE Q4W and achieved a CII in spinal pain at night at W16, 58.8 % and 66.7 % achieved an ASDAS <2.1 at W16 and W52 while 25.5 % and 29.4 % of patients also achieved ASDAS <1.3 at W16 and W52, respectively. Results at W16 and W52 show an improvement in disease activity, functioning, and health related QoL for patients who achieved a CII in spinal pain at night at W16. ConclusionA larger proportion of patients treated with IXE Q4W achieved rapid and clinically meaningful improvement in spinal pain at night versus placebo, with improvements maintained up to W52. Achieving a CII in spinal pain at night at W16 was associated with improved disease activity, functioning, PROs, and QoL at W16 and W52. Trial registrationClinicalTrials.gov NCT02696785

Rapid and Sustained Effect of Ixekizumab on Patient Global, Spinal Pain, Stiffness, and Fatigue in Chinese Patients with Radiographic Axial Spondyloarthritis.

Ixekizumab, an interleukin 17A (IL-17A) inhibitor, has demonstrated rapid and sustained improvement in the signs and symptoms in patients with active radiographic axial spondyloarthritis (r-axSpA) in global and Chinese populations. We studied the effect of ixekizumab on patient-reported outcomes (PROs) (including patient global, spinal pain, stiffness, and fatigue) and overall health-related quality of life (HRQoL) of ixekizumab in the phase3 study in China. In this Chinese phase3, randomized, double-blind, placebo-controlled study, patients with r-axSpA were randomized (1:1) to receive ixekizumab 80mg every 4weeks (IXEQ4W; starting dose 160mg) or placebo for 16weeks. At week16, patients receiving placebo were switched to IXEQ4W, and those receiving IXEQ4W continued, until week52. Data for patient global, spinal pain, spinal pain at night, stiffness, and fatigue were collected through week52. Minimally clinical important differences (MCIDs) were determined for spinal pain and spinal pain at night. The subgroup analyses by baseline disease duration since diagnosis and baseline C-reactive protein (CRP) level were conducted post hoc. Compared with placebo, patients treated with IXEQ4W reported significantly greater improvement with a rapid onset in changes from baseline of PROs (patient global, spinal pain, spinal pain at night, stiffness, and fatigue) through week16. Improvements were maintained through week52. A similar trend of improvement was also observed in MCID response in spinal pain and spinal pain at night. The improvement in overall HRQoL was supported by EQ-5D-5L assessment. Subgroup analyses demonstrated that IXEQ4W provided significantly greater efficacy at week16 compared with placebo, irrespective of baseline disease duration or baseline CRP level. IXEQ4W provided rapid and sustained improvement in clinically relevant PROs and overall HRQoL through 1-year treatment in Chinese patients with r-axSpA. Regardless of the baseline disease duration or baseline CRP level, consistent efficacy was observed. ClinicalTrials.gov identifier NCT04285229.

Comparative Efficacy of Advanced Therapies in the Treatment of Radiographic Axial Spondyloarthritis or Ankylosing Spondylitis as Evaluated by the ASDAS Low Disease Activity Criteria.

With an increasing number of biologic/targeted synthetic disease-modifying antirheumatic drug options available for the treatment of active ankylosing spondylitis (AS), also known as radiographic axial spondyloarthritis, it is of clinical interest to determine the comparative efficacy of these advanced therapies among populations with differing prior advanced therapy exposure. This study aimed to assess the comparative efficacy of approved advanced therapies for AS in tumor necrosis factor inhibitor (TNFi)-naïve and, separately, in TNFi inadequate responder/intolerant (-IR) populations. A systematic literature review was conducted to identify randomized clinical trials for TNFis, interleukin-17A inhibitors, and Janus kinase inhibitors used as advanced therapies for active AS. Clinical efficacy was considered by the Ankylosing Spondylitis Disease Activity Score low disease activity (ASDAS LDA) criteria, defined as ASDAS score less than 2.1, among approved therapies. Comparative efficacy in the TNFi-naïve population was assessed utilizing network meta-analysis, while comparative efficacy in the TNFi-IR population was assessed utilizing matching-adjusted indirect comparison. Odds ratios were calculated, from which absolute rates and numbers needed to treat were calculated. Safety in the form of trial-reported and placebo-adjusted rates of discontinuation due to adverse events (AEs) was reviewed. Among the TNFi-naïve population, the estimated ASDAS LDA rate between week12 and 16 was highest for patients treated with upadacitinib (52.8%) and lowest for patients treated with placebo (11.6%). Among the TNFi-IR population, the estimated ASDAS LDA rate was 41.3% for patients treated with upadacitinib and 17.5% for patients treated with ixekizumab. The trial-reported and placebo-adjusted rates of discontinuation due to AEs were generally low across included advanced therapies. Relative to other assessed therapies, upadacitinib demonstrated greater clinical efficacy per ASDAS LDA in the treatment of active AS in both TNFi-naïve and TNFi-IR populations. Head-to-head and real-world data comparisons are warranted to both validate these findings and aid medical decision makers.

Current treatment for spondyloarthritis: focus on netakimab. A review

Spondyloarthritis (SpA) is a group of rheumatic diseases that includes ankylosing spondylitis (AS), psoriatic arthritis (PsA) and a number of other diseases. SpA lead to a significant social problem, since it is a common pathology that debuts mainly at a young age, significantly impairing the ability to work and the ability to social contacts of the most active part of the population. For all the main types of chronic progressive SpA, biological agents (biologics) are of great importance in patients with persistent activity despite standard treatment, especially in the case of predominantly axial involvement, since in this case it is actually the only option for effective treatment, in addition to the constant use of non-steroidal anti-inflammatory drugs (NSAIDs). Over the past decade, interleukin-17A (IL-17A) inhibitors have taken the first place in therapy of SpA, because, according to modern ideas about pathogenesis, IL-17A may be a key target for therapeutic intervention in SpA. In terms of ensuring availability for Russian patients with SpA, it is of particular importance to the introduction of the original medication from the group of IL-17A inhibitors Netakimab (NTK). This review presents data from randomized clinical trials of NTK phases I, II and III in AS and PsA also post-registration observational studies of phase IV, including analysis of subpopulations of patients of special interest, in particular, patients with psoriatic spondylitis. NTK demonstrated high effectiveness in the treatment of SpA both in randomized clinical trials and in clinical practice. The drug is characterized by a rapid onset of clinical action and persistent maintenance of the achieved improvement, a complex effect on various manifestations of the disease, is able to have a structure-modifying effect and slow down the progression of both the erosive process and osteoproliferation. The safety profile of NTK is generally typical for the entire group of IL-17 inhibitors. The drug has low immunogenicity, which allows us to count on the possibility of many years of effective use. Resolutions of expert councils on the use of NTK in AS and PsA support the inclusion of this drug in clinical guidelines.

Disease modification in axial spondyloarthritis - still a controversy?

This review evaluates recent advancements in disease-modifying therapies for axial spondyloarthritis (axSpA). A recent study could not demonstrate an additional effect of NSAID therapy on golimumab [Tumor Necrosis Factor-α inhibitor (TNFi)] on structural progression; however, this might be due to the fact that the study was underpowered. While DMARDs have shown promise in suppressing inflammation, their impact on structural progression remains uncertain. A well powered trial showed no difference in spinal progression between secukinumab [Interleukin17A inhibitor (IL17Ai)] and adalimumab-biosimilar (TNFi). Preliminary data on Janus kinase inhibitors (JAKi) focus on MRI findings but lack evidence on radiographic spinal progression. While some studies suggest promising outcomes, others reveal limitations and inconclusive findings. Recent studies explore the effectiveness of NSAIDs, biological disease-modifying antirheumatic drugs like TNFi and IL-17i, as well as JAK inhibitors in axSpA. Conflicting evidence surrounds these therapies' ability to impede structural progression, with challenges in study design and interpretation. Moreover, changes in demographics and treatment methods underscore the importance of examining trends over time when assessing disease outcomes. Ultimately, ongoing research could benefit from new imaging tools when evaluating therapeutic strategies for modifying disease progression in axSpA.

Effect of Secukinumab Versus Adalimumab Biosimilar on Radiographic Progression in Patients With Radiographic Axial Spondyloarthritis: Results From a Head-to-Head Randomized Phase IIIb Study.

Spinal radiographic progression is an important outcome in radiographic axial spondyloarthritis (SpA). The objective of the phase IIIb SURPASS study was tocompare spinal radiographic progression in patients with radiographic axial SpA treated with secukinumab (interleukin-17A inhibitor) versus adalimumab biosimilar (Sandoz adalimumab [SDZ-ADL]; tumor necrosis factor inhibitor). Biologic-naive patients with active radiographic axial SpA, at high risk of radiographic progression (high-sensitivity C-reactive protein [hsCRP] ≥5 mg/L and/or ≥1 syndesmophyte[s] on spinal radiographs), were randomized (1:1:1) to secukinumab (150/300 mg) or SDZ-ADL (40 mg). The proportion of patients with no radiographic progression (change from baseline [CFB] in modified Stoke Ankylosing Spondylitis Spinal Score [mSASSS] ≤0.5) on secukinumab versus SDZ-ADL at week 104 (primary endpoint), mean CFB-mSASSS, proportion of patients with ≥1 syndesmophyte(s) at baseline with no new syndesmophyte(s), and safety were evaluated. Overall, 859 patients (78.5% male, mSASSS 16.6, Bath Ankylosing Spondylitis Disease Activity Index 7.1, hsCRP 20.4 mg/L, and 73.0% with ≥1 syndesmophyte[s]) received secukinumab 150 mg (n = 287), secukinumab 300 mg (n = 286), or SDZ-ADL (n = 286). At week 104, the proportion of patients with no radiographic progression was 66.1%, 66.9%, and 65.6% (P = not significant, both secukinumab doses) and mean CFB-mSASSS was 0.54, 0.55, and 0.72 in secukinumab 150 mg, secukinumab 300 mg, and SDZ-ADL arms, respectively. Overall, 56.9%, 53.8%, and 53.3% of patients on secukinumab 150 mg, secukinumab 300 mg, and SDZ-ADL, respectively, with ≥1 syndesmophyte(s) at baseline did not develop new syndesmophyte(s) by week 104. There were no unexpected safety findings. Spinal radiographic progression over two years was low with no significant difference between secukinumab and SDZ-ADL arms. The safety of both treatments was consistent with previous reports.

Discovery of Small Molecule Interleukin 17A Inhibitors with Novel Binding Mode and Stoichiometry: Optimization of DNA-Encoded Chemical Library Hits to In Vivo Active Compounds.

Dysregulation of IL17A drives numerous inflammatory and autoimmune disorders with inhibition of IL17A using antibodies proven as an effective treatment. Oral anti-IL17 therapies are an attractive alternative option, and several preclinical small molecule IL17 inhibitors have previously been described. Herein, we report the discovery of a novel class of small molecule IL17A inhibitors, identified via a DNA-encoded chemical library screen, and their subsequent optimization to provide in vivo efficacious inhibitors. These new protein-protein interaction (PPI) inhibitors bind in a previously undescribed mode in the IL17A protein with two copies binding symmetrically to the central cavities of the IL17A homodimer.

Comparison between super-responders and non-super-responders in psoriasis under adalimumab treatment: a real-life cohort study on the effectiveness and drug survival over one-year

Background Data on the characteristics and treatment outcomes of super-responders and non-super-responders in psoriasis under adalimumab treatment are limited. Methods A retrospective analysis from psoriatic patients treated with adalimumab was compared to characterize super-responders vs non-super-responders’ groups, identify factors associated with super response, and assess treatment outcomes after switching. Results 15 out of 70 (21.4%) patients were categorized as super-responder. The proportion of patients achieving a PASI 100 response was significantly higher in super-responders than non-super-responders at weeks 12, 24, and 52. Female sex and Charlson Co-morbidity Index were significantly associated with super-responders. A high level of high-density lipoprotein was independently associated with PASI 90 response at weeks 24 and 52. Additionally, nearly 35%–43% of non-super-responders switching to interleukin-17A (IL-17A) inhibitors may achieve a PASI 100 response at week 12. In contrast, all super-responders switching to IL-17A inhibitors achieved a PASI 100 response at week 4. Conclusions Super-responders treated with adalimumab have a higher rate of being female and fewer comorbidities. And super-responders have better PASI responses than non-super-responders, whether the patients were treated with adalimumab or switched to IL-17A inhibitors.

Interleukin-17A Inhibitors in Patients with Psoriasis and Tuberculosis Infection: A 2-Year Prospective Study on Safety Without Preventive Treatment.

The necessity for tuberculosis preventive treatment (TPT) and routine T-SPOT.TB monitoring in patients with psoriasis and tuberculosis infection (TBI) undergoing interleukin (IL)-17A inhibitor therapy remains uncertain. This study aims to evaluate the long-term safety of IL-17A inhibitors administered without TPT and analyze changes in T-SPOT.TB among these patients. It also identifies risk factors for TBI in patients with psoriasis. This single-center prospective study enrolled adult patients with plaque psoriasis and TBI receiving IL-17A inhibitors. TBI was defined as positive T-SPOT.TB results (≥ 6 spots) without symptoms or evidence of active tuberculosis (ATB). TPT administration was based on contraindications, tuberculosis risk factors, and patient preferences. The primary endpoint was the incidence of ATB over 2years. Secondary outcomes included T-SPOT.TB changes and TBI risk factors. Of the 129 patients with psoriasis and TBI enrolled in the study, 97 (75.2%) did not receive TPT, while 32 (24.8%) did. Among them, 109 patients (84.5%) completed the 2-year follow-up. During the 235 person-years of observation, no ATB cases were identified. Median T-SPOT.TB values showed no significant changes from baseline to year2 in both the non-TPT (20 vs. 17 spots, p = 0.975) and TPT groups (55 vs. 58 spots, p = 0.830). T-SPOT.TB reversed in 14 patients (12.8%), mostly in the non-TPT group. Moreover, for TBI risk factor analysis, a cohort of 212 patients with psoriasis with negative baseline T-SPOT.TB was evaluated, revealing a TBI prevalence of 37.8%. Logistic regression analysis highlighted age ≥ 45years (odds ratio [OR] 2.44, 95% confidence interval [CI] 1.50-3.99, p < 0.001) and body mass index (BMI) < 24.0 kg/m2 (OR 2.12, 95%CI 1.27-3.54, p = 0.004) as independent risk factors for TBI. IL-17A inhibitors do not appear to reactivate tuberculosis in patients with psoriasis and TBI, potentially reducing the need for routine TBI screening and preventive treatment. Chinese Clinical Trial Registry, ChiCTR2100045823.

Real-world evaluation of persistence, effectiveness and usage patterns of tofacitinib in treatment of psoriatic arthritis in Australia

ObjectivesTo describe treatment patterns and persistence of tofacitinib, interleukin 17 inhibitors (IL-17Ai) and tumour necrosis factor inhibitors (TNFi), in patients with psoriatic arthritis (PsA).MethodsData from adult patients with PsA and who had received at least one prescription of tofacitinib, IL-17Ai or TNFi between May 2019 and September 2021 were sourced from the Australian OPAL dataset. Persistence, analysed via Kaplan–Meier methods, and propensity score matching between tofacitinib and bDMARD (IL-17Ai and TNFi) groups were conducted.ResultsOf 16,692 patients with PsA, 1486 (n = 406 tofacitinib, n = 416 IL-17Ai and n = 664 TNFi) were included. More females were in the tofacitinib group (75.4%) than in the IL-17Ai (61.1%) and TNFi (64.8%) groups. Overall, 19.2% of tofacitinib patients were first line, compared with 41.8% of IL-17Ai and 62.8% of TNFi patients. In the overall population, the median persistence was 16.5 months (95% CI 13.8 to 19.5 months), 17.7 months (95% CI 15.8 to 19.6 months) and 17.2 months (95% CI 14.9 to 20.5 months) in the tofacitinib, IL-17Ai and TNFi groups, respectively. Persistence was similar in the tofacitinib/IL-17Ai matched population; however, in the tofacitinib/TNFi matched population, persistence was longer in the tofacitinib group (18.7 months, 95% CI 15.6 to 21.4 months) compared with the TNFi group (12.2 months, 95% CI 19.9 to 14.9 months).ConclusionsIn this Australian real-world dataset, tofacitinib was more frequently used in later lines and among a slightly higher proportion of female patients than IL-17Ai or TNFi. Overall, treatment persistence was similar for tofacitinib, IL-17Ai and TNFi, but tofacitinib exhibited longer persistence than TNFi in a matched population.Key Points• This is the first, large real-world study from Australia investigating the demographics, treatment patterns and comparative treatment persistence of patients with psoriatic arthritis (PsA) treated with tofacitinib and biologic disease-modifying drugs (bDMARDs).• The study suggests that tofacitinib is an effective intervention in PsA with at least comparable persistence to bDMARDs: tumour necrosis factor inhibitors (TNFi) and interleukin-17 A inhibitors (IL-17Ai).

Changes in Inflammatory Cytokines in Responders and Non-Responders to TNFα Inhibitor and IL-17A Inhibitor: A Study Examining Psoriatic Arthritis Patients.

This study aimed to examine the changes in biomarker levels in responders and non-responders to tumor necrosis factor alpha inhibitor (TNFi) and interleukin-17A inhibitor (IL-17Ai) in psoriatic arthritis (PsA) patients over a 4-month period after treatment initiation. A total of 68 PsA patients initiating either TNFi, IL-17Ai, or methotrexate treatment were included. Blood plasma and clinical outcome measures were collected adjacent to treatment initiation and after four months. A commercially available multiplex immunoassay was included to evaluate 54 biomarkers. Mean changes were used to evaluate change over time. A statistically significant decrease in pro-inflammatory cytokines IL-6 (log-transformed mean change -0.97, 95%CI -4.30; 2.37, [p = 0.032]) and an increase in anti-inflammatory IL-10 (0.38, 95%CI 1.74; 2.50 [p = 0.010]) were seen in TNFi responders. Meanwhile, a statistically significant increase in the target cytokine IL-17A was seen in both IL-17Ai responders (2.49, 95%CI -1.84; 6.85 [p = 0.031]) and non-responders (2.48, 95%CI -1.46; 6.41 [p = 0.001]). This study demonstrated differing changes in cytokine levels when comparing treatment responders and non-responders, highlighting the need to improve the understanding of the different immune response mechanisms explaining different responses to medical treatment in PsA patients.

Immune Dysregulation and Current Targeted Biologics in Hidradenitis Suppurativa

Hidradenitis Suppurativa (HS) is a debilitating cutaneous disease characterized by a vicious cycle of chronic inflammation and tissue destruction that stems from disruption of the skin microbiome and abnormal activation of both the innate and adaptive immune system. A hallmark of HS pathophysiology is dysregulation of both the innate and adaptive immune system. The role of immune system dysregulation in HS development has motivated researchers to explore the utility of biologic immunomodulators. In 2015, adalimumab, a tumor necrosis factor-α inhibitor, was approved by the Food and Drug Administration (FDA) for treatment of moderate-to-severe HS in the US. In 2023, secukinumab, an interleukin-17A (IL-17A) inhibitor, was approved by the European Medicines Agency for treatment of moderate-to-severe HS in Europe. Ongoing clinical trials have shown promising clinical responses to targeted therapies against other pro-inflammatory cytokines including IL-17, IL-12, IL-1, IL-36, IL-6, IL-10, interferon γ, C5a, and Janus kinase (JAK). We provide an update on the efficacy and clinical usage of targeted biologics in HS treatment.

Трудности подбора генно-инженерной терапии у пациента с поражением сердечно-сосудистой системы при анкилозирующем спондилите (болезни Бехтерева)

Spondylarthritis (SpA) is a group of chronic inflammatory diseases affecting the spine, joints, and entheses. It is characterized by common clinical, radiological, and genetic traits. Cardiovascular disorder (CVD) is an important factor in determining the prognosis and treatment options for SpA. Ankylosing spondylitis (AS) is the reference axial SpA, where CVD is a manifestation of both systemic inflammation and rapid atherosclerotic lesion secondary to the disease. Treating AS associated with CVD is challenging because nonsteroidal anti-inflammatory drugs and physical activity exacerbate cardiovascular disease, while experience with gene therapy and targeted therapy is limited. Therefore, it is important to accumulate real-world clinical data on treating patients with AS and CVD. This article discusses the case of a patient with AS and CVD who developed secondary resistance to tumor necrosis factor α inhibitor. The patient required complex cardiotropic therapy, including implantable cardioverter defibrillator insertion and replacement of genetically engineered drug with interleukin 17A inhibitor. The article also discusses the rationale for the chosen management strategy from a CVD perspective. KEYWORDS: ankylosing spondylitis, Bechterew's disease, axial spondylarthritis, atrioventricular block, cardiovascular comorbidity, biological therapy, interleukin 17A. FOR CITATION: Gaydukova I.Z., Sidorchuk I.V., Chudinov A.L., Inamova O.V. Difficulties in selecting genetically engineered therapy in a patient with cardiovascular disorder in ankylosing spondylitis (Bechterew's disease). Russian Medical Inquiry. 2024;8(2):89–93 (in Russ.). DOI: 10.32364/2587-6821-2024-8-2-6.

Experience of using the interleukin-17A inhibitor secukinumab in the treatment of psoriasis and psoriatic arthritis

Psoriasis is a chronic immune-inflammatory skin disease, which in 25–30% of cases occurs in combination with damage of the musculoskeletal system ― psoriatic arthritis. Nowadays, the leading role in the pathogenesis of psoriasis and psoriatic arthritis is assigned to the activation of the IL-23/IL-17 axis-key cytokines involved in the activation pathway of the effector activity of Th17 lymphocytes. The activity of proinflammatory cytokines secreted by Th17 cells in psoriasis and psoriatic arthritis is also confirmed by the high efficiency of targeted therapy aimed specifically at this pathway. One of the modern genetically engineered biological drugs blocking IL-17 which is used worldwide in the treatment of psoriasis and psoriatic arthritis is secukinumab, a recombinant, fully human monoclonal antibody of high affinity directed against IL-17A.&#x0D; The article presents data from own 52-week follow-up of secukinumab use in 40 patients with severe and moderate-severe psoriasis which was combined with psoriatic arthritis in 67.5% of cases and demonstrates high efficacy, survival and satisfactory tolerability of this therapy.

Cost-effectiveness analysis of secukinumab versus standard of care in the treatment of psoriatic arthritis: A Vietnam National health insurance perspective

Psoriatic arthritis (PsA) is a chronic, systemic inflammatory disease. This study assessed the cost-effectiveness of secukinumab, an interleukin-17A inhibitor, versus standard of care (SoC) from Vietnam’s National Health Insurance (NHI) perspective. Model-based cost-effectiveness analysis, the structure was a 3-month decision tree leading into a Markov model. Clinical parameters, including responses at 3 months, were from the FUTURE 2 trial. Cost parameters were from real data at the National Hospital of Dermatology and Venereology and a research period. The outcome included total costs and quality-adjusted life years (QALYs) over a life-time horizon (3.5% annual discount for both outcomes and cost), and incremental cost-effectiveness ratios (ICER). The robustness of the study findings was evaluated via sensitivity analysis. Patients treated with secukinumab achieved with QALY gain 1.16 versus SoC, but associated with higher total costs was 211.3 million VND over lifetime horizon. ICER for secukinumab vs SoC was 181.6 million VND lower than a willingness to pay threshold recommended in Vietnam (3GDP per capita equal to 286.8 million VND). Deterministic sensitivity analysis indicated that parameters related to Health Assessment Questionnaire scores were most influential. At the willingness to pay threshold of three times the GDPpc, the probability of secukinumab being cost-effective was 90.3% in the probabilistic sensitivity analysis. Secukinumab is a cost-effectiveness treatment versus SoC for PsA patients from the National health insurance’s perspective of Vietnam.

Molecular mechanism of interleukin-17A regulating airway epithelial cell ferroptosis based on allergic asthma airway inflammation

Interleukin-17A (IL-17A) levels are elevated in patients with asthma. Ferroptosis has been identified as the non-apoptotic cell death type associated with asthma. Data regarding the relation of ferroptosis with asthma and the effect of IL-17A on modulating ferroptosis in asthma remain largely unclear. The present work focused on investigating the role of IL-17A in allergic asthma-related ferroptosis and its associated molecular mechanisms using public datasets, clinical samples, human bronchial epithelial cells, and an allergic asthma mouse model. We found that IL-17A was significantly upregulated within serum in asthma cases. Adding IL-17A significantly increased ferroptosis within human bronchial epithelial cells (BEAS-2B). In ovalbumin (OVA)-induced allergic asthmatic mice, IL-17A regulated and activated lipid peroxidation induced ferroptosis, whereas IL-17A knockdown effectively inhibited ferroptosis in vivo by protection of airway epithelial cells via the xCT-GSH-GPX4 antioxidant system and reduced airway inflammation. Mouse mRNA sequencing results indicated that the tumor necrosis factor (TNF) pathway was the differential KEGG pathway in the OVA group compared to healthy controls and the OVA group compared to the IL-17A knockout OVA group. We further used N-acetylcysteine (TNF inhibitor) to inhibit the TNF signaling pathway, which was found to protect BEAS-2B cells from IL-17A induced lipid peroxidation and ferroptosis damage. Our findings reveal a novel mechanism for the suppression of ferroptosis in airway epithelial cells, which may represent a new strategy for the use of IL-17A inhibitors against allergic asthma.

Response to Interleukin-17A Inhibitors According to Prior Biologic Exposures: A Danish Nationwide Study.

Whether response to an interleukin (IL-17) inhibitor is different in patients with previous exposure to an IL-17 inhibitor compared with patients with exposure to biologics with other cytokine targets remains to be elucidated. Therefore, the aim of this study was to assess whether previous exposure to an IL-17A inhibitor was associated with worse response than exposure to (an)other biologic(s). All patients in the DERMBIO register treated with an IL-17A inhibitor (secukinumab or ixekizumab) were included. With an absolute Psoriasis Area and Severity Index (PASI) ≤ 2 as response, the proportion of responders treated with IL-17A inhibitors was assessed in patients previously treated with another IL-17A inhibitor and compared with patients with previous exposure to (an)other biologic(s), using a χ2 test. In total, 100, 93 and 83 patients with previous exposure to an IL-17A inhibitor and 414, 372 and 314 patients with previous exposure to (an) other biologic(s) were assessed after 3, 6 and 12 months, respectively. No differences in the proportion of patients achieving PASI ≤ 2 were observed between the 2 groups after 3 months (54% vs 57%, p = 0.59), 6months (70% vs 66%, p = 0.42) and 12 months (69% vs 60%, p = 0.14). In conclusion, when treating patients with IL-17A inhibitors the cytokine target of the previous biologic does not appear to affect the response.

258 First-in-human results from a phase 1 single- and multiple-ascending dose study in healthy participants assessing the safety, pharmacokinetics, and pharmacodynamics of the interleukin-17A inhibitor JNJ-81241459

258 First-in-human results from a phase 1 single- and multiple-ascending dose study in healthy participants assessing the safety, pharmacokinetics, and pharmacodynamics of the interleukin-17A inhibitor JNJ-81241459

Клинический случай: успешная терапия пустулезного псориаза подошв ингибитором интерлейкина-17А нетакимабом

Клинический случай: успешная терапия пустулезного псориаза подошв ингибитором интерлейкина-17А нетакимабом

Optimising psoriatic arthritis therapy with immunological methods to increase standard evaluation: the protocol of an open-label multicentre, parallel-group, two-arm randomised controlled study evaluation precision medicine approach in the treatment of psoriatic arthritis

IntroductionPsoriatic arthritis (PsA) affects around 150 000 people in the UK of whom around 50% require treatment with biologics. The most used biologics for PsA target tumour necrosis factor (TNF)...