Association Between IL-23 And Coronary Arterial Lesions In Children With Kawasaki Disease

The pathogenesis of coronary artery lesions (CALs) in KD patients has been thought of as an unknown stimulus that triggers an inflammatory cascade with activation of the immune system. However, interleukin-23 (IL-23) is supposed as a key cytokine in inflammatory and autoimmunity diseases. The role of IL-23 in the pathogenesis of CALs has not been fully elucidated. This study explored the relationship between the serum IL-23 levels and CALs in patients with KD. We collected blood specimens from 90 children with KD before intravenous immunoglobulin (IVIG) therapy. Levels of IL-23, IL-6, IL-17A, IL-10, MCP-1 and VEGF were measured in 190 cases, including 4 groups: KD with CALs (n = 46), KD without CALs (n = 44), febrile control group, (FC, n = 40) and normal control group, (NC, n = 60). Clinical parameters were tested in all subjects. IL-23 was significantly elevated in the KD group compared with the febrile and normal control groups, especially increased in the KD patients with CALs. Serum levels of IL-23 in KD patients were positively associated with WBC, CRP, IL-6, IL-17A, IL-10, MCP-1, and VEGF in children with KD. IL-23 may be involved in the pro-inflammatory process and the pathogenesis of CALs in KD patients.

The use of guselkumab in psoriatic arthritis: evidence from real clinical practice

Psoriatic arthritis (PsA) is a chronic inflammatory disease of the joints, spine and enthesis from the group of spondyloarthritis that develops in patients with psoriasis. Guselkumab is a biologic disease-modifying antirheumatic drug, an inhibitor of interleukin 23, which has been shown to be effective in the treatment of plaque psoriasis and PsA.Objective: to evaluate the effectiveness of guselkumab treatment in PsA patients.Patients and methods. The study included 16 patients with PsA. All patients received 100 mg of guselkumab subcutaneously at weeks 0, 4, 12, 20. Disease activity and treatment efficacy were assessed at weeks 0, 12 and 24 using the DAS28, ASDAS, BASDAI, DAPSA activity indices, the index of the extent and severity of psoriasis PASI.Results and discussion. During treatment, patients with PsA showed a pronounced positive dynamics of the indices of disease activity and an improvement in the skin condition. Before the treatment with guselkumab, the mean value of the DAS28 index was 4.26±0.64, DAPSA – 37.94±9.45, ASDAS – 2.7±0.65, and BASDAI – 5.49±1.39, after 12 weeks of treatment these indicators decreased to 3.03±0.49; 17.06±4.58; 1.64±0.33 and 3.48±0.66, respectively, and after 24 weeks (after the 4th injection) – to 2.32±0.18; 11.31±2.18; 1.22±0.27 and 2.62±0.78, respectively (p<0.05 for all cases). Before treatment, the average PASI index reached 30.99±15.43, after 12 weeks – 4.55±4.82, and after 24 weeks – 1.05±1.46 (p<0.05). During treatment, a significant improvement in the main manifestations of the disease was noted: regression of peripheral arthritis, spondylitis, and skin rashes.The treatment was well tolerated during the 24 weeks of the study, and no serious adverse events were reported.Conclusion. The data from real clinical practice indicate that guselkumab is highly effective and safe in the treatment of PsA.

Efficacy and safety of risankizumab for active psoriatic arthritis: 24-week results from the randomised, double-blind, phase 3 KEEPsAKE 1 trial

ObjectiveTo evaluate risankizumab, a biological therapy that inhibits interleukin 23, in patients with active psoriatic arthritis (PsA) who have responded inadequately or are intolerant to ≥1 conventional synthetic disease-modifying antirheumatic drug (csDMARD).MethodsIn the randomised, placebo-controlled, double-blind KEEPsAKE 1 trial, 964 patients with active PsA were randomised (1:1) to receive risankizumab 150 mg or placebo at weeks 0, 4 and 16. The primary endpoint was the proportion of patients achieving ≥20% improvement in American College of Rheumatology criteria (ACR20) at week 24. Here, we report the results from the 24-week double-blind period; the open-label period with all patients receiving risankizumab is ongoing.ResultsAt week 24, a significantly greater proportion of patients receiving risankizumab achieved the primary endpoint of ACR20 (57.3% vs placebo, 33.5%; p<0.001). Significant differences were also observed for risankizumab versus placebo for the first eight ranked secondary endpoints, including skin and nail psoriasis endpoints, minimal disease activity and resolution of enthesitis and dactylitis (p<0.001). Adverse events and serious adverse events were reported at similar rates in the risankizumab and placebo groups. Serious infections were reported for 1.0% and 1.2% of patients receiving risankizumab and placebo, respectively. There was one death in the risankizumab group (urosepsis deemed unrelated to the study drug).ConclusionsRisankizumab treatment results in significantly greater improvement of signs and symptoms of PsA compared with placebo and is well tolerated in patients with active PsA who have responded inadequately or are intolerant to ≥1 csDMARD.Trial registration numberNCT03675308.

An insight into anti-arthritic property of phytochemicals against Rheumatoid arthritis using molecular modelling and docking approach

Arthritis literally refers “joint inflammation”, it is a condition where one or more joints are inflamed. More than 100 different types of Arthritis were identified, most common types are rheumatoid arthritis and osteoarthritis. The present study mainly focuses on the development of the novel phytochemical inhibitors against rheumatoid arthritis and osteoarthritis using an integrative cheminformatics drug discovery platform. In this study, we identified potential 405 phytochemical drug candidates, screened against eight selected targets of rheumatoid arthritis and osteoarthritis using molecular docking tool AutoDock. Three phytochemicals Withanolide, Diosgenin and bamyrin exhibited promising binding towards multiple drug targets selected for this study. When comparing with the binding between reference drugs, withanolide showed highest activity against Interleukin-23, Matrix metalloproteinase-3 and Interleukin 8 with binding energies -11.6, -9.4 and -8.3 kcal/mol respectively. Diosgenin also exhibited best activity against three targets that were Interleukin-23, JNK alpha and MMP-3 with -11.3, -10.4, -9.5 kcal/mol binding energies respectively. This study may be important contributing factor to develop new therapeutic drugs for rheumatoid arthritis and osteoarthritis.

Cardiometabolic Comorbidities in Patients With Psoriasis: Focusing on Risk, Biological Therapy, and Pathogenesis

Psoriasis is a chronic inflammatory disease characterized by erythematous scaly plaques, accompanied by systemic damage that leads to the development of multiple comorbidities. In particular, the association between psoriasis and cardiometabolic comorbidities, including cardiovascular diseases (CVDs), obesity, diabetes mellitus, and metabolic syndrome, has been verified in a considerable number of clinical trials. Moreover, the increased risk of cardiometabolic comorbidities positively correlates with psoriasis severity. Biologic therapy targeting inflammatory pathways or cytokines substantially improves the life quality of psoriasis patients and may affect cardiometabolic comorbidities by reducing their incidences. In this review, we focus on exploring the association between cardiometabolic comorbidities and psoriasis, and emphasize the benefits and precautions of biologic therapy in the management of psoriasis with cardiometabolic comorbidities. The pathogenic mechanisms of cardiometabolic comorbidities in psoriasis patients involve common genetic factors, lipid metabolism, insulin resistance, and shared inflammatory pathways such as tumor necrosis factor-α and interleukin-23/Th-17 pathways.

Nociceptive Sensory Fibers Drive Interleukin-23 Production in a Murine Model of Psoriasis via Calcitonin Gene-Related Peptide

Neuroimmunity is involved in the pathogenesis of psoriasis, but the mechanism underlying the interaction between the nervous system and the interleukin (IL)-23/IL-17 immune axis is yet unclear. This study reveals the essential role of the sensory neuron-derived calcitonin gene-related peptide (CGRP) in imiquimod (IMQ)-induced expression of IL-23. First, we show that the increased nociceptive behavior was consistent with the development of psoriasiform dermatitis, which requires intact sensory innervation. Systemic ultrapotent Transient receptor potential vanilloid 1 (TRPV1) agonist (resiniferatoxin, RTX) treatment-induced sensory denervation resulted in a significant decrease in IL-23 expression in this model, while the recombinant IL-23 treatment induced IL-17A expression was intact after RTX treatment. In addition, IMQ exposure induced a transient increase in CGRP expression in the dorsal root ganglion. The neuron-derived CGRP expression was completely abolished by sensory denervation, thereby downregulating IL-23 expression, which could be reversed through the introduction of CGRP into the denervated dorsal skin. Our results suggest that nociceptive sensory neurons may drive the production of IL-23, resulting in IL-17A production from γδ T cells via the neuropeptide CGRP in the pathology of psoriasis.