Efficacy and safety of small molecule oral medications for psoriatic arthritis: a network meta-analysis of randomized controlled trials DOI Creative Commons
Ya‐Chu Tsai,

Chen‐Yiu Hung,

Tsen‐Fang Tsai

et al.

Therapeutic Advances in Musculoskeletal Disease, Journal Year: 2024, Volume and Issue: 16

Published: Jan. 1, 2024

Background: Although there have been network meta-analyses (NMAs) regarding the efficacy and safety of targeted immunotherapy for psoriatic arthritis, most them primarily focus on biologics. However, small molecules biologics many differences in properties onset time. This NMA put emphasis molecule drugs incorporates medications including upadacitinib deucravacitinib, which less compared previously. Objective: To compare (apremilast, tofacitinib, upadacitinib) active arthritis (PsA) using NMA. Design: study was conducted reported following guidelines Preferred Reporting Items Systematic Reviews Meta-analyses Extension Statement Network Meta-Analyses (PRISMA-NMA), with relevant articles identified through searches across electronic databases. Data sources methods: Databases PubMed, Cochrane Library, ClinicalTrial.gov were searched. Randomized controlled trials (RCTs) synthetic PsA by either placebo or comparators within weeks 12–16 eligible. A frequentist framework a random-effect model employed analysis. The revised risk-of-bias tool RCTs used to assess quality enrolled studies. Results: total 9 involving 3699 patients analyzed. Apremilast 30 mg bid, deucravacitinib 6 12 qd, tofacitinib 5 15 qd all demonstrated superior over achieving American College Rheumatology (ACR) 20/50/70, Psoriasis Area Severity Index (PASI) 75, Health Assessment Questionnaire-Disability (HAQ-DI) scores at 12–16. When adalimumab, achieved borderline superiority PASI 75 week (risk ratio (RR) = 1.20, 95% confidence interval (CI): 1.02–1.40). Among four studied, only showed significantly better HAQ-DI apremilast (RR −0.16, CI: −0.29 −0.02), no statistically significant observed other parameters. Conclusion: All oral exhibited comparable profiles. Across different assessment criteria, ACR 50, 70, HAQ-DI, consistently ranked top two positions.

Language: Английский

Deucravacitinib is an allosteric TYK2 protein kinase inhibitor FDA-approved for the treatment of psoriasis DOI Creative Commons
Robert Roskoski

Pharmacological Research, Journal Year: 2023, Volume and Issue: 189, P. 106642 - 106642

Published: Feb. 6, 2023

Psoriasis is a heterogeneous, inflammatory, autoimmune skin disease that affects up to 2% of the world's population. There are many treatment modalities including topical medicines, ultraviolet light therapy, monoclonal antibodies, and several oral medications. Cytokines play central role in pathogenesis this disorder TNF-α, (tumor necrosis factor-α) IL-17A (interleukin-17A), IL-17F, IL-22, IL-23. Cytokine signaling involves transduction mediated by JAK-STAT pathway. four JAKS (JAK1/2/3 TYK2) six STATS (signal transducer activators transcription). Janus kinases contain an inactive JH2 domain aminoterminal active JH1 domain. Under basal conditions, inhibits activity Deucravacitinib orally effective N-trideuteromethyl-pyridazine derivative targets stabilizes TYK2 thereby blocks activity. Seven other JAK inhibitors, which target family domain, prescribed for neoplastic inflammatory diseases. The use deuterium trimethylamide decreases rate demethylation slows production metabolite against variety addition TYK2. A second unique aspect development deucravacitinib targeting pseudokinase rather specific its toxic effects much less than those FDA-approved inhibitors. successful may stimulate additional ligands kinase families as well.

Language: Английский

Citations

48
Inflammation and Psoriasis: A Comprehensive Review DOI Open Access
Alessandra-Mădălina Man,

Meda Sandra Orăsan,

Oana-Alina Hoteiuc

et al.

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(22), P. 16095 - 16095

Published: Nov. 8, 2023

Psoriasis is an immune-mediated disease with a strong genetic component that brings many challenges to sick individuals, such as chronic illness, and which has multiple associated comorbidities like cardiovascular disease, metabolic syndrome, inflammatory bowel psychological disorders. Understanding the interplay between innate adaptative immune system led discovery of specific cytokine circuits (Tumor Necrosis Factor-alpha (TNF-α), IL-23, IL-17), allowed scientists discover new biomarkers can be used predictors treatment response pave way for personalized treatments. In this review, we describe footprint psoriasis leaves on skin beyond, key pathophysiological mechanisms, current available therapeutic options, drawbacks faced by existing therapies, anticipate potential future perspectives may improve quality life affected individuals.

Language: Английский

Citations

37
Emerging treatments for dermatologic diseases in infants, children, and adolescents: a systematic review of clinical trials on biologics and small molecule inhibitors DOI
Alireza Jafarzadeh, Elham Behrangi, Mina Khosravi

et al.

Inflammopharmacology, Journal Year: 2025, Volume and Issue: 33(4), P. 1617 - 1672

Published: March 5, 2025

Language: Английский

Citations

1
Upadacitinib for Moderate to Severe Atopic Dermatitis DOI
F.J. Navarro‐Triviño,

Sara Alcantara‐Luna,

J.J. Domínguez-Cruz

et al.

Immunotherapy, Journal Year: 2023, Volume and Issue: 15(11), P. 799 - 808

Published: May 17, 2023

Atopic dermatitis is an inflammatory skin disease, the prevalence of which has increased in last decade. It affects all age groups, with adult involvement being a major focus interest recent years. The unmet needs such as pruritus, sleep quality impairment and eczematous lesions, have undergone therapeutic revolution following commercialization drugs JAK inhibitors. Upadacitinib, selective JAK1 inhibitor, been positioned by both clinical trial results those observed practice fastest most effective drug reducing pruritus Eczema Area Severity Index validated Investigator Global Assessment. Although safety profile may be initially alarming, it advisable to update actual data this regard for proper management. New perspectives upadacitinib nonatopic comorbidities psoriasis alopecia areata are beginning described, learning more about its peculiarities growing.

Language: Английский

Citations

11
Updates in atopic dermatitis for the primary care physician: A review of advances in the understanding and treatment of atopic dermatitis DOI
Zi-Yi Choo,

Stephanie Mehlis,

Joel C. Joyce

et al.

Disease-a-Month, Journal Year: 2024, Volume and Issue: 70(4), P. 101687 - 101687

Published: Jan. 25, 2024

Language: Английский

Citations

4
Prostaglandins and Skin Cancer: An Old Pathway With New Insights in Cutaneous Oncology DOI Creative Commons
Krisztián Németh

International Journal of Dermatology, Journal Year: 2025, Volume and Issue: unknown

Published: April 1, 2025

Language: Английский

Citations

0
Biologics Versus JAK Inhibitors. Part I: Cancer Risk. A Narrative Review DOI Creative Commons
Miguel Mansilla‐Polo, D. Morgado‐Carrasco

Dermatology and Therapy, Journal Year: 2024, Volume and Issue: 14(6), P. 1389 - 1442

Published: May 19, 2024

Biological drugs (BD) and Janus kinase inhibitors (JAKi) have revolutionized the treatment of diverse dermatoses. However, there are concerns regarding their safety, especially risk cancer opportunistic infections. Here, we discuss associated with BD JAKi used in dermatology. A narrative review was carried out. All relevant articles evaluating or published between January 2010 February 2024 were selected. Multiple large studies evaluated association BD, risk. is a lack prospective, comparative studies. Overall, patients undergoing present cutaneous incidence similar to that general population. The more strongly non-skin anti-tumor necrosis factor (anti-TNFs) agents (especially tofacitinib oral ruxolitinib). This appears increase age, presence other factors (such as chronic immunosuppression from previous comorbidities), specific diseases such rheumatoid arthritis (RA) myelodysplastic syndrome. Conversely, interleukin (IL)-17 IL-23 may even reduce some visceral hematological malignancies. In dermatological conditions psoriasis atopic dermatitis, malignancies be lower than subgroups, probably comparable generally low. can higher elderly RA syndrome, those prolonged therapy ruxolitinib (oral), anti-TNF agents.

Language: Английский

Citations

3
Targeting IL‐23 with Small Molecule Inhibitors: A New Horizon In Psoriasis Therapy DOI

Raghad Sharbaji,

Pınar Si̇yah

ChemistrySelect, Journal Year: 2025, Volume and Issue: 10(8)

Published: Feb. 1, 2025

Abstract Interleukin‐23 (IL‐23) is a dominant cytokine in psoriasis, chronic inflammatory skin disease that severely diminishes patients' quality of life and reduces lifespan by up to 10 years. Despite therapeutic advancements, psoriasis remains clinical challenge due the absence definitive cure, treatment side effects, substantial economic burden. Notably, no small molecule inhibitors (SMIs) directly targeting IL‐23 have been developed date, leaving critical gap current therapies. In this study, SMIs emerged as promising alternatives. A high‐throughput virtual screening 1.57 million molecules was conducted, followed molecular docking dynamics (MD) simulations (1, 10, 100 ns) identify potential candidates. Machine learning‐based binary QSAR models MetaCore analysis established relevance these hits other diseases. As result, tenapanor (MM/GBSA score: −101.66 kcal/mol) ChemBridge ID 7740 360118 (−101.59 kcal/mol, −91.003 top candidates, demonstrating exceptional binding affinity stability 100‐ns simulations. These represent leads, offering an alternative existing biologics. Further vitro vivo validation will be essential confirm their efficacy first IL‐23‐targeted

Language: Английский

Citations

0
Macrophage Functions in Psoriasis: Lessons from Mouse Models DOI Open Access
Katarzyna Nazimek, Krzysztof Bryniarski

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(10), P. 5306 - 5306

Published: May 13, 2024

Psoriasis is a systemic autoimmune/autoinflammatory disease that can be well studied in established mouse models. Skin-resident macrophages are classified into epidermal Langerhans cells and dermal involved innate immunity, orchestration of adaptive maintenance tissue homeostasis due to their ability constantly shift phenotype adapt the current microenvironment. Consequently, both macrophage populations play dual roles psoriasis. In some circumstances, pro-inflammatory activated trigger psoriatic inflammation, while other cases anti-inflammatory stimulation results amelioration disease. These features make interesting candidates for modern therapeutic strategies. Owing significant progress knowledge, our review article summarizes achievements indicates future research directions better understand function

Language: Английский

Citations

3
Secondary immunodeficiencies and infectious considerations of biologic immunomodulatory therapies DOI Creative Commons
Laura Cannon,

Alice Pan,

Leonard Kovalick

et al.

Annals of Allergy Asthma & Immunology, Journal Year: 2023, Volume and Issue: 130(6), P. 718 - 726

Published: Feb. 18, 2023

Language: Английский

Citations

7