Medizinonline Medizinonline
  • News
    • News
    • Market & Medicine
  • Patients
    • Disease patterns
    • Diagnostics
    • Therapy
  • Partner Content
    • Dermatology
      • Atopic dermatitis and psoriasis news
      • Dermatology News
    • Diabetes
      • Dia-Month Club – Type 2 Diabetes
      • Diabetes in Motion
      • Diabetes Podcasts
    • Gastroenterology
      • IBD matters
      • Forum Gastroenterology
      • Ozanimod: ulcerative colitis
      • Reflux Update
    • Immunology
      • Primary immunodeficiency – exchange of experience
    • Vaccinate
      • Herpes zoster
    • Infektiologie
    • Neurology
      • EXPERT ULTRASONIC: Introduction to ultrasound-guided injection
      • MS News
      • MS Therapy in Transition
    • Oncology
      • Swiss Oncology in motion
    • Orthopedics
      • Osteoporosis in motion
    • Phytotherapie
    • Practice Management
      • Aargau Cantonal Bank
      • Claraspital
    • Psychiatry
      • Geriatric Psychiatry
    • Rheumatology
  • Departments
    • Allergology and clinical immunology
    • General Internal Medicine
    • Anesthesiology
    • Angiology
    • Surgery
    • Dermatology and venereology
    • Endocrinology and Diabetology
    • Nutrition
    • Gastroenterology and Hepatology
    • Genetics
    • Geriatrics
    • Gynecology
    • Hematology
    • Infectiology
    • Cardiology
    • Nephrology
    • Neurology
    • Emergency and intensive care medicine
    • Nuclear Medicine
    • Oncology
    • Ophthalmology
    • ORL
    • Orthopedics
    • Pediatrics
    • Pharmacology and toxicology
    • Pharmaceutical medicine
    • Phlebology
    • Physical medicine and rehabilitation
    • Pneumology
    • Prevention and health care
    • Psychiatry and psychotherapy
    • Radiology
    • Forensic Medicine
    • Rheumatology
    • Sports Medicine
    • Traumatology and trauma surgery
    • Tropical and travel medicine
    • Urology
    • Dentistry
  • CME & Congresses
    • CME continuing education
    • Congress Reports
    • Congress calendar
  • Practice
    • Noctimed
    • Practice Management
    • Jobs
    • Interviews
  • Log In
  • Register
  • My account
  • Contact
  • English
    • Deutsch
    • Français
    • Italiano
    • Português
    • Español
  • Publications
  • Contact
  • Deutsch
  • English
  • Français
  • Italiano
  • Português
  • Español
Subscribe
Medizinonline Medizinonline
Medizinonline Medizinonline
  • News
    • News
    • Market & Medicine
  • Patienten
    • Krankheitsbilder
    • Diagnostik
    • Therapie
  • Partner Content
    • Dermatology
      • Atopic dermatitis and psoriasis news
      • Dermatology News
    • Diabetes
      • Dia-Month Club – Type 2 Diabetes
      • Diabetes in Motion
      • Diabetes Podcasts
    • Gastroenterology
      • IBD matters
      • Forum Gastroenterology
      • Ozanimod: ulcerative colitis
      • Reflux Update
    • Immunology
      • Primary immunodeficiency – exchange of experience
    • Vaccinate
      • Herpes zoster
    • Infektiologie
    • Neurology
      • EXPERT ULTRASONIC: Introduction to ultrasound-guided injection
      • MS News
      • MS Therapy in Transition
    • Oncology
      • Swiss Oncology in motion
    • Orthopedics
      • Osteoporosis in motion
    • Phytotherapie
    • Practice Management
      • Aargau Cantonal Bank
      • Claraspital
    • Psychiatry
      • Geriatric Psychiatry
    • Rheumatology
  • Departments
    • Fachbereiche 1-13
      • Allergology and clinical immunology
      • General Internal Medicine
      • Anesthesiology
      • Angiology
      • Surgery
      • Dermatology and venereology
      • Endocrinology and Diabetology
      • Nutrition
      • Gastroenterology and Hepatology
      • Genetics
      • Geriatrics
      • Gynecology
      • Hematology
    • Fachbereiche 14-26
      • Infectiology
      • Cardiology
      • Nephrology
      • Neurology
      • Emergency and intensive care medicine
      • Nuclear Medicine
      • Oncology
      • Ophthalmology
      • ORL
      • Orthopedics
      • Pediatrics
      • Pharmacology and toxicology
      • Pharmaceutical medicine
    • Fachbereiche 26-38
      • Phlebology
      • Physical medicine and rehabilitation
      • Phytotherapy
      • Pneumology
      • Prevention and health care
      • Psychiatry and psychotherapy
      • Radiology
      • Forensic Medicine
      • Rheumatology
      • Sports Medicine
      • Traumatology and trauma surgery
      • Tropical and travel medicine
      • Urology
      • Dentistry
  • CME & Congresses
    • CME continuing education
    • Congress Reports
    • Congress calendar
  • Practice
    • Noctimed
    • Practice Management
    • Jobs
    • Interviews
Login

Sie haben noch keinen Account? Registrieren

  • Therapy with Small Molecules

JAK inhibitors in inflammatory dermatoses on the rise

    • Allergology and clinical immunology
    • Congress Reports
    • Dermatology and venereology
    • RX
    • Studies
  • 4 minute read

In inflammatory processes of dermatological diseases, pro-inflammatory cytokines play a central role. Therefore they are in focus therapeutic approaches when it comes to breaking critical signaling pathways. In addition to monoclonal antibodies, small-molecule agents directed against Janus kinases (JAK) are increasingly being used. The first approvals of JAK inhibitors have already been received in atopic dermatitis and psoriasis, but data to date are also promising in other inflammatory skin diseases such as vitiligo and alopecia areata.

JAK inhibitors represent a valuable addition to systemic treatment strategies for inflammatory skin diseases. “The JAK-STAT signaling pathway is an essential key in the treatment of immunological and chronic inflammatory diseases. If we succeed in stopping pro-inflammatory cytokine cascades, this has an immediate effect on the inflammatory response,” explains Prof. Michael Hertl, MD, acting President of the German Dermatological Society (DDG) and Director of the Clinic for Dermatology and Allergology, Philipps University and University Hospital Marburg [1]. By occupying the STAT docking sites, JAK inhibitors inhibit the JAK-STAT signaling pathway and thus the pro-inflammatory signaling cascade (Fig. 1). 

 

 

Specific intracellular signaling pathways are modulated

The deregulated and activated Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathway plays a key role in the pathogenesis of many inflammatory dermatoses. Four subunits of Janus kinases (JAKs) are present in human cells: JAK1, JAK2, JAK3 and TYK2. Intracellular signal transduction of numerous proinflammatory cytokines is mediated by Janus kinases. After dimerization and autophosphorylation, STAT proteins are recruited and phosphorylated, which control transcription of target genes in the nucleus. Janus kinases form homodimers or heterodimers, with JAK2 also occurring as a homodimer [2]. Pharmacological inhibition of JAKs can downregulate the activity of the JAK-STAT signaling pathway, thereby preventing intracellular signal transduction of several proinflammatory cytokines [1,2].

JAK inhibitors conquer diverse dermatological indication areas

For the treatment of adult patients with moderate to severe atopic dermatitis, baricitinib (Olumiant®) was approved in Switzerland in the first quarter of last year as the first representative from the group of oral JAK inhibitors, and in November upadacitinib (Rinvoq®) also cleared the approval hurdle [4]. Baricitinib in particular shows high potency and selectivity for the JAK1 and JAK2 subtypes, whereas upadacitinib targets JAK1 primarily (Table 1) . Abrocitinib, a third member of the Janus kinase inhibitors, has already been approved in the EU for this indication [5]. For the treatment  of adults with active psoriatic arthritis, tofacitinib (Xeljanz®) is approved in Switzerland in combination with a conventional synthetic DMARD. In addition, a phase II study demonstrated the efficacy of TYK2 inhibition using deucravacitinib-BMS986165 compared with placebo [6].

 

 

The data for JAK inhibitors also look promising with regard to their potential use in alopecia areata. In a meta-analysis of 30 small trials of JAK inhibitors for alopecia areata, 72.4% of patients responded to therapy, including 45.7% with good (50-100% hair regrowth) and 21.4% with partial response (5-50% hair regrowth) [7]. The double-blind, randomized-controlled ALLEGRO trial also evaluated the efficacy of JAK inhibitors in women and men with alopecia areata. All participants had more than 50 percent hair loss on the scalp at baseline. Treatment for 24 weeks was effective and well tolerated: compared with the placebo group, participants in the verum group had hair loss of 20% or less [8]. The side effect profile of the JAK inhibitors is clear, explains Prof. Hertl. Infections can occur more frequently, for example in the nose and throat or in the respiratory tract. Urinary tract infections, gastrointestinal disorders and acne have also been observed. “When an infection is acute, therapy with JAK inhibitors should be paused, of course,” the DDG president said. However, the expert adds that this works very well due to the oral application and short half-life of the drugs [1]. The latest developments include topically applicable JAK inhibitors. A JAK 1/2 inhibitor administered by cream improved diseased facial skin (repigmentation of vitiligo lesions) in approximately 50% of patients versus 3% with placebo in the treatment of autoimmune-induced vitiligo [9]. “These are promising results suggesting that this cream could be an effective therapeutic option for patients with vitiligo,” emphasized Prof. Hertl, adding, “The side effects known with cortisone ointments were not observed” [1].

Congress: Dermatology compact and practical

 

 

Literature:

  1. “Small molecules against atopic dermatitis, psoriasis, vitiligo and circular hair loss: JAK inhibitors in inflammatory skin diseases expand treatment spectrum,” Deutsche Dermatologische Gesellschaft e. V. (DDG), Jan. 31, 2022.
  2. Schwartz DM, et al: JAK inhibition as a therapeutic strategy for immune and inflammatory diseases. Nat Rev Drug Discov 2017; 16: 843-862.
  3. Damsky W, et al: The emerging role of Janus kinase inhibitors in the treatment of autoimmune and inflammatory diseases. J Allergy Clin Immunol 2021; 147: 814-826.
  4. Drug Information, www.swissmedicinfo.ch, (last accessed Mar. 07, 2022).
  5. Klein B, Treudler R, Simon JC: JAK inhibitors in dermatology – small molecules, big impact? Overview of mechanism of action, study results, and potential adverse effects. J Dtsch Dermatol Ges 2022; 20(1): 19-25.
  6. Papp K, et al: Phase 2 trial of selective tyrosine kinase 2 inhibition in psoriasis. N Engl J Med 2018; 379: 1313-1321.
  7. Phan K, Sebaratnam DF: JAK inhibitors for alopecia areata: a systematic review and meta-analysis. J Eur Acad Dermatol Venereol 2019; 33: 850-856.
  8. King B, et al: A phase 2a randomized, placebo-controlled study to evaluate the efficacy and safety of the oral Janus kinase inhibitors ritlecitinib and brepocitinib in alopecia areata: 24-week results. J Am Acad Dermatol 2021; 85(2): 379-387.
  9. Rosmarin D, et al: Ruxolitinib cream for treatment of vitiligo: a randomised, controlled, phase 2 trial. Lancet 2020; 396: 110-120.
  10. Alexander M, et al: Jakinibs of All Trades: Inhibiting Cytokine Signaling in Immune-Mediated Pathologies. Pharmaceuticals 2022; 15(1): 48.
  11. Bonnekoh H, Butze M, Metz M: Characterization of the effects of new therapies for the treatment of atopic dermatitis on pruritus. J Dtsch Dermatol Ges 2022; 20(2): 150-156,
  12. Karonitsch T: Place of JAK inhibitors (“small is beautiful”). J Miner Metabolism Musculoskeletal Diseases 2021; 28: 78-83.

 

DERMATOLOGIE PRAXIS 2022; 32(2): 30-31 (published 4/20/22, ahead of print).

Autoren
  • Mirjam Peter, M.Sc.
Publikation
  • DERMATOLOGIE PRAXIS
Related Topics
  • dermatoses
  • JAK Inhibitor
  • small molecules
Previous Article
  • Anti-infectives

Recognize and adequately treat COVID-19 associated aspergillosis.

  • Education
  • General Internal Medicine
  • Infectiology
  • News
  • Pneumology
  • RX
  • Studies
View Post
Next Article
  • Inflammatory rheumatic diseases

Remission as the primary treatment goal

  • Partner Content
  • RX
View Post
You May Also Like
View Post
  • 7 min
  • Moderate to severe chronic hand eczema

Delgocitinib cream – first topical pan-JAK inhibitor approved in Switzerland

    • Allergology and clinical immunology
    • Dermatology and venereology
    • Education
    • Infectiology
    • Market & Medicine
    • Pharmacology and toxicology
    • RX
View Post
  • 9 min
  • Wild-type transthyretin amyloid cardiomyopathy (ATTRwt-CA)

Diagnosis at an early stage, prognostic classifications and outlook

    • Cardiology
    • Education
    • RX
    • Studies
View Post
  • 4 min
  • Case report: Drug-induced hepatitis

Rare side effect of tirzepatide therapy

    • Cases
    • Education
    • Endocrinology and Diabetology
    • Gastroenterology and Hepatology
    • Pharmacology and toxicology
    • RX
    • Studies
View Post
  • 4 min
  • Plea for sex-specific neurology

Migraine in men: underdiagnosed, underestimated, under-researched

    • Education
    • Neurology
    • RX
    • Studies
View Post
  • 4 min
  • Prurigo nodularis

Retrospective analyses of large data sets from everyday practice

    • Allergology and clinical immunology
    • Congress Reports
    • Dermatology and venereology
    • RX
View Post
  • 3 min
  • Public Health

Outpatient care in Switzerland: situation report

    • General Internal Medicine
    • Practice Management
    • Prevention and health care
    • RX
View Post
  • 5 min
  • Practice Management

Improved quality of care aims for satisfied patients

    • CME continuing education
    • General Internal Medicine
    • Practice Management
    • Prevention and health care
    • RX
    • Studies
View Post
  • 30 min
  • Chemsex - MSM, sex, chrystal meth & co.

Medical and psychosocial perspectives

    • CME continuing education
    • General Internal Medicine
    • Infectiology
    • Pharmacology and toxicology
    • Prevention and health care
    • Psychiatry and psychotherapy
    • RX
Top Partner Content
  • Forum Gastroenterology

    Zum Thema
  • Herpes zoster

    Zum Thema
  • Dermatology News

    Zum Thema
Top CME content
  • 1
    Patience, knowledge and persistence in therapy
  • 2
    Sarcopenia and malnutrition in the context of pneumological rehabilitation
  • 3
    Medical and psychosocial perspectives
  • 4
    New nomenclature for non-alcoholic fatty liver disease
  • 5
    Examinations and considerations before therapy

Newsletter

Sign up and stay up to date

Subscribe
Medizinonline
  • Contact
  • General terms and conditions
  • Imprint

Input your search keywords and press Enter.