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

  • Journal Club: Atopic dermatitis

Modern systems therapy – status quo and prospects

    • Allergology and clinical immunology
    • Dermatology and venereology
    • Education
    • Pharmacology and toxicology
    • RX
    • Studies
  • 9 minute read

The therapeutic landscape for atopic dermatitis is changing. New findings have made it possible to develop modern treatment options that selectively target inflammatory signaling pathways. There are currently two modern therapeutic approaches among the approved system therapeutics that specifically intervene in the inflammatory mechanism: Biologics and Janus kinase inhibitors. A recently published review summarizes important points.

The corresponding author of the review article is Dr. Ilya Mukovozov, dermatologist at the Toronto Dermatology Centre (Canada) [1]. A key message from Dr. Mukovozov and colleagues is that an increasing diversity of anti-inflammatory systemic therapeutics increases the chances for a tailored treatment that is best matched to disease and patient characteristics.

Biologics

Monoclonal antibodies are genetically engineered proteins that target specific components of the immune system (e.g. cytokines or receptors) involved in the inflammatory response. By blocking these cytokine/receptor pathways, biologics modulate the excessive immune system response characteristic of AD, ultimately resulting in a reduction in skin inflammation and itching. Biologics neutralize interleukins or block receptors extracellularly.

Abbreviations
DLQI = Dermatology Life Quality Index
EASI = Eczema Area and Severity Index
Itch NRS = Numerical Rating Scale for Itching
oSCORAD = objective-SCORing Atopic Dermatitis
POEM = Patient Oriented Eczema Measure
PO-SCORAD = Patient Oriented SCORAD

Dupilumab: This monoclonal antibody binds to the α-subunit of the interleukin (IL)-4 receptor, thereby inhibiting the IL-4/IL-13 signaling pathways [3]. Dupilumab was the first biologic approved in the AD indication. It is currently approved in many countries (including Switzerland) for AD patients from the age of 6 months [4]. Dupilumab is administered subcutaneously; the dosage in adults is 600 mg, followed by 300 mg as a maintenance dose every 14 days. There is a special dosing regimen for children and adolescents, which is described in the information for healthcare professionals (KFI). The efficacy and safety of dupilumab has been demonstrated in numerous randomized controlled trials, such as SOLO 1, SOLO 2 and LIBERTY AD CHRONOS in adult AD patients and LIBERTY AD ADOL and LIBERTY AD PEDS in children and adolescents with AD [5–9]. Side effects with dupilumab are limited to local reactions at the injection site and conjunctivitis [10].

Tralokinumab: this monoclonal antibody that specifically binds to IL-13 is the second biologic approved in the AD indication. IL-13 is considered a key cytokine in the pathophysiology of AD [11,12]. In Switzerland, tralokinumab is approved for AD patients over the age of 18, in other countries from the age of 12. The initial dosage is 600 mg, followed by 300 mg every two weeks [4]. In the randomized controlled trials ECZTRA 1 and ECZTRA 2, the efficacy and safety was investigated in AD patients over the age of 18 and in ECZTRA 6 in the age group of 12-17-year-old AD patients [13,14]. Tralokinumab is also well tolerated with a similar spectrum of side effects (local reactions, conjunctivitis) as dupilumab [4].

Below is a brief overview of other promising biologics for AD that are currently (as of 23.08.2024) not approved in Switzerland for this indication.

  • Lebrikizumab: this IL-13 inhibitor is approved in the EU for the treatment of AD. In the two randomized controlled trials ADvocate1 and ADvocate2 , a significantly larger proportion of patients with lebrikizumab achieved an IGA score of 0 or 1 by week 16 compared to placebo and a reduction of ≥2 points on the itch scale compared to baseline [15]. Conjunctivitis, exacerbation of dermatitis and skin infections were reported as undesirable side effects of lebrikizumab [15].
  • Nemolizumab: the target of this monoclonal antibody is the IL-31-A receptor. IL-31-RA is considered a key factor in the itch-scratch circuit associated with AD [16]. IL-31 is a known pruritogenic inflammatory cytokine that binds to IL-31-RA and maintains the itch-scratch cycle [16,17]. Nemolizumab is approved in Switzerland for the treatment of prurigo nodularis, but is currently (as of 23.8.2024) not approved for the indication AD [4]. In the phase II XCIMA study (nemolizumab in the context of AD proved to be clearly superior to placebo in terms of both itching (VAS) and EASI [18]. Overall, nemolizumab showed a favorable safety profile; the most common adverse events included mild to moderate injection site reactions and signs of upper respiratory tract infections [17].
  • Rocatinlimab: inhibits OX40-expressing cells and reduces their number. The interaction between the co-stimulatory T cell receptor OX40 and its ligand OX40L has been shown to play an important role in the pathogenesis of AD, with OX40L-induced signaling promoting the survival and activation of various T helper (Th) cells involved in the pathogenesis of atopic dermatitis [19]. By blocking OX40, these signals are suppressed, which inhibits inflammation [19]. In a phase IIb study, a significant reduction in the EASI score was observed in all rocatinlimab groups at week 16 [19]. The most common side effects included pyrexia, nasopharyngitis, chills, headache, aphthae and nausea [19]. Rocatinlimab is currently approved for AD in the USA (as of 23.8.24).

Janus kinase inhibitors

Some of the pro-inflammatory cytokines involved in the pathogenesis of AD activate the JAK-STAT signaling pathway via their receptors and thus trigger a cytokine response. The intracellular signal transduction of numerous cytokines is mediated by Janus kinases (JAK1, JAK2, JAK3 and TYK2) [20]. The pathogenesis of AD is associated with enhanced Th2 immunity driven by key cytokines such as IL-4, IL-5 and IL-13, which are downstream of JAK-STAT signaling [21]. Based on these findings, JAK inhibitors have emerged as an innovative therapeutic approach for AD. In summary, their efficacy is based on the fact that they suppress the intracellular cytokine response [20,22].

Baricitinib: this JAK1/JAK2 inhibitor was shown to be superior to placebo plus TCS in the BREEZE-AD4 study in combination with topical corticosteroids (TCS) in patients with moderate to severe AD for whom ciclosporin treatment was ineffective at 4 mg compared to placebo plus TCS, both in terms of EASI75 at week 16 and in terms of a ≥4-point improvement on the NRS for pruritus [23]. Baricitinib is being tested in the ongoing BREEZE-AD-PEDS study in children and adolescents [24]. The interim results at week 16 were promising at the 4 mg dose.

The most common side effects included abdominal pain, acne, headaches, diarrhea, nasopharyngitis and upper respiratory tract infections [24].

Upadacitinib: this selective JAK1 inhibitor achieved the efficacy and safety endpoints as monotherapy (15 mg or 30 mg) in the Measure Up 1 and Measure Up 2 studies [25]. In the AD Up study, upadacitinib in combination with TCS in both doses proved to be superior to the placebo in terms of EASI-75 [26]. The most common adverse effects observed with upadacitinib were upper respiratory tract infections and acne [2].

Abrocitinib: this is also a selective JAK1 inhibitor, for which study results from JADE MONO 1 and JADE MONO 2, among others, are available [27,28]. In these studies, abrocitinib (100 mg or 200 mg) proved to be superior to placebo at week 12 with regard to IGA and EASI-75. Upper respiratory tract infections, nausea and elevated liver enzyme levels were reported as common side effects [27].

In addition to the JAK inhibitors baricitinib, upadactinib and abrocitinib, which are approved for the treatment of AD in Switzerland and many other countries, another drug candidate from this drug group, ruxolitinib, is currently at an advanced stage of clinical development. The effects of this JAK1/JAK2 inhibitor in AD were investigated in the TRuE-AD study, for example [29].

Conclusion

The market approval of biologics** and Janus kinase (JAK) inhibitors& has set new standards in the treatment of atopic dermatitis (AD) and raised the therapeutic goals to an unprecedented level. The main aim of any therapy is to relieve itching and inflammatory skin changes. In order to achieve this, a severity-adapted approach according to a step-by-step scheme is recommended [2]. Basic care is still the basis of any AD therapy and topical anti-inflammatory preparations can also be used for a short time in parallel with systemic therapy. Phototherapy remains another important treatment modality. Validated objective scores (oSCORAD, EASI) are available for recording the severity of atopic eczema. The use of the DLQI has proven its worth in assessing the impact on quality of life. Furthermore, the PO-SCORAD offers a practice-oriented severity assessment over time and the POEM is suitable for assessing symptoms from a subjective perspective.

** Biologics currently approved in Switzerland for the treatment of AD (as of 23.08.2024) are dupilumab and tralokinumab [4].
& JAK inhibitors currently approved in Switzerland for the treatment of AD (as of 23.08.2024) are abrocitinib, baricitinib and upadacitinib [4].

Literature:

  1. Shergill M, et al: Biologic and Small Molecule Therapy in Atopic Dermatitis. Biomedicines. 2024; 12(8): 1841. www.mdpi.com/2227-9059/12/8/1841,(last accessed 23.08.2024).
  2. S3 guideline “Atopic dermatitis”, 2023, AWMF register no. 013-027, status: 16/06/2023, https://register.awmf.org/de/leitlinien/detail/
    013-027
    , (last accessed 23/08/2024).
  3. Hamilton JD, et al: Dupilumab improves the molecular signature in skin of patients with moderate-to-severe atopic dermatitis. JACI 2014; 134: 1293-1300.
  4. Swissmedic: Medicinal product information, www.swissmedicinfo.ch,(last accessed 23.08.2024)
  5. Ratchataswan, T et al: Biologics for Treatment of Atopic Dermatitis: Current Status and Future Prospect. JACI Pract 2021; 9: 1053-1065.
  6. Simpson EL, et al: Two Phase 3 Trials of Dupilumab versus Placebo in Atopic Dermatitis. NEJM 2016; 375: 2335-2348.
  7. Blauvelt A, et al. Long-term management of moderate-to-severe atopic dermatitis with dupilumab and concomitant topical corticosteroids (LIBERTY AD CHRONOS): A 1-year, randomized, double-blinded, placebo-controlled, phase 3 trial. Lancet 2017; 389: 2287-2303.
  8. Simpson EL, et al: Efficacy and Safety of Dupilumab in Adolescents With Uncontrolled Moderate to Severe Atopic Dermatitis: A Phase 3 Randomized Clinical Trial. JAMA Dermatol 2020; 156: 44-56.
  9. Paller AS, et al: Efficacy and safety of dupilumab with concomitant topical corticosteroids in children 6 to 11 years old with severe atopic dermatitis: a randomized, double-blinded, placebo-controlled phase 3 trial. JAAD 2020; 83(5): 1282-1293.
  10. Wollenberg A et al: Laboratory safety of dupilumab in moderate-to-severe atopic dermatitis: results from three phase III trials (LIBERTY AD SOLO 1, LIBERTY AD SOLO 2, LIBERTY AD CHRONOS). BJD 2020; 182: 1120-1135.
  11. Blair HA: Tralokinumab in Atopic Dermatitis: A Profile of Its Use. Clin. Drug Investig 2022; 42: 365-374.
  12. Popovic, B, et al: Structural Characterization Reveals Mechanism of IL-13-Neutralizing Monoclonal Antibody Tralokinumab as Inhibition of Binding to IL-13Rα1 and IL-13Rα2. J Mol Biol 2017; 429: 208-221.
  13. Wollenberg A, et al: Tralokinumab for moderate-to-severe atopic dermatitis: Results from two 52-week, randomized, double-blind, multicentre, placebo-controlled phase III trials (ECZTRA 1 and ECZTRA 2). BJD 2021; 184: 437-449.
  14. Paller AS, et al: Efficacy and Safety of Tralokinumab in Adolescents With Moderate to Severe Atopic Dermatitis: The Phase 3 ECZTRA 6 Randomized Clinical Trial. JAMA Dermatol 2023; 159: 596-605.
  15. Silverberg JI, et al: Two Phase 3 Trials of Lebrikizumab for Moderate-to-Severe Atopic Dermatitis. NEJM 2023; 388: 1080-1091.
  16. Kabashima K, et al: Trial of Nemolizumab and Topical Agents for Atopic Dermatitis with Pruritus. NEJM 2020; 383: 141-150.
  17. Silverberg JI, et al: Phase 2B randomized study of nemolizumab in adults with moderate-to-severe atopic dermatitis and severe pruritus. JACI 2020; 145: 173-182.
  18. Ruzicka T, et al: Anti-Interleukin-31 Receptor A Antibody for Atopic Dermatitis. NEJM 2017; 376: 826-835.
  19. Guttman-Yassky E, et al: An anti-OX40 antibody to treat moderate-to-severe atopic dermatitis: A multicenter, double-blind, placebo-controlled phase 2b study. Lancet 2023; 401: 204-214.
  20. Schwartz DM, et al: JAK inhibition as a therapeutic strategy for immune and inflammatory diseases. Nat Rev Drug Discov 2017; 16: 843-862.
  21. Leung DYM, Guttman-Yassky E: Deciphering the complexities of atopic dermatitis: Shifting paradigms in treatment approaches. JACI 2014; 134: 769-779.
  22. Damsky W, et al: The emerging role of Janus kinase inhibitors in the treatment of autoimmune and inflammatory diseases. JACI 2021; 147: 814-826.
  23. Bieber T, et al: Efficacy and safety of baricitinib in combination with topical corticosteroids in patients with moderate-to-severe atopic dermatitis with inadequate response, intolerance or contraindication to ciclosporin: Results from a randomized, placebo-controlled, phase III clinical trial (BREEZE-AD4) BJD 2022; 187: 338-352.
  24. Torrelo A, et al: Efficacy and safety of baricitinib in combination with topical corticosteroids in paediatric patients with moderate-to-severe atopic dermatitis with an inadequate response to topical corticosteroids: Results from a phase III, randomized, double-blind, placebo-controlled study (BREEZE-AD PEDS). BJD 2023; 189; 23-32.
  25. Guttman-Yassky E, et al: Once-daily upadacitinib versus placebo in adolescents and adults with moderate-to-severe atopic dermatitis (Measure Up 1 and Measure Up 2): results from two replicate double-blind, randomized controlled phase 3 trials. Lancet 2021; 397(10290): 2151-2168.
  26. Reich K, et al: Safety and efficacy of upadacitinib in combination with topical corticosteroids in adolescents and adults with moderate-to-severe atopic dermatitis (AD Up): Results from a randomized, double-blind, placebo-controlled, phase 3 trial. Lancet 2021; 397: 2169-2181.
  27. Silverberg JI, et al: Efficacy and Safety of Abrocitinib in Patients With Moderate-to-Severe Atopic Dermatitis: A Randomized Clinical Trial. JAMA Dermatol 2020; 156: 863-873.
  28. Simpson EL, et al: Efficacy and safety of abrocitinib in adults and adolescents with moderate-to-severe atopic dermatitis (JADE MONO-1): A multicentre, double-blind, randomized, placebo-controlled, phase 3 trial. Lancet 2020; 396: 255-266.
  29. Papp K, et al: Efficacy and safety of ruxolitinib cream for the treatment of atopic dermatitis: Results from 2 phase 3, randomized, double-blind studies. JAAD 2021; 85: 863-872.

DERMATOLOGY PRACTICE 2024; 34(4): 24-25

Autoren
  • Mirjam Peter, M.Sc.
Publikation
  • DERMATOLOGIE PRAXIS
Related Topics
  • Abrocitinib
  • Atopic dermatitis
  • baricitinib
  • Biologics
  • Dupilumab
  • JAK-i
  • Janus kinase inhibitors
  • System therapy
  • tralokinumab
  • Upadacitinib
Previous Article
  • Gestational diabetes

Early therapy can bring slight benefits to newborns

  • RX
  • Education
  • Endocrinology and Diabetology
  • General Internal Medicine
  • Gynecology
  • Studies
View Post
Next Article
  • Hematology

A closer look at hemato-oncological entities

  • Congress Reports
  • Genetics
  • Hematology
  • Oncology
  • RX
  • Studies
View Post
You May Also Like
View Post
  • 12 min
  • Evidence, effectiveness and practical implications

Medicinal plants for allergic rhinitis

    • RX
    • Allergology and clinical immunology
    • Education
    • General Internal Medicine
    • ORL
    • Pharmaceutical medicine
    • Phytotherapy
    • Studies
View Post
  • 15 min
  • Current status and future prospects

Cell and gene therapies in modern cardiology

    • Cardiology
    • Education
    • Genetics
    • RX
    • Studies
View Post
  • 19 min
  • Cardiovascular risk and obesity

Pathomechanisms, secondary prevention and treatment options

    • RX
    • Cardiology
    • CME continuing education
    • Endocrinology and Diabetology
    • Nutrition
    • Sports Medicine
    • Studies
    • Training with partner
View Post
  • 14 min
  • Patient-oriented recommendations for action

Effect of heat on diabetes technology

    • RX
    • CME continuing education
    • Endocrinology and Diabetology
    • General Internal Medicine
    • Prevention and health care
    • Studies
View Post
  • 6 min
  • Ventricular arrhythmias

Indication for ICD or WCD?

    • RX
    • Cardiology
    • Congress Reports
    • General Internal Medicine
    • Studies
View Post
  • 3 min
  • Early breast cancer

Overweight and obesity worsen the prognosis

    • Congress Reports
    • Gynecology
    • Oncology
    • Prevention and health care
    • RX
    • Studies
View Post
  • 8 min
  • Psoriasis treatment with biologics

What are the latest trends?

    • Congress Reports
    • Dermatology and venereology
    • Pharmacology and toxicology
    • Rheumatology
    • RX
    • Studies
View Post
  • 4 min
  • Flu vaccination for older people

Benefit of the high-dose influenza vaccine

    • Congress Reports
    • General Internal Medicine
    • Geriatrics
    • Infectiology
    • RX
    • Studies
Top Partner Content
  • Forum Gastroenterology

    Zum Thema
  • Herpes zoster

    Zum Thema
  • Dermatology News

    Zum Thema
Top CME content
  • 1
    Pathomechanisms, secondary prevention and treatment options
  • 2
    Effect of heat on diabetes technology
  • 3
    Improved quality of care aims for satisfied patients
  • 4
    Dr. ChatGPT: Large language models in everyday clinical practice
  • 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.