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Moderne systemische Therapie des Pruritus

Modern systemic therapy for pruritus

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Zusammenfassung

Chronischer Pruritus (CP) ist ein hoch prävalentes und sehr belastendes Symptom, das schwer zu behandeln ist. Heutzutage stehen mehrere Substanzen zur Behandlung von CP zur Verfügung. Systemische Therapeutika spielen eine zentrale Rolle in der modernen Therapie des CP, insbesondere bei schweren Fällen und solchen, die auf allgemeine prurituslindernde Maßnahmen nicht ansprechen. Aktuelle Leitlinien empfehlen die Anwendung (zumeist im Off-label-Bereich) einer Vielzahl von Präparaten mit unterschiedlichen Wirkungsweisen, wie z. B. Antihistaminika, Gabapentinoiden, Antidepressiva, Immunsuppressiva und µ‑Opioidrezeptorantagonisten. Die Wahl des richtigen Medikaments hängt von der Indikation, dem Sicherheitsprofil des Arzneimittels und von patientenspezifischen Faktoren wie Komorbiditäten und Komedikation ab. Aufgrund eines tieferen Verständnisses der Pathophysiologie von CP konnten innovative Medikamente entwickelt werden, die bereits eine antipruritische Wirkung in klinischen Studien und Fallberichten gezeigt haben. Besonders vielversprechend sind monoklonale Antikörper, Neurokinin-1-Rezeptorantagonisten, Januskinaseinhibitoren und Opioidrezeptormodulatoren. Zusätzlich konnten weitere Zielstrukturen des peripheren und zentralen Nervensystems identifiziert werden, die zukünftige Therapiemöglichkeiten darstellen. Dieser Beitrag stellt einen Überblick der derzeit verfügbaren systemischen Therapien für CP dar und diskutiert innovative Wirkstoffe und vielversprechende Zielstrukturen für die Therapie des CP.

Abstract

Chronic pruritus (CP) is a highly prevalent, difficult to treat, and burdensome condition. Nowadays, multiple substances are available for the treatment of CP. Systemic therapies play a pivotal role in modern CP therapy, particularly in severe cases and those refractory to general antipruritic measures. Current guidelines recommend the use of a vast array of, mostly off-label, drugs with different mechanisms, including antihistamines, gabapentinoids, antidepressants, immunosuppressive drugs, and μ‑opioid receptor antagonists. The choice of the right agent depends on the indication, safety profile of the drug, and patient-specific features, such as comorbidities and comedication. Owing to a deeper understanding of the pathophysiology of CP, novel drugs have been developed and have already shown anti-pruritic efficacy in clinical studies and case reports. Of note, monoclonal antibodies, neurokinin‑1 receptor antagonists, Janus kinase inhibitors, and opioid receptor modulators are on the frontline of innovative CP treatment. Other promising targets include structures of the peripheral and central nervous system, e.g., histamine 4 receptors, which are involved in itch signaling. This review provides an overview of currently available systemic therapies for CP and their indications and discusses novel innovative agents and promising new targets in CP.

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Abb. 1

Abbreviations

CP:

Chronischer Pruritus

IgE:

Immunglobulin E

IL:

Interleukin

JAK:

Januskinase

KOR:

κ‑Opioidrezeptor

MOR:

μ‑Opioidrezeptor

Mrgpr:

Mas-related G protein-coupled receptor

NK1R:

Neurokinin-1-Rezeptor

nsAH:

Nicht sedierende Antihistaminika

PAR:

Protease-aktivierter Rezeptor

SSRI:

Serotoninwiederaufnahmehemmer

TRP:

Transient receptor potential

TSLP:

Thymic stromal lymphopoietin

Literatur

  1. Almustafa ZZ, Weller K, Autenrieth J et al (2019) Dupilumab in treatment of chronic Prurigo: a case series and literature review. Acta Derm Venereol 99(10):905–906

    Article  Google Scholar 

  2. Bagci IS, Ruzicka T (2018) IL-31: A new key player in dermatology and beyond. J Allergy Clin Immunol 141(3):858–866

    Article  CAS  Google Scholar 

  3. Bergasa NV, Alling DW, Talbot TL et al (1995) Effects of naloxone infusions in patients with the pruritus of cholestasis. A double-blind, randomized, controlled trial. Ann Intern Med 123(3):161–167

    Article  CAS  Google Scholar 

  4. Fowler E, Yosipovitch G (2020) A new generation of treatments for itch. Acta Derm Venereol 100(2):adv27

    Article  Google Scholar 

  5. Fukuyama T, Ganchingco JR, Mishra SK et al (2017) Janus kinase inhibitors display broad anti-itch properties: a possible link through the TRPV1 receptor. J Allergy Clin Immunol 140(1):306–309.e3

    Article  CAS  Google Scholar 

  6. Hay RJ, Johns NE, Williams HC et al (2014) The global burden of skin disease in 2010: an analysis of the prevalence and impact of skin conditions. J Invest Dermatol 134(6):1527–1534

    Article  CAS  Google Scholar 

  7. Ikoma A, Steinhoff M, Ständer S et al (2006) The neurobiology of itch. Nat Rev Neurosci 7(7):535–547

    Article  CAS  Google Scholar 

  8. Khanna R, Boozalis E (2019) Mirtazapine for the treatment of chronic pruritus. Medicines. https://doi.org/10.3390/medicines6030073

    Article  PubMed  PubMed Central  Google Scholar 

  9. Kremer AE (2019) What are new treatment concepts in systemic itch? Exp Dermatol 28(12):1485–1492

    Article  CAS  Google Scholar 

  10. Kremer M, Salvat E, Muller A et al (2016) Antidepressants and gabapentinoids in neuropathic pain: mechanistic insights. Neuroscience 338:183–206

    Article  CAS  Google Scholar 

  11. Kumada H, Miyakawa H, Muramatsu T et al (2017) Efficacy of nalfurafine hydrochloride in patients with chronic liver disease with refractory pruritus: a randomized, double-blind trial. Hepatol Res 47(10):972–982

    Article  CAS  Google Scholar 

  12. Kumagai H, Ebata T, Takamori K et al (2010) Effect of a novel kappa-receptor agonist, nalfurafine hydrochloride, on severe itch in 337 haemodialysis patients: a Phase III, randomized, double-blind, placebo-controlled study. Nephrol Dial Transplant 25(4):1251–1257

    Article  CAS  Google Scholar 

  13. Malekzad F, Arbabi M, Mohtasham N et al (2009) Efficacy of oral naltrexone on pruritus in atopic eczema: a double-blind, placebo-controlled study. J Eur Acad Dermatol Venereol 23(8):948–950

    Article  CAS  Google Scholar 

  14. Mathur VS, Kumar J, Crawford PW et al (2017) A multicenter, randomized, double-blind, placebo-controlled trial of Nalbuphine ER tablets for uremic pruritus. Am J Nephrol 46(6):450–458

    Article  CAS  Google Scholar 

  15. Matterne U, Apfelbacher CJ, Loerbroks A et al (2011) Prevalence, correlates and characteristics of chronic pruritus: a population-based cross-sectional study. Acta Derm Venereol 91(6):674–679

    Article  Google Scholar 

  16. Metz M (2019) Treatments for chronic pruritus outside of the box. Exp Dermatol 28(12):1476–1481

    Article  Google Scholar 

  17. Pariser DM, Bagel J, Lebwohl M et al (2020) Serlopitant for psoriatic pruritus: a phase 2 randomized, double-blind, placebo-controlled clinical trial. J Am Acad Dermatol. https://doi.org/10.1016/j.jaad.2020.01.056

    Article  PubMed  Google Scholar 

  18. Peer G, Kivity S, Agami O et al (1996) Randomised crossover trial of naltrexone in uraemic pruritus. Lancet 348(9041):1552–1554

    Article  CAS  Google Scholar 

  19. Pereira MP, Ständer S (2017) Chronic Pruritus: current and emerging treatment options. Drugs 77(9):999–1007

    Article  CAS  Google Scholar 

  20. Pereira MP, Ständer S (2018) Novel drugs for the treatment of chronic pruritus. Expert Opin Investig Drugs 27(12):981–988

    Article  CAS  Google Scholar 

  21. Phan NQ, Bernhard JD, Luger TA et al (2010) Antipruritic treatment with systemic mu-opioid receptor antagonists: a review. J Am Acad Dermatol 63(4):680–688

    Article  CAS  Google Scholar 

  22. Phan NQ, Lotts T, Antal A et al (2012) Systemic kappa opioid receptor agonists in the treatment of chronic pruritus: a literature review. Acta Derm Venereol 92(5):555–560

    Article  Google Scholar 

  23. Schulz S, Metz M, Siepmann D et al (2009) Antipruritic efficacy of a high-dosage antihistamine therapy. Results of a retrospectively analysed case series. Hautarzt 60(7):564–568

    Article  CAS  Google Scholar 

  24. Simpson EL, Bieber T, Guttman-Yassky E et al (2016) Two phase 3 trials of dupilumab versus placebo in atopic dermatitis. N Engl J Med 375(24):2335–2348

    Article  CAS  Google Scholar 

  25. Ständer S, Kwon P, Hirman J et al (2019) Serlopitant reduced pruritus in patients with prurigo nodularis in a phase 2, randomized, placebo-controlled trial. J Am Acad Dermatol 80(5):1395–1402

    Article  Google Scholar 

  26. Ständer S, Yosipovitch G (2019) Substance P and neurokinin 1 receptor are new targets for the treatment of chronic pruritus. Br J Dermatol 181(5):932–938

    Article  Google Scholar 

  27. Ständer S, Yosipovitch G, Legat FJ et al (2020) Trial of nemolizumab in moderate-to-severe prurigo nodularis. N Engl J Med 382(8):706–716

    Article  Google Scholar 

  28. Ständer S, Zeidler C, Augustin M et al (2017) S2k-Leitlinie zur Diagnostik und Therapie des chronischen Pruritus – Update – Kurzversion. J Dtsch Dermatol Ges 15(8):860–873

    PubMed  Google Scholar 

  29. Tsianakas A, Luger TA, Radin A (2018) Dupilumab treatment improves quality of life in adult patients with moderate-to-severe atopic dermatitis: results from a randomized, placebo-controlled clinical trial. Br J Dermatol 178(2):406–414

    Article  CAS  Google Scholar 

  30. Tsianakas A, Zeidler C, Riepe C et al (2019) Aprepitant in anti-histamine-refractory chronic nodular Prurigo: a multicentre, randomized, double-blind, placebo-controlled, cross-over, phase-II trial (APREPRU). Acta Derm Venereol 99(4):379–385

    Article  CAS  Google Scholar 

  31. Weisshaar E, Szepietowski JC, Dalgard FJ et al (2019) European S2k guideline on chronic Pruritus. Acta Derm Venereol 99(5):469–506

    Article  Google Scholar 

  32. Wikstrom B, Gellert R, Ladefoged SD et al (2005) Kappa-opioid system in uremic pruritus: multicenter, randomized, double-blind, placebo-controlled clinical studies. J Am Soc Nephrol 16(12):3742–3747

    Article  Google Scholar 

  33. Wu J, Guttman-Yassky E (2020) Efficacy of biologics in atopic dermatitis. Expert Opin Biol Ther 20(5):525–538

    Article  CAS  Google Scholar 

  34. Yosipovitch G, Ständer S, Kerby MB et al (2018) Serlopitant for the treatment of chronic pruritus: Results of a randomized, multicenter, placebo-controlled phase 2 clinical trial. J Am Acad Dermatol 78(5):882–891.e10

    Article  CAS  Google Scholar 

  35. Zuberbier T, Aberer W, Asero R (2018) The EAACI/GA(2)LEN/EDF/WAO guideline for the definition, classification, diagnosis and management of urticaria. Allergy 73(7):1393–1414

    Article  CAS  Google Scholar 

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Author information

Authors and Affiliations

  1. Dermatologische Allergologie, Klinik für Dermatologie, Venerologie und Allergologie, Charité – Universitätsmedizin Berlin, Berlin, Deutschland

    M. Metz

  2. Kompetenzzentrum Chronischer Pruritus (KCP), Klinik für Hautkrankheiten, Universitätsklinikum Münster, Von-Esmarch-Str. 58, 48149, Münster, Deutschland

    M. P. Pereira MD PhD

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Correspondence to M. P. Pereira MD PhD.

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Interessenkonflikt

M. Metz und M.P. Pereira geben an, dass kein Interessenkonflikt besteht.

Für diesen Beitrag wurden von den Autoren keine Studien an Menschen oder Tieren durchgeführt. Für die aufgeführten Studien gelten die jeweils dort angegebenen ethischen Richtlinien.

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Metz, M., Pereira, M.P. Moderne systemische Therapie des Pruritus. Hautarzt 71, 518–524 (2020). https://doi.org/10.1007/s00105-020-04604-4

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  • DOI: https://doi.org/10.1007/s00105-020-04604-4

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