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ABSTRACT
Introduction
Prurigo nodularis (PN) or chronic prurigo of nodular type (CNPG) is a subtype of chronic prurigo with severe pruritus and neuroimmune underlying pathophysiology occurring in a plethora of dermatological, systemic, neurologic, and psychiatric conditions.
Areas covered
We review the increasing repertoire of biologics in the treatment of CNPG focusing on those targeting interleukins 4, 13, 31, oncostatin M and IgE. Presented information is based on a database research on current clinical trials (clinicaltrials.gov, European Clinical Trials Database (EudraCT), US clinical trial registry ICH-GCP) and a PubMed search for latest publications conducted with the combinations of the terms ‘chronic prurigo,’ ‘prurigo nodularis,’ ‘pathophysiology,’ ‘treatment,’ ‘therapy’, and ‘biologics.’
Expert opinion
CNPG gets more and more attention as new therapeutic targets have been revealed in recent years, thus allowing the use of targeted approaches. The off-label advent of dupilumab offered advanced insight into the pathogenesis of CNPG and showed an impressive relief of pruritus in the vast majority of patients. New therapies including biologics (e.g. nemolizumab, tralokinumab, lebrikizumab), small molecules (e.g. neurokinin-1 receptor antagonists, janus kinase inhibitors) as well as mu-opioid receptor antagonists and nalbuphine, a μ-antagonist/κ-agonist, are in the pipeline and offer new hope for an improved future patient care.
Article highlights
Prurigo nodularis (PN) is a distressing chronic condition characterized by chronic pruritus (pruritus for at least 6 weeks) and prolonged scratch behavior that result in multiple localized or symmetrically distributed generalized hyperkeratotic, crusted, and excoriated nodular lesions.
Affected patients are highly burdened due to severe pruritus intensity values and a significant impairment of health-related quality of life, mental health including anxiety and depression, social interaction, sleep, and high economic burden.
PN challenges both patients and physicians as large randomized controlled trials and regulatory agency-approved treatment regimens are lacking, and therapy is usually subject to off-label use.
Recent studies and case series data of dupilumab and nemolizumab provide new hope for the future development of targeted therapies which is an important step toward a new era of personalized precision medicine.
Further research on the pathogenesis, especially the bidirectional peripheral and central neuroimmunological mechanism of prurigo nodularis, is crucial to develop novel effective multimodal treatment options to ameliorate future patient care.
Abbreviations
| CNPG | = | Chronic prurigo of nodular type |
| CSU | = | chronic spontaneous urticaria |
| DLQI | = | Dermatology Life Quality Index |
| e.g. | = | lat.: exempli gratia (≙ for example) |
| gp130 | = | glycoprotein 130 |
| IFN-α | = | interferons alpha |
| IgE | = | immunoglobulin E |
| IL | = | interleukin |
| IL-31RA | = | IL-31 receptor A |
| JAK | = | janus kinase |
| NGF | = | nerve growth factor |
| OSM | = | oncostatin M |
| OSMRβ | = | oncostatin M receptor beta subunit |
| PN | = | Prurigo nodularis |
| RCT | = | randomized controlled trial |
| sc | = | subcutaneously |
| UV | = | ultraviolet |
Declaration of interest
S Ständer has been an advisor, speaker or investigator for Almirall, Beiersdorf, Bellus Health, Cara Therapeutics, Celgene, Dermasence, Galderma, Kiniksa Pharmaceuticals, LEO Pharma, Menlo Therapeutics, Novartis, Tremi Therapeutics, Sanofi, Sienna Biopharmaceuticals, and Vanda Pharmaceuticals..
S Müller is supported by the Christine Kühne-Center for Allergy Research and Education and has been an advisor, speaker or investigator for Galderma, Incyte and Lilly..
T Bieber has been an advisor, speaker or investigator for AbbVie, Allmiral, AnaptysBio, Arena, Asana Biosciences, Astellas, BioVerSys, Böhringer-Ingelheim, Celgene, Daichi-Sankyo, Davos Biosciences, Dermavant/Roivant, DermTreat, DS Pharma, Evaxion, FLX Bio, Galapagos/MorphoSys, Galderma, Glenmark, GSK, Incyte, Kymab, LEO Pharma, Lilly, L´Oréal, MenloTx, Novartis, Pfizer, Pierre Fabre, Sanofi/Regeneron, UCB and Vectans.
The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.
Reviewer Disclosures
One of the peer reviewers has received research, speaking and/or consulting support from Arcutis, Dermavant, Galderma, GSK/Stiefel, Almirall, Alvotech, Leo Pharma, BMS, Boehringer Ingelheim, Mylan, Celgene, Pfizer, Ortho Dermatology, Abbvie, Samsung, Janssen, Lilly, Menlo, Merck, Novartis, Regeneron, Sanofi, Novan, Qurient, National Biological Corporation, Caremark, Advance Medical, Sun Pharma, Helsinn, Arena, Forte, Informa, UpToDate and National Psoriasis Foundation. They also consult for others through Guidepoint Global, Gerson Lehrman and other consulting organizations. They are also a founder and majority owner of www.DrScore.com and founder and part owner of Causa Research, a company dedicated to enhancing patients’ adherence to treatment. Peer reviewers on this manuscript have no other relevant financial relationships or otherwise to disclose.