New and Emerging Biologics and Jak Inhibitors for the Treatment of Prurigo Nodularis: A Narrative Review
Abstract
1. Introduction
2. Methods
3. Clinical Presentation
4. Conventional Therapies
5. Monoclonal Antibodies
5.1. Dupilumab
5.2. Nemolizumab
5.3. Vixarelimab
5.4. Barzolvolimab
5.5. Other Biologic Therapies
6. JAK Inhibitors
6.1. Ruxolitinib
6.2. Abrocitinib
6.3. Povorcitinib
6.4. Upadacitinib
6.5. Tofacitinib
7. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
- Liao, V.; Cornman, H.L.; Ma, E.; Kwatra, S.G. Prurigo nodularis: New insights into pathogenesis and novel therapeutics. Br. J. Dermatol. 2024, 190, 798–810. [Google Scholar] [CrossRef]
- Ständer, S.; Ketz, M.; Kossack, N.; Akumo, D.; Pignot, M.; Gabriel, S.; Chavda, R. Epidemiology of Prurigo Nodularis compared with Psoriasis in Germany: A Claims Database Analysis. Acta Derm. Venereol. 2020, 100, adv00309. [Google Scholar] [CrossRef] [PubMed]
- Kwatra, S.G. Breaking the Itch-Scratch Cycle in Prurigo Nodularis. N. Engl. J. Med. 2020, 382, 757–758. [Google Scholar] [CrossRef]
- Akarsu, S.; Ozbagcivan, O.; Ilknur, T.; Semiz, F.; Inci, B.B.; Fetil, E. Xerosis cutis and associated co-factors in women with prurigo nodularis. An. Bras. Dermatol. 2018, 93, 671–679. [Google Scholar] [CrossRef] [PubMed]
- Joel, M.Z.; Hydol-Smith, J.; Kambala, A.; Cornman, H.L.; Kwatra, S.G. Prevalence and comorbidity burden of prurigo nodularis in United States adults enrolled in the All of Us research program. J. Am. Acad. Dermatol. 2023, 89, 1056–1058. [Google Scholar] [CrossRef] [PubMed]
- Vasavda, C.; Wan, G.; Szeto, M.D.; Marani, M.; Sutaria, N.; Rajeh, A.; Lu, C.; Lee, K.K.; Nguyen, N.T.; Adawi, W.; et al. A Polygenic Risk Score for Predicting Racial and Genetic Susceptibility to Prurigo Nodularis. J. Investig. Dermatol. 2023, 143, 2416–2426.e1. [Google Scholar] [CrossRef]
- Han, J.; Palomino, A.; Estupinan, B.; Wozniak, A.; Swan, J. Psychiatric Comorbidity in Prurigo Nodularis and the Impact of Socioeconomic Status. J. Clin. Aesthet. Dermatol. 2022, 15, 53–58. [Google Scholar] [CrossRef]
- Boozalis, E.; Tang, O.; Patel, S.; Semenov, Y.R.; Pereira, M.P.; Stander, S.; Kang, S.; Kwatra, S.G. Ethnic differences and comorbidities of 909 prurigo nodularis patients. J. Am. Acad. Dermatol. 2018, 79, 714–719.e3. [Google Scholar] [CrossRef]
- Kwatra, S.G.; Das, A.K.; Chang, E.; Paydar, C.; Bahloul, D.; Chen, C.; Thomas, R.B. Healthcare Resource Utilization and Economic Burden of Prurigo Nodularis in the United States. Dermatol. Ther. 2025, 15, 413–425. [Google Scholar] [CrossRef]
- Cornman, H.L.; Kambala, A.; Chen, S.; Zhang, J.; Reddy, S.V.; Kwatra, S.G. Prevalence of tuberculosis in patients with prurigo nodularis: A multicenter cross-sectional study. J. Am. Acad. Dermatol. 2023, 89, 406–408. [Google Scholar] [CrossRef]
- Williams, K.A.; Huang, A.H.; Belzberg, M.; Kwatra, S.G. Prurigo nodularis: Pathogenesis and management. J. Am. Acad. Dermatol. 2020, 83, 1567–1575. [Google Scholar] [CrossRef] [PubMed]
- Perez, G.L.; Peters, M.S.; Reda, A.M.; Butterfield, J.H.; Peterson, E.A.; Leiferman, K.M. Mast cells, neutrophils, and eosinophils in prurigo nodularis. Arch. Dermatol. 1993, 129, 861–865. [Google Scholar] [CrossRef] [PubMed]
- Gründel, S.; Pereira, M.; Storck, M.; Osada, N.; Schneider, G.; Ständer, S.; Zeidler, C. Analysis of 325 Patients with Chronic Nodular Prurigo: Clinics, Burden of Disease and Course of Treatment. Acta Derm. Venereol. 2020, 100, adv00269. [Google Scholar] [CrossRef]
- Banerjee, S.; Biehl, A.; Gadina, M.; Hasni, S.; Schwartz, D.M. JAK-STAT Signaling as a Target for Inflammatory and Autoimmune Diseases: Current and Future Prospects. Drugs 2017, 77, 521–546, Erratum in Drugs 2017, 77, 939; Erratum in Drugs 2017, 77, 1261. [Google Scholar] [CrossRef]
- Roh, Y.S.; Choi, J.; Sutaria, N.; Belzberg, M.; Kwatra, M.M.; Kwatra, S.G. IL-31 Inhibition as a Therapeutic Approach for the Management of Chronic Pruritic Dermatoses. Drugs 2021, 81, 895–905. [Google Scholar] [CrossRef]
- Hughes, J.-D.M.; Woo, T.E.; Belzberg, M.; Khanna, R.; Williams, K.A.; Kwatra, M.M.; Hassan, S.; Kwatra, S.G. Association between Prurigo Nodularis and Etiologies of Peripheral Neuropathy: Suggesting a Role for Neural Dysregulation in Pathogenesis. Medicines 2020, 7, 4. [Google Scholar] [CrossRef] [PubMed]
- Yook, H.J.; Lee, J.H. Prurigo Nodularis: Pathogenesis and the Horizon of Potential Therapeutics. Int. J. Mol. Sci. 2024, 25, 5164. [Google Scholar] [CrossRef]
- Saraceno, R.; Chiricozzi, A.; Nisticò, S.P.; Tiberti, S.; Chimenti, S. An occlusive dressing containing betamethasone valerate 0.1% for the treatment of prurigo nodularis. J. Dermatolog Treat. 2010, 21, 363–366. [Google Scholar] [CrossRef]
- Belsito, D.V.; Fowler, J.F., Jr.; Marks, J.G., Jr.; Pariser, D.M.; Hanifin, J.; Duarte, I.A.G.; Pires, M.C.; Cruz, P.D.; Langley, R.G.B.; Patel, P.; et al. Pimecrolimus cream 1%: A potential new treatment for chronic hand dermatitis. Cutis 2004, 73, 31–38. [Google Scholar]
- Klejtman, T.; Beylot-Barry, M.; Joly, P.; Richard, M.; Debarbieux, S.; Misery, L.; Wolkenstein, P.; Chosidow, O.; Ingen-Housz-Oro, S. Treatment of prurigo with methotrexate: A multicentre retrospective study of 39 cases. J. Eur. Acad. Dermatol. Venereol. 2018, 32, 437–440. [Google Scholar] [CrossRef]
- Matsuda, K.M.; Sharma, D.; Schonfeld, A.R.; Kwatra, S.G. Gabapentin and pregabalin for the treatment of chronic pruritus. J. Am. Acad. Dermatol. 2016, 75, 619–625.e6. [Google Scholar] [CrossRef]
- Dawn, A.G.; Yosipovitch, G. Butorphanol for treatment of intractable pruritus. J. Am. Acad. Dermatol. 2006, 54, 527–531. [Google Scholar] [CrossRef] [PubMed]
- Sharma, D.; Kwatra, S.G. Thalidomide for the treatment of chronic refractory pruritus. J. Am. Acad. Dermatol. 2016, 74, 363–369. [Google Scholar] [CrossRef]
- Müller, S.; Zeidler, C.; Ständer, S. Chronic Prurigo Including Prurigo Nodularis: New Insights and Treatments. Am. J. Clin. Dermatol. 2024, 25, 15–33. [Google Scholar] [CrossRef] [PubMed]
- Avallone, G.; Cavallo, F.; Tancredi, A.; Maronese, C.A.; Bertello, M.; Fraghì, A.; Conforti, C.; Calabrese, G.; Di Nicola, M.R.; Oddenino, G.A.; et al. Association between maternal dupilumab exposure and pregnancy outcomes in patients with moderate-to-severe atopic dermatitis: A nationwide retrospective cohort study. J. Eur. Acad. Dermatol. Venereol. 2024, 38, 1799–1808. [Google Scholar] [CrossRef] [PubMed]
- Olbrich, H.; Sadik, C.D.; Ludwig, R.J.; Thaçi, D.; Boch, K. Dupilumab in Inflammatory Skin Diseases: A Systematic Review. Biomolecules. 2023, 13, 634. [Google Scholar] [CrossRef]
- Yosipovitch, G.; Mollanazar, N.; Ständer, S.; Kwatra, S.G.; Kim, B.S.; Laws, E.; Mannent, L.P.; Amin, N.; Akinlade, B.; Staudinger, H.W.; et al. Dupilumab in patients with prurigo nodularis: Two randomized, double-blind, placebo-controlled phase 3 trials. Nat. Med. 2023, 29, 1180–1190. [Google Scholar] [CrossRef]
- Sanofi. Real-World Effectiveness of Dupilumab in Patients with Prurigo Nodularis: An Observational Study (GLOBOS-PIN). US National Library of Medicine: ClinicalTrials.gov. 2024. Available online: https://clinicaltrials.gov/study/NCT05991323 (accessed on 1 March 2025).
- Sanofi. A Non-interventional Study to Describe the Dupilumab Long-Term Treatment, Safety and Patient Reported Outcomes in Chronic Nodular Prurigo (Prurigo Nodularis) in Clinical Routine (CLEAR PN). US National Library of Medicine: ClinicalTrials.gov. 2024. Available online: https://clinicaltrials.gov/study/NCT06087627 (accessed on 1 March 2025).
- Sanofi. A Study to Investigate the Pharmacokinetics and Safety of Dupilumab in Participants ≥6 Months to <18 Years of Age with Prurigo Nodularis. US National Library of Medicine: ClinicalTrials.gov. 2024. Available online: https://clinicaltrials.gov/study/NCT06293053 (accessed on 1 March 2025).
- Chaowattanapanit, S.; Wongjirattikarn, R.; Chaisuriya, N.; Ungarreevittaya, P.; Poosekeaw, P.; Winaikosol, K.; Choonhakarn, C.; Julanon, N.; Salao, K. Increased IL-31 expression in serum and tissue protein in prurigo nodularis. Ther. Adv. Chronic Dis. 2022, 13, 20406223221112561. [Google Scholar] [CrossRef]
- Ständer, S.; Yosipovitch, G.; Legat, F.J.; Reich, A.; Paul, C.; Simon, D.; Naldi, L.; Metz, M.; Tsianakas, A.; Pink, A.; et al. Efficacy and Safety of Nemolizumab in Patients With Moderate to Severe Prurigo Nodularis: The OLYMPIA 1 Randomized Clinical Phase 3 Trial. JAMA Dermatol. 2025, 161, 147–156. [Google Scholar] [CrossRef]
- Kwatra, S.G.; Yosipovitch, G.; Legat, F.J.; Reich, A.; Paul, C.; Simon, D.; Naldi, L.; Lynde, C.; De Bruin-Weller, M.S.; Nahm, W.K.; et al. Phase 3 Trial of Nemolizumab in Patients with Prurigo Nodularis. N. Engl. J. Med. 2023, 389, 1579–1589. [Google Scholar] [CrossRef]
- Galderma, R.&D. A Study to Evaluate the Durability of Response and Safety of Nemolizumab for 24 Weeks in Participants With Prurigo Nodularis. US National Library of Medicine: ClinicalTrials.gov. 2024. Available online: https://clinicaltrials.gov/study/NCT05052983 (accessed on 1 March 2025).
- Galderma. EADV 2024 Late Breaking News Sessions: New Galderma Data Demonstrating Nemolizumab’s Long-Term Efficacy and Safety in Atopic Dermatitis and Durability in Prurigo Nodularis to Be Shared During Three Oral Presentations. 2025. Available online: https://www.galderma.com/news/galdermas-nemluvior-nemolizumab-approved-european-union-moderate-severe-atopic-dermatitis-and (accessed on 1 March 2025).
- Galderma, R.&D. A Long-Term Study of Nemolizumab (CD14152) in Participants with Prurigo Nodularis (PN). US National Library of Medicine: ClinicalTrials.gov. 2024. Available online: https://clinicaltrials.gov/study/NCT04204616 (accessed on 1 March 2025).
- Sofen, H.; Bissonnette, R.; Yosipovitch, G.; Silverberg, J.I.; Tyring, S.; Loo, W.J.; Zook, M.; Lee, M.; Zou, L.; Jiang, G.-L.; et al. Efficacy and safety of vixarelimab, a human monoclonal oncostatin M receptor β antibody, in moderate-to-severe prurigo nodularis: A randomised, double-blind, placebo-controlled, phase 2a study. eClinicalMedicine 2023, 57, 101826. [Google Scholar] [CrossRef] [PubMed]
- Kiniksa Pharmaceuticals, Ltd. Study to Assess the Efficacy, Safety, and Tolerability of Vixarelimab in Reducing Pruritus in Prurigo Nodularis. US National Library of Medicine: ClinicalTrials.gov. 2024. Available online: https://clinicaltrials.gov/study/NCT03816891 (accessed on 1 March 2025).
- Terhorst-Molawi, D.; Hawro, T.; Grekowitz, E.; Kiefer, L.; Merchant, K.; Alvarado, D.; Thomas, L.J.; Hawthorne, T.; Crowley, E.; Heath-Chiozzi, M.; et al. Anti-KIT antibody, barzolvolimab, reduces skin mast cells and disease activity in chronic inducible urticaria. Allergy 2023, 78, 1269–1279. [Google Scholar] [CrossRef] [PubMed]
- Celldex Therapeutics. A Study of CDX-0159 in Patients With Prurigo Nodularis. US National Library of Medicine: ClinicalTrials.gov. 2024. Available online: https://clinicaltrials.gov/study/NCT04944862 (accessed on 1 March 2025).
- Celldex Therapeutics. A Study of Barzolvolimab in Patients with Prurigo Nodularis. US National Library of Medicine: ClinicalTrials.gov. 2024. Available online: https://clinicaltrials.gov/study/NCT06366750 (accessed on 1 March 2025).
- Waligóra-Dziwak, K.; Dańczak-Pazdrowska, A.; Jenerowicz, D. A Comprehensive Review of Biologics in Phase III and IV Clinical Trials for Atopic Dermatitis. J. Clin. Med. 2024, 13, 4001. [Google Scholar] [CrossRef]
- Amgen. A Phase 3, Placebo-Controlled, Double-Blind Study Assessing Rocatinlimab in Prurigo Nodularis. US National Library of Medicine: ClinicalTrials.gov. 2024. Available online: https://clinicaltrials.gov/study/NCT06527404 (accessed on 1 March 2025).
- Guangdong Hengrui Pharmaceutical Co., Ltd. Clinical Study of the Efficacy and Safety of SHR-1819 Injection in Adult Patients With Prurigo Nodularis. US National Library of Medicine: ClinicalTrials.gov. 2024. Available online: https://clinicaltrials.gov/study/NCT06554509 (accessed on 1 March 2025).
- Li, N.; Shakib, S.; Qian, W.; Yao, X.; Li, P.; Nip, T.K.; Bai, X.; Shen, K. Safety, pharmacokinetics, and pharmacodynamics of anti-IL-4Rα antibody SHR-1819 in healthy subjects: A randomized, controlled phase I study. Clin. Transl. Sci. 2024, 17, e13763. [Google Scholar] [CrossRef]
- Keymed Biosciences Co., Ltd. Study on the Treatment of Prurigo Nodularis With Stapokibart Injection. US National Library of Medicine: ClinicalTrials.gov. 2024. Available online: https://clinicaltrials.gov/study/NCT06424470 (accessed on 1 March 2025).
- Zhao, Y.; Li, J.-Y.; Yang, B.; Ding, Y.-F.; Wu, L.-M.; Zhang, L.-T.; Wang, J.-Y.; Lu, Q.-J.; Zhang, C.-L.; Zhang, F.-R.; et al. Long-Term Efficacy and Safety of Stapokibart in Adults with Moderate-to-Severe Atopic Dermatitis: An Open-Label Extension, Nonrandomized Clinical Trial. BioDrugs 2024, 38, 681–689. [Google Scholar] [CrossRef]
- Shanghai Mabgeek Biotech Co., Ltd. Phase III Clinical Study of MG-K10 Humanized Mab Injection in Subjects with Prurigo Nodularis. US National Library of Medicine: ClinicalTrials.gov. 2024. Available online: https://clinicaltrials.gov/study/NCT06779136 (accessed on 1 March 2025).
- Pezzolo, E.; Gambardella, A.; Guanti, M.; Bianchelli, T.; Bertoldi, A.; Giacchetti, A.; Donini, M.; Argenziano, G.; Naldi, L. Tralokinumab shows clinical improvement in patients with prurigo nodularis-like phenotype atopic dermatitis: A multicenter, prospective, open-label case series study. J. Am. Acad. Dermatol. 2023, 89, 430–432. [Google Scholar] [CrossRef]
- Gargiulo, L.; Ibba, L.; Malagoli, P.; Burroni, A.G.; Chiricozzi, A.; Dapavo, P.; Ferrucci, S.M.; Gola, M.; Napolitano, M.; Ortoncelli, M.; et al. Management of Patients Affected by Moderate-to-Severe Atopic Dermatitis with JAK Inhibitors in Real-World Clinical Practice: An Italian Delphi Consensus. Dermatol. Ther. 2024, 14, 919–932. [Google Scholar] [CrossRef]
- Fabbrocini, G.; Napolitano, M.; Megna, M.; Balato, N.; Patruno, C. Treatment of Atopic Dermatitis with Biologic Drugs. Dermatol. Ther. 2018, 8, 527–538. [Google Scholar] [CrossRef]
- Papp, K.; Szepietowski, J.C.; Kircik, L.; Toth, D.; Eichenfield, L.F.; Leung, D.Y.; Forman, S.B.; Venturanza, M.E.; Sun, K.; Kuligowski, M.E.; et al. Efficacy and safety of ruxolitinib cream for the treatment of atopic dermatitis: Results from 2 phase 3, randomized, double-blind studies. J. Am. Acad. Dermatol. 2021, 85, 863–872. [Google Scholar] [CrossRef]
- Mikhaylov, D.; Ungar, B.; Renert-Yuval, Y.; Guttman-Yassky, E. Oral Janus kinase inhibitors for atopic dermatitis. Ann. Allergy Asthma Immunol. 2023, 130, 577–592. [Google Scholar] [CrossRef] [PubMed]
- Appeldoorn, T.Y.J.; Munnink, T.H.O.; Morsink, L.M.; Hooge, M.N.L.; Touw, D.J. Pharmacokinetics and Pharmacodynamics of Ruxolitinib: A Review. Clin. Pharmacokinet. 2023, 62, 559–571. [Google Scholar] [CrossRef] [PubMed]
- Incyte Corporation. A Study to Evaluate the Safety and Efficacy of Ruxolitinib Cream in Participants With Prurigo Nodularis (PN) (TRuE-PN1). US National Library of Medicine: ClinicalTrials.gov. 2024. Available online: https://clinicaltrials.gov/study/NCT05755438 (accessed on 1 March 2025).
- Incyte Corporation. A Study to Evaluate the Efficacy and Safety of Ruxolitinib Cream in Participants With Prurigo Nodularis (PN) (TRuE-PN2). US National Library of Medicine: ClinicalTrials.gov. 2024. Available online: https://clinicaltrials.gov/study/NCT05764161 (accessed on 1 March 2025).
- Incyte Corporation. A Study to Evaluate the Safety and Tolerability of Maximal Use Ruxolitinib Cream. US National Library of Medicine: ClinicalTrials.gov. 2024. Available online: https://clinicaltrials.gov/study/NCT06213831 (accessed on 1 March 2025).
- Perche, P.O.; Cook, M.K.; Feldman, S.R. Abrocitinib: A New FDA-Approved Drug for Moderate-to-Severe Atopic Dermatitis. Ann. Pharmacother. 2023, 57, 86–98. [Google Scholar] [CrossRef]
- Johns Hopkins University. Efficacy of Abrocitinib for Reducing Pruritus in Adults with Prurigo Nodularis and Chronic Pruritus of Unknown Origin. US National Library of Medicine: ClinicalTrials.gov. 2024. Available online: https://clinicaltrials.gov/study/NCT05038982 (accessed on 1 March 2025).
- Kwatra, S.G.; Bordeaux, Z.A.; Parthasarathy, V.; Kollhoff, A.L.; Alajmi, A.; Pritchard, T.; Cornman, H.L.; Kambala, A.; Lee, K.K.; Manjunath, J.; et al. Efficacy and Safety of Abrocitinib in Prurigo Nodularis and Chronic Pruritus of Unknown Origin: A Nonrandomized Controlled Trial. JAMA Dermatol. 2024, 160, 717–724. [Google Scholar] [CrossRef] [PubMed]
- Incyte Corporation. A Study to Evaluate the Efficacy and Safety of INCB054707 in Participants With Prurigo Nodularis. US National Library of Medicine: ClinicalTrials.gov. 2024. Available online: https://clinicaltrials.gov/study/NCT05061693 (accessed on 1 March 2025).
- Kwatra, S.; Metz, M.; Yosipovitch, G. Efficacy and Safety of Oral Povorcitinib in Patients with Prurigo Nodularis: 40-Week Results from a Randomized, Double-Blind, Placebo-Controlled Phase 2 Study. In Proceedings of the 33rd European Academy of Dermatology and Venereology Congress, Amsterdam, The Netherlands, 24–28 September 2024. [Google Scholar]
- Incyte Corporation. A Study to Evaluate the Efficacy and Safety Study of Povorcitinib in Participants with Prurigo Nodularis (STOP-PN1). US National Library of Medicine: ClinicalTrials.gov. Identifier: NCT06516952. Available online: https://clinicaltrials.gov/study/NCT06516952?cond=NCT06516952&rank=1 (accessed on 1 March 2025).
- Incyte Corporation. A Study to Evaluate the Efficacy and Safety Study of Povorcitinib in Participants with Prurigo Nodularis (STOP-PN2). US National Library of Medicine: ClinicalTrials.gov. Identifier: NCT06516965. Available online: https://clinicaltrials.gov/study/NCT06516965?cond=NCT06516965&rank=1 (accessed on 1 March 2025).
- Mohamed, M.F.; Bhatnagar, S.; Parmentier, J.M.; Nakasato, P.; Wung, P. Upadacitinib: Mechanism of action, clinical, and translational science. Clin. Transl. Sci. 2024, 17, e13688. [Google Scholar] [CrossRef]
- Ibba, L.; Gargiulo, L.; Vignoli, C.A.; Fiorillo, G.; Valenti, M.; Costanzo, A.; Narcisi, A. Practical Use of Upadacitinib in Patients with Severe Atopic Dermatitis in a Real-World Setting: A Systematic Review. Clin. Cosmet. Investig. Dermatol. 2024, 17, 593–604. [Google Scholar] [CrossRef]
- Gargiulo, L.; Ibba, L.; Bianco, M.; Di Giulio, S.; Alfano, A.; Ingurgio, R.C.; Facheris, P.; Perugini, C.; Valenti, M.; Costanzo, A.; et al. Upadacitinib 30 mg for the optimal management of moderate-to-severe atopic dermatitis: A 52-week single-center real-world study. J. Dermatolog Treat. 2024, 35, 2375102. [Google Scholar] [CrossRef]
- Gargiulo, L.; Ibba, L.; Piscazzi, F.; Alfano, A.; Ingurgio, R.C.; Valenti, M.; Costanzo, A.; Narcisi, A. Effectiveness and safety of upadacitinib for moderate-to-severe atopic dermatitis in a real-world setting: A 52-week retrospective study. J. Eur. Acad. Dermatol. Venereol. 2024, 38, e152–e154. [Google Scholar] [CrossRef]
- Psoriasis Treatment Center of Central New Jersey. Upadacitinib for Prurigo Nodularis. US National Library of Medicine: ClinicalTrials.gov. Identifier: NCT06773403. Available online: https://clinicaltrials.gov/study/NCT06773403?cond=NCT06773403&rank=1 (accessed on 1 March 2025).
- Pezzolo, E.; Narcisi, A.; Gargiulo, L.; Di Lernia, V.; Napolitano, M.; Patruno, C.; Ribero, S.; Ortoncelli, M.; Foti, C.; Romita, P.; et al. Effective response to upadacitinib in patients affected by prurigo nodularis and by atopic dermatitis with a predominant prurigo nodularis pattern: A multicenter case series study. J. Am. Acad. Dermatol. 2024, 91, e147–e150. [Google Scholar] [CrossRef]
- Second Affiliated Hospital, School of Medicine, Zhejiang University. Efficacy and Safety of Tofacitinib in Patients with Prurigo Nodularis. US National Library of Medicine: ClinicalTrials.gov. Identifier: NCT06201715. Available online: https://clinicaltrials.gov/study/NCT06201715?cond=NCT06201715&rank=1 (accessed on 1 March 2025).
- Liu, T.; Chu, Y.; Wang, Y.; Zhong, X.; Yang, C.; Bai, J.; Fang, H.; Qiao, J. Successful treatment of prurigo nodularis with tofacitinib: The experience from a single center. Int. J. Dermatol. 2023, 62, e293–e295. [Google Scholar] [CrossRef]
- Peng, C.; Li, C.; Zhou, Y.; Wang, Q.; Xie, P.; Li, T.; Hao, P. Tofacitinib for Prurigo Nodularis: A Case Report. Clin. Cosmet. Investig. Dermatol. 2022, 15, 503–506. [Google Scholar] [CrossRef] [PubMed]
- Sardana, K.; Rose Mathachan, S.; Agrawal, D. Treatment of recalcitrant paediatric prurigo nodularis with tofacitinib, an exquisite example of bench-to-bedside translation of JAK-STAT expression. Indian J. Dermatol. Venereol. Leprol. 2023, 90, 238–240. [Google Scholar] [CrossRef]
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Candidate Drug | Trial Identifier | Trial Phase, Status | Arms and Intervetions | Primary Endpoint | Outcome |
---|---|---|---|---|---|
Dupilumab | NCT04183335 LIBERTY PN-PRIME | 3, completed | Drug, 300 mg subcutaneous injection once every 2 weeks: n = 75 Placebo: n = 76 | Percentage of patients achieving a WI-NRS reduction of ≥4 points at 24 weeks | Drug 300 mg once every 2 weeks: 60.0% Placebo: 18.4% |
NCT04202679 PRIME2 | 3, completed | Drug, 300 mg subcutaneous injection once every 2 weeks: n = 78 Placebo: n = 82 | Percentage of patients achieving a WI-NRS reduction of ≥4 points at 12 weeks | Drug 300 mg once every 2 weeks: 37.2% Placebo: 22.0% | |
NCT05991323 GLOBOSPIN | Observational study, recruiting | Drug, subcutaneous injection: n = 300 (estimated) | (1) Reasons for treatment iniations; (2) frequency of treatment modifications; (3) patients discontinuing treatment; (4) reasons behind discontinuations; (5) patients hospitalized due to PN. (All outcomes measured from baseline up to 36 months) | ||
NCT06087627 CLEAR PN | Observational study, recruiting | Drug, subcutaneous injection: n = 150 (estimated) | (1) Percentage of participants with an IGA score of 0 or 1 at 6 months. (2) Percentage of participants achieving a ≥4 points improvement in the WI-NRS from baseline at 6 months | ||
NCT06293053 | 3, recruiting (patients aged 6 months to 18 years) | Drug, subcutaneous injection: n = 18 (estimated) | Concentration of dupilumab in serum from day 1 to week 40 | ||
Nemolizumab | NCT04501666 OLYMPIA 1 | 3, completed | Drug 30 mg (2 subcutaneous injections at w0, then 1 injection every 4 weeks in patients weighing < 90 kg or 2 injections every 4 weeks in patients weighing ≥ 90 kg): n = 190 Placebo: n = 96 | (1) Number of participants with an improvement of ≥4 points from baseline in PP-NRS at 16 weeks; (2) number of participants achieving an IGA success at 16 weeks | (1) Drug: 58.4%, Placebo: 16.7%; (2) Drug: 26.3%, Placebo: 7.3%. |
NCT04501679 OLYMPIA 2 | 3, completed | Drug 30 mg (2 subcutaneous injections at w0, then 1 injection every 4 weeks in patients weighing < 90 kg or 2 injections every 4 weeks in patients weighing ≥ 90 kg): n = 183 Placebo: n = 91 | (1) Number of participants with an improvement of ≥4 points from Baseline in PP-NRS at week 16; (2) Number of participants achieving an IGA success at week 16 | (1) Drug: 56.3%, Placebo: 20.9%; (2) Drug: 37.7%, Placebo: 11.0%. | |
NCT05052983 OLYMPIA DURABILITY | 3, completed (study in long-term responders) | Drug 30 mg (1 subcutaneous injection every 4 weeks in patients weighing < 90 kg, 2 injections every 4 weeks in patients weighing ≥ 90 kg): n = NA Placebo: n = NA | Time from baseline to relapse meeting at least 1 of the defined criteria (from baseline up to 24 weeks) | Drug: 17% Placebo: 75% | |
NCT04204616 | 3, active, not recruiting | Drug 30 mg (1 subcutaneous injection every 4 weeks in patients weighing < 90 kg, 2 injections every 4 weeks in patients weighing ≥ 90 kg): n = 500 (estimated) | Incidence of adverse events (AEs) by severity from baseline up to 192 weeks | Results not yet available | |
Vixarelimab | NCT03816891 | 2a, completed | Drug 360 mg, subcutaneous injections (720 mg loading dose at w0, then 360 mg once a week): n = 23 Placebo: n = 26 | Percent change from baseline in WI-NRS at week 8 (Least-squares (LS); mean percent change from baseline (PCFB)) | Drug: −50.6% Placebo: −29.4% |
NCT03816891 | 2b, completed | (A) Drug 540 mg, subcutaneous injections, once every 4 weeks during the double-blind period (DBP); (B) Drug 360 mg, subcutaneous injections, once every 4 weeks during the DBP; (C) Drug 120 mg, subcutaneous injections, once every 4 weeks during the DBP; (D) Placebo; (E) Drug 360 mg, subcutaneous injections, once every 2 weeks during the open-label extension. (Numbers NA) | Percent change from baseline in WI-NRS at week 16 | Results not yet available | |
Barzolvolimab | NCT04944862 | 1b, completed | (A) Drug, 3.0 mg/kg, single intravenous injection at w0: n = 9; (B) Drug, 1.5 mg/kg, single intravenous injection at w0: n = 7; (C) Placebo: n = 8. | Proportion of participants with improvement of ≥4 points from baseline in WI-NRS at week 12 | (1) Drug 3.0 mg/kg: 57%; (2) Drug 1.5 mg/kg group: 43%; (3) Placebo: 25%. |
NCT06366750 | 2, recruiting | (A) Drug, subcutaneous injections (450 mg loading dose at w0, then 150 mg every 4 weeks); (B) Drug, subcutaneous injections (450 mg loading dose at w0, then 300 mg every 4 weeks); (C) Placebo. | Safety and tolerability as assessed by the incidence and severity of adverse events from day 1 to day 169 | One case of anaphylactic reaction in the 3.0 mg/kg group; generally, mild-to-moderate adverse events mostly consistent with PN comorbidities in all groups | |
Rocatinlimab | NCT06527404 | 3, recruiting | (A) Drug, subcutaneous injection, dose 1 during treatment period A and treatment period B (blinded treatment); (B) Drug, subcutaneous injection, dose 2 during treatment period A and treatment period B (blinded treatment); (C) Placebo during treatment period A and treatment period B (blinded treatment); (D) Drug, subcutaneous injection, dose 1 during treatment period B (open-label treatment). | Number of participants achieving a reduction from baseline in the weekly average Daily Itch Score at week 24 | |
SHR-1819 | NCT06554509 | 2/3, recruiting | (A) Drug, injection dose A; (B) Drug, injection dose B; (C) Drug, injection dose C; (D) Placebo. | (1) Proportion of subjects with a ≥4-point reduction from baseline in WI-NRS at week 16 (phase 2); (2) Proportion of subjects with a ≥4-point reduction from baseline in WI-NRS at week 24 (phase 3). | |
Stapokibart | NCT06424470 | 3, not yet recruiting | Drug, subcutaneous injection; Placebo | Propotion of subjects with improvement of ≥4 points from baseline on WI-NRS at week 24 | |
MG-K10 (Comekibart) | NCT06779136 | 3, not yet recruiting | Drug, subcutaneous injection every 4 weeks; placebo (after week 24 all patients switch to drug injection) | Proportions of subjects achieving a WI-NRS improvement of ≥4-point from baseline at week 24 |
Candidate Drug | Trial Identifier | Trial Phase, Status | Arms and Intervetions | Primary Endpoint | Outcome |
---|---|---|---|---|---|
Ruxolitinib | NCT05755438 | 3, active not recruiting | Drug 1.5% cream: n = 102 Placebo: n = 102 | Percentage of patients with WI-NRS reduction of ≥4 points at 12 weeks | Results not yet available |
NCT05764161 | 3, active not recruiting | Drug 1.5% cream: n = 95 Placebo: n = 95 | Percentage of patients with WI-NRS reduction of ≥4 points at 12 weeks | Results not yet available | |
NCT06213831 | 1, recruiting | Drug 1.5% cream: n = 24 | Percentage of patients with TEAEs over 16 weeks | ||
Abrocitinib | NCT05038982 | 2, completed | Drug 200 mg oral daily: n = 10 | Percentage reduction in weekly average PP-NRS at 12 weeks | Drug 200 mg oral daily: 78.3% |
Povorcitinib | NCT05061693 | 2, completed | (A) Drug 15 mg oral daily: n = 36; (B) Drug 45 mg oral daily: n = 35; (C) Drug 75 mg oral daily: n = 37; (D) Placebo: n = 37. | Percentage of patients with Itch-NRS4 reduction of ≥4 points at 16 weeks | Drug 15 mg oral daily: 36.1% Drug 45 mg oral daily: 44.4% Drug 75 mg oral daily: 56.8% Placebo: 8.1% |
NCT06516952 STOP-PN1 | 3, recruiting | (A) Drug Dose 1: n = 110; (B) Drug Dose 2: n = 110; (C) Placebo: n = 110. | Percentage of patients achieving Itch-NRS4 and IGA-CPG-S-TS at week 24 | ||
NCT06516965 STOP-PN2 | 3, recruiting | (A) Drug Dose 1: n = 110; (B) Drug Dose 2: n = 110; (C) Placebo: n = 110. | Percentage of patients achieving Itch-NRS4 and IGA-CPG-S-TS at week 24 | ||
Upadacitinib | NCT06773403 | 4, recruiting | Drug 15mg oral daily, optional increase to 30mg at week 8: n = 25 | Percentage of patients with WI-NRS reduction of ≥4 points at 12 weeks | |
Tofacitinib | NCT06201715 | Not applicable, not yet recruiting | Drug 5 mg oral BID: n = 24 | Percentage of patients with IGA, PAS, VAS, NRS, VRS, DLQI, and Itchy QoL change at 12 weeks |
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© 2025 by the authors. Published by MDPI on behalf of the Lithuanian University of Health Sciences. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
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Bianco, M.; D’Oria, F.; Falcidia, C.; Foggi, G.; Matteodo, E.; Di Giulio, S.; Facheris, P.; Ibba, L.; Perugini, C.; Valenti, M.; et al. New and Emerging Biologics and Jak Inhibitors for the Treatment of Prurigo Nodularis: A Narrative Review. Medicina 2025, 61, 631. https://doi.org/10.3390/medicina61040631
Bianco M, D’Oria F, Falcidia C, Foggi G, Matteodo E, Di Giulio S, Facheris P, Ibba L, Perugini C, Valenti M, et al. New and Emerging Biologics and Jak Inhibitors for the Treatment of Prurigo Nodularis: A Narrative Review. Medicina. 2025; 61(4):631. https://doi.org/10.3390/medicina61040631
Chicago/Turabian StyleBianco, Matteo, Francesco D’Oria, Costanza Falcidia, Giulio Foggi, Elena Matteodo, Sara Di Giulio, Paola Facheris, Luciano Ibba, Chiara Perugini, Mario Valenti, and et al. 2025. "New and Emerging Biologics and Jak Inhibitors for the Treatment of Prurigo Nodularis: A Narrative Review" Medicina 61, no. 4: 631. https://doi.org/10.3390/medicina61040631
APA StyleBianco, M., D’Oria, F., Falcidia, C., Foggi, G., Matteodo, E., Di Giulio, S., Facheris, P., Ibba, L., Perugini, C., Valenti, M., Vignoli, C. A., Costanzo, A., Narcisi, A., & Gargiulo, L. (2025). New and Emerging Biologics and Jak Inhibitors for the Treatment of Prurigo Nodularis: A Narrative Review. Medicina, 61(4), 631. https://doi.org/10.3390/medicina61040631