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BACKGROUND: Despite the high burden in patients with chronic prurigo (CPG), the first and so far only approved systemic therapy for this disease, dupilumab, has only been available since 2022. Therefore, treatment is mostly based on expert recommendations for off-label therapies. We aim to provide an overview of current therapies and possible future therapeutic drugs for CPG patients, which are currently in clinical trials.
METHODS: For this review, a systematic literature and clinical trial search was conducted via PubMed and Clinical Trials using the terms \"chronic prurigo\", \"chronic nodular prurigo\", \"prurigo nodularis\" and \"therapy\".
CONCLUSIONS: Multiple new therapeutic agents are currently under investigation in clinical trials, providing promising results for future treatment options. Moreover, an annotated checklist was developed recently to improve therapeutic decision-making in daily clinical practice with CPG patients.
UNASSIGNED: HINTERGRUND: Trotz des hohen Leidensdrucks der Patienten mit chronischer Prurigo (CPG) steht erst seit 2022 mit Dupilumab die erste und bislang einzige zugelassene systemische Therapie dieser Erkrankung zur Verfügung. Mehrheitlich stützt sich die Therapie der CPG daher weiterhin auf Expertenempfehlungen zu Off-label-Therapien. Ziel dieser Arbeit ist es, einen Überblick über aktuelle therapeutische Optionen der CPG sowie einen Ausblick auf potenzielle zukünftige Therapeutika zu geben, die sich derzeit in klinischer Erprobung befinden.
METHODS: Für diese Übersichtsarbeit wurde eine systematische Literatur- und klinische Studienrecherche über PubMed und Clinical Trials mit den Begriffen „Chronic Prurigo“, „Chronic Nodular Prurigo“, „Prurigo nodularis“ und „Therapy“ durchgeführt.
UNASSIGNED: Es befindet sich eine Vielzahl neuer Substanzen in verschiedenen Stadien der klinischen Erprobung mit vielversprechenden Ergebnissen, hierunter der IL(Interleukin)-31-Antikörper Nemolizumab. Zudem wurde kürzlich eine praxisorientierte Checkliste als Entscheidungshilfe für die Einleitung einer Systemtherapie der CPG entwickelt.

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UNASSIGNED: Atopic dermatitis (AD) is an inflammatory skin condition that affects millions of pediatric and adult patients with well-studied impact on morbidity and quality of life. Management occurs in a stepwise fashion beginning with preventative measures before immunomodulators are introduced. However, challenges remain in treatment of moderate-to-severe atopic dermatitis that is refractory to first- and second-line treatments and there are only few topical anti-inflammatory options, especially for pediatric patients.
UNASSIGNED: New medications are required to address these gaps as lesions may persist despite treatment or patients may discontinue treatment due to actual or anticipated adverse effects of mainstay medications. Emerging research into the pathophysiology of AD and the immune system at large has provided opportunities for novel interventions aimed at stopping AD mechanisms at new checkpoints. Clinical trials for 36 agents currently in phase 2 or phase 3 are evaluated with particular focus on the studies for, B244, CBP-201, tapinarof, lebrikizumab, nemolizumab, amlitelimab, and rocatinlimab as they explore novel pathways and have some of the most promising results.
UNASSIGNED: These clinical trials contribute to the evolution of AD treatment toward greater precision based on salient pathways with a particular focus on moderate-to-severe AD to enhance efficacy and minimize adverse effects.

UNASSIGNED: Over the last decade, increasing understanding of the immunopathogenesis of atopic dermatitis (AD) enabled the recognition of multiple therapeutic targets and subsequently the development of novel, highly effective systemic treatments, including interleukin (IL)-antagonists. To date, the IL-4Ra-inhibitor dupilumab and the IL-13 inhibitor tralokinumab have gained regulatory approval in Europe for the treatment of moderate-to-severe AD, while more than 70 new therapeutics are currently in development.
UNASSIGNED: In this review, we address the role of ILs in the pathogenesis of AD and provide an overview of the novel and investigational IL-antagonists, as regards their efficacy and safety on moderate-to-severe AD.
UNASSIGNED: Current data have established IL-4 and IL-13 inhibitors as effective and safe for the treatment of moderate-to-severe AD, as regards the rapid control of flares as well as the long-term remission of the disease. Data regarding the efficacy and safety of other IL-inhibitors, including those targeting IL-31, IL-22, IL-33, IL-36 and IL-18, are accumulating. There is still an unmet need for real-world-evidence studies and head-to-head studies for both currently available and future agents in AD treatment. Establishing predictive biomarkers of treatment response in a disorder of such considerable heterogenicity might help physicians pursue a patient-tailored therapeutic response.

Bullous pemphigoid (BP), an autoimmune bullous dermatosis, occurs predominantly in older individuals. Nemolizumab, a humanized monoclonal antibody against the interleukin (IL)-31 receptor A, is used to treat severe atopic dermatitis (AD) in Japan. However, it can cause several adverse events, such as exacerbation of AD, erythema, and eosinophilia. Herein, we describe a case of prurigo-type AD developing BP after nemolizumab administration. A 62-year-old man with prurigo-type AD and asthma presented with serious, refractory itching. After nemolizumab injection, his pruritus was relieved for 2 days. However, on day 3, erythema with blisters and erosions suddenly appeared throughout his body. Pathological examination showed typical BP and the patient\'s serum anti-BP180-NC16a antibody level was 882.5 U/mL. Oral prednisolone (PSL) was initiated and nemolizumab was never used again. Despite high-dose PSL, new blisters continued to develop, with a rapid elevation of anti-BP180-NC16a antibodies to 6930 U/mL. Adding high-dose cyclosporine and intravenous gamma globulin reduced new blister formation after 9 weeks, and PSL and cyclosporine were gradually tapered. Dupilumab, an anti-IL-4 receptor antibody, was initiated after 16 weeks, resulting in continued remission without PSL and cyclosporine. The sudden occurrence of BP in this case suggested that the patient had occult BP before the nemolizumab initiation and that nemolizumab exacerbated BP and made it overt. Blocking the IL-31 pathway may exacerbate inflammation in AD or BP, resulting in the acceleration of blister formation. This may be countered by blocking the IL-4/13 pathway with dupilumab. To our knowledge, this is the first case of nemolizumab-exacerbated BP.

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The interleukins IL-4 and IL-13 are increasingly recognized contributors to the pathogenesis of cutaneous T cell lymphomas (CTCLs), and their role in disease-associated pruritus is accepted. The prevailing Th2 profile in advanced CTCL underscores the significance of understanding IL-4/IL-13 expression dynamics from the early stages of disease, as a shift from Th1 to Th2 may explain CTCL progression. Targeted agents blocking key cytokines of type 2 immunity are established therapeutics in atopic disorders and have a promising therapeutic potential in CTCL, given their involvement in cutaneous symptoms and their contribution to the pathogenesis of disease. IL-4, IL-13, and IL-31 are implicated in pruritus, offering therapeutic targets with dupilumab, tralokinumab, lebrikizumab, and nemolizumab. This review analyzes current knowledge on the IL-4/IL-13 axis in mycosis fungoides and Sezary syndrome, the most common types of CTCL, examining existing literature on the pathogenetic implications with a focus on investigational treatments. Clinical trials and case reports are required to shed light on novel uses of medications in various diseases, and ongoing research into the role of IL-4/IL-13 axis blockers in CTCL therapy might not only improve the management of disease-related pruritus but also provide in-depth insights on the pathophysiologic mechanisms of CTCL.

BACKGROUND: Prurigo nodularis (PN) is a neuroimmunological skin disease. Severe itching is the most challenging symptom which affects patients\' quality of life. T helper 2-derived cytokines, such as interleukin-31 and oncostatin M (OSM), play a crucial role in PN pathogenesis. Nemolizumab and vixarelimab are two biologics acting as IL-31 inhibitors. Vixarelimab also suppresses the OSM activity. This systematic review evaluates the efficacy and safety of nemolizumab and vixarelimab in PN management.
METHODS: A systematic search was conducted in PubMed/Medline, Ovid Embase, and Web of Science up to September 17th, 2023. Clinical trials and cohort studies published in English were included.
RESULTS: Among a total of 96 relevant records, five were included. The results of four studies with 452 patients using nemolizumab showed that a significantly higher percentage of patients treated with nemolizumab demonstrated a reduction in peak pruritus numerical rating scale (PP-NRS) and investigator\'s global assessment along with improved sleep disturbance (SD) and quality of life than the placebo group. Moreover, one study administered vixarelimab to 49 PN patients, and their finding illustrated a higher rate of subjects who received vixarelimab experienced ≥ 4-point diminution in worst itch NRS, visual analog scale, healing of representative lesions, and SD quality compared to the placebo group.
CONCLUSIONS: IL-31 inhibitors suggest distinct advantages in improving pruritus, sleep quality, and overall quality of life in subjects with moderate-to-severe PN. Further clinical studies are recommended to compare the effectiveness of these biologics to other therapeutic choices.

UNASSIGNED: Prurigo nodularis (PN) is a chronic inflammatory skin condition that presents with intensely pruritic, hyperkeratotic nodules. The pathophysiology underlying PN is not entirely clear, making treatment challenging. Patients often require a multimodal approach, although many of the available therapies have low efficacy or adverse effects.
UNASSIGNED: In this review, we discuss the use of nemolizumab for the treatment of PN in adults. Nemolizumab is a biological therapy that reduces type 2 cytokines and the neuroimmune response implicated in the pathophysiology of PN. It also helps maintain skin barrier integrity, which may be damaged during the vicious itch-scratch cycle. Nemolizumab has demonstrated great efficacy in improving itch and clearing lesions in recent clinical trials with respectable tolerance.
UNASSIGNED: Nemolizumab is a promising drug for PN that seems comparable to the recently approved dupilumab in terms of its therapeutic effect and excellent safety profile, although nemolizumab may work more rapidly on itch. JAK inhibitors are also emerging as competitors of biologics for PN, however, their safety profile in this population may differ. Trials evaluating these drugs are needed to assess which is preferable. Additional data on the durability and longevity of nemolizumab for PN treatment is highly anticipated.