Unmet needs in treating itch: reaching beyond eczema

Figures & data

Figure 1. The overall prevalence of conditions presenting with chronic pruritus in the general population. Prevalence data has been extracted from epidemiological studies referenced in this article.

CPUO: chronic pruritus of unknown origin, LSC: lichen simplex chronicus

Table 1. Summary of treatments approved by the FDA and current trials under investigation for the treatment of itch in various diseases.

Disease	Approved, with antipruritic evidence	Treatments under investigation*	Phase / Population	ClinicalTrials.Gov Identifier
Chronic pruritus of unknown origin	None	-Dupilumab (anti-IL-4/R α mAb)	-Phase 3 / two parallel trials for adults aged 18 - 90	NCT05263206
		-CM310 (anti-IL-4/R α mAb)	-Phase 2 / 50 adults ≥18	NCT05452343
Geriatric Itch	None
Genital Itch	None
Scalp Itch	None
Notalgia Paresthetica	None	-Difelikefalin (selective KOR agonist)	-Phase 2 and 3, 440 adults aged 18-80	NCT05978063
		-CLE-400 topical gel (α2 adrenergic receptor agonist)	-Phase 2, 40 adults aged 18-80	NCT06262607
Lichen Sclerosus et Atrophicus	None	-CO2 laser vs topical clobetasol 0.05%	-Phase 3 / 198 women ≥18 years with lichen sclerosus of the vulva and/or perineum and/or perianal area	NCT05010421
		-MC2-25 (isocyanate scavenger)	-Phase 2, 40 women ≥18 years with vulvar lichen sclerosus	NCT06132919
		-steroid plus CO2 laser	-Phase 2/3, 52 adults aged 18-85 with biopsy-proven lichen sclerosus and significant symptoms	NCT05243563
Lichen Simplex Chronicus	Doxepin hydrochloride cream, 5%	-KM-001 (TRPV3 inhibitor)	-Phase 1, 51 adults aged 18-75	NCT05454462
Lichen Amyloidosis	None
Bullous Pemphigoid	None	Rituximab (anti-CD20 mAb) combined with omalizumab	-Phase 3/15 adults aged 18-90	NCT04128176
		Dupilumab	-Phase 2/3, 106 adults aged 18-90	NCT04206553
		Avdoralimab (anti-C5aR1 mAb)	-Phase 2/15 adults ≥18	NCT04563923
		Efgartigimod (anti-Fc receptor)	-Phase 2/3, 98 adults ≥18	NCT05267600
Dermatitis Herpetiformis	None
Post-burn Pruritus	None	-Dupilumab	-Phase 2, 46 adults aged 18-60	NCT06226610
Scabies Itch	Permethrin 5% cream, Crotamiton 10% lotion/cream, Spinosad 0.9% topical suspension	-Moxidectin (antiparasitic)	-Phase 2, 200 adults ≥18	NCT05875441
		-Ivermectin (antiparasitic)	-Phase 2, 399 children aged 2 months-5 years	NCT04332068
Keloids	-Triamcinolone	-Dupilumab	-Phase 2, 20 adults aged 18-65	NCT05128383
		-siSPARC Microneedle Patch vs siSPARC + siLR4A Microneedle Patch	-Phase 3, 50 adults aged 21-75	NCT06138964
Scleroderma	None‡	Vixarelimab (anti-OSMRβ)	-Phase 2/320 adults aged 18-85	NCT05785624
Dermatomyositis	IVIG	PF-06823859 (anti-IFNB mAb)	-Phase 3/270 adults ≥18	NCT05895786
Ichthyosis	None
Epidermolysis Bullosa	-Birch triterpenes -Beremagene geperpavec-svdt (HSV-1-based vector, genetically modified to express COL7)	Diacerein 1% Ointment (IL-1β system inhibitor)	-Phase 2/3, 80 children/adults 6 months and older	NCT06073132
		Autologous skin equivalent grafts (genetically corrected with COL7A1-encoding SIN retroviral vector)	-Phase 1/2, 3 adults ≥18	NCT04186650
Keratodermas	None
Cutaneous t-cell lymphoma	-Mogamulizumab (anti-CCR4) -Brentuximab (anti-CD30) -Denileukin (anti-IL-2R) -Vorinostat (anti-HDAC) -Alemtuzumab (anti-CD52)	Hypericin ointment and visible light	-Phase 2/50 adults ≥18	NCT05872854
		Durvalumab (anti-PD-L1)	-Phase 1/2, 62 adults ≥18	NCT03011814
		Resminostat (HDAC inhibitor)	-Phase 2/201 adults ≥18	NCT02953301

* Trials were only included if they specific evaluated itch severity as a primary or secondary endpoint.

^‡ Several therapies have been approved for the treatment of lung disease associated with scleroderma, but none that have been tested for anti-pruritic effect.

FDA: United States Food and Drug Administration, mAb: monoclonal antibody, KOR: kappa opioid receptor; HDAC: histone deacetylase, PD-L: programmed death ligand, CD: cluster of differentiation, CCR: chemokine receptor, C5aR1: complement component 5a receptor 1, IVIG: intravenous immunoglobulin, OSMRβ: oncostatin M receptor beta, HSV: herpes simplex virus, COL7: collagen 7, siSPARC: small interfering RNA Against SPARC, siLR4A: small interfering RNA against IL-4 Receptor A, CO2: Carbon dioxide; TRPV3: transient receptor potential vanilloid-3.

Figure 2. The prevalence of itch in patients diagnosed with various genetic, autoimmune, and cancerous cutaneous diseases. The prevalence for each condition was extracted from epidemiological studies referenced in this review. Where multiple studies were available, all values were combined into boxes showing the 2nd and 3rd quartiles. The upper- and lowermost points on the vertical axis represent the minimum and maximum prevalences reported in each condition. Where only one epidemiological study was found, a horizontal line represents the prevalence instead of a box.

BP: bullous pemphigoid, LA: lichen amyloidosis, DH: dermatitis herpetiformis, EB: epidermolysis bullosa, CTCL: cutaneous t-cell lymphoma

Figure 3. The unmet needs of treating itch from the patient, provider, and research perspectives.