Table 1.

Therapeutic potential of the biologic agent-type 2 inflammation-related regulation of itch in atopic dermatitis.

Mediator	Mechanism	Drug	Status	Clinical Effects	References
IL-4, IL-13	Anti-IL-4Rα	Dupilumab	Approved for moderate-to-severe AD (FDA)	Improvement in pruritus NRS by ≥4 points; IGA, EASI, SCORAD, DLQI	[53,84,85,86]
IL-13	Anti-IL-13	Lebrikizumab	Phase 2b	Improvement in pruritus NRS by ≥4 points; EASI, IGA, BSA, POEM	[87]
		Tralokinumab	Phase 3	Improvement in pruritus NRS by ≥4 points; IGA, BSA, EASI, SCORAD, POEM	[88,89]
IL-31	Anti-IL-31	BMS-981164	Phase 1	Data not yet released	https://clinicaltrials.gov/ct2/show/NCT01614756 (accessed on 15 September 2021)
	Anti-IL-31Rα	Nemolizumab	Phase 3	Improvement in pruritus VAS by 40–60%	[69,90,91,92]
JAK	JAK1/JAK2 inhibitor	Baricitinib	Approved for AD in Japan and the EU; undergoing phase 3 trials in other countries	Improvement in pruritus NRS by ≥4 points; IGA, EASI, SCORAD, skin pain, POEM, DLQI	[93,94] https://clinicaltrials.gov/ct2/results?cond=Atopic+Dermatitis&term=baricitinib&cntry=&state=&city=&dist= (accessed on 15 September 2021)
	JAK1, JAK2, JAK3, and a tyrosine kinase 2 inhibitor	Delgocitinib 0.5% (topical)	Approved for AD in Japan; undergoing phase 3 trials in other countries	Improvement in pruritus NRS points; IGA, EASI, BSA	[95,96] https://clinicaltrials.gov/ct2/show/NCT04949841?term=delgocitinib&cond=Atopic+Dermatitis&draw=2&rank=6 (accessed on 15 September 2021)
	JAK1/3 inhibitor	Tofacitinib 2% (topical)	Phase 2a	Improvement in ISI; EASI, PGA, BSA	[54]
	JAK1 inhibitor	Abrocitinib (oral)	Phase 3	Improvement in pruritus NRS by ≥4 points; IGA, EASI	[97,98]
		Upadacitinib (oral)	Phase 3	Improvement in pruritus NRS by ≥4 points; IGA, EASI	[99,100,101]
PDE4	PDE4 inhibitor	Crisaborole 2% (topical)	Approved for mild-to-moderate AD (FDA)	Improvement in the severity pruritus scale & NRS points; IGA, AD signs, DLQI	[102,103,104]
TSLP	Anti-TSLPR	Tezepelumab	Phase 2a	Improvement in pruritus NRS points & the 5-D itch scale; EASI, IGA, SCORAD (Numerical improvement *)	[105]
#IL-33	Anti-IL-33	Etokimab	Phase 2a proof-of-concept study	Improvement in 5D itch scores; EASI, SCORAD, IGA, DLQI	[106]

* No significant difference; ^# Proof-of-concept study; NRS = Numerical Rating Scale; FDA = Food and Drug Administration; IGA = Investigator Global Assessment; EASI = Eczema Area and Severity Index; SCORAD= SCORing Atopic Dermatitis; DLQI= Dermatology Life Quality Index; VAS = Visual Analog Score; ISI = Itch Severity Item; BSA = Body Surface Area; POEM = Patient-Oriented Eczema Measure.