The Pathology of Type 2 Inflammation-Associated Itch in Atopic Dermatitis
Abstract
:1. Introduction
2. Disease Burden of AD
3. Type 2 Inflammation and AD
4. Neuroimmune Interactions Associated with Type 2 Inflammation in Pruritic AD
4.1. IL-4 and IL-13
4.2. IL-31
4.3. IL-33
4.4. TSLP
5. Treatment for Itch in AD
5.1. Anti-IL-4 Receptor Antibody
5.2. Anti-IL-13
5.3. Anti-IL-31 Signaling
5.3.1. Anti-IL-31
5.3.2. Anti-IL-31RA
5.4. JAK Inhibitors
5.5. A Phosphodiesterase 4 (PDE4) Inhibitor
5.6. Anti-TSLP
5.7. Anti-IL-33
6. Conclusions
Funding
Conflicts of Interest
References
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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] |
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Moniaga, C.S.; Tominaga, M.; Takamori, K. The Pathology of Type 2 Inflammation-Associated Itch in Atopic Dermatitis. Diagnostics 2021, 11, 2090. https://doi.org/10.3390/diagnostics11112090
Moniaga CS, Tominaga M, Takamori K. The Pathology of Type 2 Inflammation-Associated Itch in Atopic Dermatitis. Diagnostics. 2021; 11(11):2090. https://doi.org/10.3390/diagnostics11112090
Chicago/Turabian StyleMoniaga, Catharina Sagita, Mitsutoshi Tominaga, and Kenji Takamori. 2021. "The Pathology of Type 2 Inflammation-Associated Itch in Atopic Dermatitis" Diagnostics 11, no. 11: 2090. https://doi.org/10.3390/diagnostics11112090
APA StyleMoniaga, C. S., Tominaga, M., & Takamori, K. (2021). The Pathology of Type 2 Inflammation-Associated Itch in Atopic Dermatitis. Diagnostics, 11(11), 2090. https://doi.org/10.3390/diagnostics11112090