PMID- 36672173 OWN - NLM STAT- MEDLINE DCOM- 20230124 LR - 20230212 IS - 2073-4409 (Electronic) IS - 2073-4409 (Linking) VI - 12 IP - 2 DP - 2023 Jan 5 TI - Effects of Dupilumab on Itch-Related Events in Atopic Dermatitis: Implications for Assessing Treatment Efficacy in Clinical Practice. LID - 10.3390/cells12020239 [doi] LID - 239 AB - Dupilumab attenuates itch and skin inflammation in patients with atopic dermatitis (AD). However, itch-related events that are improved by dupilumab remain unclear. Therefore, the present study investigated changes in clinical scores, serum biomarkers, and the number of intraepidermal nerve fibers (IENFs) using skin biopsies and blood samples from 12 patients with moderate to severe AD before and after treatment with dupilumab. Clinical manifestations were assessed using eczema area and severity index (EASI) and visual analogue scale (VAS) scores at baseline and after 8 and 16 weeks of treatment. Serum levels of total immunoglobulin E (IgE), thymus and activation-regulated chemokine (TARC), interleukin (IL)-4, IL-13, IL-22, and IL-31 were examined by electrochemiluminescence, chemiluminescent enzyme immunoassays, ProQuantum immunoassays, and enzyme-linked immunosorbent assays (ELISA) at baseline and after 8 and 16 weeks of treatment. In skin biopsies from AD patients at baseline and after 16 weeks of treatment, IENFs were examined immunohistochemically with the anti-protein gene product (PGP) 9.5 antibody. The dupilumab treatment significantly improved EASI and VAS scores and decreased serum levels of TARC, IgE, and IL-22, whereas those of IL-13 and IL-31, and the number of IENFs remained unchanged and those of IL-4 increased. VAS scores were positively correlated with serum TARC, IL-22, and IgE levels and the degree of epidermal thickening. Serum IL-31 levels were positively correlated with the number of IENFs. These results suggest that serum TARC, IL-22, and IgE levels and epidermal thickness are itch-related events associated with dupilumab treatment and that serum IL-31 levels may reflect the degree of IENF density in AD patients. Therefore, dynamic changes may be used to assess the efficacy of dupilumab treatment to treat itching and inflammation in patients with AD. FAU - Kishi, Ryoma AU - Kishi R AUID- ORCID: 0000-0003-3999-1609 AD - Juntendo Itch Research Center (JIRC), Institute for Environmental and Gender-Specific Medicine, Juntendo University Graduate School of Medicine, 2-1-1 Tomioka, Urayasu 279-0021, Chiba, Japan. AD - Department of Dermatology, Juntendo University Urayasu Hospital, 2-1-1 Tomioka, Urayasu 279-0021, Chiba, Japan. FAU - Toyama, Sumika AU - Toyama S AUID- ORCID: 0000-0003-3606-245X AD - Juntendo Itch Research Center (JIRC), Institute for Environmental and Gender-Specific Medicine, Juntendo University Graduate School of Medicine, 2-1-1 Tomioka, Urayasu 279-0021, Chiba, Japan. FAU - Tominaga, Mitsutoshi AU - Tominaga M AUID- ORCID: 0000-0002-1254-1803 AD - Juntendo Itch Research Center (JIRC), Institute for Environmental and Gender-Specific Medicine, Juntendo University Graduate School of Medicine, 2-1-1 Tomioka, Urayasu 279-0021, Chiba, Japan. AD - Anti-Aging Skin Research Laboratory, Juntendo University Graduate School of Medicine, 2-1-1 Tomioka, Urayasu 279-0021, Chiba, Japan. FAU - Kamata, Yayoi AU - Kamata Y AUID- ORCID: 0000-0002-3477-5715 AD - Juntendo Itch Research Center (JIRC), Institute for Environmental and Gender-Specific Medicine, Juntendo University Graduate School of Medicine, 2-1-1 Tomioka, Urayasu 279-0021, Chiba, Japan. AD - Anti-Aging Skin Research Laboratory, Juntendo University Graduate School of Medicine, 2-1-1 Tomioka, Urayasu 279-0021, Chiba, Japan. FAU - Komiya, Eriko AU - Komiya E AD - Juntendo Itch Research Center (JIRC), Institute for Environmental and Gender-Specific Medicine, Juntendo University Graduate School of Medicine, 2-1-1 Tomioka, Urayasu 279-0021, Chiba, Japan. FAU - Kaneko, Takahide AU - Kaneko T AD - Department of Dermatology, Juntendo University Urayasu Hospital, 2-1-1 Tomioka, Urayasu 279-0021, Chiba, Japan. FAU - Suga, Yasushi AU - Suga Y AUID- ORCID: 0000-0003-3643-2879 AD - Department of Dermatology, Juntendo University Urayasu Hospital, 2-1-1 Tomioka, Urayasu 279-0021, Chiba, Japan. AD - Anti-Aging Skin Research Laboratory, Juntendo University Graduate School of Medicine, 2-1-1 Tomioka, Urayasu 279-0021, Chiba, Japan. FAU - Takamori, Kenji AU - Takamori K AUID- ORCID: 0000-0002-0644-0504 AD - Juntendo Itch Research Center (JIRC), Institute for Environmental and Gender-Specific Medicine, Juntendo University Graduate School of Medicine, 2-1-1 Tomioka, Urayasu 279-0021, Chiba, Japan. AD - Department of Dermatology, Juntendo University Urayasu Hospital, 2-1-1 Tomioka, Urayasu 279-0021, Chiba, Japan. AD - Anti-Aging Skin Research Laboratory, Juntendo University Graduate School of Medicine, 2-1-1 Tomioka, Urayasu 279-0021, Chiba, Japan. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20230105 PL - Switzerland TA - Cells JT - Cells JID - 101600052 RN - 420K487FSG (dupilumab) RN - 0 (Interleukin-13) RN - 37341-29-0 (Immunoglobulin E) SB - IM MH - Humans MH - *Dermatitis, Atopic/complications/drug therapy MH - Interleukin-13 MH - Pruritus/drug therapy MH - Treatment Outcome MH - Immunoglobulin E MH - Inflammation PMC - PMC9857157 OTO - NOTNLM OT - atopic dermatitis OT - dupilumab OT - epidermal thickness OT - intraepidermal nerve fibers OT - serum biomarkers COIS- The authors declare no conflict of interest. EDAT- 2023/01/22 06:00 MHDA- 2023/01/25 06:00 PMCR- 2023/01/05 CRDT- 2023/01/21 01:11 PHST- 2022/11/11 00:00 [received] PHST- 2022/12/23 00:00 [revised] PHST- 2023/01/03 00:00 [accepted] PHST- 2023/01/21 01:11 [entrez] PHST- 2023/01/22 06:00 [pubmed] PHST- 2023/01/25 06:00 [medline] PHST- 2023/01/05 00:00 [pmc-release] AID - cells12020239 [pii] AID - cells-12-00239 [pii] AID - 10.3390/cells12020239 [doi] PST - epublish SO - Cells. 2023 Jan 5;12(2):239. doi: 10.3390/cells12020239.