Selective inhibition of JAK1 in treatment of atopic dermatitis: Prescription features and experience with upadacitinib
https://doi.org/10.33667/2078-5631-2022-8-35-40
Abstract
Therapy of moderate-to-severe atopic dermatitis (AD) is associated with a number of diffculties due to the propensity of the disease to a chronic relapsing course, the tendency to develop in childhood and young age. However, a new selective JAK1 inhibitor, which suppresses cytokineinduced inflammation in the skin, has been added to the arsenal of AD systemic therapy.
Objective. To evaluate the effcacy, antipruritic activity, impact on quality of life, levels of anxiety and depression, and safety of upadacitinib treatment of moderate-to-severe AD in adult patients.
Material and methods. The inclusion criteria were the presence of moderate-to-severe AD, age over 18 years, signed informed consent of the patient to participate in the study. Effcacy was assessed based on clinical indices. All patients received upadacitinib (RANVEK) 15 mg once daily with or without food, topical corticosteroids (if needed), and emollients.
Results. The number of patients with an IGA score of 0 or 1 was 50%. The dynamics of the maximum intensity of pruritus according to NRS during 16 weeks of therapy was 56.4%. The proportion of patients with an improvement in the assessment of the maximum severity of itching according to NRS ≥3 points at week 16 relative to the baseline was 77.8%. The dynamics of the EASI index in percent was 65.3%, and the number of patients who achieved an EASI-50 response at week 16 was 83.3%, EASI-75 was 61.1%. The dynamics of the overall SCORAD index as a percentage of the initial value for 16 weeks was 76.9%. The DLQI decreased by 68.9%. The number of patients with HADS less than 7 points on a scale of both anxiety and depression was 88.9%.
Conclusions. Thus, upadacitinib demonstrates high effcacy in terms of the effect on rashes and pruritus, favorably affects the quality of life and psychosomatic characteristics of patients, and has a favorable safety profle in the treatment of moderate and severe AD in adults.
About the Authors
L. S. Kruglova
Central State Medical Academy of the Administrative Department of the President of Russia
Russian Federation
Russian Federation
Kruglova Larisa S., DM Sci (habil.), professor, head of Dermatovenerology and Cosmetology Dept
A. V. Michenko
Central State Medical Academy of the Administrative Department of the President of Russia; Medical Scientifc and Educational Centre at Moscow State University n.a. M.V. Lomonosov
Russian Federation
Russian Federation
Michenko Anna V., PhD Med, associate professor at Dermatovenerology and Cosmetology Dept
A. N. Lvov
Central State Medical Academy of the Administrative Department of the President of Russia; Medical Scientifc and Educational Centre at Moscow State University n.a. M.V. Lomonosov
Russian Federation
Russian Federation
Lvov Andrei N., DM Sci (habil.), professor, head of Dept of Postgraduate Studies and Residency, professor at Dermatovenerology and Cosmetology Dept1, chief researcher
A. A. Hotko
Clinical Dermatovenerologic Dispensary
Russian Federation
Russian Federation
Hotko Alkes A., PhD Med, associate professor, deputy chief physician
References
1. Khamaganova I.V., Novozhilova O.L., Vorontsova I.V. Epidemiology of atopic dermatitis. Clinical Dermatology and Venereology 2017; 14:21–25.
2. Barbarot S., Auziere S., Gadkari A., Girolomoni G., Puig L., Simpson E.L., et al. Epidemiology of atopic dermatitis in adults: results from an international survey. Allergy. 2018 Jun; 73 (6): 1284–93.
3. Flohr C., Mann J. New insights into the epidemiology of childhood atopic dermatitis. Allergy. 2014 Jan; 69 (1):3–16.
4. Tamagawa-Mineoka R., Katoh N. Atopic dermatitis: identifcation and management of complicating factors. Int J Mol Sci. 2020; 21 (8): 2671.
5. Yamamoto-Hanada K., Yang L., Ishitsuka K., et al. Allergic profles of mothers and fathers in the Japan Environment and Children’s Study (JECS): a nationwide birth cohort study. World Allergy Organ J. 2017; 10 (1): 24.
6. Palmer C.N., Irvine A.D., Terron-Kwiatkowski A., Zhao Y., Liao H, Lee S.P., et al. Common loss-of function variants of epidermal barrier protein flaggrin are a major predisposing factor for atopic dermatitis. Nat Genet. 2006; 38: 441–6.
7. Rajagopalan M., De A., Godse K., et al. Guidelines on Management of Atopic Dermatitis in India: An Evidence-Based Review and an Expert Consensus. Indian J Dermatol. 2019; 64 (3): 166–181.
8. Siegfried E.C., Jaworski J.C., Mina-Osorio P. A Systematic Scoping Literature Review of Publications Supporting Treatment Guidelines for Pediatric Atopic Dermatitis in Contrast to Clinical Practice Patterns. Dermatol Ther (Heidelb). 2018; 8 (3): 349–377. DOI: 10.1007/s13555–018–0243–4.
9. Cornez I., Yajnanarayana S. P., Wolf A. M., Wolf D. JAK/STAT disruption induces immuno-defciency: rationale for the development of JAK inhibitors as immunosuppressive drugs. Mol Cel Endocrinol. 2017; 451: 88–96.
10. Cotter D. G., Schairer D., Eichenfeld L. Emerging therapies for atopic dermatitis: JAK inhibitors. J Am Acad Dermatol. 2018; 78 (3 Suppl 1): S53–S62.
11. Damsky W., King B.A. JAK inhibitors in dermatology: the promise of a new drug class. J Am Acad Dermatol. 2017; 76 (4): 736–744.
12. Cosgrove S.B., Wren J.A., Cleaver D.M., et al. A blinded, randomized, placebo-controlled trial of the effcacy and safety of the Janus kinase inhibitor oclacitinib (Apoquel®) in client-owned dogs with atopic dermatitis. Vet Dermatol. 2013; 24 (6): 587.e142.
13. Guttman-Yassky E., Teixeira H.D., Simpson E.L., Papp K.A., Pangan A.L., Blauvelt A., Thaçi D.., Chu CY., Hong H.C., Katoh N., Paller A.S., Calimlim B., Gu Y., Hu X., Liu M., Yang Y., Liu J., Tenorio A. R., Chu A. D., Irvine A. D. Once-daily upadacitinib versus placebo in adolescents and adults with moderate-to-severe atopic dermatitis (Measure Up 1 and Measure Up 2): results from two replicate double-blind, randomised controlled phase 3 trials. Lancet. 2021 Jun 5; 397 (10290): 2151–2168.
14. Guttman-Yassky E., Thaçi D., Pangan A.L., et al. Upadacitinib in adults with moderate to severe atopic dermatitis: 16-week results from a randomized, placebo-controlled trial. J Allergy Clin Immunol. Published online November 29, 2019.
15. Nakashima C., Yanagihara S., Otsuka A. Innovation in the treatment of atopic dermatitis: Emerging topical and oral Janus kinase inhibitors. Allergol Int. 2022 Jan; 71 (1): 40–46.
16. Nguyen J., Chen J. K., Honari G., Pol-Rodriguez M., Ko J. M., Chiou A. S. Bridging to a selective Janus kinase 1 inhibitor in severe atopic dermatitis: An instructive case with upadacitinib. JAAD Case Rep. 2020 Nov 6; 7: 65–67.
17. Silverberg J. I., Thyssen J. P., Fahrbach K., et al. Comparative effcacy and safety of systemic therapies used in moderate-to-severe atopic dermatitis: a systematic literature review and network meta-analysis. J Eur Acad Dermatol Venereol. 2021; 35 (9): 1797–1810.
18. Silverberg J. I., Thyssen J. P., Fahrbach K., et al. Comparative effcacy and safety of systemic therapies used in moderate-to-severe atopic dermatitis: a systematic literature review and network meta-analysis. J Eur Acad Dermatol Venereol. 2021; 35 (9): 1797–1810.
19. Guttman-Yassky E., et al. Oral presentation at EADV 2020, D3T03.4B
20. Guttman-Yassky E., et al. Lancet 2021; 397: 2151–68
21. Ardern-Jones M.R., et al. ISAD2021 (PE-21)
22. Eyerich K., et al. ISAD2021 (PE-20)
23. Reich K., et al. ISAD2021 (PE-19)
Review
For citations:
Kruglova L.S., Michenko A.V., Lvov A.N., Hotko A.A. Selective inhibition of JAK1 in treatment of atopic dermatitis: Prescription features and experience with upadacitinib. Medical alphabet. 2022;(8):35-40. (In Russ.) https://doi.org/10.33667/2078-5631-2022-8-35-40
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