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. 2024 Jan;25(1):127-138.
doi: 10.1007/s40257-023-00810-7. Epub 2023 Aug 25.

Interpreting the Relationship Among Itch, Sleep, and Work Productivity in Patients with Moderate-to-Severe Atopic Dermatitis: A Post Hoc Analysis of JADE MONO-2

Gil Yosipovitch  1 , Melinda J Gooderham  2 , Sonja Ständer  3 , Luz Fonacier  4 , Jacek C Szepietowski  5 , Mette Deleuran  6 , Giampiero Girolomoni  7 , John C Su  8   9 , Andrew G Bushmakin  10 , Joseph C Cappelleri  10 , Claire Feeney  11 , Gary Chan  10 , Andrew J Thorpe  12 , Hernan Valdez  13 , Pinaki Biswas  13 , Ricardo Rojo  10 , Marco DiBonaventura  13 , Daniela E Myers  14
Affiliations

Interpreting the Relationship Among Itch, Sleep, and Work Productivity in Patients with Moderate-to-Severe Atopic Dermatitis: A Post Hoc Analysis of JADE MONO-2

Gil Yosipovitch et al. Am J Clin Dermatol. 2024 Jan.

Abstract

Background: Abrocitinib, an oral, once-daily Janus kinase 1-selective inhibitor, improved itch severity, sleep, and work productivity versus placebo in patients with moderate-to-severe atopic dermatitis.

Objective: The aim of this study was to investigate relationships among itch, sleep, and work productivity in the phase III JADE MONO-2 clinical trial.

Methods: A repeated-measures longitudinal model was used to examine relationships between itch (using the Peak Pruritus Numerical Rating Scale [PP-NRS] or Nighttime Itch Scale [NTIS]) and sleep disturbance/loss (using the Patient-Oriented Eczema Measure sleep item and SCORing AD Sleep Loss Visual Analog Scale) and, separately, between itch and work productivity (using the Work Productivity and Activity Impairment-Atopic Dermatitis Version 2.0 questionnaire). Mediation modelling was used to investigate the effect of treatment (abrocitinib vs placebo) on work impairment via improvements in itch and sleep.

Results: The relationships between itch/sleep and itch/work productivity were approximately linear. PP-NRS scores of 0, 4-6, and 10 were associated with 0 days, 3-4 days, and 7 days per week of disturbed sleep, respectively. PP-NRS or NTIS scores of 0-1, 4-5, and 10 were associated with 0-10%, 20-30%, and >50% overall work impairment, respectively. Seventy-five percent of the effect of abrocitinib on reducing work impairment was indirectly mediated by improvement in itch, followed by sleep.

Conclusion: These results quantitatively demonstrate that reducing itch severity is associated with improvements in sleep and work productivity. Empirical evidence for the mechanism of action of abrocitinib showed that itch severity is improved, which reduces sleep loss/sleep disruption and, in turn, improves work productivity.

Clinical trial registration: NCT03575871.

Plain language summary

Atopic dermatitis (AD), also called atopic eczema, is a common skin disease that is associated with itch and reduced quality of life. Abrocitinib, a recently approved medicine for AD, was shown in clinical trials to improve itch, which is considered the most bothersome symptom to people with AD. Abrocitinib also improved sleep outcomes and work productivity in people with moderate or severe AD. It is unknown if improvement in itch can lead to improvement in sleep and work productivity. We analyzed data from the JADE MONO-2 study, which included 391 people who received treatment with abrocitinib or placebo for 12 weeks. We used mathematical modelling to study relationships between itch and sleep or work productivity. We also wanted to study if the improvements in itch and sleep with abrocitinib treatment had an impact on work productivity. We found that a relationship existed between itch, sleep disturbance, and work impairment; as itch improved, so too did sleep disturbance and work impairment. When people were treated with abrocitinib, they experienced relief from itch, which improved sleep, which in turn reduced work productivity loss. Larger and longer studies are needed to confirm these results. This analysis further informs the expectations of patients with moderate or severe AD as it relates to progression of symptom relief after treatment with abrocitinib.

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Conflict of interest statement

Gil Yosipovitch is a consultant and advisor for Cara Therapeutics, Eli Lilly, Escient, Galderma, GlaxoSmithKline, Kiniksa, LEO Pharma, Novartis, Pfizer Inc., Regeneron, Sanofi, Trevi Therapeutics, and Vifor and a principal investigator for Arcutis, Celldex, Eli Lilly, Escient, Galderma, Kiniksa, LEO Pharma, Novartis, Pfizer Inc., and Sanofi Regeneron. Melinda J. Gooderham has received grants, personal fees, honoraria, and/or nonfinancial support from AbbVie, Amgen, AkrosPharma, AnaptysBio, Arcutis, ASLAN Pharmaceuticals, Bausch Health (Valeant), Bristol Myers Squibb, Boehringer-Ingelheim, Celgene, Dermavant Sciences, Dermira, Eli Lilly, Galderma, Janssen, Kyowa Kirin, LEO Pharma, MedImmune, Meiji, Merck, Novartis, Pfizer Inc., Roche, Sanofi Genzyme, Regeneron, Sun Pharma, and UCB. Sonja Ständer is a principal investigator for Almirall, Dermasence, Galderma, Kiniksa, LEO Pharma, Menlo Therapeutics, Novartis, Sanofi, and Trevi Therapeutics; a member of scientific advisory boards for Beiersdorf, Celgene, Galderma, Kiniksa, Pfizer, and Trevi Therapeutics; and a consultant for Bellus Health, Galderma, Novartis, Sanofi, and Vifor. Luz Fonacier received research grants (made to NYU Langone Hospital-LI) from AstraZeneca, Pfizer, Regeneron, and Shire and was a consultant and advisor for AbbVie, Eli Lilly, Pfizer, and Regeneron. Jacek C. Szepietowski has been a consultant/advisory board member for LEO Pharma, Novartis, Sanofi Genzyme, Trevi, and Viofor; a speaker for AbbVie, LEO Pharma, Novartis, Sanofi Genzyme, and Sunfarm; and an investigator for AbbVie, Bristol Myers Squibb, Galapagos, Galderma, Helm, Incyte, InfaRX, Janssen-Cilag, Novartis, Pfizer, Regeneron, UCB, and Trevi. Mette Deleuran has been a principal investigator in clinical trials and an advisory board member and/or speaker for AbbVie, ASLAN, Arena Pharmaceuticals, Eli Lilly, Incyte, La Roche Posay, LEO Pharma, Novartis, Pfizer, Pierre Fabre, Regeneron, and Sanofi Genzyme. Giampiero Girolomoni has been principal investigator in clinical trials sponsored by and/or has received personal fees from AbbVie, Almirall, Amgen, Biogen, Boehringer-Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly, Fresenius Kabi, Genzyme, LEO Pharma, Menlo Therapeutics, Novartis, OM Pharma, Pfizer, Regeneron, Samsung Bioepis, and Sanofi. John Su has received grants/research funding for his role as an investigator for AbbVie, Amgen, AstraZeneca, Bristol Myers Squibb, Eli Lilly, Galderma, Janssen, Novartis, Pfizer Inc., Pierre Fabre, and Sanofi; has received honoraria for serving on advisory boards for Eli Lilly, GSK, Janssen, LEO Pharma, L’Oréal, Novartis, Pfizer Inc., and Sanofi; and has received honoraria for serving as a speaker for Ego Pharmaceuticals and Pierre Fabre. Andrew G. Bushmakin, Pinaki Biswas, Claire Feeney, Hernan Valdez, Andrew J. Thorpe, Gary Chan, Joseph C. Cappelleri, Marco DiBonaventura, and Daniela E. Myers are employees and shareholders of Pfizer Inc. Ricardo Rojo is a former employee and current shareholder of Pfizer Inc.

Figures

Fig. 1
Fig. 1
Relationships between a PP-NRS and NTIS and b SCORAD and POEM sleep items. NTIS Night Time Itch Scale, POEM Patient-Oriented Eczema Measure, PP-NRS Peak Pruritus Numerical Rating Scale, SCORAD Sleep Loss VAS SCORing of Atopic Dermatitis Sleep Loss Visual Analog Scale, WPAI-AD Work Productivity and Activity Impairment-Atopic Dermatitis
Fig. 2
Fig. 2
Relationships between outcomes and PP-NRS as the anchor (continuous predictor or categorical predictor): a PP-NRS and POEM Sleep item, b PP-NRS and SCORAD Sleep Loss VAS, and c PP-NRS and WPAI overall work impairment. NTIS Night Time Itch Scale, POEM Patient-Oriented Eczema Measure, PP-NRS Peak Pruritus Numerical Rating Scale, SCORAD Sleep Loss VAS SCORing of Atopic Dermatitis Sleep Loss Visual Analog Scale, WPAI Work Productivity and Activity Impairment questionnaire
Fig. 3
Fig. 3
Relationships between outcomes and NTIS as the anchor (continuous predictor or categorical predictor): a NTIS and POEM sleep item, b NTIS and SCORAD Sleep Loss VAS, and c NTIS and WPAI overall work impairment. NTIS Night Time Itch Scale, POEM Patient-Oriented Eczema Measure, PP-NRS Peak Pruritus Numerical Rating Scale, SCORAD Sleep Loss VAS SCORing of Atopic Dermatitis Sleep Loss Visual Analog Scale, WPAI Work Productivity and Activity Impairment questionnaire
Fig. 4
Fig. 4
Interpretation of the association between itch and a sleep and b overall work impairment. NTIS Night Time Itch Scale, POEM Patient-Oriented Eczema Measure, PP-NRS Peak Pruritus Numerical Rating Scale, SCORAD Sleep Loss VAS SCORing of Atopic Dermatitis Sleep Loss Visual Analog Scale, WPAI-AD Work Productivity and Activity Impairment-Atopic Dermatitis questionnaire version 2.0
Fig. 5
Fig. 5
Mediation modeling: a direct and overall indirect effects, b path via itch, c path via sleep, and d path via itch and sleep. WPAI-AD Work Productivity and Activity Impairment—Atopic Dermatitis questionnaire version 2.0. Solid, single-headed arrows indicate direct paths; Dashed, single-headed arrows, indicate indirect paths
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