Growth analysis among adolescents with moderate-to-severe atopic dermatitis receiving upadacitinib in combination with topical corticosteroids in Japan: A case study series from a phase 3, randomized, controlled trial (Rising Up)

Abstract

Background: Treatment options for adolescents with moderate-to-severe atopic dermatitis (AD) are limited. Oral corticosteroid therapies are used to treat children and adolescents with moderate-to-severe AD; however, long-term use is not recommended because of potential growth impairment. Upadacitinib, an oral Janus kinase inhibitor, is approved to treat moderate-to-severe AD in the United States, Japan, and Europe. To investigate potential effects of upadacitinib on growth, we analyzed height and height velocity in 6 adolescent patients in the phase 3 Rising Up study who were in the decline phase of pubertal growth at the time of study entry.

Methods: The randomized, double-blind, Rising Up (NCT03661138) study compared upadacitinib plus topical corticosteroids (TCS) to placebo plus TCS in adolescents and adults with moderate-to-severe AD in Japan. Eligible adolescents (aged 12-17 years) were randomized 1:1:1 to receive once-daily upadacitinib 15 mg, upadacitinib 30 mg, or placebo in combination with TCS for 16 weeks. After 16 weeks, patients randomized to receive placebo were rerandomized 1:1 to receive upadacitinib 15 mg or upadacitinib 30 mg. Historical height measurements were obtained when available. Individual growth and growth velocity curves were compared with standard curves for Japanese youths. This non-prespecified analysis used 52-week data.

Results: Of the 29 adolescents enrolled, 6 were in the decline phase of pubertal growth at enrollment. Growth curves and growth velocity curves for these 6 patients remained within the normal range for Japanese adolescents throughout the study. Biomarkers of bone metabolism generally remained stable over the course of the study. No musculoskeletal adverse events were reported.

Conclusions: No cases suggested that upadacitinib negatively affected adolescent growth. Ongoing studies will continue to assess height and adverse effects related to bone growth to further inform on this patient group.

Trial registration: ClinicalTrials.gov Identifier NCT03661138.

Keywords: Atopic dermatitis; Growth; Janus kinase inhibitors; Reference growth curves; Upadacitinib.

© 2022 The Author(s).

Figures

Fig. 1

Patient 1 (male, aged 14 years) in the upadacitinib 15-mg dose group. A. Growth curve vs. standard growth curves for Japanese males, with red line indicating on-study measurements. Grey shading indicates periods of oral steroid use. B. Growth velocity curve vs. standard growth velocity curves for Japanese males, with red points indicating on-study measurements. Grey shading indicates periods of oral steroid use. C. EASI score (blue) and percent EASI score reduction (orange) by visit. D. Baseline characteristics. AD, atopic dermatitis; BMI, body mass index; BMI-SDS, body mass index standard deviation score; EASI, Eczema Area and Severity Index; PBO, placebo; UPA, upadacitinib.

Fig. 2

Patient 2 (female, aged 13 years) in the upadacitinib 15-mg dose group. A. Growth curve vs. standard growth curves for Japanese females, with red line indicating on-study measurements.B. Growth velocity curve vs. standard growth velocity curves for Japanese females, with red points indicating on-study measurements. C. EASI score (blue) and percent EASI score reduction (orange) by visit. D. Baseline characteristics. AD, atopic dermatitis; BMI, body mass index; BMI-SDS, body mass index standard deviation score; EASI, Eczema Area and Severity Index; UPA, upadacitinib.

Fig. 3

Patient 3 (female, aged 16 years) in the upadacitinib 15-mg dose group. A. Growth curve vs. standard growth curves for Japanese females, with red line indicating on-study measurements.B. Growth velocity curve vs. standard growth velocity curves for Japanese females, with red points indicating on-study measurements. C. EASI score (blue) and percent EASI score reduction (orange) by visit (C). D. Baseline characteristics. AD, atopic dermatitis; BMI, body mass index; BMI-SDS, body mass index standard deviation score; EASI, Eczema Area and Severity Index; UPA, upadacitinib.

Fig. 4

Patient 4 (male, aged 13 years) in the upadacitinib 30-mg dose group. A. Growth curve vs. standard growth curves for Japanese males, with red line indicating on-study measurements,B. Growth velocity curve vs. standard growth velocity curves for Japanese males, with red points indicating on-study measurements. C. EASI score (blue) and percent EASI score reduction (orange) by visit. D. Baseline characteristics. AD, atopic dermatitis; BMI, body mass index; BMI-SDS, body mass index standard deviation score; EASI, Eczema Area and Severity Index; UPA, upadacitinib.

Fig. 5

Patient 5 (male, aged 14 years) in the upadacitinib 15-mg dose group. A. Growth curve vs. standard growth curves for Japanese males, with red line indicating on-study measurements.B. Growth velocity curve vs. standard growth velocity curves for Japanese males, with red point indicating on-study measurement. C. EASI score (blue) and percent EASI score reduction (orange) by visit. D. Baseline characteristics. AD, atopic dermatitis; BMI, body mass index; BMI-SDS, body mass index standard deviation score; EASI, Eczema Area and Severity Index; UPA, upadacitinib.

Fig. 6

Patient 6 (male, aged 14 years) in the placebo (16-week)/upadacitinib 15-mg dose group. A. Growth curve vs. standard growth curves for Japanese males, with red line indicating on-study measurements.B. Growth velocity curve vs. standard growth velocity curves for Japanese males, with red points indicating on-study measurements. C. EASI score (blue) and percent EASI score reduction (orange) by visit. D. Baseline characteristics. AD, atopic dermatitis; BMI, body mass index; BMI-SDS, body mass index standard deviation score; EASI, Eczema Area and Severity Index; PBO, placebo; UPA, upadacitinib.