Dupilumab Significantly Modulates Pain and Discomfort in Patients With Atopic Dermatitis: A Post Hoc Analysis of 5 Randomized Clinical Trials

Jonathan I Silverberg, Eric L Simpson, Emma Guttman-Yassky, Michael J Cork, Marjolein de Bruin-Weller, Gil Yosipovitch, Laurent Eckert, Zhen Chen, Marius Ardeleanu, Brad Shumel, Thomas Hultsch, Ana B Rossi, Jennifer D Hamilton, Jamie M Orengo, Marcella Ruddy, Neil M H Graham, Gianluca Pirozzi, Abhijit Gadkari, Jonathan I Silverberg, Eric L Simpson, Emma Guttman-Yassky, Michael J Cork, Marjolein de Bruin-Weller, Gil Yosipovitch, Laurent Eckert, Zhen Chen, Marius Ardeleanu, Brad Shumel, Thomas Hultsch, Ana B Rossi, Jennifer D Hamilton, Jamie M Orengo, Marcella Ruddy, Neil M H Graham, Gianluca Pirozzi, Abhijit Gadkari

Abstract

Background: Pain is a frequent symptom of atopic dermatitis (AD).

Objectives: The aims of the study were to evaluate the effects of dupilumab on pain/discomfort in AD and to determine whether pain correlates with other outcomes.

Methods: This was a post hoc analysis of 5 randomized, placebo-controlled clinical trials in which adults with chronic AD received placebo or dupilumab 300 mg every 2 weeks or once weekly with and without topical corticosteroids. Proportions of patients with no pain/discomfort on this dimension of the 5-dimension EuroQoL (EQ-5D) at week 16 (all trials) and week 52 (CHRONOS) were compared between placebo and dupilumab. Correlations were evaluated between pain/discomfort and signs and symptoms of AD.

Results: Among 2632 evaluated patients, 72.9% to 83.1% reported at least moderate pain/discomfort at baseline. Higher proportions treated with dupilumab reported no pain/discomfort at week 16 relative to placebo; risk differences ranged from 22.3% (95% confidence interval = 11.5%-33.1%) to 42.2% (95% confidence interval = 26.6%-57.8%, all P ≤ 0.0001), with similar effects observed at week 52. Correlations at baseline of pain/discomfort with signs and symptoms of AD were low to moderate.

Conclusions: Pain/discomfort, present in a substantial proportion of patients with moderate-to-severe AD, was significantly reduced by dupilumab treatment. Given the low-to-moderate correlations with other AD symptoms at baseline, pain likely represents a distinct AD symptom.Trial Registration: ClinicalTrials.gov identifiers NCT01859988, NCT02277743, NCT02277769, NCT02260986, and NCT02755649.

Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Contact Dermatitis Society.

Figures

Figure 1
Figure 1
Pain/discomfort at baseline as reported by the patients on the EQ-5D pain/discomfort dimension.
Figure 2
Figure 2
Proportions of patients who reported “no pain/discomfort” on the EQ-5D pain/discomfort dimension over the duration of the studies. Numbers are shown only for baseline, first significant time point versus placebo, week 16, and week 52 (CHRONOS). Values after first rescue treatment were set to missing (censored), and patients with missing responses at week 16 were considered nonresponders. *P ≤ 0.0001 and †P < 0.05 versus placebo.
Figure 3
Figure 3
Association of peak itch severity with pain/discomfort using the baseline data pooled from the SOLO 1&2 + CHRONOS trials.
Figure 4
Figure 4
Association of the SCORAD excoriation severity with pain/discomfort using the baseline data of pooled treatment groups.

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