Early Itch Response With Abrocitinib Is Associated With Later Efficacy Outcomes in Patients With Moderate to Severe Atopic Dermatitis

Abstract 

BACKGROUND

Abrocitinib, an oral Janus kinase 1 inhibitor, provided significant itch relief by week 2 in patients with moderate-to-severe atopic dermatitis (AD) in the phase III JADE COMPARE trial.

OBJECTIVES

This post-hoc analysis of JADE COMPARE aimed to further characterize itch response and determined whether early itch relief could predict subsequent improvements in AD severity.

METHODS

JADE COMPARE was a randomized, double-blind, double-dummy, placebo-controlled trial. Adult patients (aged ≥ 18 years) with moderate-to-severe AD were randomly assigned to receive oral abrocitinib 200 mg or 100 mg once daily, subcutaneous dupilumab 300 mg every other week (after a 600-mg loading dose), or placebo, plus medicated topical therapy for 16 weeks. Assessments were ≥ 4-point improvement in Peak Pruritus Numerical Rating Scale (PP-NRS4) from days 2 to 15, Eczema Area and Severity Index (EASI), Investigator's Global Assessment (IGA) response, and Dermatology Life Quality Index (DLQI) scores at week 12. Association between week 2 PP-NRS4 and efficacy at week 12 was evaluated by chi-squared tests. The predictive value of early response for later efficacy was assessed by area under the receiver operating characteristic curve.

RESULTS

As early as day 4 after treatment, a significantly greater proportion of patients achieved PP-NRS4 response with abrocitinib 200 mg (18.6%) versus dupilumab (5.6%; p < 0.001) and placebo (6.0%; p < 0.003). A similar trend was observed with abrocitinib at the 100-mg dose, with significantly greater PP-NRS4 response rates versus placebo as early as day 9. With both doses of abrocitinib, week 12 IGA 0/1, EASI-75, EASI-90, and DLQI 0/1 response rates were greater in week 2 PP-NRS4 responders than nonresponders; no differences were observed between week 2 PP-NRS4 responders and nonresponders in the dupilumab and placebo groups. Early improvement in PP-NRS at week 2 was associated with skin clearance at week 12 in abrocitinib-treated patients.

CONCLUSIONS

Abrocitinib resulted in rapid relief from itch in patients with moderate-to-severe AD, with significant improvement in itch as early as day 4 after treatment with abrocitinib 200 mg compared with dupilumab and placebo. Abrocitinib-induced itch relief by week 2 was associated with subsequent improvements at week 12. [Video abstract available.]

Written by

 

 

Matthew J. Zirwas MD

For those of us who have treated a significant number of atopic dermatitis patients with systemic JAK inhibitors, the speed of onset of itch relief has been amazing — I have had a number of patients tell me that their itch started to get better by the evening they took their first dose of the medication. This is a subanalysis of the JADE COMPARE trial, which compared abrocitinib 100 mg daily versus abrocitinib 200 mg daily versus dupilumab (600 mg on day 1, then 300 mg every 2 weeks) versus placebo over 12 weeks.  All participants were also treated with background prescription topicals. This subanalysis tells us that early itch response with abrocitinib is predictive of overall efficacy at 12 weeks, while the same was not true for dupilumab or placebo (likelihood of overall clinical response at 12 weeks was not predicted by itch response at week 2).

To summarize the key data, I'll only discuss the abrocitinib 100 mg once-daily data, as that is the approved starting dose. Patients who had a 4-point reduction in the PP-NRS (Peak Pruritus Numerical Rating Scale) score at 14 days were nearly twice as likely to reach an IGA score of 0/1 at 12 weeks compared with those who didn't have a 4-point reduction by week 2 (57.4% vs 30.9%). Similar results held for reaching EASI-90 by week 12 (54.4% vs 32.2%), while the results weren't quite as dramatic for reaching EASI-75 by week 12 (73.5% vs 57.9%).  

When I'm talking to a patient about how likely it is that a drug is going to work, I describe reaching EASI-90 or IGA 0/1 as the chances of having a great response and reaching EASI-75 as the chances of having a really good response. So, my main takeaway is that the itch response at week 2 is a very good indicator of who is going to have a great response by week 12, but that even those who don't reach a 4-point improvement in PP-NRS by week 2 still have over a 50% chance of having a really good response.

TAKE-HOME MESSAGE

• In this post hoc analysis of a randomized phase III trial, 837 patients with moderate to severe atopic dermatitis were characterized as Peak Pruritus Numerical Rating Scale (PP-NRS4) responders or nonresponders by week 2. In the abrocitinib-treated groups, more PP-NRS4 responders experienced significant improvements in the Investigator's Global Assessment score and the Eczema Area and Severity Index percentage from baseline at week 12 than PP-NRS4 nonresponders. A similar trend was not seen in the groups treated with dupilumab or placebo.
• Patients with moderate to severe atopic dermatitis who do not achieve early itch reduction with abrocitinib may consider a change in therapy.

–  Ruth McTighe, MD

American Journal of Clinical Dermatology

Early Itch Response with Abrocitinib Is Associated with Later Efficacy Outcomes in Patients with Moderate-to-Severe Atopic Dermatitis: Subgroup Analysis of the Randomized Phase III JADE COMPARE Trial

Am J Clin Dermatol 2022 Dec 13;[EPub Ahead of Print], S Ständer, SG Kwatra, JI Silverberg, EL Simpson, JP Thyssen, G Yosipovitch, F Zhang, MC Cameron, RR Cella, H Valdez, M DiBonaventura, C Feeney 

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Benjamin Hidalgo-Matlock
Skin Care Physicians of Costa Rica

Clinica Victoria en San Pedro: 4000-1054
Momentum Escazu: 2101-9574

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