Treatment of Moderate to Severe Atopic Dermatitis: Highlights From AAD 2023

Emma Guttman-Yassky, MD, PhD
Icahn School of Medicine at Mount Sinai, New York City, New York

Key Takeaways

  • Progress in translational research has expanded the development of new treatments for atopic dermatitis (AD).
  • Multiple studies examining dupilumab found it to be safe and effective for the treatment of AD; it was not found to be linked to greater risk of malignancy or infection.
  • Drugs targeting OX40, a costimulatory molecule expressed on activated T cells, may represent a promising avenue for the development of novel therapies for AD.
  • There are persistent discrepancies across racial lines regarding the prescription rates for dupilumab in patients with AD.

From March 17 to 21, 2023, the American Academy of Dermatology (AAD) Annual Meeting hosted thousands of dermatologists from around the world, capturing the latest research on the treatment and management of a range of inflammatory skin diseases and other conditions. Emma Guttman-Yassky, MD, PhD, is the Waldman Professor of Dermatology and Immunology and Health System Chair of Dermatology at the Icahn School of Medicine at Mount Sinai in New York City and is Director for the Occupational Dermatitis Clinic and the Laboratory for Inflammatory Skin Diseases. In this article, Dr Guttman discusses the most exciting research on the treatment of moderate to severe AD presented at AAD 2023.

AAD 2023 included a significant amount of research on AD. Which of the presentations did you find most practice-changing, specifically in terms of advancing the treatment of moderate to severe AD?

AD and chronic hand eczema are finally at the center of attention because of progress in translational research, from target discovery to the development of new treatments. What I found most exciting at the meeting were data from early studies of new agents that may show some hint of disease modification, meaning that the disease does not flare as soon as treatment stops. For example, data that my colleagues and I presented from a phase 2 trial of rocatinlimab, an anti-OX40 monoclonal antibody, suggest that the majority of patients maintained their response 20 weeks after stopping treatment.1 The question I get from patients all the time is, “Can I either stop treatment or give it much less often?” We may be able to do exactly that soon, so this is very exciting, although we are not quite there yet.

A number of abstracts reported data on the long-term safety and efficacy of dupilumab among adults and children with moderate to severe AD.2-6 How do you think these data will impact clinical management of the disease? Do you think they will make providers feel more comfortable about long-term use of dupilumab, especially in young children (younger than 5 years of age)?

Dupilumab is a front-line treatment for both adults and adolescents with moderate to severe AD, and more recently for younger children too. Thus, it is important to put the data out there in multiple ways and to see whether safety and efficacy data from real-world studies are in line with clinical trial data. This will give the reassurance clinicians need to start using it and other new treatments in their patients.

An abstract you submitted found no association between dupilumab therapy and primary or recurrent malignancy among patients with AD, based on a retrospective study of electronic medical records.7 Research, including a study presented at AAD 2023, has found an association between AD and certain cancers,8-9 and there are still questions about whether dupilumab may increase cancer risk.10 Do your findings provide reassurance that individuals taking dupilumab may not have elevated cancer risk?

This study is another example of real-world safety data agreeing with what was found in clinical trials. It is important because it adds to the bulk of safety data for dupilumab. We published a study last year that found that dupilumab may protect patients from COVID-19 symptoms because patients who became infected while taking dupilumab had milder symptoms.11 So the data suggest that this treatment is not linked to greater risk of malignancy or infection, and it again gives additional reassurance for its use in patients, as historical treatments for this condition like cyclosporin A are associated with increased infections and malignancies.

The data suggest that dupilumab is not linked to greater risk of malignancy or infection, and it again gives additional reassurance for its use in patients, as historical treatments for this condition like cyclosporin A are associated with increased infections and malignancies.

Several abstracts reported updates from clinical trials that supported the long-term safety and efficacy of abrocitinib for adults with moderate to severe AD12-16 and of upadacitinib for adolescents and adults.17-19 How do you think these findings will impact the role of these oral Janus kinase (JAK) inhibitors in the treatment landscape? Do you think the data will ease concerns that providers may have about these therapies, particularly because of the boxed warning regarding the risk of cardiovascular events, serious infection, and other adverse events?

I think these data will lead to an expansion of the use of JAK inhibitors for treating moderate to severe AD, particularly because abrocitinib and upadacitinib are approved for both adults and adolescents. There are many patients, particularly adolescents, who do not want an injection. Also, many patients with moderate disease want to be able to stop and restart medication, which is not possible with biologics such as dupilumab.
 
Some providers and patients may still have concerns about the boxed warning for these medications. I think the best way to address those concerns would be to show good safety data from clinical trials and real-world studies following these patients for 3, 4, or 5 years, which are now ongoing.

Several safety warnings have been issued with regard to JAK inhibitor use from data derived from use in patients with rheumatoid arthritis (RA).20 Can you comment on the extrapolation of JAK inhibitor safety data to dermatologic indications, including AD? What are the implications of these warnings? 

We cannot extrapolate from what happens in the RA population to see what will happen in the AD population. I think AD patients generally have fewer safety concerns because they are younger and healthier than patients with RA. Of course, it would be nice to have amazing safety data for RA patients because AD patients should have even fewer safety issues. I understand the reason for the US Food and Drug Administration’s safety warnings, but I think the agency should have said that these drugs will be evaluated in AD and other inflammatory skin diseases, and adapt the safety concerns based on the dermatologic indications. I do hope that over time, when long-term safety data are available in dermatology-related indications, that the agency will lift the boxed warning from the dermatology indications.

Targeting OX40, a costimulatory molecule expressed on activated T cells, represents a novel treatment approach for AD.21 Data presented from the phase 2 trial of rocatinlimab and a phase 2 trial of amlitelimab, a monoclonal antibody that binds the OX40 ligand, suggest these agents may be safe and efficacious for treating moderate to severe AD.1,22,23 Do you think targeting OX40 could potentially provide patients with an important new treatment option? What are the questions that you would like to see addressed in ongoing clinical studies of these agents?

This is a new treatment class that may provide patients with the potential for disease modification. The completed phase 2 trials have demonstrated favorable safety, and at least for rocatinlimab, response durability about 20 weeks after participants stopped treatment. I would like to see studies that follow patients in clinical trials and real-world settings for longer periods of time to see if the disease returns. It is possible there might be a treatment that allows us to stop the disease and have it not come back for 6 months or 1 year.

An abstract reported that Black and Asian patients with AD received fewer prescriptions for dupilumab than White patients, based on a study of the AAD DataDerm Clinical Registry, even though the disease disproportionately affects Black and Asian individuals.24 What steps do you think should be taken to educate providers and help reduce these disparities?

At Mount Sinai, we are not seeing that Black and Asian patients receive fewer prescriptions. It is possible that in more remote areas, patients are receiving care from clinicians who are not dermatologists or who have less experience caring for AD in non-White patient groups for whom AD may have different clinical presentation than in White patients. It is important to make sure that all ethnicities can be treated with new available treatments, and that physician and provider education is offered to assure it.

This Q&A was edited for clarity and length.

Disclosures

Emma Guttman-Yassky, MD, PhD, reported affiliations with Boehringer Ingelheim Pharmaceuticals, Inc; LEO Pharma, Inc; Pfizer, Inc; Cara Therapeutics, Inc; UCB Pharma, Inc; Kyowa Kirin; RAPT; Amgen, Inc; GlaxoSmithKline PLC; Incyte Corporation; Sanofi-Aventis US LLC; Bristol-Meyers Squibb Company; Aslan; Regeneron Pharmaceuticals, Inc; Anaptysbio; Concert Pharmaceuticals, Inc; Janssen Biotech, Inc; AbbVie, Inc; Almirall, SA; AstraZeneca Pharmaceuticals, LP; Biolojic Design; Connect Pharma; DBV Technologies; Eli Lilly and Company; EMD Serono; Evidera; Galderma, SA; Gate Bio; Genentech, Inc; Inmagene; Merck & Co, Inc; Q32 Bio; SATO; Siolta; Target; and Ventyx.

References

1. Guttman-Yassky E, Chong C, Esfandiari E. Rocatinlimab demonstrates a significant reduction in IgE concentrations in addition to clinical efficacy measures in patients with moderate–severe atopic dermatitis (msAD) in a randomised, double-blind, placebo-controlled phase 2 trial. Poster presented at: American Academy of Dermatology (AAD) Annual Meeting; March 17-21, 2023; New Orleans, LA. Poster 42999.
 
2. Merola JF, Chiou AS, During E, et al. Dupilumab improves sleep disturbance in adults with moderate-to-severe atopic dermatitis. Poster presented at: American Academy of Dermatology (AAD) Annual Meeting; March 17-21, 2023; New Orleans, LA. Poster 43006.
 
3. Paller A, Siegfried E, Sidbury R, et al. Treatment-emergent adverse events in patients aged 6 months to 5 years with moderate-to-severe atopic dermatitis treated with dupilumab in an open-label extension clinical trial. Poster presented at: American Academy of Dermatology (AAD) Annual Meeting; March 17-21, 2023; New Orleans, LA. Poster 42924.
 
4. Siegfried EC, Cork MJ, Lockshin B, et al. Long term hematologic laboratory safety of dupilumab in patients aged 6 months to 5 years with moderate-to-severe atopic dermatitis. Poster presented at: American Academy of Dermatology (AAD) Annual Meeting; March 17-21, 2023; New Orleans, LA. Poster 42008.
 
5. Simpson EL, Lockshin B, Lee LW, Chen Z, Daoud M, Korotzer A. Real-world effectiveness of dupilumab in adult and adolescent patients with atopic dermatitis: 2-year data from the PROSE registry. Poster presented at: American Academy of Dermatology (AAD) Annual Meeting; March 17-21, 2023; New Orleans, LA. Poster 41658.
 
6. Kim J, Kim Y, Won S, et al. Clinical efficacy and safety of dupilumab for the treatment of moderate to severe atopic dermatitis in Korea. Poster presented at: American Academy of Dermatology (AAD) Annual Meeting; March 17-21, 2023; New Orleans, LA. Poster 42002.
 
7. Owji S, Ungar B, Dubin D, et al. No association between dupilumab use and cancer development in atopic dermatitis patients. Poster presented at: American Academy of Dermatology (AAD) Annual Meeting; March 17-21, 2023; New Orleans, LA. Poster 40890.
 
8. Zhu Y, Wang H, He J, et al. Atopic dermatitis and skin cancer risk: a systematic review. Dermatol Ther (Heidelb). 2022;12(5):1167-1179. doi:10.1007/s13555-022-00720-2
 
9. Huang MY, Miao KL, Lee K, et al. The risk of skin cancer among patients with atopic dermatitis: a population-based cohort study. Poster presented at: American Academy of Dermatology (AAD) Annual Meeting; March 17-21, 2023; New Orleans, LA. Poster 40532
 
10. Siliquini N, Viola R, Giura MT, Fierro MT, Ribero S, Ortoncelli M. Case of bladder cancer during dupilumab therapy: just an incidental event? Dermatol Ther. 2020;33(6):e13854. doi:10.1111/dth.13854
 
11. Ungar B, Glickman JW, Golant AK, et al. COVID-19 symptoms are attenuated in moderate-to-severe atopic dermatitis patients treated with dupilumab. J Allergy Clin Immunol Pract. 2022;10(1):134-142. doi:10.1016/j.jaip.2021.10.050
 
12. Simpson EL, Silverberg JI, Nosbaum A, et al. Integrated safety analysis of abrocitinib in 3802 patients with moderate-to-severe atopic dermatitis with over 5000 patient-years of exposure. Poster presented at: American Academy of Dermatology (AAD) Annual Meeting; March 17-21, 2023; New Orleans, LA. Poster 44115.
 
13. Reich K, Silverberg JI, de Bruin-Weller M, et al. Abrocitinib long-term efficacy for up to 96 weeks in patients with moderate-to-severe atopic dermatitis: interim analysis of JADE EXTEND, a long-term extension study. Poster presented at: American Academy of Dermatology (AAD) Annual Meeting; March 17-21, 2023; New Orleans, LA. Poster 44042.
 
14. Thyssen JP, Silverberg JI, Yosipovitch G, et al. Efficacy and safety of abrocitinib and dupilumab in patients with moderate-to-severe atopic dermatitis in the presence or absence of comorbid asthma or allergic rhinitis: a post hoc pooled analysis of JADE COMPARE and JADE DARE. Poster presented at: American Academy of Dermatology (AAD) Annual Meeting; March 17-21, 2023; New Orleans, LA. Poster 43916.
 
15. Gooderham M, Simpson E, Geng B, et al. Influence of baseline disease severity defined by investigator’s global assessment on abrocitinib efficacy for up to 96 weeks in patients with moderate-to-severe atopic dermatitis: interim analysis of JADE EXTEND, a long-term extension study. Poster presented at: American Academy of Dermatology (AAD) Annual Meeting; March 17-21, 2023; New Orleans, LA. Poster 44180.
 
16. Silverberg JI, Reich K, de Bruin-Weller M, et al. Response to abrocitinib up to week 96 according to short-term response: a post hoc analysis of the JADE-EXTEND phase 3 trial. Poster presented at: American Academy of Dermatology (AAD) Annual Meeting; March 17-21, 2023; New Orleans, LA. Poster 44095.
 
17. Lio P, Eichenfield LF, Marcoux D, et al. Improvement in itch, symptoms, and quality of life with upadacitinib through week 16 in adults and adolescents with atopic dermatitis: results from phase 3 studies (Measure Up 1, Measure Up 2, and AD Up). Poster presented at: American Academy of Dermatology (AAD) Annual Meeting; March 17-21, 2023; New Orleans, LA. Poster 42065.
 
18. Paller A, Mendes-Bastos P, Eichenfield LF, et al. Efficacy and safety of upadacitinib in adults and adolescents with moderate-to-severe atopic dermatitis: subgroup analysis of the Measure Up 1, Measure Up 2, and AD Up phase 3 clinical trials at 52 weeks. Poster presented at: American Academy of Dermatology (AAD) Annual Meeting; March 17-21, 2023; New Orleans, LA. Poster 43049.
 
19. Silverberg JI, Deleuran M, Gold LS, et al. Sustained improvement over 52 weeks in patient-reported itch, symptoms, and quality of life with upadacitinib in patients with atopic dermatitis: results from phase 3 studies (Measure Up 1, Measure Up 2, and AD Up).Poster presented at: American Academy of Dermatology (AAD) Annual Meeting; March 17-21, 2023; New Orleans, LA. Poster 42262.
 
20. FDA requires warnings about increased risk of serious heart-related events, cancer, blood clots, and death for JAK inhibitors that treat certain chronic inflammatory conditions. News release. US Food and Drug Administration. Updated January 14, 2022. Accessed April 3, 2023. https://www.fda.gov/drugs/fda-drug-safety-podcasts/fda-requires-warnings-about-increased-risk-serious-heart-related-events-cancer-blood-clots-and-death
 
21. Fu Y, Lin Q, Zhang Z, Zhang L. Therapeutic strategies for the costimulatory molecule OX40 in T-cell-mediated immunity. Acta Pharm Sin B. 2020;10(3):414-433. doi:10.1016/j.apsb.2019.08.010
 
22. Simpson E, Williams A, Chong C, Esfandiari E. Rocatinlimab demonstrates improvements in patient-reported outcomes in adult patients with moderate–severe atopic dermatitis in a phase 2 trial. Poster presented at: American Academy of Dermatology (AAD) Annual Meeting; March 17-21, 2023; New Orleans, LA. Poster 42942.
 
23. Weidinger S, Cork M, Reich A, et al. Safety of amlitelimab in a phase 2a clinical trial of patients with moderate-to-severe atopic dermatitis.Poster presented at: American Academy of Dermatology (AAD) Annual Meeting; March 17-21, 2023; New Orleans, LA. Poster 41343.
 
24. Hydol-Smith J, Sivesind T, Burnette C, Adelman M, Dellavalle R. Prescribing patterns of dupilumab for atopic dermatitis: an analysis of the AAD DataDerm database.Poster presented at: American Academy of Dermatology (AAD) Annual Meeting; March 17-21, 2023; New Orleans, LA. Poster 44482.

Posted by Haymarket’s Clinical Content Hub. The editorial staff of Dermatology Advisor had no role in this content’s preparation.

Reviewed April 2023