Clinical Edge Journal Scan

Commentary: IL-31 inhibitor, e-cigarettes, and upadacitinib in AD, April 2023

Dr. Feldman scans the journals, so you don’t have to!

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Steven R. Feldman, MD, PhD

Writing in the American Journal of Clinical Dermatology , Silverberg and colleagues describe the efficacy and safety of dupilumab in over 2000 patients aged 60 years or older with atopic dermatitis who were treated in clinical trials. Not surprisingly, dupilumab worked well in these older patients and was both effective and safe.

Good news! There's not a lot to say about this. Dupilumab is so easy. No blood work, no immunosuppression. Dupilumab is highly effective and very safe. It's safe enough for children as young as 6 months! It's so effective that if it is not working, I question my diagnosis (Could it be contact dermatitis or mycosis fungoides instead?) and whether the patient is taking the medication properly.

Boesjes and colleagues describe in Acta Dermato-Venereologica the Dutch experience with upadacitinib in patients who have not been successfully treated with dupilumab or baricitinib. Presumably, such patients, because treatment with dupilumab or baricitinib or both was unsuccessful, have very resistant atopic dermatitis (either due to strong genetic propensity or perhaps because they don't take their medications). Despite having such refractory disease, most patients did well on the treatment with rapid disease improvement. Upadacitinib didn't work for everyone, though. About 30% of the patients di scontinued upadacitinib treatment due to ineffectiveness, adverse events, or both (8.5%, 14.9%, and 6.4%, respectively).

How much of that ineffectiveness was due to poor adherence to taking the treatment was not assessed. Upadacitinib is extraordinarily effective for atopic dermatitis. I didn't think I would ever see a drug more effective than dupilumab for atopic dermatitis, but a low dose of upadacitinib (15 mg/day) seems about twice as effective as dupilumab for complete clearing of atopic dermatitis. The higher dose of 30 mg may be 3.5 times as effective as dupiliumab at getting atopic dermatitis completely clear. 1

I dislike the word significant. Significant is ambiguous. It could mean that an observed association would not be likely to occur by chance, or it could mean that an observed association is clinically meaningful. Smith and colleagues in "A ssociation between electronic cigarette use and atopic dermatitis among United States adults" reported finding a "significant" association between e-cigarette use and atopic dermatitis. A total of 23% of 2119 e-cigarette users had atopic dermatitis vs 17.1% of 26,444 nonusers. Clearly, the observed association was statistically significant (the 6% difference was not likely to occur due to chance alone). Is the finding clinically meaningful? I don't think it would affect our practice in any way.

The authors made the point that the study doesn't tell us whether e-cigarette use causes atopic dermatitis or if atopic dermatitis causes people to smoke. I wonder if just being younger (or some other factor) might make people more likely to use e-cigarettes and more likely to have atopic dermatitis (assuming atopic dermatitis gradually subsides over time, a dogma that may not be true).

Kabashima and colleagues report on the efficacy of the interleukin (IL)–31 antagonist nemolizumab. IL-31 mediates itch and having a new drug to block IL-31 may be a great treatment for our itchy patients. In this study, patients who had greater itch reduction had greater improvement in eczema and in quality of life. I'm quite sure that reducing itch improves patients' quality of life. But when it comes to the itch and the inflammation, I'm not sure which comes first. Does controlling the itch make the inflammation better? Maybe. Does controlling inflammation make itch better? Certainly.

For atopic patients with inflammation, controlling that inflammation seems to me to be the best approach, and we don't need more new treatments to accomplish that. For those patients who have a lot of itch and little inflammation, an IL-31 antagonist may be a revolutionary addition to our treatment options.

Additional References

1. Blauvelt A, Teixeira HD, Simpson EL, et al. Efficacy and safety of upadacitinib vs dupilumab in adults with moderate-to-severe atopic dermatitis: a randomized clinical trial. JAMA Dermatol. 2021;157:1047-1055. doi: 10.1001/jamadermatol.2021.3023. Erratum in: JAMA Dermatol. 2022;158:219. doi: 10.1001/jamadermatol.2021.5451

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