Atopic Dermatitis Biologics are Working, but Precision Care Remains a Goal

Diamant Thaci, MD

Credit: International Psoriasis Society

Biologic therapies and Janus kinase (JAK) inhibitors have come to represent the burgeoning future of severe atopic dermatitis disease management; more than a half-dozen marketed agents across the drug classes are associated with significant opportunity to skin clearance and symptom relief outcomes, and long-term assessments in many cases indicate the benefit is sustained for those who do respond to the treatment.

The issue of how to treat patients who are unresponsive to said treatment has frequently been a matter of recent research. But another question to consider is whether the topline clinical research data supporting these agents’ ascension to the precedent for severe atopic dermatitis management is reflected in adequate real-world patient prescribing and sustained outcomes.

In a session during the Revolutionizing Atopic Dermatitis (RAD) 2023 Spring Conference in Washington, DC, this weekend, Prof. Diamant Thaci, MD, of the Institute and Comprehensive Center for Inflammation Medicine at University of Lubeck in Germany, reviewed the state of biologic therapies in managing real-world patients with atopic dermatitis.

“If you’re in front of a patient with moderate to severe atopic dermatitis, the first question you ask yourself is, ‘Is this a candidate for a JAK (inhibitor), or is this a candidate for a biologic?’” Thaci prosed. Of course, JAK inhibitors are currently not approved for younger pediatric patients with atopic dermatitis, and dupilumab was the first of its class to receive such an indication from the US Food and Drug Administration (FDA) for children ≥6 months old last year.

In the case of a biologic, the clinician is navigating between dupilumab and tralokinumab, Thaci explained.

He highlighted real-world evidence from the TREAT Germany trial—an assessment of one of the largest atopic dermatitis registries worldwide (>1400 patients with moderate to severe disease). The trial showed consistent short- and long-term efficacy and safety outcomes among real-world patients receiving dupilumab compared to clinical trials assessing moderate to severe disease; the rate of patients achieving Eczema Area Severity Index (EASI) 50 and 90 increased from 3 months to 12 months. Conjunctivitis impacted more than 20% of observed treated patients, while facial eczema and arthritis—worried to be potential risk factors among patients in clinical assessment—impacted <4% of patients.

Interestingly, data from the prospective, observational PROLEAD trial showed an overwhelming proportion of patients (95.1%) initiated dupilumab for moderate to severe atopic dermatitis because a lone topical therapy was insufficient in care. Another 42.3% stated it was due to the risk-benefit ratio of the biologic, and 25.7% stated it was due to the high risk of relevant adverse events associated with other systemic options.

In a similar US-based assessment, three-fourths American prescribers stated they initiated a patient on dupilumab due to previous treatment failure (74.9%); 16.1% due to disease exacerbation; and 24.8% due to atopic dermatitis severity at baseline meeting guideline standards per EASI 50 – 72.

“If you go further and look for other treatment options in the past, you might see that not a lot of people have had another different systemic treatment,” Tachi said.

Updated data from GLOBOSTAD provided further context on prior treatment usage in patients with atopic dermatitis who initiated dupilumab. Recently presented data showed just 9.5% of patients reported prior systemic therapy use for their atopic dermatitis in the last 12 months; another 2.9% had previously used a JAK inhibitor and less than half (47.2%) tried a topical corticosteroid (TCS).

Some agents including mycophenolate mofetil had virtually never been initiated in patients—either as a standard or systemic concomitant therapy—with moderate to severe atopic dermatitis who initiated dupilumab.

“We always advise at the beginning not to stop topical treatment, to continue with topical treatment, and if the patients are using a systemic treatment, do not stop it,” Thaci said. “It’s interesting that only half of the physicians have done this. The vast majority of them have used only topical treatment, and the systemic treatment was not used.”

Even more interestingly, Thaci noted from PROLEAD, is that 14.5% of patients were still receiving concomitant antihistamine at baseline with dupilumab initiation—despite evidence not critically supporting its effect on patient pruritus.

Thaci expressed belief the field has provided beneficial biologic agents to address the type 2 inflammation associated with atopic dermatitis—however, there remains untapped non-type 2 pathways that remain lesser addressed by dupilumab and tralokinumab including interleukin 17 (IL-17), IL-22, IL-12/23, IL-1. There are additionally pathogenic pathways of atopic dermatitis disease that which lack even fewer drug candidates to currently consider in the armamentarium.

What’s more, these components may simply interact uniquely within the individual patient; tailored treatment remains out of reach while not all 3 components are considered. Thaci stressed the need to learn more about atopic dermatitis phenotyping to provide pharmacotherapy development a clear blueprint—as well as clinicians a more refined guideline for prescribing strategies.

“If we find out some specific atopic dermatitis genetic information, it might be that it’ll drive toward the (appropriate inflammatory pathways),” Thaci said. “This is something that will happen in the future, and I think the future will bring us some new data and information about how we’ll select a new treatment option regarding IL-4, IL-13, IL-17, IL-31 or really the others.”

References

1. ^{Thaci D. New insights into using biologics. Presentation. Revolutionizing Atopic Dermatitis 2023 Spring Conference. April 30, 2023.}
2. ^{Butera A. FDA Approves Dupilumab as Add-On for Youngest Atopic Dermatitis Patients. Published June 7, 2022. https://www.hcplive.com/view/fda-approves-dupilumab-add-on-treatment-pediatric-ad}
3. ^{Stölzl D, Sander N, Heratizadeh A, et al. Real-world data on the effectiveness, safety and drug survival of dupilumab: an analysis from the TREATgermany registry. Br J Dermatol. 2022;187(6):1022-1024. doi:10.1111/bjd.21794}
4. ^{Thaçi, D., Bauer, A., von Kiedrowski, R. et al. Dupilumab Treatment of Atopic Dermatitis in Routine Clinical Care: Baseline Characteristics of Patients in the PROLEAD Prospective, Observational Study. Dermatol Ther (Heidelb) 12, 2145–2160 (2022). https://doi.org/10.1007/s13555-022-00791-1}
5. ^{Ferruci SM, et al. Treatment patterns and prior medication usage before dupilumab treatment initiation in patients with AD: Real-world data from GLOBOSTAD. Paper presented at: American Academy of Dermatology 2023 Annual Meeting.}