New Document Guides Clinical Decision-Making on Atopic Dermatitis Treatment – Medpage Today

A recent review has found that high-dose upadacitinib is among the most effective therapies for addressing multiple outcomes in moderate-to-severe atopic dermatitis (AD), but is also among the most harmful. High-dose abrocitinib and low-dose upadacitinib are effective, but also among the most harmful.

The review included 149 trials, comprising 28,686 patients with moderate-to-severe AD and 75 separate interventions. It was undertaken to inform forthcoming AD treatment guidelines from the American Academy of Allergy, Asthma & Immunology and the American College of Allergy, Asthma & Immunology.

High-dose upadacitinib was effective in 5 of 6 patient-important outcomes. JAK inhibitors, meanwhile, significantly increased adverse events. With high-certainty, dupilumab, lebrikizumab, and tralokinumab were of intermediate effectiveness and among the safest. Low-dose baricitinib was among the least-effective therapies.

As part of the report, published in The Journal of Allergy and Clinical Immunology, investigators created a summary Table designed for use in patient interactions and clinical decision-making. One of the investigators was Derek Chu, MD, PhD, a dermatologist-researcher and assistant professor of medicine with McMaster University Faculty of Health Sciences in Canada. Chu's discussion with the Reading Room has been edited for length and clarity.

What was the impetus for conducting this review?

Chu: There are quite a number of patients with mild to moderate eczema whose condition remains uncontrolled despite topical treatments and good skin care. Dermatologists face a big challenge in determining the best option for these patients.

So, we needed to get to the bottom of how we inform patients and clinicians about what's the next best step if topical treatments are not cutting it. That's what our comparative efficacy and safety analysis, or network meta-analysis, set out to do.

Can you walk through your findings? They were quite comprehensive.

Chu: There are a number of key medications to look at. First, there are some classical medications that we've been using for a long time: immunosuppressants. For many of these, the existing trials are small, at risk of bias, and have limitations, so we don't actually have full confidence in how good they are. Anecdotally, we have a lot of clinical experience, but the best options available are cyclosporine and methotrexate and, much less so, other drugs such as azathioprine or mycophenolate.

Light therapy, even ultraviolet therapy, does have some decent effects, But we are less certain about many treatments because the trials just weren't as big and weren't as well done and they didn't measure all patient important outcomes.

How about some of the newer agents, such as JAK inhibitors?

Chu: In the past 10 years or so, we've really seen a revolution in AD care. There are new drugs, such as biologic medications and monoclonal antibodies, that have really changed the game. Among the most effective and safe were the biologics such as dupilumab. Following that, slightly less effective were tralokinumab and lebrikizumab.

They're also very safe. So, really little to no harms, except for some conjunctivitis that would happen in about 7%-8% of individuals, and that can be managed.

There are even newer drugs -- oral JAK inhibitors -- that are very effective. A number of these were even more effective than the biologics in improving multiple patient outcomes. They improved everything from the actual skin signs of the eczema, to how the patient feels, to how much itch they experience and their quality of life. The downside, however, is these agents also increase the number of harms; these include only abdominal pain and infections, but also they also have a black box warning of increasing serious harm, such as malignancy, death, and/or cancer. We're really uncertain about the safety of these drug in the long-term. They might be completely safe, but we just don't have enough data yet to robustly say exactly where they fall.

This review was created with the bedside in mind. How can it help clinicians manage people with AD who may need to explore systemic treatment options?

Chu: This review includes a Table summary that can easily be used at the bedside to shape clinical decision-making and discussions with patients.

This review could inform clinicians on what to do if they don't have access to these expensive medications, like biologics and oral JAK inhibitors, and how to make the best choice among the limited options. And if you do have access to all of them, how do you choose between things like biologics alone? About oral JAK inhibitors? Which one falls out better than the others?

I think this can be quite an interesting review and really helpful.

Chu did not disclose any relevant financial relationships with industry.

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New Document Guides Clinical Decision-Making on Atopic Dermatitis Treatment - Medpage Today