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Betty Bellman from Dermatologist Nation, Ellen Gordon from Dermatologist Nation Commented on a Post
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JAK Inhibitors in Atopic Dermatitis

Atopic dermatitis (AD), also known as atopic eczema, is a chronic, pruritic, relapsing inflammatory dermatological condition. The exact cause of the disease is unknown; however, certain factors such as epigenetic, genetic, immunological, and environmental interactions with overlapping skin barrier defects are indicated in its pathogenesis.

Oral Janus kinase (JAK) inhibitors have been approved for use in treating patients with rheumatoid arthritis and other inflammation & immunity disorders. Signaling proteins linked to cytokine receptors activate transcription factors, called signal transducer and activator of transcription (STAT) and modulate the expression of thousands of genes associated with inflammatory processes. JAK inhibition of type 2 cytokine signaling has recently shown pruritic benefit in clinical trials. JAK inhibition is not restricted to systemic administration but has also been developed as a topical treatment option.

• Which clinical trial endpoints would be most impactful for you in assessing a drug’s efficacy for atopic dermatitis (ex. IGA, EASI, SCORAD, pruritus, QOL)?
• In what patient subset or severity would you consider using a JAK inhibitor?
• Would the availability of a topical JAK impact the prescribing trends for topical calcineurin inhibitors or crisaborole?


Reference: https://www.cell.com/action/showPdf?pii=S0092-8674%2817%2930931-5 

  • from Dermatologist Nation 6 days 3 hours
    If the QOL & pruritus are severe, I would consider topical JAK inhibitor Rx. This will be par with Protopic ointment and superior to Eucrisa. The patient must have exhausted all known therapies and has severe recalcitrant atopic dermatitis. The patient must have tried and failed Dupixent. Then, if they agree to the Black Box warning and multiple risks of oral JAK inhibitors, I may consider using them.
  • from Dermatologist Nation 1 week 1 day
    Any of the clinical trial endpoints would be useful if used consistently by all observers and are measurable. Consider creating graphic for each patient. Consider using more than one clinical endpoint.

    I would consider use of JAK inhibitor as second line unless there is a contraindication of first line therapy. AD severity should be a least strongly moderate or severe.

    The availabilty of topical JAK inhibitors may decrease use of other topicals but will depend on cos, if there is a blackbox warning and coverage as well as prior auth hassels.
  • from Dermatologist Nation 1 week 4 days
    -At least 2 step improvement in IGA to no worse than 0 or 1; 75% or better improvement in EASI score; no or almost no pruritus
    - Moderate to severe, unresponsive or inadequate response to topicals; probably would use Dupixent before considering oral JAK inhibitors
    - I am not a big fan of Eucrisa, and would likely use topical JAK inhibitor before calcineurin inhibitors
  • from Dermatologist Nation 1 week 5 days
    Clinical endpoints would be no pruritus: zero itching, zero scratching, no lichenified patches, no eyelid eczema. Lack of would affect QOL.
    AD would have to be the severe, after trying everything.
    Topical JAK would probably replace the other topicals
    until it has been used and studied for a few years.
  • from Dermatologist Nation 1 week 5 days
    In clinical practice 1)visual assessment by the clinician and the patients reporting of symptoms and how they impact their life are important 2) Analog itch scales are also important JAK inhibitors show high efficacy in abating signs and symptoms of inflammatory disease in the skin and joints The biggest question is whether they will carry a black box warning as a class If this occurs I think usage will be limited due to fear of incurring malpractice risk
  • from Dermatologist Nation 1 week 6 days
    Easi score and pruritus score most impactful. Would use In all subsets of AD from mild to severe. Would definitely prefer JAK inhibitor over topical calcineurin inhibitors or eucrisa due to better efficacy and tolerability