Eligibility and selection of JAK inhibitors for constitutional eczema

“In recent years, 3 JAK inhibitors, baricitinib, upadacitinib, and abrocitinib, have become available for the treatment of constitutional eczema,” said Dr Dirk Jan Hijnen (Erasmus MC, the Netherlands) [1]. “Other targeted therapies available to treat this condition are the biologic therapies dupilumab and tralokinumab.” According to Dr Hijnen, dupilumab is the most frequently prescribed first-line targeted therapy, since clinicians have the longest experience with this agent. During his presentation, Dr Hijnen discussed eligibility for these newer agents and the selection process for each of them.

When to choose a JAK inhibitor?

The Dutch guidelines dictate that patients should first receive intensive local therapy to treat their constitutional eczema [2]. If this treatment does not lead to the intended treatment result, a ‘classic’ systemic therapy should be prescribed, being either methotrexate, cyclosporin A, azathioprine, or enteric-coated mycophenolate sodium. If this first systemic therapy fails after 16 weeks, 1 of the available biologic therapies or JAK inhibitors should be considered.

“How does one choose between the various available targeted therapies?” asked Dr Hijnen. “First, women who wish to have children should receive either cyclosporin A or azathioprine. Second, patients over 65 years of age, patients who have a history of cancer, those with high risk for thromboembolic events, or patients who have a long history of smoking cigarettes, should preferably receive 1 of the biologic therapies, in my opinion. If all these criteria are not applicable, either a JAK inhibitor or a biologic therapy could be selected.”

Dr Hijnen added that biologics are injected therapies, which may be less convenient for the patients than the orally administered JAK inhibitors. On the other hand, JAK inhibitors require lab testing and screening, which slows down the initiation of the therapy. “Patients with concurrent asthma may experience alleviation of both eczema and asthma from biologics, whereas patients with concomitant conjunctivitis may benefit more from JAK inhibitors,” explained Dr Hijnen. Finally, JAK inhibitors usually result in a swift reduction of itching of the skin, whereas the effect of biologics takes weeks or months to kick in. When opting for a JAK inhibitor, several considerations should be made to select the right JAK inhibitor for the right patient.

Selecting the right JAK inhibitor for the right patient

“In my opinion, the largest difference between baricitinib on the one side and upadacitinib and abrocitinib on the other side is the displayed efficacy in clinical trials, favouring upadacitinib and abrocitinib over baricitinib,” stated Dr Hijnen. He added that baricitinib may be more effective in patients over 60 years compared with younger patients because it inhibits a relatively broad range of cytokines. “In young patients with severe eczema, I prefer to initiate with a high dose of either upadacitinib (30 m daily) or abrocitinib (200 mg daily) and reduce these doses to 15 mg and 100 mg when the clinical situation allows these reductions.”

For patients >65 years or those with risk factors such as obesity or a history of smoking, Dr Hijnen would start with a lower dose of 1 of these agents. Furthermore, he said that screening for latent tuberculosis should be done before the initiation of therapy with JAK inhibitors, because the re-activation of tuberculosis may be atypical while being treated with JAK inhibitors. He also explained that patients with herpes zoster or herpes simplex should interrupt their intake of JAK inhibitors, possibly start therapy with valaciclovir, and re-start JAK inhibitor therapy when the patient does not show new symptoms, which is generally within 1 to 2 weeks.

Another consideration is acne, which is a possible side effect of JAK inhibitors. “There is no one-size-fits-all therapy for this JAK inhibitor-induced acne,” mentioned Dr Hijnen. “Normally, we follow standard acne therapies. However, I would recommend having at least 2 different JAK inhibitors in the therapeutical arsenal, so one has the option to switch if these kinds of side effects occur. In practice, I see that the selectivity of upadacitinib and abrocitinib is relative and that patients respond differently to these agents.” Dr Hijnen concluded that there are currently no known absolute contra-indications to JAK inhibitors in the dermatological populations.

1. 
   
   1. Hijnen DJ, et al. JAK remmers voor de behandeling van constitutioneel eczeem. Blok 3, Dermatologendagen 2023, 9–10 March, Ermelo, the Netherlands.
   2. Richtlijn Constitutioneel eczeem 2019. Retrieved from https://nvdv.nl/professionals/richtlijnen-en-onderzoek/richtlijnen/richtlijn-constitutioneel-eczeeml [Accessed on 14 March 2023].

 

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Posted on 10 May, 202328 March, 2024