A group of experts from Australia and New Zealand has published over 100 clinical practice statements regarding the use of JAK inhibitors in atopic dermatitis.
Unsure about how to best use JAK inhibitors in atopic dermatitis? The Australasian Medical Dermatology Group has a wealth of helpful suggestions.
JAK inhibitors have been shown to be safe and effective for the treatment of atopic dermatitis, but there is little practical advice regarding their use.
To address this shortcoming, the Australasian Medical Dermatology Group – a collective of roughly a dozen experienced dermatologists – has developed a consensus collection of clinical practice statements regarding the use of JAKis in Australasia and published its findings in the Australasian Journal of Dermatology.
Clinical Associate Professor Kurt Gebauer, an AMDG member who contributed to the development of the clinical practice statements, described the process as a great learning experience.
“Since we all know each other, there’s no agendas – everyone’s quite happy to talk. I know what I’m doing, but [sometimes] I have no idea what they’re doing in Melbourne or Sydney,” the Western Australian-based senior medical dermatologist told Allergy & Respiratory Republic.
Dr Marius Rademaker, the lead author of the new publication, agreed that the consensus process went well.
“The workshop itself was quite invigorating – engagement was very high, and it really demonstrated the experience and knowledge of the workshop members,” the New Zealand-based dermatologist said.
“This allowed a wider acceptance of other people’s clinical practice, for example, ‘whilst I wouldn’t do that test, I understand that you find comfort in doing that test is reasonable’.”
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The group undertook a literature review that yielded 90 clinical trials, systematic reviews and meta-analyses exploring the use of JAKis in atopic dermatitis. These publications were combined with the group’s collective expertise to prepare 133 clinical practice statements that were voted on as part of a Delphi process.
Professor Gebauer felt the Delphi process was now considered a more acceptable way of getting people together and forming a consensus view, rather than a smaller group of authors going it alone.
“I think the process is a lot more social, and the results are a lot more acceptable to readers when they can see a group of 10 or 12 people and they recognise most or all of the names,” he said.
The statements fell into several distinct groups, including screening, vaccination, monitoring, starting and stopping a JAKi, concomitant therapies and the use of JAKis in children. One item was removed part way through the process as the group felt it was a repeat of two other statements, leaving a total of 132 statements.
After two rounds of deliberation, a complete consensus (defined as all group members scoring the statement as a minimum of 7 on a nine-point Likert scale, where 1-3 represents disagree and 7-9 represents agree) was achieved on 42 of the 132 items (32%), a close consensus (where a at least 75% of members scored the item 7-9) was achieved on 85/132 items (64%) and no consensus was formed on the remaining four items (3%).
Examples of statements where the group reached a complete consensus were:
- Pre-JAKI treatment screening should involve investigation for metabolic health, including triglycerides and cholesterol.
- Starting a JAKi should be delayed if the:
- Total white blood cell count is less than or equal to 2500/μL
- Absolute neutrophil count is less than or equal to 1200/μL
- Absolute lymphocyte count is less than or equal to 750/μL
- Platelet count is less than or equal to 100,000/μL
- Haemoglobin is less than or equal to 9g/dL
- Pre-JAKi treatment should include recommendation for vaccination against varicella or shingles, as immunisation with live vaccines is relatively contraindicated in patients who have already commenced JAKi treatment.
- Common treatment emergent adverse events with JAKi include acne vulgaris, acneiform eruptions (JAKneiform eruption or JAKne), nausea, headache, upper respiratory tract infection (URTI), herpes simplex and herpes zoster infection, and mild laboratory test abnormalities.
- When used for dermatology indications, there does not appear to be an increased risk of malignancy, other than possibly non-melanoma skin cancer, but long-term safety data are still immature.
Statements where the group reached a close consensus included:
- The core pre-JAKi treatment investigations should include full blood count, renal and liver function tests, screening for TB (e.g., Interferon-gamma release assays (IGRAs), HIV, and Hepatitis B and C).
- Delay starting a JAKi if:
- Serum aspartate transaminase (AST) or serum alanine transaminase (ALT) is greater than 2-3× upper limit of normal
- The estimated glomerular filtration rate (GFR) is less than 30-40 mL/min/1.73 m2
- Annual vaccination against Sars-Cov-2 (covid-19) and seasonal influenza are strongly recommended (using age-specific national vaccine guidelines).
- Annual full-skin examinations are recommended.
- The starting dose of a JAKi should be based on individual patient characteristics.
- Initial treatment of a flare of atopic dermatitis, whilst on a JAKi ,should include a topical corticosteroid and/or a topical calcineurin inhibitor, depending on the body site.
The four items the group were unable to come to a consensus on were:
- Pre-JAKi treatment screening should involve assessment of antibody status for varicella zoster.
- After commencing a JAKi, full blood count and liver enzymes should be done at week four then every three months.
- More frequent cervical cancer screening (i.e., reduced intervals between screening) should be considered for people with a cervix on JAKi (e.g. annual cytology-based screening or three-yearly HPV swab screening).
- If increasing the dose of the JAKi does not improve Eczema Area and Severity Index (EASI) or Dermatology Life Quality Index (DLQI) scores sufficiently, consider a short course (one to three weeks) of a systemic steroid.
Dr Rademaker was pleased with the consensus reached by the group, but noted there were still differences in opinion between members.
“On a personal level, I was happy to be more aggressive in using concomitant systemic therapies in slow/poor responders but acknowledged that the evidence base for such is low/non-existent, particularly around the lack of safety data,” he told ARR.
“I was [also] slightly disappointed in the watering down of the statement on agreeing minimal and aspirational goals with the patient but again acknowledge the additional time element required for doing this in an already busy clinic.”
While happy with the process and the outcome, Professor Gebauer highlighted that this “living” consensus would continue to develop and evolve over time.
“There’s going to be a flood of research coming out of Europe… so what’s going to happen in a year or two is that [this process] will need to be repeated, because we’ll have a lot more information and a better understanding. But this is what we’re doing at the moment; this is what we think is reasonable,” he said.
Professor Gebauer hoped that the consensus statements would reassure healthcare practitioners that JAKis were safer and more effective than previous treatment options for atopic dermatitis.
“[These statements] give our colleagues with less experience the freedom to contact us and ask about what we are doing with these medications, which hopefully demystifies them,” he said.
“It would be terrible for patients to go untreated because the doctor looking after them didn’t feel comfortable using JAKis.”
Dr Rademaker felt there were two outstanding issues regarding the use of JAKis for the treatment of atopic dermatitis – the cost (which would result in inequity with respect to accessing the treatment) and the lack of certainty around how long patients should be treated for.
Dr Diana Rubel, a dermatologist from Woden Dermatology in the ACT, echoed Dr Rademaker’s concerns about ensuring patients have access to JAKis.
“Equitable access is a separate issue to suitability, efficacy and safety – but it needs to be addressed and will ultimately lead to more experience and real-world evidence,” the principal investigator at Paratus Clinical Woden told ARR.
