Why the Conversation Is the Real Hurdle
Buchi Neita, PA-C, and Shanna Miranti, PA-C open by naming what many APPs actually fear about JAK inhibitors: not the drugs themselves, but the patient conversation. As Neita puts it, his early hesitation "wasn't so much with the JAKs themselves and their potential adverse reactions" — it was figuring out how to "coast through this without scaring the patient away." Both hosts agree that finding small tips and tricks to guide that discussion has raised both their confidence and their patients' confidence.
Miranti notes that when JAK inhibitors first arrived for atopic dermatitis, many PAs and NPs were shy about prescribing them and felt more comfortable with biologics. That has shifted as the class has expanded across multiple disease states. She points out that alopecia areata was a turning point for adoption: with three oral JAKs (baricitinib, ritlecitinib, and deuruxolitinib) as the only FDA-approved options, many APPs gained comfort using JAKs there first because there were simply no other choices.
The Expanding JAK Landscape and How They Work
The hosts walk through the current approvals. For atopic dermatitis: upadacitinib and abrocitinib (oral, ages 12 and up) plus topical ruxolitinib cream (ages 2 and up). For alopecia areata: three oral agents. For non-segmental vitiligo: topical ruxolitinib cream (ages 12 and up, with pediatric trials ongoing). For chronic hand eczema: topical delgocitinib, a pan-JAK inhibitor. Neita flags that more is coming, including a soon-to-arrive oral agent expected for HS and vitiligo, and expresses excitement about the potential in conditions like cutaneous lupus where "we've had really nothing."
Miranti offers a quick mechanism refresher: JAKs are small molecules, so whether oral or topical, they penetrate the phospholipid bilayer without needing a cytokine receptor. There are four — JAK1, JAK2, JAK3, and TYK2 — and blocking them stops the STATs from docking and carrying the pro-inflammatory signal to the nucleus. She adds a practical point: failing one JAK inhibitor doesn't mean the others won't work, even within the same condition.
Lead With the Benefits: Speed, Efficacy, and Steroid Relief
Neita's advice is to lead with the benefits, because that's what engages patients. In AD, upadacitinib and abrocitinib deliver some of the highest efficacy scores, with many patients reaching over 90% clinical improvement and head-to-head data against dupilumab. Miranti emphasizes the rapid onset — the "jackrabbit start" — which matters enormously for AD patients who are miserable with itch and want fast relief.
Both hosts frame JAKs as a way out of chronic steroid reliance. Neita describes prescribing a topical JAK that same day for a patient used to triamcinolone, noting the relief of offering "something comparable to these steroids without all of the side effects." Miranti also raises the emerging role of gene rearrangement testing from a lesion scraping to identify better JAK responders — a nod to personalized medicine, though she notes she hasn't used it yet.
Putting the Box Warning in Context
Miranti explains that the boxed warning on JAK inhibitors — including topical ruxolitinib, though notably not delgocitinib — originates from the ORAL Surveillance trial. That was a randomized, open-label post-marketing safety study of tofacitinib in rheumatoid arthritis patients who were over 50, often current smokers, frequently with prior cardiovascular history, and already on methotrexate. Patients were randomized to tofacitinib or a TNF inhibitor. "Patients that had comorbidities did have some bad outcomes," she summarizes, and that produced the "JAK five": serious infection, MACE, all-cause mortality, malignancy, and thromboembolic events like DVT or PE.
Neita counters with dermatology-specific reassurance: he cites a JAMA Dermatology meta-analysis of 35 randomized clinical trials showing no increased risk of MACE, VTE, or all-cause mortality versus placebo in the derm population, which tends to be younger and healthier than rheumatology patients. Both stress that the warning still warrants a conversation — especially for patients over 50, smokers, or those with cardiovascular risk — and that documenting that discussion is essential. Neita reframes monitoring as a benefit: regular labs and check-ins can prompt patients to stay on top of cholesterol, cancer screenings, and primary-care basics they might otherwise skip.
The Risks That Actually Matter in Derm — and the Monitoring Checklist
Miranti calls herpes zoster reactivation the most clinically significant infection risk and recommends vaccination for essentially every candidate, including patients under 50. Beyond that, the hosts describe common but manageable adverse events: "JAKne" (JAK-induced acne, the most common AE across trials and something dermatology providers are well equipped to treat), plus nausea, headache, nasopharyngitis, and elevated CPK. They point to long-term data showing stable adverse events with upadacitinib from year one to year five. A key reminder: oral JAKs are contraindicated in pregnancy and breastfeeding, though contraception is not required to prescribe.
For initiation, the hosts recommend a saved, easily accessible checklist: CBC, liver function, lipids, viral hepatitis and tuberculosis screening, pregnancy testing when needed, shingles vaccination, and any age-appropriate vaccines (get live vaccines done before starting, especially in pediatric patients). Follow-up labs vary — some at four weeks, some at 12 — so check the product label, and continue annual skin cancer screenings. Dosing can start high and taper or start low and increase, adjusted for age, severity, and patient preference.
Shared Decision-Making: Slugs, Sledgehammers, and the Long Game
Neita borrows an analogy he attributes to Dr. Hilary Baldwin: some patients are "slugs" who are patient and prefer lower-efficacy, higher-safety options, while others are "sledgehammers" who need fast relief because their disease is crushing their quality of life. Sometimes, he adds, you have to be the sledgehammer for the patient — waking them up to the fact that it is not normal to be up itching several times a night, and reassuring underestimating patients that they genuinely qualify for these therapies.
Miranti closes on the chronic-disease framing. AD, alopecia areata, and non-segmental vitiligo won't "poof disappear," so she sets expectations up front that treatment may last years. She likes the diabetes-and-insulin analogy to help patients understand why they shouldn't stop once they feel better. In the end, both hosts return to the same theme: efficacy and safety data inform the decision, but it lives between the clinician and the patient, and increasingly, with patients arriving armed with AI-generated questions, knowing how to have this conversation confidently matters.