Can Janus Kinase Inhibitors Provide Relief for the Itch?

🔍 Key Finding JAK inhibitors, especially selective JAK1 inhibitors, demonstrate rapid and significant itch reduction across various dermatological conditions, including atopic dermatitis, psoriasis, prurigo nodularis, and chronic pruritus. While generally safe, potential adverse effects like infections, cytopenias, and elevated CPK levels warrant further investigation and cautious use, particularly in elderly patients.

🔬 Methodology Overview

• Design: Narrative review
• Data Sources: PubMed (until July 2022)
• Search Terms: “itch AND JAK inhibitor”, “pruritus AND JAK inhibitor”, plus disease-specific terms (atopic dermatitis, psoriasis, prurigo nodularis, chronic pruritus of unknown origin)
• Selection Criteria: English language articles focusing on JAK inhibitors and itch relief. Quantitative results for itch reduction prioritized.
• Analysis Approach: Qualitative synthesis of findings from clinical trials and case reports.
• Scope: Efficacy and safety of JAK inhibitors for pruritus in various dermatological conditions.

📊 Results Here are the key findings of the provided research article regarding the use of Janus Kinase (JAK) inhibitors for itch:

• Topical JAK inhibitors for AD: Showed significant itch reduction compared to vehicle. Tofacitinib ointment reduced itch by approximately -3 on the Numerical Rating Scale (NRS) by day 2 and -4.4 by week 4. Ruxolitinib cream and delgocitinib ointment also demonstrated significant itch improvement.
• Oral JAK inhibitors for AD: Upadacitinib and abrocitinib (selective JAK1 inhibitors) demonstrated higher response rates for itch relief than baricitinib (JAK1/2 inhibitor). Upadacitinib was found to be the most effective in a network meta-analysis.
• JAK inhibitors vs. Dupilumab for AD: Oral JAK1 inhibitors (upadacitinib and abrocitinib) appeared more effective and provided faster itch reduction than dupilumab. Upadacitinib showed a 31.4% improvement from baseline NRS scores at week 1 vs. 8.8% for dupilumab.
• JAK inhibitors for Psoriasis: Limited data available on itch specifically. Topical tofacitinib showed significant itch improvement. Oral JAK inhibitors primarily focused on PASI scores with limited pruritus assessment.
• JAK inhibitors for other conditions: Showed promise in treating refractory itch in prurigo nodularis, chronic pruritus of unknown origin, and lichen planus, based on case reports and small studies.
• Safety of JAK inhibitors: Topical JAK inhibitors generally caused mild to moderate adverse events, such as nasopharyngitis and application site reactions. Oral JAK inhibitors had a slightly higher risk of adverse events, including CPK elevations, opportunistic infections, herpes zoster, and cytopenias, but were generally comparable to biologics. Concerns remain regarding long-term safety, particularly regarding cardiovascular events and malignancies.

💡 Clinical Impact JAK inhibitors offer a rapid and effective treatment option for chronic and refractory pruritus in various dermatological conditions, including atopic dermatitis, psoriasis, prurigo nodularis, and lichen planus. This may shift clinical practice towards earlier consideration of JAK inhibitors, especially in patients unresponsive to conventional antipruritic therapies.

🤔 Limitations

• Limited long-term safety data on JAK inhibitors.
• Warnings about use in elderly people.
• Potential for increased incidence of cardiovascular diseases.
• Potential for increased incidence of malignancies.
• Higher risk of adverse effects with upadacitinib and abrocitinib compared to baricitinib.
• Limited data on pruritus in psoriasis for oral JAK inhibitors.
• Limited data comparing the safety profiles between different JAK inhibitors.

✨ What It Means For You JAK inhibitors offer a rapid and effective treatment option for chronic and refractory pruritus in various dermatological conditions, including atopic dermatitis, psoriasis, and prurigo nodularis. While generally safe, doctors should be aware of potential adverse effects like nasopharyngitis, acne, elevated CPK levels, and rare but serious events like infections and cytopenias, and consider these risks, especially in elderly patients, when prescribing JAK inhibitors. Further research is needed to fully elucidate long-term efficacy and safety compared to existing biologics.

Reference Han Y, Woo YR, Cho SH, Lee JD, Kim HS. Itch and Janus Kinase Inhibitors. Acta Derm Venereol. 2023;103:adv00869. https://doi.org/10.2340/actadv.v103.5346