Jakinibs for AD in Asians: Is one better than the other?

Treatment with oral Janus kinase (JAK) inhibitors or jakinibs appeared well tolerated in patients with atopic dermatitis  (AD) as shown in an Asian retrospective cohort study.

Of the three oral jakinibs studied, abrocitinib and upadacitinib appeared more effective compared with baricitinib over 12 weeks, said Dr Yik Weng Yew, senior consultant dermatologist at the National Skin Centre, Singapore.

Jakinibs inhibit the activity of one or more of the JAK family of enzymes (JAK1, JAK2, JAK3, TYK2), thereby interfering with the JAK-STAT signalling pathway.

Abrocitinib is an oral once daily JAK1 selective inhibitor. Upadacitinib is an oral, small-molecule JAK inhibitor that has greater inhibitory potency for JAK 1 than JAK 2, JAK 3, or tyrosine kinase. Both drugs were US FDA-approved for moderate-to-severe AD. Upadacitinib approval for AD in patients 12 years and older is supported by three pivotal studies (MEASURE Up 1 and 2, and AD UP).

Baricitinib is also an oral JAK inhibitor (JAK1 and JAK2).

AD can be persistent in most patients and various treatments may be needed to control the disease. Even with treatment success, symptoms may return. Patients with AD need several options and until a few years ago, clinicians did not have any systemic treatments safer than immunosuppressants such as cyclosporin and methotrexate. Until recently, the only approved drug for AD was oral prednisone but with safety concerns.

12-week efficacy

Yew and his team analysed the 12-week efficacy of oral JAK inhibitors in this Asian cohort with AD seeking consultation at the National Skin Centre in Singapore. All received either one of the three jakinibs from July to December 2022. [WCD 2023, abstract LB05]

Outcome measures assessed included body surface area (BSA), investigator global assessment (IGA), itch scores, and self-reported improvement. The known adverse effects of JAK inhibitors were also assessed.

Forty-two patients received either abrocitinib 100 or 200 mg (n=13), baricitinib 4 mg (n=19) or upadacitinib 15 or 30 mg (n=10). Mean age of the patients was 35.1 years; 64 percent were male. Over 90 percent were Chinese. Eleven patients had used more than one JAK inhibitors.

Treatment responses

Overall, patients had good treatment responses with oral jakinibs. The response rates (reduced BSA or IGA 2 or below) with abrocitinib, baricitinib, and upadacitinib were 76.9 percent, 32.2 percent, and 80 percent, respectively, at week 12.

By and large, oral jakinibs were well tolerated. More than half reported mild pustular form of acne. Six patients had increased serum creatinine kinase but were asymptomatic. Three patients had abnormal haematological abnormalities while four developed uncomplicated herpes zoster. Other common adverse effects included headache and abdominal bloating.

Oral JAK inhibitors appeared to have good effect on itch response as well.

Larger sample size with longer follow-up and in the form of a treatment registry would be encouraged to monitor long-term efficacy and adverse effects, Yew concluded.