JAK Inhibitors Offer New Treatment Options for Atopic Dermatitis

Participants in a recent Pharmacy Times Peer Exchange provided an overview of atopic dermatitis, the unmet needs that remain regarding treatment, the potential use of Janus Kinase (JAK) inhibitors in managing the condition, and the critical role of pharmacists.

Peter Lio, MD, moderated the August 30, 2021, discussion. Participants included Kristen Demundo, PharmD, supervising pharmacist at Long Island Apothecary in Commack, New York; Jamie L. McConaha, PharmD, NCTTP, BCACP, CDE, an associate professor of pharmacy practice at Duquesne University School of Pharmacy in Pittsburgh, Pennsylvania; and Shannon M. Rotolo, PharmD, BCPS, a clinical pharmacy specialist at University of Chicago Medicine in Illinois.

Following the discussion in September, the FDA approved JAK inhibitor ruxolitinib (Opzelura, Incyte) to treat atopic dermatitis.

There are 2 models of atopic dermatitis, McConaha told the panel. The first suggests that atopic dermatitis is caused by genetic epidermal barrier defects that trigger abnormal keratinocyte hyperplasia. The second is immune based, suggesting that abnormal epidermal phenotype in lesional atopic dermatitis is initiated by increases in cytokines that cause these abnormalities, she said.

The JAK and signal transducer and activator transcription pathway binds the ligands to the receptors and activates JAK, McConaha said.

The highest incidence of atopic dermatitis is reported in patients aged 3 to 6 months, and most cases develop by the age of 5 years, she said.
In terms of treatment for atopic dermatitis, topical options include calcineurin, pimecrolimus, and tacrolimus, though adverse effects (AEs) include burning, erythema, and pruritus, Demundo said.

In addition, crisaborole (Eucrisa), a newer medication, helps patients achieve clear or almost clear skin, she said.

Three systemic agents used for individuals with more moderate or severe cases can also be used for those who have not responded to topical therapies, McConaha said.

One of the agents, azathioprine, has AEs that include bloating, cramping, and vomiting. The second agent, cyclosporine, has AEs such as headaches, hypertension, necrotoxicity, and tremors. Finally, methotrexate has AEs that include bone marrow suppression, nausea, and pulmonary fibrosis.

Rotolo discussed dupilumab (Dupixent), the first systemic therapy for atopic dermatitis approved by the FDA, which may cause an injection site reaction.

THERAPY SCHEDULE

“Every 2 weeks is certainly more convenient than some of the daily therapies but can be a lot more challenging in terms of adherence for patients,” Rotolo said.

The panelists discussed the different treatment options with JAK inhibitors. JAK inhibitors are a “promising new class of drug,” because they block the pathway of these enzymes, which leads to cytokine production, Demundo said.

There are oral and topical JAK inhibitors. Abrocitinib is an oral JAK inhibitor being studied in adolescents and adults that can be taken at 100-mg or 200-mg doses. Baricitinib is another oral drug with a 1-mg, 2-mg, and 4-mg dosage. Ruxolitinib (Opzelura) is a topical inhibitor that comes in a 1.5% strength and should be applied twice daily. Upadacitinib, another oral JAK inhibitor, is available in 15-mg and 30-mg strengths. Other than Ruxolitinib (Opzelura), all these drugs are still in the drug trial phase and not approved by the FDA.

Rotolo discussed the features of JAK inhibitors and the unique management of atopic dermatitis, mentioning that there may be some limitations for individuals with cardiac diseases or gastrointestinal disorders.

PHARMACISTS’ ROLE

Pharmacists have an important role in treating atopic dermatitis in terms of OTC recommendations.

“We’ve got hydrocortisone in a couple of different strengths in a couple of different formulations, in creams and in ointments,” Rotolo said.

She also discussed the importance of specifying dosages of topicals, given that the term “pea-sized amount” can mean different quantities to different individuals.

In terms of specific product lines, CeraVe and Eucerin work well to hydrate the skin, McConaha said.

Finally, if there is no improvement in a case of atopic dermatitis after 6 weeks or if it creates psychosocial disruptions, such as missed days at school or work, the pharmacist should advise the patient to see a physician, she said.