The treatment pipeline for dermatologic diseases is full of excitement, with several new promising therapeutics on the horizon. David Altman, MD, FAAD, provided an overview of these therapies, discussing the basic science and supporting evidence, at the Society of Dermatology Physician Assistants Annual Summer Dermatology Conference 2021 in Chicago, IL.

First, Dr Altman discussed Janus kinase (JAK) inhibitors. “What you need to know is that the JAK protein is on the inside of the cell, and it tells the cell to start transducing whatever signal it is based on the cytokine that binds to the receptor. The [JAKs] are paired, and the JAK pairs are pretty specific for different receptors,” explained Dr Altman.

In psoriasis, tofacitinib has been studied in topical formulation, though with marginal results likely due to the vehicle (oral dosage previously was not approved by the FDA for psoriasis); ruxolitinib (inhibits JAK1 and JAK2) has also shown some efficacy in phase 2 trials. Based on two large phase 3 trials, deucravacitinib (inhibits TYK2) seems to be a promising medication for both psoriasis and psoriatic arthritis.

For atopic dermatitis (AD), baracitinib, topical ruxolitinib, upadacitinib (JAK1), deucravacitinib, and abrocitinib (JAK1) are under FDA review. Each of these drugs, particularly the second-generation JAK inhibitors of abrocitinib and upadacitinb, have strong efficacy and overall tolerability, though each shows a generally higher rate of herpes zoster. Dr Altman recommended having patients with AD who may be candidates for these oral medications receive the shingles vaccine.

JAK inhibitors for alopecia areata (AA) have a lot of potential. Dr Altman noted that the science of AA is still relatively unknown, but it could be very possible that the pigment cells being attacked, as supported by patients who grow back white hair after initiation of JAK inhibitor treatment. Though most of the data come from anecdotal and small case series, approximately 70% of patients with AA responded to tofacitinb. However, the most studied so far is baricitinib, which has demonstrated good efficacy with greater than 80% regrowth in one-third of patients in the most recent trial results.

Vitiligo is another target for JAK Inhibitors, which is thought to be primarily affected by interferon gamma. So far, topical ruxolitinib and oral tofacitinb showed roughly 58% improvement across nine pooled studies.

“In my own opinion here…I think we’re going to have some black box warnings,” said Dr Altman of oral JAK inhibitors. The serious adverse events include venous thromboembolism, increased herpes zoster, and increased infections. Common class-related side effects, regardless of the condition being treated, are acne and increased cholesterol.

Switching gears, Dr Altman covered monoclonal antibodies, which he said he prefers because these agents are more selective. One exciting development is bimekizumab, a humanized IgG monoclonal antibody that targets IL-17A and IL-17F; in clinical trials for psoriasis, many patients achieved PASI 100 and ACR 70. Nemolizumab, which blocks the receptor for IL-31 (a byproduct of T_H2 cells and though to be an itch mediator), has demonstrated significant effect on AD and itch. This IL-31 inhibitor may also be promising for prurigo nodularis. Tralokinumab and lebribizumab, both of which block IL-13, are additional options in development.

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