Janus Kinase Inhibitors Successfully Combat Psoriasis, Inflammatory Diseases, Review Finds

A recently published review in Frontiers in Immunology highlights the efficacy of Janus kinase (JAKs) inhibitors as treatments for several dermatological ailments, including psoriasis.

Authors described how newly researched pathologic factors have changed therapeutic practices used to treat inflammation and autoimmunity.

Interactions among cytokines, immune, and tissue cells are responsible for propagating inflammation in the skin, they explain. “Multiple cytokine receptors signal through JAKs and associated signal transducer and activators of transcription (STATs). Inhibition of JAKs can simultaneously block the function of multiple cytokines,” said the authors.

For this reason, JAK inhibitors are an emerging new class of drugs, capable of being administered both orally and topically. In the review, authors outline the immunological basis and current development stages of JAK inhibitors, pointing out their effective treatment of conditions such as atopic dermatitis and vitiligo.

“A variety of monoclonal antibodies (mAbs) targeting cytokines and small molecules interfering with intracellular signaling pathways have been developed,” the authors wrote. These recent breakthroughs can help combat diseases like alopecia areata, hidradenitis suppurativa, and psoriasis.

Specifically, “the implication of multiple cytokines…in psoriasis pathogenesis suggests that the inhibition of JAKs could be a powerful and more profound treatment than a treatment with a single mAb.” The authors also noted that JAKi tend to have lower production costs than mAbs, making them a more favorable option for dermatologists.

Studies have been conducted in both mice and humans with psoriasis. Both have yielded positive results due to the administration of JAK inhibitors. In addition, in the study conducted on humans only 6% of the patients treated reported adverse effects.

Based on the research, authors noted that oral administrations were superior to topical remedies. Multiple clinical trials are underway to test both forms.

“The expected results…will be a major step toward extending the therapeutic spectrum of psoriasis and psoriasis arthritis by oral compounds,” the authors said.

The anti-inflammatory properties of the treatment have been illustrated on multiple occasions, but authors urge caution due to the lack of long-term studies conducted on JAK inhibitors.

“We urgently need more evidence and larger double-blind placebo-controlled studies to confirm efficacy and safety of JAKi,” they said. Additionally, the simultaneous inhibition of multiple cytokines resulting from a systematic administration of JAK inhibitors “bears the risk for fatal outcomes during severe infections and possibly also the risk for cancer development on the long run.”

Reference

Solimani F, Meier K, Ghoreschi K. Emerging topical and systemic JAK inhibitors in dermatology. Front Immunol. 2019;10:2847. doi: 10.3389/fimmu.2019.02847.