Skin diseases such as atopic dermatitis and hair loss: how jak inhibitors can help

Alfred Domke

Woman scratches her upper arm

JAK inhibitors are used primarily in rheumatoid arthritis. The medication could also help with skin diseases such as neurodermatitis, psoriasis and hair loss. (Image: Gina Sanders/stock.adobe.com)

JAK inhibitors against skin diseases and hair loss

Janus kinase inhibitors (JAK inhibitors or JAK inhibitors) are agents used particularly in moderate to severe active rheumatoid arthritis (RA). They have also produced convincing results in skin diseases such as atopic dermatitis and psoriasis. And they could also help with hair loss.

As the German Dermatological Society (DDG) writes in a recent communication, cytokines (signaling substances), enzymes and intracellular signaling pathways play a central role in inflammatory processes of dermatological diseases. Therefore, they are the focus of therapeutic approaches when it comes to disrupting these signaling pathways. In addition to antibodies, which are successfully used for moderate to severe atopic dermatitis and psoriasis, small molecules directed against Janus kinases (JAK) are increasingly being used.

Impressive effects

Inflammatory dermatoses include common skin diseases such as atopic dermatitis, psoriasis, vitiligo (white spot disease) and circular hair loss (alopecia areata). For treatment, dermatologists use systemic (internal) drugs when therapy with externally applied drugs does not respond. In addition to successfully used antibody-based therapies (biologics), impressive effects have been demonstrated in recent years with so-called small molecules, according to the DDG.

Successfully used in rheumatoid arthritis

As explained in the communication, many inflammatory dermatoses result from proinflammatory cytokines. These signaling substances are essential for the growth and differentiation of cells, and they play a role in the immune defense system.

But they are also causative in the development of autoimmune diseases. The signaling pathway involves special enzymes called Janus kinases, which phosphorylate binding sites for STAT proteins in the cell. These proteins are involved in switching certain DNA segments on and off, i.e., they control transcription during protein biosynthesis.

"The JAK-STAT pathway is key in the treatment of immunological and chronic inflammatory diseases. If we succeed in stopping pro-inflammatory cytokine cascades, this has an immediate effect on the inflammatory response," explains DDG President Professor Dr. med. Michael Hertl. This is exactly what the JAK inhibitors do by occupying the STAT docking sites and interrupting the signaling cascade.

The approach of inhibiting cytokines is not new. In comparison to biologics, which also inhibit cytokines, JAK inhibitors are directed not only against individual cytokines, but against several cytokines at once. JAK inhibitors have been used successfully for several years in rheumatoid arthritis; they have also produced convincing results in moderate to severe atopic dermatitis and psoriasis, leading to the approval of several JAK inhibitors in the EU.

Also promising for inflammatory skin diseases

"However, these system therapeutics are also promising for other inflammatory skin diseases, such as alopecia areata (circular hair loss), and furthermore for severely itchy skin diseases," says Hertl, director of the Department of Dermatology and Allergology at Marburg University Hospital.

In a meta-analysis of 30 small studies with JAK inhibitors in alopecia areata published in the Journal of the European Academy of Dermatology and Venereology, 72.4 percent of patients responded to the therapy, of which 45.7 percent had a good response (50-100 percent hair regrowth) and 21.4 percent had a partial response (5-50 percent hair regrowth).

The double-blind, randomized, controlled ALLEGRO study, published in the Journal of the American Academy of Dermatology (JAAD), investigated the efficacy of JAK inhibitors in women and men with alopecia areata. All participants had more than 50 percent hair loss on the scalp at the beginning. The 24-week therapy was effective and well tolerated: Compared to the placebo group, participants in the verum group (treatment group) had hair loss of 20 percent or less.

The side effect profile is clear

According to the data, the side effect profile of JAK inhibitors is clear. Infections can occur more frequently, for example in the nose and throat or in the respiratory tract. Urinary tract infections, gastrointestinal complaints and acne were also observed. "If an infection is acute, therapy with JAK inhibitors should be paused, of course," explains Hertl. However, this works very well due to the oral application and short half-life of the medication, according to the DDG president.

In the treatment of autoimmune white spot disease (vitiligo), a JAK 1/2 inhibitor administered by cream improved the affected facial skin in around 50 percent of patients compared to three percent with placebo (repigmentation of vitiligo lesions). These study results were published in the scientific journal "The Lancet".

"These are promising results that suggest this cream could be an effective treatment option for patients with vitiligo," says Hertl. "The side effects known with cortisone ointments were not observed."

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