Promising New Treatments: JAK Inhibitors

Atopic dermatitis, also called atopic eczema, is a chronic, more severe form of eczema, which is a common skin condition.1 Both are characterized by distinctive scaly patches of dry skin, redness, inflammation, and itching. AD is a relapsing condition. People with AD experience recurring “flares,” when symptoms become more severe, followed by periods of relief, when symptoms lessen. AD affects up to 25% of children and 2-3% of adults.2

Causes of atopic eczema

The exact cause of atopic dermatitis is not fully understood, but it is thought to stem from a combination of genetic and environmental factors.3 Researchers believe it results from an overly active immune system responding to normally benign triggers or irritants by producing an overproduction of immune factors and inflammation. These are responsible for the redness, swelling, and itching that are common symptoms in people with AD.

Avoiding flares

The first line of defense for managing the symptoms of AD is routine skin care. Doctors recommend:

Medications to manage AD

When routine skincare is not enough to manage the symptoms of AD, there are a variety of over-the-counter and prescription medications available. These include:6

  • Topical corticosteroids (like hydrocortisone): These are available in over-the-counter and prescription strength formulations. Topical corticosteroids reduce redness, itching, and inflammation.
  • Topical calcineurin inhibitors: These are prescription medications that block an element of the overactive immune response and reduce itching and redness. There are two topical calcineurin inhibitors currently available: Protopic and Elidel.
  • Topical PDE4 Inhibitors: There is currently one prescription PDE4 (phosphodiesterase-4) inhibitor that was recently approved as Eucrisa (crisaborole). It blocks certain cyctokines, or immune system messengers, that cause inflammation. Multiple varieties of PDE inhibitor are currently in clinical trials.7,8
  • Systemic immunomodulators: These are oral or injectable prescription medications that tamp down the dysfunctional immune response. They have been approved by the FDA to manage an overactive immune response for other conditions, including organ transplantation or arthritis. When used to treat AD, they are prescribed to treat AD “off-label,” meaning they haven’t been specifically approved for that purpose by the FDA. Common names for these medications include azathioprine, methotrexate, and cyclosporine.9
  • Systemic cytokine therapies: These are injectable prescription medications that modulate immune dysfunction by blocking cytokines, immune signals in the body that trigger inflammation. Actimmune, BayGam, and Xolair are brand names of available cytokine therapies.

What are JAK inhibitors?

A new class of oral and topical medications, called JAK (Janus kinase) inhibitors, is causing excitement for dermatologists and patients living with AD. The advances come in part thanks to a deeper understanding of the causes of AD, including greater insight into the immune system factors that underlie its symptoms.8

JAK proteins (there are four—JAK1, JAK2, JAK3, and TYK2) sit in the cell wall and mediate the production of specialized immune cells and proteins that lead to inflammation, redness, and persistent itching. JAK inhibitors are small chemicals that block JAK proteins and impede their ability to function.10

JAK inhibitor clinical trials

Two successful phase 2 clinical trials recently concluded, and there are at least 4 more underway, all looking at how effectively different JAK inhibitors manage AD symptoms. The completed trials, of upadacitinib and baricitinib were conducted by AbbVie and Eli Lilly, respectively. Both showed significant improvement in patient EASI scores as well as remarkable reduction in itch.11

Baricitinib is not yet FDA approved.10 But many of the new drugs in these studies and others have already been FDA approved for different autoimmune diseases, including rheumatoid arthritis. In fact, their ability to help regulate an overactive immune system was in part what brought them to the attention of dermatology researchers.

JAK inhibitors and dupilumab

Like dupilumab, JAK inhibitors target specific chemical messengers that affect the production of additional immune cells and signaling factors related to inflammation and itching. Dupilumab is an injectable monoclonal antibody that disrupts interleukin-4 and interleukin-13. It is a biologically derived medication that relies on human cells for production. In contrast, JAK inhibitors are conventional medicines that are manufactured in a laboratory without the involvement of human cells.12 So far the new oral drugs have not been compared with each other or with dupilumab to evaluate their relative efficacy.12

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