JAK Inhibitors Play Key Role in Treating Various Skin Conditions

Fall Clinical Dermatology 2023, which takes place from October 19 to October 22, 2023, in Las Vegas, featured a panel hosted by Mona Shahriari, MD, and Lisa Swanson, MD, that described the key role that Janus kinase (JAK) inhibitors play in targeting the itch pathway in dermatological conditions and managing dermatological conditions as well as helping to identify patients who would benefit from JAK inhibitors for treatment.

Shahriari is an assistant clinical professor of dermatology at Yale University School of Medicine and associate director of clinical trials at CCD Research PLLC, and Swanson practices at Ada West Dermatology, St Luke’s Children’s Hospital, and Treasure Valley Medical Research.

JAK Inhibitors in Itch

JAK inhibitors play an important role in reducing itch in skin conditions, including atopic dermatitis, Shahriari explained. Itching can cause irritation and further inflammation of skin conditions if left untreated.

Closeup girl is scratching her hand with nails. Reddened, inflamed body parts causes discomfort and itching | Image credit: Monstar Studio - stock.adobe.com

Swanson delved into the evidence that topical ruxolitinib improves itch by 4 points or more in the Itch Numerical Rating Scale (NRS) Score by week 4 of use, in both 0.75% and 1.5% doses compared with the vehicle. This improvement was maintained by week 8 with slight improvements on average for both dosage groups. The daily Itch NRS Score also had a mean change from baseline in both the 0.75% and 1.5% dosage groups, with the 0.75% group seeing a –2.97 change in score and the 1.5% group seeing a change of –3.53 in the TRuE-AD1 study by day 56 compared with –1.51 in the vehicle group in the same time period. The TRuE-AD2 study found similar results, with the 0.75% dosage (–3.04) and 1.5% dosage (–3.17) seeing greater changes in mean Itch NRS Score compared with the vehicle (–1.33) in a 56-day time period.

The percentage of patients who achieved an Itch NRS Score of 0/1 was 49.5% in the 1.5% dosage group, 43.9% in the 0.75% dosage group, and 18.3% in the vehicle group after 8 weeks. The ruxolitinib had results as soon as 7 days for 36.0% of the 1.5% dosage group and 29.0% of the 0.75% dosage group compared with 9.2% of the vehicle group.

“That’s a big deal, you guys. An itch of 0 is no itch at all [and] an itch of 1 is like, ‘Oh I think that kind of itches right there,’” Swanson said. “These patients are able to feel and live normal lives with an itch score of 0 or 1.”

Ruxolitinib was also found to be effective when used with systemic agents, such as oral JAK inhibitors for atopic dermatitis. Itch was found to be improved by 4 points or more on the Itch NRS score in more than 40% of patients when abrocitinib in a 200-mg daily dose was used alongside ruxolitinib. Upadacitinib in a 30-mg daily dose was found to be more effective in improving Pruritus NRS score, with nearly 60% of patients reporting an improvement of 4 points or more compared with less than 40% of patients using dupilumab 300 mg injected every 2 weeks.

Treating Skin Conditions With JAK Inhibitors

Moving beyond itch, the 2 panelists focused on skin conditions that could be imrpoved through treatment with JAK Inhibitors. These included less common skin diseases that have FDA-approved treatments that may not always work with every patient and other treatments that are currently being tested.

This included prurigo nodularis, which is characterized by an unrelenting itch. Dermatologists can identify the condition by looking for papules, nodules, ulcerations or erosions, and plaques. The condition also features symmetric and bilateral favoring extensor surfaces and postinflammatory pigment alteration. Patients also may experience a mental health burden from the rash being across their body. Currently, dupilumab is approved by the FDA for treatment of the skin condition but a phase 2 trial of abrocitinib 200 mg daily has found that participants have a 78.3% improvement in itch by week 12 and 60% of patients reported an NRS score of 0/1 by week 12 with no serious adverse events.

Ruxolitinib cream is currently being evaluated as a potential treatment for lichen sclerosus. A double-blind, randomized, vehicle-controlled study is being sponsored by Incyte Corporation to assess the efficacy and safety of the cream in patients with this rare condition. Swanson also gave an anecdotal story of seeing success in treating lichen sclerosus in pediatric patients by using topical ruxolitinib.

Lichen planus, said Shahriari, needs signaling through the JAK/STAT apthway for the effects of the disease to occur, which makes JAK inhibition something that clinicians should consider to treat the disease. Lichen planus doesn’t have any FDA-approved treatments, but recently, tofacitinib, baricitinib, ruxolitinib, and upadacitinib have presented as newer options for treatment in addition to more traditional treatments like topical corticosteroids and systemic steroids.

JAK Inhibitors for Treating Non-Itch Skin Conditions

JAK inhibitors have also seen an uptick in use in skin conditions that do not involve improving itch. These include vitiligo, alopecia areata, and hidradenitis suppurativa. In the case of vitiligo, ruxolitinib has been approved for patients 12 years and older for nonsegmental vitiligo. This works best in areas that are sun exposed, including the face. However, it does take time for the treatment to work, as it takes time for the pigment to be made again. There’s a 30% chance of recurrence once the patient’s skin is pigmented again. Phase 2 studies are also looking into povorcitinib, upaddacitinib, ritlecitinib, baricitinib, and beprocitinib in treatment of nonsegmental vitiligo.

Alopecia areata, a hair loss condition that can be treated through medications aimed at the scalp, is also seeing JAK inhibitors used as treatment. Baricitinib at 2-mg and 4-mg doses has been FDA approved in patients 18 years and older whereas ritlecitinib at 50-mg doses has been approved for patients 12 years and older, with effective results. Shahriari presented results from her own practice of a woman who received the 4 mg dose of baricitinib and had results as early as 5 months.

“The most important thing a girl wears is her confidence and these medicines have the ability to give our patients their confidence back, which is really special,” said Swanson.

Adalimumab has been approved by the FDA in the treatment of hidradenitis suppurativa but more than 1 concomitant treatment will likely be needed for disease control in the long term. There is an ongoing phase 2 clinical trial of ruxolitinib 1.5% that will have primary endpoint completion in December of 2023. For hidradenitis suppurativa in particular, Shahriari believes that any topical ruxolitinib treatment would need to be chronic application to achieve the best results.

Safety in Treatment

JAK Inhibitors have several boxed warnings, including serious infections, mortality, malignancies, thrombosis, and major adverse cardiovascular events. However, both Swanson and Shahriari pointed out that all of the boxed warnings came from a study on tofacitinib in patients 50 years and older with rheumatoid arthritis.

The panelists recommend that all doctors take a past medical history for each of their patients when selecting who should receive JAK inhibitors. This includes checking for smoking history, liver/kidney issues, cardiovascular issues, and their interest in pregnancy in the near future. Checking their medicine list for interactions is also a necessary step.

“It is a risk-benefit analysis. Prescribing a JAK is like prescribing any medicine, you have to weigh the risks and the benefits to best serve the patients sitting in front of you,” said Shahriari.

Even with topical ruxolitinib approved for treatment of atopic dermatitis and vitiligo, the safety warnings should be considered before giving the treatment to patients. More studies on the long-term effects of ruxolitinib in real-world usage will help to illuminate the full scope of potential uses for JAK inhibitors as well as any safety concerns in the future.

“Understanding these JAK inhibitors is a journey. We’re still at the beginning of that journey,” said Swanson. “As we get more real-life experience and more long-term studies, we’re going to feel better and better [and] we’re going to know more and more.”