Ruxolitinib cream controls atopic dermatitis over 52 weeks with as-needed treatment

Key takeaways:

• Body surface area percentages fell from 9.6% to 2.9% at week 8 with continuous treatment and 1.4% at week 52 with as-needed treatment.
• Patients spent 43.9% of the as-needed period off treatment.

ANAHEIM, Calif. — Patients with atopic dermatitis achieved long-term disease control with as-needed use of ruxolitinib cream, according to a presentation at the American College of Allergy, Asthma & Immunology Annual Scientific Meeting.

“It’s an important topic,” Bob Geng, MD, assistant clinical professor at University of California, San Diego School of Medicine, said during his presentation.

Bob Geng

“As much as we’re focusing on systemic therapies, and we’re focusing on targeted and precision medicine, we also need to not forget that targeted, precision medicine is not just always systemic. It can be topical as well,” he continued. “We’re looking at this from a regional perspective.”

Background

Durable long-term disease control is important because it puts treatment on a path toward disease modification, Geng said.

“Anybody can achieve remission, [meaning] you’re doing fine on drug,” he said. “But what is the capability of something to get people in control off therapy as well? That is going to be the Holy Grail.”

The different cytokines involved in AD signal through self-surface receptors, which do not have massive cytosolic compartments, Geng explained. They all depend on common JAK/STAT pathways that signal through intracellularly to get this information to the nucleus and translate it into inflammatory proteins, he continued.

“We want to look for common pathways,” Geng said. “We want to hit a few birds with one stone, not just two birds with one stone.”
and gamma interferon, among other cytokines.

“We can use a whole bunch of extracellular monoclonals for that purpose. We have to look at what is the common denominator underneath the cytosolic membrane,” Geng said. “And that’s going to be looking at inhibiting the JAK/STAT pathway.”

Ruxolitinib (Opzelura, Incyte) is a selective JAK1 and JAK2 inhibitor that can be applied topically. In a previous study, continuous use of 1.5% ruxolitinib cream applied twice a day achieved anti-inflammatory activity with rapid and sustained antipruritic action, in addition to effective disease and symptom control with as-needed use.

The current study

Researchers enrolled patients aged 12 years and older who had AD for 2 years or longer with an Investigator’s Global Assessment (IGA) score of 2 or 3 and a body surface area (BSA) total of 3% to 20%.

“We’re looking at the mild to moderate population,” Geng said.

Researchers randomly assigned these patients 2:2:1 to receive 0.75% ruxolitinib cream twice a day, 1.5% ruxolitinib cream twice a day or vehicle for 8 weeks.

The 428 patients (median age, 31 years; 61.4% female; 70.6% white; IGA 2, 23.4%; IGA 3, 76.6%) using 1.5% of ruxolitinib cream had a mean of 5.1 recurrent AD flares in the 12 months before treatment.

“With initial continuous application of the 1.5% ruxolitinib cream, symptom and disease control was very rapid,” Geng said.

The mean affected BSA score fell from 9.6% at baseline to 2.9% at week 8 with the 1.5% cream. Also, 67.1% of this group achieved an IGA of 0 or 1 at week 8.

Continuous application was halted at 8 weeks, and patients were told they could use the cream as needed to treat active lesions, stopping 3 days after clearance and resuming treatment upon recurrence, for the next 44 weeks.

“With subsequent application, disease control was actually maintained over time,” Geng said.

Patients recorded their treatment application during the as-needed period in daily diaries.

“We’re not trying to go for recall bias,” Geng said. “We want people to record this as things are happening.”

The researchers also evaluated disease control every 4 weeks. BSA fell from 2.9% at week 8 to 1.4% at week 52 among the 244 patients who stayed on treatment until this point. Plus, because of lesion clearance, patients with the 1.5% cream spent a median total cumulative percentage of 43.9% of this period off treatment.

“If you’re going to forget everything else I say, please pay attention to this,” Geng said.

Specifically, percentages of time off treatment with the 1.5% dose included 25% between 8 and 12 weeks, 46.4% between 16 and 20 weeks, 50% between 28 and 32 weeks, 56.7% between 40 and 44 weeks, and 52.8% between 48 and 52 weeks.

“That’s a substantial amount of time that people are able to spend off treatment,” Geng said.

“That’s really important that we’re actually inducing these patients not just to be in remission, which is defined as disease control while on therapy, but also how much we’re able to spare patients from even needing to be on therapy, demonstrating some durable results,” he continued.

Geng called these times off as-needed ruxolitinib cream monotherapy substantial regardless of the extent or the severity of the disease as well.

In the 1.5% cream group, patients with a baseline IGA score of 2 had a median of 60.7% time off treatment, and those with a baseline IGA score of 3 had a median of 40.6%. Also, those with a BSA less than 10% spent 57% of time off treatment, and those with a BSA of 10% or more had 36.4% time off treatment.

During the as-needed period, Geng said, mild or worse skin disease appeared slowly. Patients in the 1.5% cream group who achieved an IGA of 0 or 1 at week 8 had a median time of 36.1 weeks before developing mild or worse disease, classified as an IGA score of 2 or higher. But then, Geng said, skin clearance was rapidly recaptured with a median time of 4.9 weeks. The 0.75% cream group had similar results.

“As soon as it comes back, you put it on, and you’re able to achieve control again,” Geng said. “That’s a really key take home point.”

Both doses of ruxolitinib were well tolerated with no safety signals observed over the 52-week study period, Geng continued.

“A very wise, elderly allergist in San Diego once told me that the first tenet of medicine is do no harm for any type of therapy,” Geng said. “So, I think it’s important that we focus on safety as well.”

In the 1.5% cream group, 62.6% of patients experienced a treatment-emergent adverse event, 7.4% experienced a treatment-related adverse event, 1.8% had a serious treatment-emergent adverse event, and one patient (0.2%) discontinued treatment due to a treatment-emergent adverse event.

The most common treatment-emergent adverse events included upper respiratory tract infections (11.4%), nasopharyngitis (9.9%), headache (4.5%), bronchitis (3.4%), atopic dermatitis (2.5%), influenza (2.5%), asthma (2.5%), hypertension (2.2%) and rhinitis (2%).

Conclusions

Based on these findings, Geng concluded that ruxolitinib demonstrated durable long-term disease control and substantial time off treatment when patients with AD use it as monotherapy treatment as needed.

“Of course, as-needed ruxolitinib cream monotherapy has potential to reduce the need for therapy escalation over a 52-week period,” Geng said.