Late-Breaking Abstracts Highlight Promising Therapies in AD, Hidradenitis Suppurativa

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Treatments for atopic dermatitis (AD) and hidradenitis suppurativa (HS) made up the majority of the research presented at the second late-breaking research session at American Academy of Dermatology Annual Meeting 2024. Researchers presented posters on both topical and systemic treatments, with biologics and Janus kinase (JAK) inhibitors of particular interest.

Effectiveness of AD Treatments Highlighted

Topical and biologic therapies for AD made up the majority of new research presented, with studies including pediatric patients, patients with skin of color, and patients with moderate-to-severe AD.

Lawrence F. Eichenfield, MD, chief of pediatric and adolescent dermatology at Rady Children’s Hospital in San Diego, presented the results of a phase 3, randomized, controlled trial that evaluated the efficacy of roflumilast cream 0.05% in patients who were aged 2 to 5 years and had mild to moderate AD.¹ Topical roflumilast is a nonsteroidal cream and foam that can applied once daily and has had success in treating patients with psoriasis, AD, and seborrheic dermatitis. Roflumilast was also found to be effective at a 0.15% dose in a phase 3 trial of patients aged 6 years and older. This study aimed to determine efficacy in patients aged 2 to 5 years.

“[Participants] had mild or moderate [AD], they had a minimum body surface area of 3%, and an [Eczema Area and Severity Index] (EASI) score of 5 or greater,” Eichenfield said.

All patients were randomized 2:1 to roflumilast vs vehicle. The primary end point was Validated Investigator Global Assessment for Atopic Dermatitis (vIGA-AD) success after 4 weeks, with secondary end points including a vIGA-AD score of clear or almost clear at the first, second, and fourth week along with vIGA-AD success at the first and second week. An EASI-75 score at Week 4 and an improvement in the Worst Itch Numeric Rating Scale (WI-NRS) were secondary end points.

The participants in the roflumulast group were primarily White (67.4%) and male (51.6%), with 15.6% reporting that they were Black.

“Over half of the patients had a history of either inadequate response or problems with topical corticosteroids,” said Eichenfield. A total of 17.0% had inadequate response to topical calcineurin inhibitors and 9.2% had inadequate response to crisaborole.

vIGA-AD success was seen in 25.4% of the patients treated with roflumilast cream 0.05%, compared with only 10.7% who were using the vehicle by week 4, with this difference being 21.2% vs 6.8%, respectively, in week 2. These percentages increased when looking at the vIGA-AD clear or almost clear, with 35.4% of the roflumilast group having clear or almost clear scores at week 4 compared with 14.6% of the vehicle group. WI-NRS also improved in more patients on roflumilast at 35.3% success compared with 18.0% in the vehicle group. Only 1.1% of patients in the roflumilast group required discontinuation due to an adverse event, which was lower compared with the vehicle (2.3%).

Eichenfield concluded that the roflumilast cream 0.05% improved AD in children aged 2 to 5 years, with assessments of the safety and efficacy of the cream past 4 weeks currently being conducted.

Jill S. Waibel, MD, FAAD, subsection chief of dermatology at Baptist Hospital, presented research² on the efficacy of lebrikizumab in patients with moderate-to-severe AD who had skin of color. She presented the 16-week interim data of a 24-week study that aimed to assess the efficacy of lebrikizumab in adults and adolescents with skin of color.

All participants got a 500 mg dose of lebrikizumab at baseline and at 2 weeks before switching to a 250 mg dose every 2 weeks through the 16th week. Participants who met the primary end point had the frequency changed to every 4 weeks, whereas those who did not meet the primary end point continued with receiving it every 2 weeks. Race and ethnicity were self-reported, but all participants had a Fitzpatrick skin tone of IV, V, or VI. There were 50 participants total.

The study found that 68% of participants had EASI 75 after 16 weeks, 46% had EASI 90, and the EASI percentage change from baseline was –79%. A total of 39% of patients had an IGA improvement of 2 points or more, 56% had an improvement in pruritus numerical rating scale (NRS) of 4 points or more and 66% had an improvement of 3 points or more.

“I think this is very exciting because it really is the first time there has been a trial focusing on skin of color with moderate-to-severe eczema in Fitzpatrick phenotypes IV through VI,” said Waibel.

Waibel also presented a new scale to compare post-inflammatory lesions with unaffected normal skin, which demonstrated skin tones for people with post-inflammatory hypopigmentation through post-inflammatory hyperpigmentation. When asked if the scale would be available for everyone to use, she assured everyone that Eli Lilly was interested in sharing the scale.

Jonathan I. Silverberg, MD, PhD, MPH, FAAD, director of clinical research at The George Washington University School of Medicine and Health Sciences, presented his own research into the efficacy of nemolizumab in patients with moderate-to-severe AD. The results came from the phase 3 studies ARCADIA-1 and ARCADIA-2.³

All participants received nemolizumab 30 mg every every 4 weeks for the first 16 weeks alongside topical corticosteroids and/or a topical calcineurin inhibitor. Participants were then randomized 1:1:1 to receive either nemolizumab at a 30 mg dose every 4 weeks, nemolizumab in a 30 mg dose every 8 weeks, or a placebo every 4 weeks. This dosage lasted through 48 weeks and all participants continued to take a topical corticosteroid and/or a topical calcineurin inhibitor.

Silverberg and coauthors found that nemolizumab 30 mg was effective over both 4-week and 8-week periods when it came to the percentage of EASI 75 success (76.3% and 75.7%) and IGA success (61.5% and 60.4%) compared with the placebo (63.9% and 49.7% respectively). However, nemolizumab every 4 weeks proved more effective when measuring an improvement in peak pruritus of 4 points or more (76.2 vs 59.7) compared with every 8 weeks and was also more effective in earning a peak pruritus NRS score of less than 2 (64.0% vs 52.9%) compared with every 8 weeks. However, both treatments were significantly more effective than placebo.

“Importantly, that 8-week dosing was very good and actually very similar to that continuous 4-week dosing with respect to a number of end points [which] suggests that this may be an option for a large subset of patients and certainly something that might be preferred because it gives them the opportunity for less dosing,” Silverberg said.

JAK, IL Inhibitors Prove Effective in Treating HS

HS was also a big focus of late-breaking research. Martina J. Porter, MD, dermatologist at Beth Israel Deaconess Medical Center, presented the results of a phase 2 study on the efficacy of ruxolitinib cream in patients with HS.⁴ Porter explained that treating milder HS can lead to inadequate results due to no approved therapy for this subset of patients. The study aimed to assess the efficacy of 1.5% ruxolitinib cream applied twice daily over the course of 16 weeks.

Participants aged 18 years and older with an HS diagnosis for 3 months or longer and had no draining tunnels were split into 2 groups: a ruxolitinib cream group and a vehicle group. These treatments were given for 16 weeks to assess whether there was a change in baseline abscess and inflammatory nodule (AN) count. The mean (SD) AN count at baseline in the vehicle group was 5.3 (1.8) and 5.6 (1.8) in the ruxolitinib group. The mean itch and pain scores were about 4 for both groups.

AN count saw a greater change in the ruxolitinib cream group (–3.61) compared with the vehicle group (–2.42). There were also more participants who achieved AN50 (79.2%), AN75 (54.2%), AN90 (20.8%), and AN100 (20.8%) in the ruxolitinib group compared with the vehicle group (56.3%, 25.0%, 12.5%, and 12.5% respectively).

“There’s a very high placebo rate, which we always see in trials as we get milder in HS patients,” explained Porter. “If you do the math for patients that have very low numbers of lesions…you can either achieve AN 50 or you’re clear. You can’t ever get 75 or 90 just based on the math. So those are things we have to think about.”

There were no serious adverse events related to treatment reported in the patients who used the ruxolitinib cream. Porter concluded by saying that the twice daily dose of ruxolitinib 1.5% was able to significantly reduce AN count in patients with HS after 16 weeks when compared with a vehicle. Porter said that milder patients may need modifications to traditionally accepted clinical end points in these studies, as most of the accepted end points have moderate-to-severe patients in mind.

Brian Kirby, professor at St. Vincent’s Private Hospital in Dublin, Ireland, presented data on a phase 2 study looking into the efficacy of an IL-17A and IL-17F inhibitor Nanobody sonelokimab who had moderate-to-severe HS.⁵ Sonelokimab, Kirby explained, was designed to penetrate inflamed tissues better and for longer.

Patients in the study were those with moderate-to-severe HS with lesions in at least 2 anatomical areas with a total AN count of 5 or more lesions. Patients who were taking either sonelokimab 120 mg or 240 mg for the first 12 weeks were kept on the treatment, whereas those who were on placebo were randomized into 120 mg and 240 mg groups. The primary end point was hidradenitis suppurativa clinical score (HiSCR) 75.

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HiSCR 50 was experienced by 69.0% of patients who used the 120 mg dose and 60.3% of those who used the 240 mg dose. Similar results were found in the total number of patients who achieved HiSCR 75, with 56.9% achieving it in the 120 mg group and 37.9% achieving it in the 240 mg dose group. HiSCR 90 was achieved by a lower amount of patients at 37.9% for the 120 mg group and 27.6% in the 240 mg group. Patients who were rerandomized from placebo to the sonelokimab also had effective results.

“We can see that at week 24, 12 weeks after treatment, 50% of patients had a HiSCR of 75. And this is similar to the corresponding value in the first 12 weeks of the trial,” said Kirby.

Lesion resolution also improved in all patients, with 31.0% of patients on the 120 mg dose and 20.7% of patients on the 240 mg dose achieving AN 100 after 24 weeks of treatment, an improvement of 14.9% and 10.6%, respectively, at week 12. A total of 49.0% of patients on the 120 mg dose and 39.1% of the patients on 240 mg dose also had a complete resolution of draining tunnels. Inflammatory remission was found in 24.1% of patients on the 120 mg dose and 15.5% of patients on the 240 mg dose after 24 weeks. Safety was also as expected.

“As of this morning, the phase 3 trial design has been enhanced and this data supports the progression of this drug to phase 3 of the 120 mg dose,” said Kirby.

The late-breaking session gave insight into the various new treatments being tested to approach AD, HS, and various other skin conditions. The results were promising for the future treatment of different skin conditions and provide an idea of the future of treating AD and HS in a wide range of patients.

References

1. Eichenfield L, Browning J, Funk T, et al. Efficacy and safety of once-daily roflumilast cream 0.05% in pediatric patients 2 to 5 years of age with mild to moderate atopic dermatitis (INTEGUMENT-PED): a phase 3 randomized controlled trial. Presented at American Academy of Dermatology Annual Meeting; March 8-12, 2024; San Diego, CA. Abstract 56905
2. Alexis A, et al. Efficacy and safety of lebrikizumab in adult and adolescent patients with skin of color and moderate-to-severe atopic dermatitis: an ainterim analysis of the open-label phase 3b trial, ADmirable. Presented at American Academy of Dermatology Annual Meeting; March 8-12, 2024; San Diego, CA. Abstract 56925
3. Silverberg JI, Woltenberg A, Legat FJ, et al. Maintenance of efficacy and safety with nemolizumab at week 48: results from two global phase 3 pivotal studies (ARCADIA-1 and ARCADIA-2) in patients with moderate-to-severe atopic dermatitis. Presented at American Academy of Dermatology Annual Meeting; March 8-12, 2024; San Diego, CA. Abstract 56887
4. Porter MJ, Ferreira-Cornwell C, Wang M, Nawaz H, Gooderham MJ. Efficacy and safety of ruxolitinib cream in patients with hidradenitis suppurativa (Hurley stage I and II): results from a randomized, double-blind, vehicle-controlled phase 2 study. Presented at American Academy of Dermatology Annual Meeting; March 8-12, 2024; San Diego, CA. Abstract 57015
5. Kimball AB, Kirby B, Bechara FG, et al. Efficacy and safety of the IL-17A- and IL-17F-inhibiting Nanobody® sonelokimab in patients with moderate-to-severe hidradenitis suppurativa (HS); week 24 results from the phase 2 MIRA trial. Presented at American Academy of Dermatology Annual Meeting; March 8-12, 2024; San Diego, CA. Abstract 56014