American Academy of Dermatology Annual Meeting
This year’s annual meeting of the American Academy of Dermatology attracted over 18,000 attendees, and included over 375 educational sessions from international leaders in the field of dermatology. Here we report on just a few of the new drugs, developments and research that were discussed.
1 What’s New in Acne and Rosacea?
Dr. Diane M. Thiboutot (Penn State University College of Medicine Hershey, PA, USA) gave an update on the therapeutics of these common disorders and mentioned some drugs in the pipeline for acne. One is topical minocycline foam, which has completed a phase 2 study in moderate to severe acne vulgaris . The second is topical olumacostat glasaretil, an inhibitor of acetyl-coenzyme A carboxylase, an enzyme involved in fatty acid synthesis, which has completed a phase 2a study . The third, a nitric oxide-releasing compound, SB204, has just completed 2 phase 3 trials, one of which met all 3 primary endpoints, while the second trial met only one of three primary endpoints [3, 4]. Recently approved by the US FDA is dapsone 7.5% gel .
For rosacea, in January 2017 the US FDA approved 1% oxymetazoline topical cream (an α1A adrenergic receptor agonist) for the treatment of adults with facial erythema associated with rosacea.
2 What’s New in Hair Disorders?
Dr. Antonella Tosti (Miller School of Medicine, University of Miami, FL, USA) discussed recent developments in alopecia, including the JAK inhibitors ruxolitinib (a selective inhibitor of JAK1/2) and tofacitinib (a pan-JAK inhibitor) for the treatment of alopecia areata. Ruxolitinib has 2 reported studies, one with oral  and the other with topical treatment . Tofacitinib has been studied in 5 trials, 2 prospective [8, 9] and 3 retrospective [10, 11, 12]. These agents are effective, with responses in approximately 32–77% of patients; however, relapse occurs 4-8 weeks after discontinuation, so they don’t represent a cure. Therefore, costs and adverse effects should be considered. Other JAK inhibitors are also in development.
3 What’s New in Infections?
Dr. Ted Rosen (Baylor College of Medicine, Houston, TX, USA) gave an update on new developments in infectious disease. Ozenoxacin is a new topical antibiotic formulated as a 1% cream for the treatment of impetigo. It is bactericidal for Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus. In a multicenter, randomized, placebo- and retapamulin-controlled clinical trial (n = 465), clinical/microbiological success was similar to retapamulin. The FDA is currently reviewing the New Drug Application for this agent .
According to a recent study in 48 states of the US, 42 states had 100% resistance of all head lice to pyrethrins or pyrethroid insecticides . However, there is a new drug, abametapir, under development. Abametapir works by blocking metalloproteinases, preventing eggs from opening (no nymphs), and interfering with vital enzymes in adult lice. It is ovicidal and pediculocidal after a single 10 min application . In phase 3 studies of 704 patients presented at the American Academy of Pediatrics (AAP) 2016 National Conference, 90% of patients were lice-free on day 1, 80% on day 7, and 81–82% on day 14. No nit combing was required . Also of interest is a small, randomized study (n = 62) conducted in Egypt comparing oral ivermectin 200 µg/kg with a single application of 1% ivermectin solution in patients over the age of 5 years. Treatment could be repeated once if symptoms persisted after 1 week, and this was required in 4 topically treated patients and 8 orally treated patients. At week 4 there was no itching, no rash, and negative microscopy in 100% of patients in both oral and topical groups . There is currently no ivermectin solution available for human use in the USA; a 1% ivermectin cream is approved for use in rosacea.
4 What’s New in Atopic Dermatitis?
According to Dr. Emma Guttman-Yassky (Icahn School of Medicine at Mount Sinai, NY, USA), we now have evidence that atopic dermatitis (AD) is a reversible and immune-driven disease, much like psoriasis. Recent studies have tested the contribution of different immune axes in atopic dermatitis by examining the effects of specific targeted therapies.
IL-4 and IL-13 targeting Dupilumab potently inhibits IL-4 and IL-13 signaling, and has been shown to correct both the inflammation and the barrier dysfunction of AD [18, 19]. In the phase 3 SOLO 1 and 2 trials, Eczema Area And Severity Index (EASI)-75 response was achieved in 53 and 48% of dupilumab recipients and 15 and 12% of placebo recipients, respectively . In order to test whether IL-13 inhibition alone is enough to control AD, the TREBLE phase 2 study of the IL-13 inhibitor lebrikizumab was conducted in patients with moderate to severe AD . In this trial, the 125 mg every 4 week dose achieved an EASI-50 response in 82% of patients vs 62% of placebo recipients (p < 0.05), whereas the lower doses were not significantly different from placebo. The reason for the high placebo response in this study was likely due to the concomitant use of topical corticosteroids.
IL-31 targeting To test the effects of IL-31 inhibition in AD, and in particular itch, a phase 2 study of anti-IL-31 receptor A monoclonal antibody nemolizumab was conducted . Changes on the pruritus visual analogue scale were −63% in the 2.0-mg group vs −21% in the placebo group (P < 0.01). EASI score changes were −41 vs −27%, respectively. These results demonstrated the efficacy of targeting the IL-31 receptor A.
IL-22 targeting IL-22 is thought to be involved in the epidermal hyperplasia and barrier defects in AD, so Dr Guttman-Yassky’s group are currently conducting a trial with an anti-IL-22 antibody (ILV-094) in 60 moderate-to-severe AD patients and are feeling “cautiously optimistic” (NCT01941537).
IL-23 targeting A phase 2 study of the IL-12/IL-23p40 antagonist ustekinumab was conducted in 32 patients with moderate-to-severe AD using psoriasis dosing. Background therapy with mild topical corticosteroids was allowed to promote retention. The SCORing Atopic Dermatitis (SCORAD)-50 responses at 12, 16 and 20 weeks were higher with ustekinumab than placebo, but the difference between groups was not significant, possibly because of the high placebo response that might have been due to background topical corticosteroids. Ustekinumab resulted in early and robust gene modification towards a non-lesional profile .
Intracellular targets The PDE4 inhibitor topical crisaborole has recently been FDA approved for mild-to-moderate AD in patients 2 years of age and older after it achieved significant efficacy in 2 phase 3 trials . Oral tofacitinib (a JAK1/3 inhibitor) has been shown to be potentially useful in a small case series of patients with recalcitrant AD , while a phase 2a study of topical 2% tofacitinib in patients with mild-to-moderate AD has shown rapid and significant improvement across all efficacy endpoints at 4 weeks .
In summary, it remains to be clarified how many immune axes need to be targeted and to what extent to fully reverse the pathogenic disease phenotype, but the therapeutic landscape for AD is rapidly evolving with the promise of better disease control.
5 What’s New in Psoriasis?
There were some interesting studies presented in the Late Breaking Research session.
Dr. Alice Gottlieb (New York Medical College, Valhalla, NY, USA) presented 16-week primary results of certolizumab pegol treatment for chronic plaque psoriasis from two phase 3, multicenter, randomized, placebo-controlled studies (CIMPASI-1 and -2). Psoriasis Area And Severity Index (PASI)-75 responder rates were 76 and 83% at the 400 mg dose vs 7 and 12% for placebo, respectively. Physician’s global assessment (PGA) 0/1 (clear/almost clear) rates for this dose were 58 and 72% vs 4 and 2% for placebo, respectively. There was a clinically meaningful improvement in Dermatology Life Quality Index (DLQI) and a good safety profile to date.
Dr. Kristian Reich (Dermatologikum Hamburg, Germany) presented results from IXORA-S, a randomized head-to-head trial of ixekizumab compared with ustekinumab after 24 weeks of treatment in patients with moderate-to-severe plaque psoriasis. The drugs were given according to label. PASI-90 rates at 24 weeks were 83% for ixekizumab and 59% for ustekinumab, PASI-75 rates were 91 vs 82%, and PASI-100 rates were 49 vs 24%. Static PGA 0/1 response rates were 87 vs 69%. There was comparable safety between agents in this study.
Dr. Jianzhong Zhang (Peking University People’s Hospital, Beijing China) presented results of a comparator-controlled, phase 3 study of topical 1% benvitimod (GSK-2894512; WBI-1001) cream for the treatment of mild to moderate plaque psoriasis. Benvitimod is a small molecule, non-steroidal and non-immunosuppressive anti-inflammatory compound. At 12 weeks, PASI-75 response rates were 51% vs 38% vs 15% for benvitimod vs 0.005% calcipotriol vs placebo. There were more adverse events (most commonly application site irritation) reported for benvitimod compared with calcipotriol and placebo. Of the 59 patients followed for 40 weeks, 49% remained in remission.
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