Recent Developments in Dermatologic Therapies
Published February 2017
In July 2016, the US FDA approved adapalene 0.1% topical gel for over-the-counter use for acne treatment in patients 12 and older. This is the first over-the-counter retinoid approval as well as the first new over-the-counter anti-acne compound introduced since the 1980s. The over-the-counter approval was based upon post-marketing data, consumer comprehension studies, and a maximal-use trial showing minimal systemic absorption with extensive application of the medication. The product is recommended for once daily use in acne-affected skin.Babaeinejad SH, Fouladi RF. The efficacy, safety, and tolerability of adapalene versus benzoyl peroxide in the treatment of mild acne vulgaris: a randomized trial. J Drugs Dermatol. 2013 Jul 1;12(7):790-4.
FDA.gov. FDA approves Differin Gel 0.1% for over-the-counter use to treat acne. July 8, 2016. https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm510362.htm
FDA.gov. Briefing document for April 15, 2016. https://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/NonprescriptionDrugsAdvisoryCommittee/UCM495797.pdf
In December 2016, the US FDA approved crisaborole 2% ointment, the first of a new class of topical phosphodiesterase 4 (PDE4) inhibitors. In a phase III vehicle-controlled study of atopic dermatitis patients ages 2 and older, Investigator’s Static Global Assessment (ISGA) scores improved to clear or almost clear at 51.7% vs. 40.6% and 48.5% vs. 29.7% in the treatment and vehicle groups, respectively. Response time and time to improvement of pruritus were also significantly shorter in the crisaborole treated group. Treatment related adverse effects were minimal, with the most frequently reported being application site pain in 4.4% of the treatment group vs. 1.2% in the vehicle group, and this symptom resolved within one day for most patients.Paller AS, Tom WL, Lebwohl MG, Blumenthal RL, Boguniewicz M, Call RS, Eichenfield LF, Forsha DW, Rees WC, Simpson EL, Spellman MC, Stein Gold LF, Zaenglein AL, Hughes MH, Zane LT, Hebert AA. Efficacy and safety of crisaborole ointment, a novel, nonsteroidal phosphodiesterase 4 (PDE4) inhibitor for the topical treatment of atopic dermatitis (AD) in children and adults. J Am Acad Dermatol. 2016 Sep;75(3):494-503.e4. http://dx.doi.org/ 10.1016/j.jaad.2016.05.046
In December 2016, the United States Food and Drug Administration (US FDA) officially banned powdered gloves from use in both medicine and surgery. The ban was originally proposed in March 2016 and is based on an association between the use of powdered gloves by physicians and adverse events, including severe allergic reactions, lung inflammation and injury, asthma, and postoperative peritoneal adhesions.
In February 2017, the US FDA issued a Safety Communication on chlorhexidine gluconate, a frequently used antiseptic found in surgical soaps, mouthwashes, swabs, and sponges. This compound has been implicated in a growing number of cases of severe allergic reactions, including anaphylaxis.FederalRegister.gov. Food and Drug Administration, HHS. Banned Devices; Powdered Surgeon's Gloves, Powdered Patient Examination Gloves, and Absorbable Powder for Lubricating a Surgeon's Glove. Final rule. Fed Register. 2016 Dec 19;81(243):91722-31. Available at https://www.federalregister.gov/documents/2016/12/19/2016-30382/banned-devices-powdered-surgeons-gloves-powdered-patient-examination-gloves-and-absorbable-powder
FDA.gov. Chlorhexidine Gluconate: Drug Safety Communication - Rare But Serious Allergic Reactions. February 2, 2017. http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm539575.htm
Researchers at Stanford University trained a deep convolutional neural network using 129,540 biopsy-confirmed clinical images of over 2,000 dermatologic conditions. The artificial intelligence platform was then able to correctly differentiate keratinocyte carcinomas from seborrheic keratoses, and melanomas from benign nevi, at a level comparable to 21 board-certified dermatologists, using images of mobile phone camera quality. This demonstrated, with the largest clinical image set to date, the viability of machine learning in dermatologic diagnosis with significant implications for increasing access to teledermatologic care.Esteva A, Kuprel B, Novoa RA, Ko J, Swetter SM, Blau HM, Thrun S. Dermatologist-level classification of skin cancer with deep neural networks. Nature. 2017 Feb 2;542(7639):115-118. http://dx.doi.org/10.1038/nature21056
In February 2017, the US FDA approved brodalumab, a human monoclonal interleukin 17-A receptor antagonist, for the treatment of moderate to severe plaque psoriasis. A meta-analysis of six clinical trials involving 4,118 patients demonstrated increased rates of achieving Psoriasis Area and Severity Index (PASI) scores of 75, 90, and 100% over placebo (risk ratios 12.61, 28.72, and 61.23, respectively). The effect size was associated with the dose of medication. Brodalumab treated patients had slightly increased risks of adverse events compared to placebo, with the most common being headaches, arthralgias, nasopharyngitis, and upper respiratory tract infections. Notably, there were six suicides in clinical trials as well as increased suicidal ideation, leading the FDA to issue a boxed warning and restrict availability with a Risk Evaluation and Mitigation Strategy (REMS) Program. Brodalumab is dosed at 210 mg subcutaneously every two weeks.
In November 2016, the US FDA expanded its approval of etanercept, a recombinant TNF inhibitor consisting of a fusion protein of TNF-alpha receptor and IGG1 antibody, to children ages 4-17 with moderate to severe plaque psoriasis. The approval was based on the results of a phase III trial with a five-year open label extension study in this patient population, demonstrating good rates of PASI75, PASI90 of 60-70% and 30-40% out to week 264 of the study. Eight serious adverse events were reported of which only one episode of cellulitis was deemed to be treatment-related, and there were no reports of opportunistic infection or malignancy. This represents the first FDA approval of a systemic medication for pediatric psoriasis. Pediatric dosing for etanercept is 50 mg SC weekly in patients 63 kg and above, and 0.8 mg/kg weekly in patients under 63 kg.Attia A, Abushouk AI, Ahmed H, Gadelkarim M, Elgebaly A, Hassan Z, Abdel-Daim MM, Negida A. Safety and Efficacy of Brodalumab for Moderate-to-Severe Plaque Psoriasis: A Systematic Review and Meta-Analysis. Clin Drug Investig. 2017 Feb 14. http://dx.doi.org/10.1007/s40261-017-0500-9
FDA.gov. FDA New Announcement: FDA Approves New Psoriasis Drug. February 15, 2017. https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm541981.htm
Paller AS, Siegfried EC, Pariser DM, Rice KC, Trivedi M, Iles J, Collier DH, Kricorian G, Langley RG. Long-term safety and efficacy of etanercept in children and adolescents with plaque psoriasis. J Am Acad Dermatol. 2016 Feb;74(2):280-7.e1-3. http://dx.doi.org/10.1016/j.jaad.2015.09.056
In January 2017, the US FDA approved oxymetazoline hydrochloride 1% cream for treating rosacea-associated facial redness. This alpha-1 adrenoceptor agonist was applied to the face once daily for 29 days in two multicenter randomized vehicle controlled trials. In the more recent trial, 224 patients received the medication with 12%, 16%, 18%, and 15% achieving the primary endpoint of 2-point reduction in erythema on Clinician Erythema Assessment (CEA) and Subject Self-Assessment (SSA) compared to 6%, 8%, 6%, and 6% of the 221 patients receiving the vehicle.ClinicalTrials.gov. Safety and Efficacy of Oxymetazoline HCl Cream 1.0% in Patients With Persistent Erythema Associated With Rosacea. June 22, 2016. https://clinicaltrials.gov/ct2/show/results/NCT02132117
Shanler SD, Ondo AL. Successful treatment of the erythema and flushing of rosacea using a topically applied selective alpha1-adrenergic receptor agonist, oxymetazoline. Arch Dermatol. 2007 Nov;143(11):1369-71. http://dx.doi.org/10.1001/archderm.143.11.1369