Advances in Dermatology: 2023 in Review
Advances in Dermatology:
2023 in Review
Cather McKay MD, FAAD
This year has been yet another exciting year in the field of dermatology with some of the highlights detailed below.
Atopic dermatitis, prurigo nodularis, and urticaria
The American Academy of Dermatology published guidelines for the management of atopic dermatitis (AD) in adults with topical, light, and systemic therapies this year.1,2
Topical therapies first used in psoriasis are showing promise in AD. Phosphodiesterase-4 (PDE4) inhibitor roflumilast cream 0.15% (Zoryve) has data available for ages 6 years and up,3 and a 0.05% cream is proving safe and effective in phase 3 trials for ages 2-5 years.4 Tapinarof 1% cream (Vtama) is being studied for patients down to the age of 2 years.5
The indication for oral abrocitinib (Cibinqo) was lowered to the age of 12 this year. Oral baricitinib (Olumiant) is currently approved for alopecia areata in the US but may gain an indication for AD in the future based on its approval abroad6. Topical ruxolitinib (Opzelura) is safe and effective thus far in trials for ages 2-12 years.7 Novel JAK inhibitors still under investigation include delgocitinib ointment8 and oral gusacitinib9 for chronic hand eczema, and topical brepocitinib10 for mild to moderate AD.
IL-31 inhibitor nemolizumab completed phase 3 trials for prurigo nodularis,11 and atopic dermatitis in adults and children aged 6-12 years12,13. IL-13 inhibitor lebrikizumab is available in Europe for ages 12 and up based on successful phase 3 studies14, but approval in the US has been delayed. Data for IL-13 inhibitor tralokinumab (Adbry) in adolescents was published this year as well15.
Options for chronic spontaneous urticaria may be on the horizon with dupilumab (Dupixent) under FDA review and the oral tyrosine kinase inhibitor remibrutinib succeeding in phase 3 trials16.
Psoriasis
Roflumilast 0.3% cream (Zoryve), approved for patients aged 12 and up with psoriasis in 2022, gained approval down to the age of 6 years in October. A foam formulation for scalp and body psoriasis and seborrheic dermatitis is expected in the near future.17 Oral roflumilast, available for COPD since 2011, may be an effective and affordable option for psoriasis according to data published this year.18 An additional oral PDE4 inhibitor, orismilast, is in trials.19
Bimekizumab (Bimzelx) gained approval in October as the first IL-17A and 17F inhibitor for moderate to severe plaque psoriasis.
Oral interleukin inhibitors are under investigation, including an oral IL-23 inhibitor peptide starting phase 3 trials.20 A second IL-36 inhibitor imsidolimab has succeeded in phase 3 trials this year.21
Biosimilars
This year has seen a rapid increase in the approval of biosimilars but with continued uncertainty of their role. Eight adalimumab biosimilars launched, with two labeled “interchangeable” by the FDA, meaning they can be used by the pharmacy without permission from the prescriber if state law allows. Biosimilars designated “interchangeable” undergo more arduous switching studies to show no difference in efficacy or safety compared to the original monoclonal antibody. A ustekinumab biosimilar was also approved and is expected to be available in 2025.
Acne
Triple combination clindamycin phosphate 1.2%, adapalene 0.15% and benzoyl peroxide 3.1% cream (Cabtreo) was approved for acne in those age 12 and older.22
Hair loss
JAK inhibitors continue to revolutionize treatment for alopecia areata. A second oral option, ritlecitinib (Litfulo), was approved in June for patients aged 12 years and older.23 Additional options may be to come with deuruxolitinib24 and ivarmacitinib25 in trials.
A novel topical botanical solution containing coacillium 22.25% twice daily for 24 weeks showed improvement in moderate to severe alopecia areata in children and adolescents compared to placebo26. No irritation was seen, and results were retained 24 weeks after treatment was complete.
More patients with androgenic alopecia demonstrated a negative hair pull test after once monthly platelet-rich plasma vs. twice daily topical 5% minoxidil for 12 weeks27.
Hidradenitis suppurativa
IL-17A inhibitor secukinumab (Cosyntex) became the second biologic option for adults with moderate to severe HS in November. IL-17A and F inihibitor bimekizumab is in phase 3 trials,28 as is the oral JAK inhibitor upadacitinib (Rinvoq) after promising phase 2 results.29 JAK1 inhibitor povorcitinib30, oral PDE4 inhibitor orismilast31, and IL-17A nanobody izokibep32, are all under investigation.
The role of surgery was emphasized in a randomized clinical trial showing improved efficacy and patient satisfaction when combining adalimumab and surgery33.
Other medical dermatology
Case series supporting new uses for already available medications were presented this year, including rituximab in systemic sclerosis34, tofacitinib in sarcoidosis35, and baracitinib in lichen planus36.
A phase 3 trial began after vilobelimab, a first in class anti-complement factor 5a antibody, was granted orphan drug and fast track designations for pyoderma gangrenosum.
A new in-office treatment for axillary hyperhidrosis consisting of an alkali thermolysis single-use, disposable patch received FDA clearance this year (Brella). Topical 20% oxybutynin for palmar hyperhidrosis proved more effective than placebo in a phase 3 study.37
Genodermatoses
Topical COL7A1 gene therapy for dystrophic epidermolysis bullosa, beremagene geperpavec-svdt (Vyjuvek), was approved for patients 6 months and older. Topical isotretinoin ointment continues in phase 3 trials for congenital icthyosis38, with safety data showing minimal systemic absorption.
Non melanoma skin cancer (NMSC)
This year the US Preventative Services Task Force reaffirmed prior recommendations on skin cancer screening, citing insufficient evidence to support routine exams in asymptomatic individuals with no prior history of skin cancer or precancerous lesions.39
Studies published this year suggest higher risk of skin cancer in patients taking methotrexate for psoriasis40 and those taking hydrochlorothiazide compared to calcium channel blockers.41 Long term UVB phototherapy for atopic dermatitis showed no increase in skin cancer risk according to a study by Ko, et al.42 Non-ablative fractional laser treatment was associated with a lower risk of NMSC in a retrospective cohort study.43
Chemoprevention was previously demonstrated with oral nicotinamide; however, this benefit was not seen in solid organ transplant patients according to phase 3 data44.
PD-1 inhibitor retifanlimab (Zynz) was approved in March for metastatic or recurrent locally advanced Merkel cell carcinoma (MCC).
Melanoma
The Society for Immunotherapy of Cancer updated melanoma clinical practice guidelines this year,45 offering recommendations on adjuvant and neoadjuvant treatment in a variety of settings.
Researchers continue to explore and refine treatment combinations for advanced melanoma. Examples include the addition of a personalized mRNA-based cancer vaccine to pembrolizumab in patients with resected high-risk melanoma,46 and neoadjuvant talimogene laherparepvec (T-VEC) prior to surgery for eligible patients with resectable disease.47
PD-1 inhibitor nivolumab (Opdivo) was approved for adjuvant treatment of resected stage IIB and IIC melanoma. Pembrolizumab (Keytruda) has had this indication since 2021.
Cosmetics
Restylane Eyelight was approved for the treatment of undereye hollows in those 21 years of age and older. Juvederm Skinvive was launched as an intradermal injection for skin smoothness of the cheeks. Sculptra received a new indication for the cheeks. Galderma’s novel liquid relabotulinumtoxinA was submitted for FDA review after successful phase 3 trials.48
Happy holidays from the WDS Editorial Committee!
References
1. Sidbury R, Alikhan A, Bercovitch L, et al. Guidelines of care for the management of atopic dermatitis in adults with topical therapies. J Am Acad Dermatol. 2023 Jul;89(1):e1-e20.
2. Davis DMR, Drucker AM, Alikhan A, et al. Guidelines of care for the management of atopic dermatitis in adults with phototherapy and systemic therapies. J Am Acad Dermatol. 2023 Nov 3:S0190-9622(23)02878-5.
3. Eichenfield LF. Efficacy and safety of roflumilast cream 0.15% in adults and children aged ≥ 6 with mild to moderate atopic dermatitis in two phase 3 trials (INTEGUMENT-1 and INTEGUMENT-2). Presented at: American Academy of Dermatology Annual Meeting; March 17-21, 2023; New Orleans.
4. Arcutis. Sept. 19, 2023. Arcutis Announces Positive Results from INTEGUMENT-PED Pivotal Phase 3 Trial of Roflumilast Cream 0.05% for the Treatment of Atopic Dermatitis in Children Ages 2 to 5. https://www.arcutis.com/arcutis-announces-positive-results-from-integument-ped-pivotal-phase-3-trial-of-roflumilast-cream-0-05-for-the-treatment-of-atopic-dermatitis-in-children-ages-2-to-5/
5. Simpson E. Rapid and early onset of itch relief with tapinarof cream 1% once daily in two pivotal phase 3 trials in adults and children down to 2 years of age with moderate to severe atopic dermatitis. Presented at: EADV Congress; Oct. 11-14, 2023; Berlin.
6. Torrelo A, Rewerska B, Galimberti et al. Efficacy and safety of baricitinib in combination with topical corticosteroids in paediatric patients with moderate-to-severe atopic dermatitis with an inadequate response to topical corticosteroids: results from a phase III, randomized, double-blind, placebo-controlled study (BREEZE-AD PEDS). Br J Dermatol. 2023 Jul 7;189(1):23-32.
7. Leung DYM, Paller AS, Zaenglein AL, et al. Safety, pharmacokinetics, and efficacy of ruxolitinib cream in children and adolescents with atopic dermatitis. Ann Allergy Asthma Immunol. 2023 Apr;130(4):500-507.e3.
8. Bissonnette R. Efficacy and safety of delgocitinib cream in adults with moderate to severe chronic hand eczema: Results of the Phase 3 DELTA 1 trial. Presented at: American Academy of Dermatology Annual Meeting; March 17-21, 2023; New Orleans.
9. Jimenez PA, Sofen HL, Bissonnette R, et al. Oral spleen tyrosine kinase/Janus Kinase inhibitor gusacitinib for the treatment of chronic hand eczema: Results of a randomized phase 2 study. J Am Acad Dermatol. 2023 Aug;89(2):235-242.
10. Landis MN, Arya M, Smith S, et al. Efficacy and safety of topical brepocitinib for the treatment of mild-to-moderate atopic dermatitis: a phase IIb, randomized, double-blind, vehicle-controlled, dose-ranging and parallel-group study. Br J Dermatol. 2022 Dec;187(6):878-887.
11. Kwatra SG, Yosipovitch G, Legat FJ, et al. Phase 3 Trial of Nemolizumab in Patients with Prurigo Nodularis. N Engl J Med. 2023 Oct 26;389(17):1579-1589. doi: 10.1056/NEJMoa2301333. PMID: 37888917.
12. Silverberg J, et al. Nemolizumab improves skin lesions, itch and sleep disturbance in patients with moderate-to-severe atopic dermatitis: Results from two identical phase 3 multinational studies (ARCADIA 1 and ARCADIA 2). Presented at: EADV 2023.
13. Igarashi A, Katsunuma T, Matsumura T, et al. Efficacy and safety of nemolizumab in paediatric patients aged 6-12 years with atopic dermatitis with moderate-to-severe pruritus: Results from a phase III, randomised, double-blind, placebo-controlled, multicentre study. Br J Dermatol. 2023 Jul 31:ljad268.
14. Silverberg JI, Guttman-Yassky E, Thaçi D, et al. Two Phase 3 Trials of Lebrikizumab for Moderate-to-Severe Atopic Dermatitis. N Engl J Med. 2023 Mar 23;388(12):1080-1091.
15. Paller AS, Flohr C, Cork M, et al. Efficacy and Safety of Tralokinumab in Adolescents With Moderate to Severe Atopic Dermatitis: The Phase 3 ECZTRA 6 Randomized Clinical Trial. JAMA Dermatol. 2023 Jun 1;159(6):596-605.
16. Jain V, Giménez-Arnau A, Hayama K, et al. Remibrutinib demonstrates favorable safety profile and sustained efficacy in chronic spontaneous urticaria over 52 weeks. J Allergy Clin Immunol. 2023 Oct 20:S0091-6749(23)01346-5.
17. Zirwas MJ, Draelos ZD, DuBois J, et al. Efficacy of Roflumilast Foam, 0.3%, in Patients With Seborrheic Dermatitis: A Double-blind, Vehicle-Controlled Phase 2a Randomized Clinical Trial. JAMA Dermatol. 2023 Jun 1;159(6):613-620.
18. Gyldenløve M, Meteran H, Sørensen JA, et al. Efficacy and safety of oral roflumilast for moderate-to-severe psoriasis-a randomized controlled trial (PSORRO). Lancet Reg Health Eur. 2023 Apr 21;30:100639.
19. Warren RB, French LE, Blauvelt A, et al. Orismilast in moderate-to-severe psoriasis: Efficacy and safety from a 16-week, randomized, double-blinded, placebo-controlled, dose-finding, and phase 2b trial (IASOS). J Am Acad Dermatol. 2023 Nov 10:S0190-9622(23)03187-0.
20. Janssen. Jul 4, 2023. Janssen Announces Positive Topline Results for JNJ-2113—a Novel, First and Only Oral IL-23 Receptor Antagonist Peptide in Development for Moderate-to-Severe Plaque Psoriasis. https://www.janssen.com/janssen-announces-positive-topline-results-jnj-2113-novel-first-and-only-oral-il-23-receptor
21. Warren RB, Reich A, Kaszuba A, et al. Imsidolimab, an anti-interleukin-36 receptor monoclonal antibody, for the treatment of generalized pustular psoriasis: results from the phase II GALLOP trial. Br J Dermatol. 2023 Jul 17;189(2):161-169.
22. Stein Gold L, Lain E, Del Rosso JQ, et al. Clindamycin phosphate 1.2%/adapalene 0.15%/benzoyl peroxide 3.1% gel for moderate-to-severe acne: Efficacy and safety results from two randomized phase 3 trials. J Am Acad Dermatol. 2023 Nov;89(5):927-935.
23. King B, Zhang X, Harcha WG, et al. Efficacy and safety of ritlecitinib in adults and adolescents with alopecia areata: a randomised, double-blind, multicentre, phase 2b-3 trial. Lancet. 2023 May 6;401(10387):1518-1529.
24. King B. Results from Thrive-Aa2: A double blind, placebo-controlled phase 3 clinical trial of deuruxolitinib (Ctp-543), an oral JAK inhibitor, In adult patients with moderate to severe alopecia areata. Presented at: American Academy of Dermatology Annual Meeting; March 17-21, 2023; New Orleans.
25. Zhou C, Yang X, Yang B, et al. A randomized, double-blind, placebo-controlled phase II study to evaluate the efficacy and safety of ivarmacitinib (SHR0302) in adult patients with moderate-to-severe alopecia areata. J Am Acad Dermatol. 2023 Nov;89(5):911-919.
26. Blume-Peytavi U, et al. Efficacy and safety of coacillium in children and adolescents with moderate to severe alopecia areata: a randomized, double-blind, multicenter, phase 2-3 trial. Presented at: EADV Congress; Oct. 11-14, 2023; Berlin.
27. Asim M, Shah R, Sharif S, et al. A Randomized Control Trial Comparing the Efficacy of Platelet-Rich Plasma and 5% Topical Minoxidil for the Treatment of Androgenetic Alopecia. J Drugs Dermatol. 2023 Sep 1;22(9):905-909.
28. Zouboulis C, Gottlieb A, Forman S, et al. Bimekizumab efficacy and safety in patients with moderate to severe hidradenitis suppurativa: Analysis of pooled data from BE HEARD I and II phase 3, randomised, double-blind, placebo-controlled, multicentre studies. Oral presentation at EADV 2023, Berlin, Germany.
29. Kimball AB, et al. Efficacy and safety of upadacitinib in moderate to severe hidradenitis suppurativa: A phase 2, randomized, placebo-controlled study. Presented at: American Academy of Dermatology Annual Meeting; March 17-21, 2023; New Orleans.
30. Kirby JS, Okun MM, Alavi A, et al. Efficacy and safety of the oral Janus kinase 1 inhibitor povorcitinib (INCB054707) in patients with hidradenitis suppurativa in a phase 2, randomized, double-blind, dose-ranging, placebo-controlled study. J Am Acad Dermatol. 2023 Oct 21:S0190-9622(23)03037-2.
31. Union Therapeutics. June 21, 2023. UNION therapeutics announces positive topline results from the OSIRIS investigator-initiated proof-of-concept study of oral orismilast in patients with hidradenitis suppurativa. https://uniontherapeutics.com/union-therapeutics-announces-positive-topline-results-from-the-osiris-investigator-initiated-proof-of-concept-study-of-oral-orismilast-in-patients-with-hidradenitis-suppurativa/
32. Papp K, et al. Izokibep, a novel IL-17 inhibitor, demonstrated HiSCR100 response in moderate to severe hidradenitis suppurativa: Week 12 results of open-label part A of a phase 2b/3 study. Presented at: American Academy of Dermatology Annual Meeting; March 17-21, 2023; New Orleans.
33. Aarts P, van Huijstee JC, van der Zee HH, et al. Adalimumab in conjunction with surgery compared with adalimumab monotherapy for hidradenitis suppurativa: A Randomized Controlled Trial in a real-world setting. J Am Acad Dermatol. 2023 Oct;89(4):677-684.
34. Kuzumi A, Ebata S, Fukasawa T, et al. Long-term Outcomes After Rituximab Treatment for Patients With Systemic Sclerosis: Follow-up of the DESIRES Trial With a Focus on Serum Immunoglobulin Levels. JAMA Dermatol. 2023 Apr 1;159(4):374-383.
35. Damsky W. Jak inhibitors in the treatment of sarcoidosis. Presented at: Skin of Color Society Scientific Symposium; March 16, 2023; New Orleans.
36. Hwang A, et al. Baracitinib in the treatment of cutaneous lichen planus. Presented at: American Academy of Dermatology Annual Meeting; March 17-21, 2023; New Orleans.
37. Fujimoto T, Terahara T, Okawa K, et al. A novel lotion formulation of 20% oxybutynin hydrochloride for the treatment of primary palmar hyperhidrosis: A randomized, placebo-controlled, double-blind, phase III study. J Am Acad Dermatol. 2023 Jul;89(1):62-69.
38. Murrell DF, Teng JMC, Guenthner S, et al. Phase IIb randomized CONTROL study demonstrates a novel topical isotretinoin formulation, TMB-001, is safe and effective in participants with either recessive X-linked or autosomal recessive lamellar congenital ichthyosis. Clin Exp Dermatol. 2023 Jun 5;48(6):623-630.
39. US Preventive Services Task Force. Screening for Skin Cancer: US Preventive Services Task Force Recommendation Statement. JAMA. 2023 Apr 18;329(15):1290-1295.
40. Lang Houser ME, Stewart JR, Brewer JD. Psoriasis Patients Treated With Methotrexate Have an Increased Risk of Nonmelanoma Skin Cancer: A Systematic Review and Meta-Analysis. Cureus. 2023 Apr 5;15(4):e37174.
41. Azoulay L, St-Jean A, Dahl M, et al. Hydrochlorothiazide use and risk of keratinocyte carcinoma and melanoma: A multisite population-based cohort study. J Am Acad Dermatol. 2023 Aug;89(2):243-253.
42. Ko MJ, Tsai WC, Tsai PH, et al. Ultraviolet B phototherapy does not increase the risk of skin cancer among patients with atopic dermatitis: A population-based retrospective cohort study. J Am Acad Dermatol. 2023 Sep;89(3):496-503.
43. Benson TA, Hibler BP, Kotliar D, Avram M. Nonablative Fractional Laser Treatment Is Associated With a Decreased Risk of Subsequent Facial Keratinocyte Carcinoma Development. Dermatol Surg. 2023 Feb 1;49(2):149-154.
44. Allen NC, Martin AJ, Snaidr VA, et al. Nicotinamide for Skin-Cancer Chemoprevention in Transplant Recipients. N Engl J Med. 2023 Mar 2;388(9):804-812.
45. Pavlick AC, Ariyan CE, Buchbinder EI, et al. Society for Immunotherapy of Cancer (SITC) clinical practice guideline on immunotherapy for the treatment of melanoma, version 3.0. J Immunother Cancer. 2023 Oct;11(10):e006947.
46. Khattak A, et al. Abstract CT001. Presented at: American Association for Cancer Research Annual Meeting; April 14-19, 2023; Orlando.
47. Dummer R, Gyorki DE, Hyngstrom JR, et al. Final 5-Year Follow-Up Results Evaluating Neoadjuvant Talimogene Laherparepvec Plus Surgery in Advanced Melanoma: A Randomized Clinical Trial. JAMA Oncol. 2023 Oct 1;9(10):1457-1459.
48. Galderma. November 30, 2023. Results from Galderma’s phase IIIb trials demonstrate rapid and long-lasting effect of RelabotulinumtoxinA on crow’s feet and frown lines. https://www.galderma.com/news/results-galdermas-phase-iiib-trials-demonstrate-rapid-and-long-lasting-effect-0
Thank you for providing such valuable information! Your insights have been incredibly helpful and have enriched our knowledge on Keep up the great work! Looking forward to learning more from you in the future Chair Executive
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