associated with an increased risk of malignancy and may be used in patients with hepatitis B or C infections.45 As shown in Table 1, the rates of serious adverse events with brodalumab, secukinumab, and ixekizumab ranged from 1.0% to 1.8%, comparable to the rates reported with placebo.29,37-40 The most common adverse events reported with these agents included nasopharyngitis, upper respiratory tract infection, headache, and arthralgia.29,37,38
In a systematic review of clinical trials of patients with psoriasis or psoriatic arthritis, Candida infections were reported in 4.0% of patients treated with brodalumab, 1.7% of patients treated with secukinumab, and 3.3% of patients treated with ixekizumab compared with 0.3%, 2.3%, and 0.8% in those receiving placebo, ustekinumab, or etanercept, respectively.46 The majority of Candida infections in anti–IL-17 biologic clinical trials occurred in the oral cavity and were of mild severity.47 Exacerbation of IBD has also been reported in trials of anti– IL-17 agents in psoriasis, including 1 case of Crohn disease with brodalumab.48 In a study of ixekizumab, incidence rates of Crohn disease and ulcerative colitis were 0.10 and 0.20 per 100 patient-years, respectively, and were 0.11 and 0.15 per 100 patient-years, respectively, in a study of secukinumab.48 On the basis of these observations, caution should be used in patients with possible or diagnosed IBD.48
In a systematic review of clinical trials of patients with psoriasis or psoriatic arthritis, Candida infections were reported in 4.0% of patients treated with brodalumab, 1.7% of patients treated with secukinumab, and 3.3% of patients treated with ixekizumab compared with 0.3%, 2.3%, and 0.8% in those receiving placebo, ustekinumab, or etanercept, respectively.46 The majority of Candida infections in anti–IL-17 biologic clinical trials occurred in the oral cavity and were of mild severity.47 Exacerbation of IBD has also been reported in trials of anti– IL-17 agents in psoriasis, including 1 case of Crohn disease with brodalumab.48 In a study of ixekizumab, incidence rates of Crohn disease and ulcerative colitis were 0.10 and 0.20 per 100 patient-years, respectively, and were 0.11 and 0.15 per 100 patient-years, respectively, in a study of secukinumab.48 On the basis of these observations, caution should be used in patients with possible or diagnosed IBD.48
SUMMARY
The IL-17 pathway plays a crucial role in the immunopathogenesis and development of psoriasis. Currently, 3 US Food and Drug Administration–approved agents affect this pathway for treatment of psoriasis (brodalumab, secukinumab, and ixekizumab) with others in development (bimekizumab).49 Brodalumab is a highly selective IL-17 receptor A antagonist that blocks multiple downstream inflammatory cytokines that are elevated in psoriasis, including IL-17C and IL-17E, which may correlate with the observed efficacy of brodalumab. Secukinumab and ixekizumab selectively bind to and neutralize only IL-17A. Inhibition of the IL-17 pathway with these agents results in improvements in clinical, histologic, and genetic characteristics of psoriasis. The immunomodulation produced by these agents has been associated with a favorable safety profile. Overall, the clinical improvement and normalization of genetic hallmarks of psoriasis provide a strong case for the unique role of IL-17 receptor blocking as an important therapeutic mechanism of action in treating psoriasis. Understanding the unique mechanisms by which each of these biologics interacts with the IL-17 pathway to inhibit downstream proinflammatory signal cascade will be of benefit to dermatologists in making informed treatment decisions.
DISCLOSURES
Lawrence Green has served as an investigator, consultant, or
speaker for Amgen, AbbVie, Bausch Health, Celgene, Sun Pharma, Pharma,
Eli Lilly, and Novartis. Jeffrey M. Weinberg serves as an
investigator for Boehringer Ingelheim, LEO Pharma, and Novartis
and serves as a speaker for and/or advisor to AbbVie, Amgen,
Celgene, Eli Lilly, LEO Pharma, and Novartis. Alan Menter has
received compensation from or served as an investigator, consultant,
advisory board member, or speaker for AbbVie, Allergan,
Amgen, Anacor, Boehringer Ingelheim, Celgene, Dermira, Eli
Lilly, Galderma, Janssen Biotech, LEO Pharma, Merck, Neothetics,
Novartis, Pfizer, Regeneron, Symbio/Maruho, Vitae, and
Xenoport. Jennifer Soung has served as an investigator, consultant,
advisory board member, or speaker for AbbVie, Actavis,
Actelion, Allergan, Amgen, Boehringer Ingelheim, Cassiopeia,
Celgene, Dr. Reddy, Eli Lilly, Galderma, GSK, Janssen, Kadmon,
LEO Pharma, Menlo, National Psoriasis Foundation (nonprofit),
Novan, Novartis, Ortho Dermatologics, Pfizer, Regeneron, and
UCB. Edward Lain has received compensation from or served as
an investigator, consultant, advisory board member, or speaker
for AbbVie, Allergan, Boehringer Ingelheim, Celgene, Dermira,
Eli Lilly, Galderma, LEO Pharma, Neothetics, Novartis, Pfizer,
Sol-Gel, Endo Pharmaceuticals, Dr Reddy, Kadmon, Thync Global,
Cassiopeia, Menlo, UCB, Kiniksa, Glenmark, Sienna, Sebacia,
BMS, Vanda, Chemocentryx, Brickell, Aclaris, and Novan. Abby
Jacobson is an employee of Ortho Dermatologics and holds
stock and/or stock options in Bausch Health.
ACKNOWLEDGMENT
This study was sponsored by Ortho Dermatologics. Editorial
assistance was provided under the direction of the authors by
Angela Cimmino, PharmD, Rebecca Slager, PhD, and David
Boffa, ELS, of MedThink SciCom, with support from Ortho Dermatologics.
REFERENCES
1. Rachakonda TD, Schupp CW, Armstrong AW. Psoriasis prevalence among adults in the United States. J Am Acad Dermatol. 2014;70(3):512-516.
2. Meephansan J, Subpayasarn U, Komine M, Ohtsuki M. Pathogenic role of cytokines and effect of their inhibition in psoriasis. Chiriac A, ed. An Interdisciplinary Approach to Psoriasis: London, UK: InTech Open; 2017.
3. Silfvast-Kaiser A, Paek SY, Menter A. Anti-IL17 therapies for psoriasis. Expert Opin Bil Ther. 2019;19(1):45-54.
4. Elmets CA, Leonardi CL, Davis DMR, et al. Joint AAD-NPF guidelines of care for the management and treatment of psoriasis with awareness and attention to comorbidities. J Am Acad Dermatol. 2019;80(4):1073-1113.
5. Prussick RB, Miele L. Nonalcoholic fatty liver disease in patients with psoriasis: a consequence of systemic inflammatory burden? Br J Dermatol. 2018;179(1):16-29.
6. Takeshita J, Grewal S, Langan SM, et al. Psoriasis and comorbid diseases: epidemiology. J Am Acad Dermatol. 2017;76(3):377-390.
7. Baliwag J, Barnes DH, Johnston A. Cytokines in psoriasis. Cytokine. 2015;73(2):342-350.
8. Kim J, Krueger JG. The immunopathogenesis of psoriasis. Dermatol Clin. 2015;33(1):13-23.
9. Nestle FO, Kaplan DH, Barker J. Psoriasis. N Engl J Med. 2009;361(5):496-509.
10. Hawkes JE, Chan TC, Krueger JG. Psoriasis pathogenesis and the development of novel targeted immune therapies. J Allergy Clin Immunol. 2017;140(3):645-653.
11. Martin DA, Towne JE, Kricorian G, et al. The emerging role of IL-17 in the pathogenesis of psoriasis: preclinical and clinical findings. J Invest Dermatol. 2013;133(1):17-26.
12. Senra L, Stalder R, Alvarez Martinez D, Chizzolini C, Boehncke WH, Brembilla NC. Keratinocyte-derived IL-17E contributes to inflammation in psoriasis. J Invest Dermatol. 2016;136(10):1970-1980.
2. Meephansan J, Subpayasarn U, Komine M, Ohtsuki M. Pathogenic role of cytokines and effect of their inhibition in psoriasis. Chiriac A, ed. An Interdisciplinary Approach to Psoriasis: London, UK: InTech Open; 2017.
3. Silfvast-Kaiser A, Paek SY, Menter A. Anti-IL17 therapies for psoriasis. Expert Opin Bil Ther. 2019;19(1):45-54.
4. Elmets CA, Leonardi CL, Davis DMR, et al. Joint AAD-NPF guidelines of care for the management and treatment of psoriasis with awareness and attention to comorbidities. J Am Acad Dermatol. 2019;80(4):1073-1113.
5. Prussick RB, Miele L. Nonalcoholic fatty liver disease in patients with psoriasis: a consequence of systemic inflammatory burden? Br J Dermatol. 2018;179(1):16-29.
6. Takeshita J, Grewal S, Langan SM, et al. Psoriasis and comorbid diseases: epidemiology. J Am Acad Dermatol. 2017;76(3):377-390.
7. Baliwag J, Barnes DH, Johnston A. Cytokines in psoriasis. Cytokine. 2015;73(2):342-350.
8. Kim J, Krueger JG. The immunopathogenesis of psoriasis. Dermatol Clin. 2015;33(1):13-23.
9. Nestle FO, Kaplan DH, Barker J. Psoriasis. N Engl J Med. 2009;361(5):496-509.
10. Hawkes JE, Chan TC, Krueger JG. Psoriasis pathogenesis and the development of novel targeted immune therapies. J Allergy Clin Immunol. 2017;140(3):645-653.
11. Martin DA, Towne JE, Kricorian G, et al. The emerging role of IL-17 in the pathogenesis of psoriasis: preclinical and clinical findings. J Invest Dermatol. 2013;133(1):17-26.
12. Senra L, Stalder R, Alvarez Martinez D, Chizzolini C, Boehncke WH, Brembilla NC. Keratinocyte-derived IL-17E contributes to inflammation in psoriasis. J Invest Dermatol. 2016;136(10):1970-1980.
