Brodalumab: a promising option in the management of psoriasis
Keywords:Psoriasis, Interlukin-17, Biologics, AMAGINE, Brodalumab
Brodalumab, a human monoclonal antibody approved as a biological therapy for treating psoriasis. Due to its consistent results across several clinical studies in treating patients with plaque psoriasis, in 2016 it was first approved worldwide in Japan followed by US FDA approval in 2017 and the European medicines agency. Brodalumab, selectively binds with higher affinity to IL-17RA, thereby blocking the actions of IL-17A, E and F. This act as a novel mechanism to inhibit the inflammation, hyperproliferation, skin thickening and other clinical symptoms associated with psoriasis. The safety and adverse effects of Brodalumab were similar to other IL-17 inhibitors, frequently reported adverse events were nasopharyngitis, neutropenia, and candidiasis. The FDA has recommended a boxed warning for the suicidal tendencies that could occur among Brodalumab users. This review is an endeavor to depict the drug's mode of action, pharmacokinetics, safety, and efficacy as well as its current status among other drugs targeting IL-17.
Goff KL, Karimkhani C, Boyers LN, Weinstock MA, Lott JP, Hay RJ, et al. The global burden of psoriatic skin disease. Br J Dermatol. 2015;172:1665-8.
Mease PJ, Genovese MC, Greenwald MW, Ritchlin CT, Beaulieu AD, Deodhar A, et al. Brodalumab, an anti-IL17RA monoclonal antibody, in psoriatic arthritis. New England J Med. 2014;370(24):2295-306.
Papp KA, Leonardi C, Menter A, Ortonne JP, Krueger JG, Kricorian G, et al. Brodalumab, an anti-interleukin-17 receptor antibody for psoriasis. New England J Med. 2012;366(13):1181-9.
Farahnik B, Beroukhim K, Abrouk M, Nakamura M, Zhu TH, Singh R, et al. Brodalumab for the treatment of psoriasis: a review of phase III trials. Dermatology Therapy. 2016;6(2):111-24.
Food and Drug Administration. Dermatologic and Ophthalmic Drugs Advisory Committee Meeting Background Package for Bla 761032 Siliq (Brodalumab) Injection, 210 mg/15 ml. Silver Spring, MD: Food and Drug Administration; 2016.
Abuhilal M, Walsh S, Shear N. The role of IL-17 in the pathogenesis of psoriasis and update on IL-17 inhibitors for the treatment of plaque psoriasis. J Cutan Med Surg. 2016;20(6):509-16.
Siliq (brodalumab). Bridgewater, NJ: Valeant Pharmaceuticals North America LLC; 2017.
Roostaeyan O, Kivelevitch D, Menter A. A review article on brodalumab in the treatment of moderate-to-severe plaque psoriasis. Immunotherapy. 2017;9(12):963-78.
Blauvelt A, Chiricozzi A. The immunologic role of IL-17 in psoriasis and psoriatic arthritis pathogenesis. Clinical reviews in allergy and immunology. 2018;55(3):379-90.
Roman M, Chiu MW. Spotlight on brodalumab in the treatment of moderate-to-severe plaque psoriasis: design, development, and potential place in therapy. Drug Design Development Therapy. 2017;11:2065.
Russell CB, Rand H, Bigler J, Kerkof K, Timour M, Bautista E, et al. Gene expression profiles normalized in psoriatic skin by treatment with brodalumab, a human anti-IL-17 receptor monoclonal antibody. J Immunology. 2014;192(8):3828-36.
European Commission, Community register of medicinal products for human use, Kyntheum® (brodalumab); 2017.
Papp K, Reich K, Leonardi C, Paul C, Blauvelt A, Baran W, et al. Efficacy and safety of brodalumab in patients with moderate to severe plaque psoriasis: Results of AMAGINE-1, a phase 3, randomized, double-blind, placebo-controlled study through week 12: 275. J Am Academy Dermatology. 2015;72(5).
Puig L, Lebwohl M, Bachelez H, Sobell J, Jacobson AA. Long-term efficacy and safety of brodalumab in the treatment of psoriasis: 120-week results from the randomized, double-blind, placebo-and active comparator-controlled phase 3 AMAGINE-2 trial. J Am Academy Dermatology. 2020;82(2):352-9.
Strober B, Langley R, Blicharski T, Paul C, Lacour JP, Tyring S, et al. AMAGINE-3: a phase 3 study of efficacy and safety of brodalumab compared with placebo and ustekinumab in moderate to severe plaque psoriasis subjects: 1146. J Am Academy Dermatology. 2015;72(5).
Blauvelt A, Papp KA, Lebwohl MG, Green LJ, Hsu S, Bhatt V, et al. Rapid onset of action in patients with moderate-to-severe psoriasis treated with brodalumab: a pooled analysis of data from two phase 3 randomized clinical trials (AMAGINE-2 and AMAGINE-3). J Am Academy Dermatology. 2017;77(2):372-4.
Papp KA, Gordon KB, Langley RG, Lebwohl MG, Gottlieb AB, Rastogi S, et al. Impact of previous biologic use on the efficacy and safety of brodalumab and ustekinumab in patients with moderate‐to‐severe plaque psoriasis: integrated analysis of the randomized controlled trials AMAGINE‐2 and AMAGINE‐3. British J Dermatology. 2018;179(2):320-8.
Lebwohl M, Strober B, Menter A, Gordon K, Weglowska J, Puig L, et al. Phase 3 studies comparing brodalumab with ustekinumab in psoriasis. New England J Med. 2015;373(14):1318-28.
Sawyer L, Fotheringham I, Wright E, Yasmeen N, Gibbons C, Moller HA. The comparative efficacy of brodalumab in patients with moderate-to-severe psoriasis: a systematic literature review and network meta-analysis. J Dermatological Treatment. 2018;29(6):557-68.
Sallehy RS, Gooderham M, Papp K. Brodalumab: a review of safety. Skin Therapy Lett. 2018;23(2):1-3.
Foulkes AC, Warren RB. Brodalumab in psoriasis: evidence to date and clinical potential. Drugs Context. 2019;8.
Papp KA, Reich K, Paul C, Blauvelt A, Baran W, Bolduc C, et al. A prospective phase III, randomized, double‐blind, placebo‐controlled study of brodalumab in patients with moderate‐to‐severe plaque psoriasis. British J Dermatology. 2016;175(2):273-86.
Parsons L. Leo Pharma to market Astrazenecea’s Brodalumab Outside Europe United Kingdoms, PM Group Worldwide Ltd; 2019. Available at http://www.pmlive.com/pharma_news/leo_pharma_to_market_astrazenecas_brodalumab_outside_europe_1297.