OVERVIEW

PRODUCT INFORMATION

CHEMICAL FORMULA AND STRUCTURE

ANNOTATED BIBLIOGRAPHY

References updated: 02 October 2017

• Zimmerman HJ. Drugs used to treat rheumatic and musculospastic disease. In, Zimmerman HJ. Hepatotoxicity: the adverse effects of drugs and other chemicals on the liver. 2nd ed. Philadelphia: Lippincott, 1999, pp. 517-54.

  (Expert review of hepatotoxicity published in 1999, well before the availability of most monoclonal antibody therapies).
• Reuben A. Hepatotoxicity of immunosuppressive drugs. In, Kaplowitz N, DeLeve LD, eds. Drug-induced liver disease. 3rd ed. Amsterdam: Elsevier, 2011, pp. 569-91.

  (Review of hepatotoxicity of immunosuppressive agents; mentions rituximab and problems of reactivation of hepatitis B, but also states that "the biological immunosuppressants are largely free from hepatotoxicity, with the exception of the TNF alpha antagonists"; brodalumab is not specifically mentioned).
• Krensky AM, Vincenti F, Bennett WM. Immunomodulators. In, Brunton LL, Lazo JS, Parker KL, eds. Goodman & Gilman's the pharmacological basis of therapeutics. 11th ed. New York: McGraw-Hill, 2006, pp. 1405-88.

  (Textbook of pharmacology and therapeutics).
• Langley RG, Elewski BE, Lebwohl M, Reich K, Griffiths CE, Papp K, Puig L, et al.; ERASURE Study Group; FIXTURE Study Group. Secukinumab in plaque psoriasis--results of two phase 3 trials. N Engl J Med 2014; 371: 326-38. [PubMed: 25007392]

  (Among 1044 patients with plaque psoriasis treated with secukinumab [anti-17A] or placebo in two large 52 week clinical trials, common side effects were nasopharyngitis, upper respiratory infection and diarrhea; no mention of ALT elevations or hepatotoxicity).
• Papp KA, Leonardi C, Menter A, Ortonne JP, Krueger JG, Kricorian G, Aras G, et al. Brodalumab, an anti-interleukin-17-receptor antibody for psoriasis. N Engl J Med 2012; 366: 1181-9. [PubMed: 22455412]

  (Among 198 patients with plaque psoriasis treated with 4 dose regimens of brodalumab or placebo for 12 weeks, rates of symptomatic improvement were above 80% with the higher doses vs 16% with placebo, while adverse event rates were similar in all groups; no liver related serious adverse events and mention of ALT elevations).
• Papp K, Leonardi C, Menter A, Thompson EH, Milmont CE, Kricorian G, Nirula A, et al. Safety and efficacy of brodalumab for psoriasis after 120 weeks of treatment. J Am Acad Dermatol 2014; 71: 1183-1190. [PubMed: 25313095]

  (Among 181 patients with psoriasis treated with brodalumab sc every 2 weeks in an open label extension trial [Papp 2012], half [51%] had persistent clearance of plaque lesions at week 120 and adverse events were usually mild, 15 patients [8%] having a serious adverse event, but none were liver related and most were considered unrelated to therapy).
• Pavelka K, Chon Y, Newmark R, Lin SL, Baumgartner S, Erondu N. A study to evaluate the safety, tolerability, and efficacy of brodalumab in subjects with rheumatoid arthritis and an inadequate response to methotrexate. J Rheumatol 2015; 42: 912-9. [PubMed: 25877498]

  (Among 252 patients with rheumatoid arthritis treated with brodalumab [70, 140 or 210 mg] or placebo injections, rates of symptomatic improvement were similar in all 4 groups as were adverse events, both total [55% vs 51%] and serious [2.6% vs 3.2%]; no mention of ALT elevations or hepatotoxicity).
• Drugs for psoriasis. Med Lett Drugs Ther 2015; 57 (1470): 81-4. [PubMed: 26035746]

  (Concise summary of options for therapy of psoriasis as of 2015 including topical agents, phototherapy, oral systemic drugs, and biologic agents including secukinumab [anti-IL-17A], but not brodalumab [anti-IL-17A receptor] or ixekizumab [anti-IL-17A]; mentions that serious infections occurred in 1.2% of secukinumab treated patients; no mention of hepatotoxicity).
• Lebwohl M, Strober B, Menter A, Gordon K, Weglowska J, Puig L, Papp K, et al. Phase 3 studies comparing brodalumab with ustekinumab in psoriasis. N Engl J Med 2015; 373: 1318-28. [PubMed: 26422722]

  (Among 3712 patients enrolled in two controlled trials of brodalumab [140 or 210 mg], ustekinumab [45 or 90 mg] or placebo for 12 weeks followed by maintenance dosing of either monoclonal, common adverse events were upper respiratory symptoms, headache and arthralgia; among 1613 patients receiving brodalumab, one was listed as having drug induced liver injury compared to none of 313 on ustekinumab, but no details were provided).
• Papp KA, Reich K, Paul C, Blauvelt A, Baran W, Bolduc C, Toth D, et al. A prospective phase III, randomized, double-blind, placebo-controlled study of brodalumab in patients with moderate-to-severe plaque psoriasis. Br J Dermatol 2016; 175: 273-86. [PubMed: 26914406]

  (Among 648 patients with plaque psoriasis treated in an extension trial with brodalumab [140 or 210 mg every 2 weeks], 1 patient with preexisting cirrhosis died after variceal hemorrhage, but there were no other liver related serious adverse events and no mention of ALT elevations).
• Nakagawa H, Niiro H, Ootaki K; Japanese brodalumab study group. Brodalumab, a human anti-interleukin-17-receptor antibody in the treatment of Japanese patients with moderate-to-severe plaque psoriasis: Efficacy and safety results from a phase II randomized controlled study. J Dermatol Sci 2016; 81: 44-52. [PubMed: 26547109]

  (Among 151 patients with plaque psoriasis treated with brodalumab [70, 140 or 210 mg] or placebo for 12 weeks, symptomatic improvements occurred in 60-90% with the higher doses compared to 0-8% with placebo; while adverse event rates were similar, common side effects from brodalumab were nasopharyngitis [12% vs 8%], diarrhea [5% vs 0%], folliculitis [3.5% vs 0%]; no mention of ALT elevations or hepatotoxicity).
• Farahnik B, Beroukhim K, Abrouk M, Nakamura M, Zhu TH, Singh R, Lee K, et al. Brodalumab for the treatment of psoriasis: A review of phase III trials. Dermatol Ther (Heidelb) 2016; 6: 111-24. [PMC free article: PMC4906115] [PubMed: 27221323]

  (Review of results from 3 phase III trials of brodalumab in patients with psoriasis found clinical response rates at 12 weeks of 83-86% with 210 mg, 60-69% with 140 mg, and 3-8% with placebo, while adverse event rates were only slightly higher with brodalumab; no liver related adverse events listed).
• Targan SR, Feagan B, Vermeire S, Panaccione R, Melmed GY, Landers C, Li D, et al. A randomized, double-blind, placebo-controlled phase 2 study of brodalumab in patients with moderate-to-severe Crohn's disease. Am J Gastroenterol 2016; 111 1599-1607. [PubMed: 27481309]

  (Among 130 patients with Crohn disease treated with brodalumab [210, 350 or 700 mg] or placebo subcutaneously at baseline and week 4, overall symptom scores at week 6 worsened with brodalumab, but adverse event rates were similar in all groups; ALT values were not reported).
• Umezawa Y, Nakagawa H, Niiro H, Ootaki K; Japanese Brodalumab Study Group. Long-term clinical safety and efficacy of brodalumab in the treatment of Japanese patients with moderate-to-severe plaque psoriasis. J Eur Acad Dermatol Venereol 2016; 30: 1957-60. [PubMed: 27358210]

  (Among 145 patients with plaque psoriasis treated with brodalumab [140 or 210 mg] every 2 weeks for 1 year as an extension study of a controlled trial, clinical responses were maintained and no patient developed a liver related serious adverse event).
• Yamasaki K, Nakagawa H, Kubo Y, Ootaki K; Japanese Brodalumab Study Group. Efficacy and safety of brodalumab in patients with generalized pustular psoriasis and psoriatic erythroderma: results from a 52-week, open-label study. Br J Dermatol 2017; 176: 741-51. [PubMed: 27106510]

  (Among 145 Japanese patients with plaque psoriasis treated with brodalumab [140 or 210 mg every 2 weeks for 52 weeks] as a part of an extension study of a controlled trial, no patient developed a liver related serious adverse event).