OVERVIEW

PRODUCT INFORMATION

CHEMICAL FORMULA AND STRUCTURE

ANNOTATED BIBLIOGRAPHY

References updated: 25 May 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"; ixekizumab is not specifically mentioned).
• Kensky 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. 1005-30.

  (Textbook of pharmacology and therapeutics).
• Burkhart C, Morrell D, Goldsmith L. Biologic agents. Dermatological pharmacology. In, Brunton LL, Lazo JS, Parker KL, eds. Goodman & Gilman's the pharmacological basis of therapeutics. 11th ed. New York: McGraw-Hill, 2006, pp. 1824-7.

  (Textbook of pharmacology and therapeutics).
• Leonardi C, Matheson R, Zachariae C, Cameron G, Li L, Edson-Heredia E, Braun D, Banerjee S. Anti-interleukin-17 monoclonal antibody ixekizumab in chronic plaque psoriasis. N Engl J Med 2012; 366: 1190-9. [PubMed: 22455413]

  (Among 142 patients with psoriasis treated with ixekizumab [10, 25, 75 or 150 mg] or placebo for 16 weeks, clinical response rates were above 75% at high doses of ixekizumab but only 8% with placebo, and there were no serious adverse events or deaths while mean values of ALT and bilirubin “showed no change from baseline”).
• Gordon KB, Leonardi CL, Lebwohl M, Blauvelt A, Cameron GS, Braun D, Erickson J, et al. A 52-week, open-label study of the efficacy and safety of ixekizumab, an anti-interleukin-17A monoclonal antibody, in patients with chronic plaque psoriasis. J Am Acad Dermatol 2014; 71: 1176-82. [PubMed: 25242558]

  (Among 120 patients with psoriasis enrolled in an open label extension study after a controlled trial [Leonardi 2012], clinical response rates increased and were maintained through 52 weeks; among 15 serious adverse events, none were liver-related and most were considered unrelated to therapy).
• 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-IL-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).
• Genovese MC, Greenwald M, Cho CS, Berman A, Jin L, Cameron GS, Benichou O, et al. A phase II randomized study of subcutaneous ixekizumab, an anti-interleukin-17 monoclonal antibody, in rheumatoid arthritis patients who were naive to biologic agents or had an inadequate response to tumor necrosis factor inhibitors. Arthritis Rheumatol 2014; 66: 1693-704. [PubMed: 24623718]

  (Among 348 patients with rheumatoid arthritis treated with ixekizumab [3, 10, 30, 80 or 180 mg] vs placebo for 12 weeks, clinical improvements were more frequent at the higher doses [39-54%] than with placebo [23-35%], while adverse event rates were similar; one patient on ixekizumab developed ALT elevations above 5 times ULN without bilirubin or Alk P elevations which resolved spontaneously without dose adjustment).
• Griffiths CE, Reich K, Lebwohl M, van de Kerkhof P, Paul C, Menter A, Cameron GS, et al.; UNCOVER-2 and UNCOVER-3 investigators. Comparison of ixekizumab with etanercept or placebo in moderate-to-severe psoriasis (UNCOVER-2 and UNCOVER-3): results from two phase 3 randomised trials. Lancet 2015; 386 (9993): 541-51. [PubMed: 26072109]

  (Among 2570 patients with plaque psoriasis treated with etanercept, placebo or ixekizumab for 12 weeks, clinical improvements were more frequent with ixekizumab [78-90%] than etanercept [42-53%] or placebo [2-7%] as were adverse events, including injection site reactions and headache while “overall, we noted no clinically important changes from baseline in mean liver biochemical test results… in any treatment group”).
• Drugs for psoriasis. Med Lett Drugs Ther 2015; 57 (1470): 81-4. [PubMed: 26035746]

  (Concise summary of current options for therapy of psoriasis 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).
• Genovese MC, Braun DK, Erickson JS, Berclaz PY, Banerjee S, Heffernan MP, Carlier H. Safety and efficacy of open-label subcutaneous ixekizumab treatment for 48 weeks in a phase II study in biologic-naive and TNF-IR patients with rheumatoid arthritis. J Rheumatol 2016; 43: 289-97. [PubMed: 26669919]

  (Among 300 patients with rheumatoid arthritis treated with ixekizumab in a controlled trial [Genovese 2014] who were maintained on ixekizumab for 48 weeks in an open label extension study, clinical responses were maintained and adverse events included one instance of ALT elevations above 5 times ULN that resolved despite continuing therapy without dose adjustment).
• Fragoulis GE, Siebert S, McInnes IB. Therapeutic targeting of IL-17 and IL-23 cytokines in immune-mediated diseases. Annu Rev Med 2016; 67: 337-53. [PubMed: 26565676]

  (Review of the discovery and elucidation of the IL-17 and IL-23 cytokine pathways and their potential role as targets for therapy of immune mediated diseases).
• Gordon KB, Blauvelt A, Papp KA, Langley RG, Luger T, Ohtsuki M, Reich K, et al.; UNCOVER-1 Study Group.; UNCOVER-2 Study Group.; UNCOVER-3 Study Group. Phase 3 trials of ixekizumab in moderate-to-severe plaque psoriasis. N Engl J Med 2016; 375: 345-56. [PubMed: 27299809]

  (Among 3866 patients with plaque psoriasis in controlled trials of ixekizumab who were given extended therapy for at least 60 weeks, clinical responses were maintained in 80% of patients, while serious adverse events included inflammatory bowel disease in 11 and neutralizing antibody in 19 patients [1.7%], but no mention of ALT elevations or hepatotoxicity).
• Ixekizumab (Taltz)--a second IL-17A inhibitor for psoriasis. Med Lett Drugs Ther 2016; 58 (1494): 59-60. [PubMed: 27148922]

  (Concise review of the mechanism of action, clinical efficacy, safety and costs of ixekizumab shortly after its approval in the United States for plaque psoriasis; mentions common adverse effects, but does not mention ALT elevations or hepatotoxicity).
• Saeki H, Nakagawa H, Nakajo K, Ishii T, Morisaki Y, Aoki T, Cameron GS, Osuntokun OO; Japanese Ixekizumab Study Group. Efficacy and safety of ixekizumab treatment for Japanese patients with moderate to severe plaque psoriasis, erythrodermic psoriasis and generalized pustular psoriasis: Results from a 52-week, open-label, phase 3 study (UNCOVER-J). J Dermatol 2017; 44: 355-62. [PMC free article: PMC5412888] [PubMed: 27726163]

  (Among 92 Japanese patients with psoriasis treated with ixekizumab for 52 weeks, clinical responses occurred in 81% and adverse events in 89% including ALT elevations in 5 [6%]; no details provided, but there were no liver related serious adverse events).
• Strober B, Leonardi C, Papp KA, Mrowietz U, Ohtsuki M, Bissonnette R, Ferris LK, et al. Short- and long-term safety outcomes with ixekizumab from 7 clinical trials in psoriasis: Etanercept comparisons and integrated data. J Am Acad Dermatol 2017; 76: 432-40 . [PubMed: 27889292]

  (Among 4209 patients with psoriasis enrolled in 7 clinical trials of ixekizumab and treated for 12-60 weeks, infections were more frequent with ixekizumab, but were mostly mild; no cases of active tuberculosis or invasive fungal infections occurred and no mention of ALT elevations or hepatoxicity).
• Callis Duffin K, Bagel J, Bukhalo M, Mercado Clement IJ, Choi SL, Zhao F, Gill A, et al. Phase 3, open-label, randomized study of the pharmacokinetics, efficacy and safety of ixekizumab following subcutaneous administration using a prefilled syringe or an autoinjector in patients with moderate-to-severe plaque psoriasis (UNCOVER-A). J Eur Acad Dermatol Venereol 2017; 31: 107-13. [PMC free article: PMC5215575] [PubMed: 27500949]

  (Among 204 patients with plaque psoriasis treated with ixekizumab using prefilled syringes vs autoinjectors, clinical response rates at 12 weeks were similar [89% vs 87%] as were adverse events [50% vs 45%]; no mention of ALT elevations or hepatotoxicity).
• Mease PJ, van der Heijde D, Ritchlin CT, Okada M, Cuchacovich RS, Shuler CL, Lin CY, et al.; SPIRIT-P1 Study Group. Ixekizumab, an interleukin-17A specific monoclonal antibody, for the treatment of biologic-naïve patients with active psoriatic arthritis: results from the 24-week randomised, double-blind, placebo-controlled and active (adalimumab)-controlled period of the phase III trial SPIRIT-P1. Ann Rheum Dis 2017; 76: 79-87. [PMC free article: PMC5264219] [PubMed: 27553214]

  (Among 417 patients with active psoriatic arthritis treated with adalimumab, placebo or ixekizumab [80 mg every 2 or 4 weeks] for 24 weeks, clinical response rates were highest with ixekizumab [60% vs 50% and 30%] as were adverse events rates [66% vs 64% vs 47%] including ALT elevations that occurred in 3-4% on ixekizumab vs none on placebo).