OVERVIEW

PRODUCT INFORMATION

CHEMICAL FORMULA AND STRUCTURE

ANNOTATED BIBLIOGRAPHY

References updated: 26 June 2018

• 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; does not mention guselkumab specifically but discusses the problems of reactivation of hepatitis B and states that "the biological immunosuppressants are largely free from hepatotoxicity, with the exception of the TNF alpha antagonists").
• Chabner BA, Barnes J, Neal J, Olson E, Mujagiv H, Sequist L, Wilson W, et al. Targeted therapies: tyrosine kinase inhibitors, monoclonal antibodies, and cytokines. In, Brunton LL, Chabner BA, Knollman BC, eds. Goodman & Gilman's the pharmacological basis of therapeutics. 12th ed. New York: McGraw-Hill, 2011, pp. 1731-53.

  (Textbook of pharmacology and therapeutics).
• Leonardi CL, Kimball AB, Papp KA, Yeilding N, Guzzo C, Wang Y, Li S, et al.; PHOENIX 1 study investigators. Efficacy and safety of ustekinumab, a human interleukin-12/23 monoclonal antibody, in patients with psoriasis: 76-week results from a randomised, double-blind, placebo-controlled trial (PHOENIX 1). Lancet 2008; 371 (9625): 1665-74. [PubMed: 18486739]

  (Among 766 patients with psoriasis treated with 1 of 2 doses of ustekinumab or placebo for 12 weeks, response rates were 67% and 66% with ustekinumab vs 3% with placebo, and side effects were similar and "results of laboratory results were much the same" in the 3 groups).
• Papp KA, Langley RG, Lebwohl M, Krueger GG, Szapary P, Yeilding N, Guzzo C, et al.; PHOENIX 2 study investigators. Efficacy and safety of ustekinumab, a human interleukin-12/23 monoclonal antibody, in patients with psoriasis: 52-week results from a randomised, double-blind, placebo-controlled trial (PHOENIX 2). Lancet 2008; 371 (9625): 1675-84. [PubMed: 18486740]

  (Among 1230 patients with psoriasis treated for 12 weeks with 1 of 2 doses of ustekinumab or placebo, clinical response rates were 67% and 76% with ustekinumab vs 4% with placebo, and "rates of laboratory abnormalities were similar between groups, and no differences were noted in liver aminotransferase concentrations").
• Gottlieb A, Menter A, Mendelsohn A, Shen YK, Li S, Guzzo C, Fretzin S, et al. Ustekinumab, a human interleukin 12/23 monoclonal antibody, for psoriatic arthritis: randomised, double-blind, placebo-controlled, crossover trial. Lancet 2009; 373 (9664): 633-40. [PubMed: 19217154]

  (Among 146 patients with psoriatic arthritis treated with either ustekinumab or placebo, responses at week 12 were more frequent with ustekinumab [42% vs 10%] and, while overall rates of adverse events were similar [61% vs 63%], ALT elevations occurred in 4% of ustekinumab vs 1% of placebo recipients).
• Griffiths CE, Strober BE, van de Kerkhof P, Ho V, Fidelus-Gort R, Yeilding N, Guzzo C, et al.; ACCEPT Study Group. Comparison of ustekinumab and etanercept for moderate-to-severe psoriasis. N Engl J Med 2010; 362: 118-28. [PubMed: 20071701]

  (Among 903 patients with psoriasis treated with 1 of 2 doses of ustekinumab vs etanercept for 12 weeks, clinical response rates were higher with ustekinumab [68-74% vs 57%], while rates of ALT elevations were similar [0.5-0.9% vs 1.2%]).
• Opel D, Economidi A, Chan D, Wasfi Y, Mistry S, Vergou T, Antoniou C, Sofen H. Two cases of hepatitis B in patients with moderate to severe psoriasis with ustekinumab. J Drugs Dermatol 2012; 11: 1498-501. [PubMed: 23377523]

  (Two men, 33 and 40 years old, with severe psoriasis developed acute hepatitis B during ustekinumab therapy and recovered with clearance of HBsAg).
• Chiu HY, Chen CH, Wu MS, Cheng YP, Tsai TF. The safety profile of ustekinumab in the treatment of patients with psoriasis and concurrent hepatitis B or C. Br J Dermatol 2013; 169: 1295-303. [PubMed: 23746170]

  (Among 18 patients with psoriasis and concurrent hepatitis B or C, reactivation of HBV occurred in 2 of 11 with HBsAg, but with a rise in HBV DNA levels only, without symptoms or ALT elevations, while reactivation of HCV occurred in 1 of 4 patients marked by a rise in HCV RNA without change in ALT).
• Motaparthi K, Stanisic V, Van Voorhees AS, Lebwohl MG, Hsu S; Medical Board of the National Psoriasis Foundation. From the Medical Board of the National Psoriasis Foundation: Recommendations for screening for hepatitis B infection prior to initiating anti-tumor necrosis factor-alfa inhibitors or other immunosuppressive agents in patients with psoriasis. J Am Acad Dermatol 2014; 70: 178-86. [PubMed: 24220724]

  (Mentions that little is known about the effects of ustekinumab on HBV infection, but that screening for hepatitis B markers is "advisable" before its use).
• Sofen H, Smith S, Matheson RT, Leonardi CL, Calderon C, Brodmerkel C, Li K, et al. Guselkumab (an IL-23-specific mAb) demonstrates clinical and molecular response in patients with moderate-to-severe psoriasis. J Allergy Clin Immunol 2014; 133: 1032-40. [PubMed: 24679469]

  (Among 24 patients with moderate-to-severe psoriasis treated with a single dose of guselkumab [10, 30, 100 or 300 mg] or placebo, clinical responses occurred in 60% to 100% of those given the higher doses but in no placebo recipient; the adverse events were similar in the 5 groups and there were no serious adverse events).
• Gordon KB, Duffin KC, Bissonnette R, Prinz JC, Wasfi Y, Li S, Shen YK, et al. A phase 2 trial of guselkumab versus adalimumab for plaque psoriasis. N Engl J Med 2015; 373: 136-44. [PubMed: 26154787]

  (Among 293 patients with moderate-to-severe plaque psoriasis treated with one of 5 regimens of guselkumab vs placebo or adalimumab for 16 weeks, clinical improvements were greater with higher doses of guselkumab while rates of adverse events were similar).
• Blauvelt A, Papp KA, Griffiths CE, Randazzo B, Wasfi Y, Shen YK, Li S, et al. Efficacy and safety of guselkumab, an anti-interleukin-23 monoclonal antibody, compared with adalimumab for the continuous treatment of patients with moderate to severe psoriasis: Results from the phase III, double-blinded, placebo- and active comparator-controlled VOYAGE 1 trial. J Am Acad Dermatol 2017; 76: 405-17. [PubMed: 28057360]

  (Among 837 patients with psoriasis treated with guselkumab [329], placebo [174] or adalimumab [334], clinical responses were more frequent with guselkumab [85%] than placebo [7%] or adalimumab [66%], while adverse event rates were similar; no mention of ALT elevations or hepatotoxicity).
• Reich K, Armstrong AW, Foley P, Song M, Wasfi Y, Randazzo B, Li S, et al. Efficacy and safety of guselkumab, an anti-interleukin-23 monoclonal antibody, compared with adalimumab for the treatment of patients with moderate to severe psoriasis with randomized withdrawal and retreatment: Results from the phase III, double-blind, placebo- and active comparator-controlled VOYAGE 2 trial. J Am Acad Dermatol 2017; 76 (3): 418-31. [PubMed: 28057361]

  (Among 992 patients with psoriasis treated with guselkumab [496], placebo [280] or adalimumab [248], clinical responses were more frequent with guselkumab [84%] than placebo [9%] or adalimumab, while adverse event rates were similar and 1% of both treated groups developed a serious infection; no mention of ALT elevations or hepatotoxicity).
• Langley RG, Tsai TF, Flavin S, Song M, Randazzo B, Wasfi Y, Jiang J, et al. Efficacy and safety of guselkumab in patients with psoriasis who have an inadequate response to ustekinumab: Results of the randomized, double-blind, Phase 3 NAVIGATE trial. Br J Dermatol 2018; 178: 114-23. [PubMed: 28635018]

  (Among 268 patients with psoriasis who had an inadequate response to a 16-week course of ustekinumab, response rates after 52 weeks were greater in those who switched to guselkumab [36%] than in those who remained on ustekinumab [17%], while adverse events were more frequent with guselkumab [64% vs 56%] including infections requiring antibiotics [16% vs 10%]; no mention of ALT elevations or hepatotoxicity).
• Nakamura M, Lee K, Jeon C, Sekhon S, Afifi L, Yan D, Lee K, et al. Guselkumab for the treatment of psoriasis: a review of phase III trials. Dermatol Ther (Heidelb) 2017; 7: 281-92. [PMC free article: PMC5574739] [PubMed: 28639011]

  (Summary of results of 2 phase III randomized controlled trials of guselkumab in psoriasis [Blauvent 2017, Reich 2017]; no mention of ALT elevations or hepatotoxicity).
• Smolen JS, Agarwal SK, Ilivanova E, Xu XL, Miao Y, Zhuang Y, Nnane I, et al. A randomised phase II study valuating the efficacy and safety of subcutaneously administered ustekinumab and guselkumab in patients with active rheumatoid arthritis despite treatment with methotrexate. Ann Rheum Dis 2017; 76: 831-9. [PMC free article: PMC5530337] [PubMed: 28087506]

  (Among 274 patients with rheumatoid arthritis and an inadequate response to methotrexate, response rates were similar at week 28 after adding guselkumab [41%], ustekinumab [54%] or placebo [40%], while adverse event rates were similar in the 3 groups and serious infections were rare [~1%] in both groups treated with biologics).
• Guselkumab (Tremfya) for psoriasis. Med Lett Drugs Ther 2017; 59 (1533): 179-80. [PubMed: 29125591]

  (Concise review of the mechanism of action, clinical efficacy, safety and costs of guselkumab shortly after its approval as therapy of psoriasis in the US; mentions that hepatic enzyme elevations occurred in 2.6% of patients compared to 1.9% of controls and that reactivation of tuberculosis has been reported with its use).
• Deodhar A, Gottlieb AB, Boehncke WH, Dong B, Wang Y, Zhuang Y, Barchuk W, CNTO1959PSA2001 Study Group. Efficacy and safety of guselkumab in patients with active psoriatic arthritis: a randomised, double-blind, placebo-controlled, phase 2 study. Lancet 2018; 391 (10136): 2213-24. [PubMed: 29893222]

  (Among 149 patients with psoriatic arthritis treated with guselkumab or placebo for 24 weeks, clinical responses were more frequent with guselkumab and side effects were mild, ALT elevations occurring in 9% vs 1%, although none were associated with symptoms or jaundice and none required early discontinuation of treatment).
• Terui T, Kobayashi S, Okubo Y, Murakami M, Hirose K, Kubo H. Efficacy and safety of guselkumab, an anti-interleukin 23 monoclonal antibody, for palmoplantar pustulosis: a randomized clinical trial. JAMA Dermatol 2018; 154: 309-16. [PMC free article: PMC5885837] [PubMed: 29417135]

  (Among 49 patients with palmoplantar pustulosis treated with guselkumab or placebo in a 24 week trial, severity index scores improved more with guselkumab than placebo, while adverse event rates were similar and changes in “laboratory values were not clinically relevant).