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Role of biologics: ustekinumab


receiving ustekinumab 45mg versus 60.3% in the 90mg group)(Figure 1).33 Of the patients with dactylitis at baseline, 60.8% in the 45mg ustekinumab group and 53.8% in the 90mg group showed a complete improvement at week 52. The corresponding percentages of patients with enthesitis at baseline who showed improvement at week 52 were 44.4% and 45.8%.33


Administration


For plaque psoriasis, ustekinumab is approved for administration as a 45mg injection followed by a 45mg dose four weeks later, and then every 12 weeks thereafter. For patients with a body weight >100kg, the initial dose is 90mg, followed by a 90mg dose four weeks later, and then every 12 weeks thereafter.12


In


these patients, 45mg was also shown to be efficacious. However, 90mg resulted in greater efficacy.21–23,35


For psoriatic


arthritis, ustekinumab is approved as an initial dose of 45mg, followed by a 45mg dose four weeks later, and then every 12 weeks thereafter. Alternatively, 90mg may be used in patients with a body weight >100kg.12


Ustekinumab is administered by SC injection. Its half-life is approximately three weeks (range: 15–32 days).32 l


References


1. Toussirot E, Michel F, Béreau M, Binda D. Ustekinumab in chronic immune-mediated diseases: a review of long term safety and patient improvement. Patient Prefer Adherence 2013;26(7):369–77.


2. Benson JM et al. Therapeutic targeting of the IL-12/23 pathways: generation and characterization of ustekinumab. Nat Biotechnol 2011;29(7):615–24.


3. Benson JM et al. Discovery and mechanism of ustekinumab: a human monoclonal antibody targeting interleukin-12 and interleukin-23 for treatment of immune-mediated disorders. MAbs 2011;3(6):535–45.


4. Hong K et al. IL-12, independently of IFN-gamma, plays a crucial role in the pathogenesis of a murine psoriasis-like skin disorder. J Immunol 1999;162(12):7480–91.


5. Aggarwal S et al. Interleukin-23 promotes a distinct CD4 T cell activation state characterized by the production of interleukin-17. J Biol Chem 2003;17;278(3):1910–4.


6. Di Cesare A, Di Meglio P, Nestle FO. The IL-23/ Th17 axis in the immunopathogenesis of psoriasis. J Invest Dermatol 2009;129(6):1339–50.


16


7. Elliott M et al. Ustekinumab: lessons learned from targeting interleukin-12/23p40 in


www.hospitalpharmacyeurope.com


immunemediated diseases. Ann N Y Acad Sci 2009;1182:97–110.


8. Kurzeja M, Rudnicka L, Olszewska M. New interleukin-23 pathway inhibitors in dermatology: ustekinumab, briakinumab, and secukinumab. Am J Clin Dermatol 2011;12(2):113–25.


9. Toussirot E. The IL23/Th17 pathway as a therapeutic target in chronic inflammatory diseases. Inflamm Allergy Drug Targets 2012;11(2):159–68.


10. Sherlock JP et al. IL-23 induces


spondyloarthropathy by acting on ROR-[gamma] t+ CD3+ CD4-CD8-entheseal resident T cells. Nat Med 2012;18(7): 1069–76.


11. Stelara Full Prescribing Information. http://www. accessdata.fda.gov/spl/data/69e4e4b9-e2da- 4113-963d-623665a5102a/69e4e4b9-e2da-4113- 963d-623665a5102a.xml#section-1.2. Accessed January 2014.


12. Stelara Summary of Product Characteristics. http://www.ema.europa.eu/docs/en_GB/ document_library/EPAR_-_Product_Information/ human/000958/WC500058513.pdf. Accessed January 2014.


13. Sandborn WJ et al. Ustekinumab induction and maintenance therapy in refractory Crohn’s disease. N Engl J Med 2012;367(16):1519–28.


14. Sandborn WJ et al. A randomized trial of Ustekinumab, a human interleukin-12/23 monoclonal antibody, in patients with moderate- to-severe Crohn’s disease. Gastroenterology 2008;135(4):1130–41.


15. Study identifier: NCT01369355. http://clinicaltrials.gov/ ct2/show/NCT01369355. Accessed January 2014.


16. Study identifier: NCT01369342. http://clinicaltrials.gov/ ct2/show/NCT01369342. Accessed January 2014.


17. Study identifier: NCT01369329. http://clinicaltrials.gov/ ct2/show/NCT01369329. Accessed January 2014.


18. Study identifier: NCT01330901. http://clinicaltrials.gov/ ct2/show/NCT01330901. Accessed January 2014.


19. Study identifier: NCT01645280. http://clinicaltrials.gov/ ct2/show/NCT01645280. Accessed January 2014.


20. Segal BM et al. Repeated subcutaneous injections of IL12/23 p40 neutralising antibody, ustekinumab, in patients with relapsing- remitting multiple sclerosis: a phase II, double-blind, placebo-controlled, randomised, dose-ranging study. Lancet Neurol 2008;7(9):796–804.


21. Krueger GG et al. CNTO 1275 Psoriasis Study Group. A human interleukin-12/23 monoclonal antibody for the treatment of psoriasis. N Engl J Med 2007;8;356(6):580–92.


22. Leonardi CL et al. PHOENIX1 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;17:1665–74.


23. Papp KA et al. PHOENIX 2 study investigators. Efficacy and safety of ustekinumab, a human


interleukin-12/23 monoclonal antibody, inpatients with psoriasis: 52-week results from a randomised, double-blind, placebo-controlled trial (PHOENIX 2). Lancet 2008;17:1675–84.


24. Papp KA et al. Long-term Safety of Ustekinumab in Patients With Moderate-to-Severe Psoriasis. Final Results From 5 Years of Follow-Up. Br J Dermatol 2013;168(4):844–54.


25. Kimball AB et al. Long-term efficacy of ustekinumab in patients with moderate-to-severe psoriasis treated for up to 5 years in the PHOENIX 1 study. J Eur Acad Dermatol Venereol 2013;27(12):1535–45.


26. Ghislain P et al. Maintenance of long-term efficacy of ustekinumab through year 3 for patients with moderate-to-severe psoriasis [abstract no. P589]. 19th Congress of the Eur Acad Dermatol and Venerol 2010;6–10, Gothenburg.


27. Lebwohl M et al. Ustekinumab improves health-related quality of life in patients with moderate to severe psoriasis: results from the PHOENIX I trial. Br J Dermatol 2010;162(1):137–46.


28. Langley RG et al. Ustekinumab significantly improves symptoms of anxiety, depression, and skin related quality of life in patients with moderate to severe psoriasis: results from a randomized, double-blind, placebo controlled phase III trial. J Am Acad Dermatol 2010;63(3):457–65.


29. Guenther L et al. Impact of ustekinumab on health related quality of life and sexual difficulties associated with psoriasis: results from two phase III clinical trials. J Eur Acad Dermatol Venereol 2011;25(7):851–7.


30. Reich K et al. One year safety and efficacy of ustekinumab and results of dose adjustment after switching from inadequate methotrexate treatment: the TRANSIT randomized trial in moderate-to-severe plaque psoriasis. Br J Dermatol Sept 2013 [Epub ahead of print].


31. Griffiths CEM et al. Comparison of ustekinumab and etanercept for moderate to severe psoriasis. N Engl J Med 2010;362(2):118–28.


32. Croxtall JD. Ustekinumab: a review of its use in the management of moderate to severe plaque psoriasis. Drugs 2011;71(13):1733–53.


33. McInnes IB et al. PSUMMIT 1 Study Group. Efficacy and safety of ustekinumab in patients with active psoriatic arthritis: 1 year results of the phase 3, multicentre, double-blind, placebo- controlled PSUMMIT 1 trial. Lancet 2013;382(9894):780–9.


34. Ritchlin CT et al. Ustekinumab in active psoriatic arthritis including patients previously treated with anti-TNF agents: results of a phase 3, multicentre, double-blind, placebo-controlled study. Arthritis Rheum 2012;64(Suppl 10):S1080–1.


35. Lebwohl M et al. Impact of weight on the efficacy and safety of ustekinumab in patients with moderate to severe psoriasis: rationale for dosing recommendations. J Am Acad Dermatol 2010;63:571–9.


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