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Long-term safety – part 2/2

and herpes zoster than adalimumab and infliximab. Ustekinumab, launched more recently, is recommended in the British Association of Dermatologists biologic guidelines as second-line biologic therapy in patients with moderate-to-severe plaque psoriasis, due to a relative lack of long-term safety data at the time of publication. The short- and long-term risk of MACE for ustekinumab remains to be more precisely elucidated. However, recent data provided by Papp and colleagues suggests that long-term treatment with ustekinumab is not associated with an increased risk of MACE.14

Conclusions from the authors The above review of the AEs occurring in patients treated long-term (two to five years) with the biologics did not reveal any evidence of cumulative toxicity of either the anti-TNFa agents or ustekinumab. As expected, the anti-TNFs produced a slightly higher rate of serious infections and NMSC, but a larger number of patients and a longer observation time are needed to determine whether there is any increase in other known AEs listed in Tables 1 and 2. Biological agents seem to decrease the cumulative risk of MACE in psoriasis patients. The mean duration of drug exposure necessary to produce a single AE is in the range of 50 years and the risk of occurrence of any unpredicted AE is likely to be below 0.1%/year. Thus, the benefit/risk ratio for the biologics is very high, possibly even exceeding that of conventional systemic agents used in the therapy of psoriasis. Given that long-term safety is a critical determinant in the choice of treatment for chronic conditions, it is important that further studies be carried out for all of the biologics in order to establish their individual long-term safety profiles in patients with moderate-to-severe plaque psoriasis. It is expected that registries will contribute significantly to the safety dataset for biologics, especially with regard to real-world use, and a combination of data sources should provide the most comprehensive view of safety for biologics over the long term. l

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14. 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.

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22. Papp KA et al. PSOLAR: design, utility, and preliminary results of a prospective, international, disease-based registry of patients with psoriasis who are receiving, or are candidates for, conventional systemic treatments or biologic agents. J Drugs Dermatol 2012;11(10):1210–7.

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24. Gniadecki R, Kragballe K, Dam TN, Skov L. Comparison of drug survival rates for adalimumab, etanercept and infliximab in patients with psoriasis vulgaris. Br J Dermatol 2011;164(5):1091–6.

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29. Lebwohl M et al. Long term safety experience of ustekinumab in patients with moderate-to-severe psoriasis (Part I of II): results from analyses of general safety parameters from pooled Phase 2 and 3 clinical trials. J Am Acad Dermatol 2012;66:731–41.

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