Ustekinumab
DefinitionThis section has been translated automatically.
Antipsoriatically effective drug from the group of biologicals. Ustekinumab is a human monoclonal antibody directed against the p40 subunits of the cytokines interleukin-12(IL-12) and -23 (IL-23).
Pharmacodynamics (Effect)This section has been translated automatically.
Pathogenetic principle using human IL-12 antibody or IL-23 antibody directed against the P40 subunits of these interleukins and thus inhibiting their activity. IL-12 and IL-23 are significantly involved in the immune response of the psoriatic reaction. 80% of psoriatics under ustekinumab treatment achieve a PASI response of 75% after an average therapy duration of 112 days.
Field of application/useThis section has been translated automatically.
Approved for the treatment of moderate to severe plaque psoriasis in adults in whom other basic therapies (e.g. MTX, cyclosporine, fumarates, PUVA) have failed to respond or have failed adequately, or in whom contraindications or intolerances have arisen.
Dosage and method of useThis section has been translated automatically.
Initial: 45 mg s.c. as ED at the start of therapy and after 4 weeks. Subsequently 45 mg s.c. every 12 weeks. In case of resistance to therapy, the dosage can be increased to 90 mg s.c. every 12 weeks.
Improvements can be expected after 4-6 weeks.
Undesirable effectsThis section has been translated automatically.
Frequent: Infections, especially of the upper respiratory tract (> 10 %). Depression, dizziness, headache, diarrhoea, itching, muscle pain and fatigue occur in 1-10 % of patients. Inflammatory reactions at the injection site have been observed.
Immunogenicity: Antibodies against ustekinumab are observed in 4-6% of treated patients. It is not known whether the effectiveness of treatment suffers from this (Altenburg A et al. 2018).
PreparationsThis section has been translated automatically.
Stelara®
Note(s)This section has been translated automatically.
The approval of ustekinumab is based on two large placebo-controlled Phase III studies. In the PHOENIX 1 study, 766 patients with moderate to severe psoriasis were treated. In the PHOENIX 2 study, 1230 patients were treated. The primary endpoint in both studies was the proportion of patients who achieved a reduction in psoriasis of at least 75% of the PASI at week 12. The direct comparison (head-to-head study) to the TNF-alpha blocker etanercept (50 mg/week) showed a clear superiority of the interleukin antibody ustekinumab in a larger study (ACCEPT study; 903 patients), with comparable tolerability. In a meta-analysis of 15 randomized controlled trials, ustekinumab (45mg) achieved a convincing effect compared to adalimumab, etanercetp and infliximab(PASI 50 - 90%; PASI 75 - 75%; PASI 90 - 46%).
It is important to pre-clear tuberculosis status, as reactivation is possible with therapy.
Ustekinumab is not effective in atopic dermatitis (Saeki H et al. 2017).
LiteratureThis section has been translated automatically.
- Altenburg A et al (2018) Biologic side effects in psoriasis. Dermatologist 69: 290-297
- Leonardi CL et al (2008) 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 17: 1665-1674
- Griffith C et al (2008) EADV Meeting, Abstract 1336
- Metheson R et al (2010) Ustekinumab shows uniform response across different body regions and PASI components in moderately severe to severe plaque psoriasis: Results of the PHOENIX I and PHOENIX II studies: JDDG 8: 956
- Reich K et al(2012) Efficacy of biologics in the treatment of moderate to severe psoriasis: a network meta-analysis of randomized controlled trials. Br J Dermatol 166: 179-188
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Saeki H et aal. (2017) Efficacy and safety of ustekinumab in Japanese patients with severe atopic dermatitis: a randomized, double-blind, placebo-controlled, phase II study. Br J Dermatol 177:419-427.