Ustekinumab

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.

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.

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).

Stelara®

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).

1. Altenburg A et al (2018) Biologic side effects in psoriasis. Dermatologist 69: 290-297
2. 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
3. Griffith C et al (2008) EADV Meeting, Abstract 1336
4. 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
5. 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

6. 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.