Brodalumab

Recombinant, fully human, monoclonal immunoglobulin IgG2 antibody. The antibody binds with high affinity to human IL-17RA(interleukin-17 receptor), thereby inhibiting the biological activities of the pro-inflammatory cytokines IL-17A, IL-17C, IL-17F, IL-17A / F heterodimer and IL-25, resulting in broad inhibition of psoriatic inflammation.

The results of two phase III studies (AMAGINE-2 and AMAGINE-3) in more than 1,800 patients with moderate to severe plaque psoriasis showed that 36.7% of patients in the 210 mg brodalumab group, 18.5% in a group with the IL-12/-23 antagonist ustekinumab (Stelara®), and 0.3% in the placebo group were completely appearance-free (PASI 100) (Lebwohl M et al. 2015).

85.1% in the brodalumab group (210mg), 69.3% of the Stelara group and 6% of the placebo group achieved a PASI 75.

Other smaller studies showed analogous results in psoriasis vulgaris and psoriatic arthritis. (Mease PJ et al. 2014)

Medium to severe plaque psoriasis(psoriasis vulgaris). Directly approved in the EU for first-line treatment. In the USA, only approved as second-line therapy under the name Siliq.

In the first 3 weeks of treatment 210mg Brodulmab 1x/week s.c. Thereafter 210mg Brodulmab every 2 weeks s.c.

Significantly increased risk of infection. During a 12-week study, 0.5% of the volunteers developed severe infections. Special caution is required in patients with chronic or recurrent infections. Patients with active tuberculosis should not be treated with Brodalumab. Patients with Crohn's disease may experience activation of the disease.

Other common side effects include arthralgia and myalgia, headache and sore throat, fatigue, diarrhoea, nausea, local reactions at the injection site, neutropenia and fungal infections (Papp KA et al. 2012).

There are reports of suicidal thoughts and attempts of suicide under Brodalumab therapy in the trials, including completed suicide. A causal link between treatment with Brodalumab and an increased risk of suicidal thoughts and behaviour has not been proven.

Brodalumab (Kyntheum®)

1. Lebwohl M et al (2015) Phase 3 Studies Comparing Brodalumab with Ustekinumab in Psoriasis. N Engl J Med 373:1318-1328.
2. Bauer E et al (2015) Brodalumab -an IL-17RA monoclonal antibody for psoriasis and psoriatic arthritis. Expert Opinion Biol Ther 15:883-893.
3. Malakouti M et al. (2015) The role of IL-17 in psoriasis. J Dermatolog Treat 26:41-44.
4. Mease PJ et al (2014) Brodalumab, an anti-IL17RA monoclonal antibody, in psoriatic arthritis. N Engl J Med 370:2295-2306.
5. Papp K et al (2014) Safety and efficacy of brodalumab for psoriasis after 120 weeks of treatment. J Am Acad Dermatol 71:1183-1190.
6. Papp KA et al (2012) Brodalumab, an anti-interleukin-17-receptor antibody for psoriasis. N Engl J Med 366:1181-1189.