Psoriasis – brodalumab

Psoriasis is a chronic autoimmune condition characterised by thick and scaly red or pink patches forming on the skin. These most commonly form on the elbows, knees, scalp and trunk. Treatment has been revolutionised by the development of monoclonal antibody drugs that act on the immune system in a disease modifying manner. The previous options open to patients, including methotrexate, retinoids and the immunosuppressant cyclosporin, give only symptomatic relief.

Brodalumab is a new antibody that is being investigated in autoimmune conditions including psoriasis. The drug, being co-developed by Amgen and AstraZeneca, is a monoclonal antibody that binds to the interleukin-17 receptor. This prevents native IL-17 from binding, interfering with the signalling cascade that leads to inflammation.

In a Phase II randomised, double blind, placebo-controlled, dose ranging clinical trial, 198 patients with at least 10% of their body surface area affected by psoriasis were given 20, 140 or 210mg of brodalumab at day one and further doses at weeks 1, 2, 4, 6, 8 and 10, 280mg once a month, or placebo.¹ After 12 weeks, mean percentage improvements in psoriasis area-and-severity index (PASI) scores ranged from 45% in the lowest dose to 86% in the highest fortnightly dose, 76% in the monthly dose group, and just 16% in those who were given placebo. Two instances of grade 3 neutropoenia occurred in the 210mg group, and the most common adverse events were naso-pharyngitis, upper respiratory tract infection and injection side erythema.

It is also being assessed in psoriatic arthritis. This is a common affliction in patients with psoriasis, who experience joint pain, stiffness and swelling that often gets worse over time, leading to irreversible joint damage. A Phase II randomised, double blind, placebo-controlled study has been carried out in 168 patients with psoriatic arthritis, who were given 140 or 280mg subcutaneous doses of the antibody or placebo on day one and at weeks 1, 2, 4, 6, 8 and 10.² Those still participating in the study at week 12 were offered open label 280mg doses of the antibody every two weeks.

Of those who enrolled, 159 completed the double blind phase, and 134 completed 40 weeks of open label extension. At week 12, those given the antibody had significantly greater improvements in disease response criteria than those given the placebo. Placebo-treated patients switched to brodalumab in the open label extension also experienced significant improvements once they were given the antibody. Similar improvements were seen in patients who had previously been treated with another antibody and those who had not. By week 12, 3% of patients given brodalumab had experienced a serious adverse event, and 2% of the placebo group.

The drug is now in Phase III trials for psoriasis. It is also being developed as a potential treatment for asthma, for which it is in Phase II trials.

References

1. K.A. Papp et al. N. Engl. J. Med. 2012, 366, 1181

2. P.J. Mease et al. N. Engl. J. Med. 2014, 370, 2295