Behcet’s uveitis – gevokizumabn

5-Nov-2012

Behçet’s disease causes severe non-infectious uveitis in about half of all patients and if not treated rapidly, can lead to blindness

Behçet’s disease commonly affects adults in their 20s, 30s and 40s, and is characterised by vasculitis, a chronic inflammation of the blood vessels. The neurological, pulmonary, cardio-vascular and gastrointestinal systems can all be affected, and patients commonly suffer from painful mouth and genital ulcers. It is particularly common in people from the eastern Mediterranean countries and Turkey, Korea and Japan.

It causes severe non-infectious uveitis in about half of all patients, with recurrent acute attacks, and if not treated rapidly, it can lead to detached retina, vitreous haemorrhage, glaucoma and blindness. Symptoms include vitreous haze that can cause complete loss of vision during an exacerbation. Treatments are limited, and include corticosteroids and off-label immunosuppressants, but significant side-effects are common.

Gevokizumab is being developed by Servier, under licence from Xoma, as a potential treatment for Behçet’s uveitis. It is a humanised anti-interleukin-1β monoclonal antibody, and is thought to interfere with the inflammatory pathway mediated by this cytokine via the interleukin-1 receptor by binding to IL-1β, which is believed to be involved in Behçet’s uveitis and a range of other autoinflammatory diseases.1 By inhibiting the activation of its receptor, it modulates the cellular signalling effects that lead to inflammation.

A safety and pharmacokinetic evaluation was carried out in four patients who were resistant to azathioprine and/or cyclosporin and receiving 10mg/day or less of prednisolone.2 They were given 0.3mg/kg of bevacizumab, with immuno-suppressants being stopped at the start of the trial. Intraocular inflammation resolved in all patients from the first day, and a complete resolution of retinal problems and vitreous haze was achieved within seven to 14 days.

In a second open-label pilot study, seven Behçet’s patients with acute posterior or paneuveitis, either with or without retinal vasculitis, were treated for 98 days.3 Immuno-suppressant drugs were discontinued, and they were given a single infusion of 0.3mg/kg of the antibody. Patients experienced a rapid and durable clinical response, with complete resolution of intraocular inflammation achieved in 4–21 days. The median duration of response was 49 days, with one patient remaining free from exacerbations throughout. A Phase III trial is now under way.

References

1. M.K. Roell et al. J. Biol. Chem. 2010, 151, 2515

2. A. Gül et al. Ann. Rheum. Dis. 2010, 69 (Suppl. 3), 178

3. A. Gül et al. Ann. Rheum. Dis. 2012, 71, 563

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