Brodalumab, sold under the brand name Siliq in the US and Kyntheum in the EU, is a human monoclonal antibody designed for the treatment of inflammatory diseases.In February 2017, it received US FDA approval to treat moderate to severe plaque psoriasis in people who have not improved with other treatments. Mechanism of action
Brodalumab binds to the interleukin-17 receptor and so prevents interleukin 17 (IL-17) from activating the receptor. This mechanism is similar to that of another anti-psoriasis antibody, ixekizumab, which however binds to IL-17 itself. History
Brodalumab was developed by Amgen, Inc. as AMG 827. In 2013, it was in two phase III clinical trials for the treatment of moderate to severe psoriasis.In November 2014, Amgen and AstraZeneca reported encouraging results for the compound. The companies stated that the compound met the primary endpoint showing superior skin clearance in a Phase III trial when compared to ustekinumab and a placebo.However, in May 2015, Amgen announced that it was ending its participation in co-development of the compound because of reports of patients having "events of suicidal ideation and behavior". AstraZeneca will be solely responsible for any future development and marketing of brodalumab in all territories except for certain Asian territories such as Japan, where Kyowa Hakko Kirin has rights to brodalumab and continued as KHK4827. In September 2015, AstraZeneca announced a partnership with Valeant Pharmaceuticals in which Valeant took over exclusive rights to develop and commercialize brodalumab.
In most cases of familial inheritance, the benign variant of the disease has been present.Due to the lack of knowledge of the pathomechanism for this condition prevention strategies are not known. However, in order to prevent worsening of symptoms, consistent evaluations should be conducted by a physician. Mechanism
Although this disease has been known for around 70 years, the pathomechanism underlying it is still unknown. Several hypotheses have been developed regarding the underlying mechanism for Degos disease. One theory suggests that inflammation of blood vessels may trigger the condition. Another theory has to do with Degos disease as a coagulopathy. Development of a thrombus and resulting reduction of blood flow is common in this condition. A reduction in blood flow throughout the body can lead to damaged endothelial cells and may perhaps lead to the formation of the characteristic papules. Another hypothesis suggests that abnormal swelling and proliferation of the vascular endothelium can lead to intestinal and central nervous system thrombosis, and ultimately lead to development of symptoms associated with Degos disease. Overall, individuals with Degos disease have abnormal blockages in their arteries and veins; however, the cause of these blockages is unknown. Diagnosis
Clinical evaluation and identification of characteristics papules may allow a dermatologist to diagnose Degos disease. The papules have a white center and are bordered with a red ring. After lesions begin to appear, the diagnosis for Degos disease can be supported by histological findings. Most cases will show a wedge-shaped connective tissue necrosis in the deep corium.