Managed Care - April 2008 - (Page 57) TOMORROW’S MEDICINE and is the most severe form of the disease. NOMID also involves chronic meningitis, mental retardation, seizures, joint and bone deformities, stunted growth, hepatomegaly, leukocytosis, and sensory organ dysfunction that results in deafness and loss of vision. Rilonacept Hoffman took a keen interest in CAPS and pursued this disease with the zeal of a CSI detective. He put out the word to patients with this disease residing in San Diego, as well as to the greater clinical community. He arranged to attend patients’ family reunions throughout the United States to discuss the disorder. Many of the people he spoke with knew they had a problem, but they and their local physicians were stumped as to the cause or treatment. In addition to sharing his knowledge at family reunions in Texas, Georgia, and California, he drew blood — lots of blood — from about 200 different patients. By 1999 he was able to identify the chromosome on which the gene resided that contributed to CAPS and by 2001 the actual gene was discovered. Shortly thereafter the regulatory nature of this gene became evident. This led to research on a potential treatment. That research culminated on Feb. 27, 2008, with an announcement by Regeneron Pharmaceuticals, headquartered in Tarrytown, N.Y., that the FDA had approved rilonacept (brand name Arcalyst), a lyophilized IL-1 blocker. It is indicated for the treatment of CAPS, including FCAS and MWS in adults and children ages 12 and older. Rilonacept was not tested in patients with NOMID and hence does not have an FDA indication for this form. This drug is a true biologic as it is the result of recombinant DNA technology. Rilonacept blocks IL-1β signaling by acting as a soluble decoy receptor that binds serum IL1 and prevents its interaction with cell surface receptors. Rilonacept also binds IL-1α and IL1 receptor antagonist with reduced affinity. Warnings and precautions Blocking IL-1 may interfere with immune response to infections. Live vaccines should not be given concurrently with rilonacept. The most common adverse reactions reported by patients were injection site reactions and upper respiratory tract infections. Six serious adverse reactions were reported by four patients during the clinical trials. These included Mycobacterium intracellular infection, gastrointestinal bleeding and colitis, sinusitis and bronchitis, and Streptococcus pneumoniae meningitis. The pivotal trial population included 47 patients with CAPS (FCAS and MWS) between ages 22 and 78, with the average age 51. Six pediatric patients were enrolled directly into the open label extension phase. There were two sequential parts (A and B) to the clinical trial that involved the same patients with CAPS. All patients were Caucasian. Part A of the clinical trial was a randomized, doubleblind, placebo-controlled six-week study in patients with CAPS who were naïve to treatment with rilonacept. Twenty-four patients received the active ingredient and 23 received placebo. Part B consisted of a nine-week patient-blind period during which time all patients received the active drug followed by a nine-week doubleblind randomized withdrawal period in which patients were randomly assigned either to remain on rilonacept (160 mg subcutaneously once weekly) or to receive placebo. Patients were then given the opportunity to enroll in a 24-week open label treatment extension in which all patients were treated with rilonacept weekly. The end point was a mean symptom score — a five-point composite endpoint that included joint pain, rash, feeling of fever/chills, eye redness/pain, and fatigue. In the actively treated arm of parts A and B, a significant reduction in symptoms was observed. Interestingly, the elevated C-reactive protein and serum amyloid A in patients with CAPS returned to normal levels in the actively treated patients. In fact, resolution of symptoms and these laboratory abnormalities is expected and can help to confirm the diagnosis in patients whose genetic testing is non-confirmatory. At a yearly cost of $250,000, there is good reason to verify the diagnosis! The CAPS family is a rare, geneticallymediated group of diseases for which a therapy APRIL 2008 / MANAGED CARE 57
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