Interleukin-1 Trap to Treat Autoinflammatory Diseases

• INCLUSION CRITERIA:

Male or female subjects with inflammatory disease greater than or equal to 18 years of age.

Participation in NIH study number 94-AR-0105 ("Genetics and Pathophysiology of FMF and Related Disorders")

Subjects presenting with active NOMID, MWS, FCAS, FMF, or adult Still's disease based on clinical signs/symptoms and/or biochemical markers such as acute phase reactants (CRP, SAA or ESR). Subjects need not have both clinical features and biochemical markers of disease to be enrolled. However, both clinical and laboratory responses will be evaluated in each subject for improvement as outcome measures (even improvement of laboratory values found to be within the normal range at baseline).

• NOMID, MWS, and FCAS: Diagnosis will be based on the history of classical features of disease including fevers, rash, joint involvement, CNS involvement. Approximately half of all subjects with these clinical syndromes are mutation negative; however, in the experience of the principal investigator these subjects show favorable clinical response to IL-1 blockade with anakinra. Therefore, subjects with or without recognized mutations in CIAS1 will be eligible to enroll in this study. Active disease will be defined as either the presence of aforementioned classical features, or a history of such features that became quiescent in the setting of therapy with anakinra. However, before a patient who has quiescent disease and is currently taking anakinra can receive study drug, he/she must fulfill criteria for active disease after anakinra has been discontinued.
• FMF will be diagnosed on the basis of documented presence of one or two mutant alleles of MEFV as well as the history of classical clinical features of FMF such as periodic fevers, rash, arthritis, arthralgia, or episodes of serositis. Subjects must be considered non-responsive to colchicine (up to 2 milligrams per day) on the basis of continued symptoms or flares (greater than or equal to one per month) or elevated acute phase reactants (ESR, CRP or SAA greater than or equal to 1.5 times the upper limit of normal between attacks) despite treatment with maximally tolerated doses of colchicine. Positive genetic test will be required for FMF to rule out the possibility that non-response to colchicine is due to misdiagnosis.
• Adult Still's disease will be diagnosed on the basis of history of classical clinical features such as fevers, evanescent salmon-pink rash, arthritis, arthralgia, and myalgia. Active disease will be defined as presence of one or more of these features and/ or elevation of acute phase reactants (ESR, CRP or SAA greater than or equal to 1.5 times the upper limit of normal).
• Subjects currently treated with anakinra may be enrolled in this study even though autoinflammatory disease may be quiescent. For these subjects a history of active autoinflammatory disease prior to treatment with anakinra will be sufficient. Subjects must be greater than 48 hours from their last dose of anakinra before beginning IL-1 Trap therapy, and will not take anakinra for the remainder of their enrollment in the study. However, before study drug is administered subjects have to manifest signs of active disease as described above

Stable dose of steroids, NSAIDs, DMARDs, or colchicine for four weeks prior to enrollment visit.

Females of childbearing potential (young women who have had at least one menstrual period regardless of age) must have a negative urine pregnancy test at screening and a negative serum pregnancy test at baseline prior to performance of any radiologic procedure or administration of study medication.

Women of childbearing age and men able to father a child, who are sexually active, who agree to use a form of effective birth control, including abstinence.

Negative PPD test using 5 T.U. intradermal testing per CDC guidelines, and no evidence of active TB on chest X-ray. Subjects with latent TB (positive PPD test) currently treated with adequate therapy