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 initiated for at least one month prior to first dose of study medication may be included. Full prophylaxis regimens will be completed. Subjects who have been BCG-vaccinated will also be skin-tested. Able to understand, and complete study-related questionnaires. Able and willing to give informed consent and abide with the study procedures. EXCLUSION CRITERIA: Treatment with a live virus vaccine during 3 months prior to baseline visit. No live vaccines will be allowed throughout the course of this study. Current treatment with TNF inhibitors or recent discontinuation of TNF inhibitors (use within less than 5 half-lives of TNF inhibitor agent). Presence of active infections or a history of pulmonary TB infection with or without documented adequate therapy. Subjects with current active TB, or recent close exposure to an individual with active TB are excluded from the study. Chest x-ray read by a radiologist with pleural scarring and/or calcified granuloma consistent with prior TB. Positive test for or prior history of HIV, Hepatitis B or C. History or concomitant diagnosis of congestive heart failure. History of malignancy. Subjects deemed cured of superficial malignancies such as cutaneous basal or squamous cell carcinomas, or in situ cervical cancer may be enrolled. Known hypersensitivity to CHO cell derived biologicals or any components of IL 1 Trap. Presence of any additional rheumatic disease or significant systemic disease. For example, major chronic infectious/ inflammatory/ immunologic disease (such as inflammatory bowel disease, psoriatic arthritis, spondyloarthropathy, SLE in addition to autoinflammatory disease). Presence of any of the following laboratory abnormalities at enrollment visit: creatinine greater than 1.5 times the upper limit of normal, WBC less than 3.6 x 10(9)/mm(3); platelet count less than 150,000 mm(3); ALT or AST greater than 2.0 x ULN (ALT/AST greater than 2.0 x ULN in an adult Still's disease patient would prompt a hepatology consult prior to enrollment unless these abnormalities are considered by the Principal Investigator to be reflective of the underlying Still's disease). Lactating females or pregnant females. Subjects with asthma not adequately controlled on current therapy. Enrollment in any other investigational treatment study or use of an investigational agent, or has not yet completed at least 4 weeks or 5 half-lives, whichever is longer, since ending another investigational device or drug trial. Subjects for whom there is concern about compliance with the protocol procedures. Presence of other severe acute or chronic medical or psychiatric condition, or significant laboratory abnormality requiring further investigation that may cause undue risk for the subject's safety, inhibit protocol participation, or interfere with interpretation of study results, and in the judgment of the investigator would make the subject inappropriate for entry into this study.