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Clinical Conference Allele and antigen-specific treatment of rheumatoid arthritis: a double blind, placebo controlled phase 1 trial. 2003
Kavanaugh A, Genovese M, Baughman J, Kivitz A, Bulpitt K, Olsen N, Weisman M, Matteson E, Furst D, van Vollenhoven R, Anderson J, Cohen S, Wei N, Meijerink J, Jacobs C, Mocci S. · Division of Rheumatology, Allergy and Immunology, University of California, San Diego, San Diego, CA 92037-0943, USA. · J Rheumatol. · Pubmed #12610799 No free full text.
Abstract: OBJECTIVE: Human cartilage glycoprotein 39 (HC gp-39) appears to be a relevant autoantigen in patients with rheumatoid arthritis (RA). Administration of major histocompatibility complex (MHC) Class II complexed antigens without requisite costimulatory signals can induce immunologic tolerance. We evaluated the safety, pharmacokinetics, and preliminary efficacy of AG4263 in patients with RA. AG4263 is a soluble complex of native HLA-DR4 (beta*0401) complexed to Org 36601, a 13-mer peptide derived from HC gp-39 (also referred to as CDP263). METHODS: Thirty-one HLA-DRB1*0401 positive patients with persistent RA disease activity despite concurrent methotrexate were randomized to 7 infusions of AG4263 (n = 24) or placebo (n = 7) over 6 weeks. The initial dose of 0.5 micro g/kg was escalated in subsequent cohorts to a maximum of 150 micro g/kg. Safety analyses included recording of adverse events and measurement of CD4/CD8 counts, reactivity to recall antigens, and development of antibodies to HLA-DR4. Efficacy was assessed using the Paulus 20 criteria. RESULTS: Treatment was well tolerated, with injection site reaction the most common adverse event. There was no loss of reactivity to recall antigens, change in cell counts, or antibodies to HLA-DR. The mean half-life of AG4263 was 12.5 h. Some evidence of clinical response was seen; responses were more common among patients receiving the highest doses of AG4263 and among those with baseline T cell reactivity to CDP263. CONCLUSION: AG4263 was safe, well tolerated, and without evidence of generalized immune suppression. Along with the observed trend toward clinical efficacy, the results suggest that this therapeutic approach warrants further investigation in patients with RA.
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Article Clinical response of rheumatoid arthritis-associated pulmonary fibrosis to tumor necrosis factor-alpha inhibition. free! 2002
Vassallo R, Matteson E, Thomas CF. · Thoracic Diseases Research Unit, Division of Pulmonary, Critical Care and Internal Medicine, Mayo Clinic and Foundation, Rochester, MN, USA. · Chest. · Pubmed #12226061 links to free full text
Abstract: Treatment options for patients with pulmonary fibrosis associated with rheumatoid disease are limited. We report a case of a 71-year-old man with a 3-year history of seropositive rheumatoid arthritis (RA) referred to the pulmonary clinic because of progressive pulmonary symptoms associated with radiographic fibrosis that was progressive in spite of corticosteroid treatment. In an attempt to control his articular symptoms and alter the course of his pulmonary fibrosis, treatment with IV infusion of the tumor necrosis factor (TNF)-alpha inhibitor infliximab was initiated. Following 1 year of therapy with this agent, the patient reported sustained improvement in dyspnea, cough, and exercise tolerance, in addition to improvement in joint symptoms. Stabilization of pulmonary function was indicated by repeat pulmonary function test findings. This report suggests that inhibition of TNF-alpha may be of significant benefit to patients with fibrosing lung conditions in the setting of RA.
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