Targeted Biological Therapeutics in the Treatment of Autoimmune and Inflammatory Diseases
Chronic Autoimmune Urticaria
Inflammatory Arthritis (Rheumatoid arthritis, psoriatic arthritis)
My primary research interest is in the application of targeted biological therapeutic agents for the treatment of autoimmune and inflammatory diseases. Increasingly the knowledge gained in the laboratory concerning the pathogenesis of inflammatory and autoimmune diseases is leading to the identification of novel therapeutic targets. The advent of specific inhibitors of proteins and molecules involved in these inflammatory diseases has provided the ability to test in “proof of concept” studies the role of these molecules in human disease. With rheumatoid arthritis as an example, a proinflammatory cytokine, TNF-a was identified as a possible therapeutic target. Monoclonal antibodies (adalimumab, infliximab) and soluble receptor constructs (etanercept) directed against this molecule were used initially in clinical trials for RA patients with impressive efficacy and eventual FDA approval beginning in 1999 of a class of agents that were able to turn off the effects of TNF, now with clinical remission and states of very low disease activity possible in up to 40% of patients treated with these agents and inhibition of radiographic joint damage in most patients. Additional studies have shown the effectiveness of specifically inhibiting TNF in other immune-mediated and inflammatory diseases including psoriasis, ankylosing spondylitis, and Crohn’s disease. Similarly recent studies have shown that a monoclonal antibody directed against CD20, a cell surface molecule on B lymphocytes (rituximab), is effective not only in certain forms of lymphoma, for which the drug was initially used, but also in rheumatoid arthritis and lupus. Unfortunately in autoimmune diseases not everyone responds even to a promising treatment, thus there is a need for additional options. Fortunately a rich pipeline of investigational agents offers tremendous hope for the future for patients with autoimmune and inflammatory diseases.
Many cases of chronic urticaria may be autoimmune in nature, with an autoantibody-driven process leading to mast cell degranulation and the resultant skin lesions. We will be starting an investigation to evaluate the safety and preliminary efficacy of a targeted biological therapeutic agent with effectiveness in rheumatoid arthritis and lupus, two other diseases associated with autoantibodies, for the treatment of patients with chronic urticaria refractory to antihistamine therapy with a goal to improve symptoms and decrease requirement for other medications. The study design represents a novel model to study other investigational agents in this disease. These studies are being conducted in concert with Dr. Sarbit Saini who will be evaluating the effectiveness of this treatment on laboratory measures of basophil function correlated with the clinical efficacy.
If we are able to demonstrate safety in this initial study, we anticipate a larger multicentered clinical trial to follow.
An opportunity to participate in clinical trials of investigational therapeutics may be available in the future. Please inquire via email to Clifton.email@example.com