cj-Remicade COPE.ppt

Development of Disability in RA Unmet needs in Rheumatoid Arthritis combination therapy failures therapies superior to “best practice” influencing symptoms, signs, radiographs, function and quality of life complete suppression of inflammation improved safety profiles favourable cost benefits over the long term Prolonged synthesis of IL-1a in inflamedrheumatoid synovium Early evidence of efficacy of repeated infliximab therapy The ATTRACT trial: sustained clinical improvement over 54 weeks The ATTRACT trial: sustained prevention of structural damage Already of Proven Value in : RA, JCA, Crohn’s Disease, Ankylosing Spondylitis, Psoriatic Arthritis, Psoriasis Trials Not Completed: Ulcerative Colitis, Behcet’s Syndrome, Vasculitis, Glomerulonephritis, Steroid Resistant Asthma, Sciatica Pilot Studies: SLE, Hepatitis, Polymyositis, Joint Prosthesis Loosening, Systemic Sclerosis, Amyloidosis, Sarcoidosis, Ovarian Cancer, Osteoarthritis Clinical Failures: Congestive Heart Failure, Multiple Sclerosis, Primary Sjogren’s syndrome, Wegener’s Granulomatosis, COPD Summary: Remicade therapy in RA Control of symptoms: pain, stiffness and fatigue Control of signs: joint swelling and tenderness Control of joint destruction (even in clinical non-responders) Initiation of joint repair: reduced sharp scores Improvement in quality of life: HAQ More than 700,000 patients treated Sustained benefit and well tolerated; best in early RA Overview The biology of TNF – a new therapeutic target TNF blockade with Remicade in patients with RA Mechanism of action studies The immunopathogenesis of rheumatoid arthritis NORMAL JOINT ARTHRITIC JOINT 1 0 Day 1200 2000 1300 0830 ** *** -140 -120 -100 -80 -60 -40 -20 0 20 IL-6 change from day 0 (pg/ml) 28 21 7 0 Day 14 1 3 * ** *** ** ** *** *** *** *** *** *** Charles et al 1999 J Immunol 163:1521 Placebo 1mg/kg anti-TNFa 10mg/kg anti-TNFa Rapid attenuation of the acute phase response Paleolog et al Ar