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Tampa JIA Connect Day “Arthritis Medicines”. Renee Modica, MD, MSED University of Florida Gainesville, FL 10-29-11. Goals. Define autoimmune “rheumatic” disease Briefly discuss treatments Rationale Safety concerns Goals of treatment. Importance. Rheumatic Diseases in Childhood
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Tampa JIA Connect Day“Arthritis Medicines” Renee Modica, MD, MSED University of Florida Gainesville, FL 10-29-11
Goals • Define • autoimmune “rheumatic” disease • Briefly discuss treatments • Rationale • Safety concerns • Goals of treatment
Importance • Rheumatic Diseases in Childhood • ~300,000 children in the U.S. suffer from rheumatic disease • Childhood inflammatory arthritis • #1 cause of acquired disability in children • Effective therapies may alter this fact
What happens to the joint…. What is the role of the immune system…..
Immune System • Protects against • Infection • Cancer • Autoimmune diseases • Remains “balanced” by distinguishing • “self” from “non-self” to function properly
Components of the Immune System (Body’s defense system) • “weapons” = • Antibodies & • inflammatory proteins • “army” = white blood cells
“The Army” White blood cells “The General” Gives orders to B cells & other inflammatory cells “The Troops” Antibodies Inflammatory proteins ***Treatments target specific areas of the immune system
key inflammatory proteins The Weapons: • 1L-1 , IL-6 , and • TNF = Tumor Necrosis Factor • In the body they “help destroy tumors” and infections • In JIA they destroy the joints
Autoimmune “Rheumatic” Disease:Imbalanced immune system “weapons” TNF IL1 IL6 • Immune system gets confused • Becomes “overactive” • Attacks SELF • (thinks there is a joint infection) Cells
Inflammatory Arthritis progressed over time… Can cause erosions or bony fusion if not controlled
Treatment Strategyremove inflammatory cells and proteins ANTI-Inflammatory Help with pain, swelling and stiffness • NSAIDS • Joint injection • Steroids-systemic Rehabilitation Synovectomy Counseling • Methotrexate • Biologic agents • Steroids Immunosuppressvie “tips the scales the other way” other
Immunosuppression • “lowers” the immune system activity • everywhere, not just the joint • Targets and removes specific components • Cells • Inflammatory proteins Methotrexate Biologics
Targets of Immunosuppression Methotrexate/chemo/steroids rituxan “The General” In charge of B cells and other inflammatory cells “The Troops” “Biologics” TNF-a->Enbrel, remicade, humira IL-1->anakinra IL-6actimera orencia Auto-AB Inflammatory proteins IVIG
Inflammation control Inflammation high Arthritis active Autoimmunity Immunosuppression: Inflammation lowered Treats autoimmune disease ( goal =remission) Immune system rebalances But….Less “weapons to fight” infection or suppress malignancy
Possible Side effects of prolonged Immunosupression • If lowered too much • Immune system cannot “see/fight” infection or cancer as well • may theoretically increase risk of infection and malignancy • Actual risk is not entirely clear • Not thought to “cause” cancer or infection but possibly increase risk
Considerations: • What’s not known is: • How underlying disease contributes (JIA, IBD, Etc) • Impact of combination therapy • methotrexate, steroids, cytoxan, other biologics • Exposure: • Length of treatment • Dose • Side effects have been reported to FDA • both pre/post the “biologic era”
Risk vs Benefit Ratio • Patient are very closely monitored • Labs • Physical exam • Imaging • TB testing • Vaccinations • NO live virus vaccines while on immunosuppression • New research • FDA reporting-ongoing monitoring • New studies (Dr Nickeson)
History of Drug DevelopmentNew drugs are in developmentCombination treatments proposed CURE? New biologics Orencia Scleroderma vaccine antiCD40L Actimera RA vaccine Rituximab Remicade SLE vaccine CTLA4Ig Humira JRA vaccine Enbrel Anakinra methotrexate Arava Gene therapy Bone marrow transplant gold cortisone NSAIDS etc aspirin COX 2 inhibitors etc 1900 1920 1940 1960 1980 2000 2020
Treatment Goals • Quality of life • Clinical Remission • Defined by: • No evidence of active disease by: • Clinical symptoms, MD exams, labs, radiology • 2 scenarios: • On meds • Off meds • Difficult to predict • Research underway