SEMINAR 5: Pharmacotherapy and biomarkers of rheumatoid arthritis

Context:

Rheumatoid Arthritis (RA) is one of the poorly understood rheumatic diseases that is characterised by joint disorders, followed by infectious, metabolic, immunologic and neo-plastic processes. It is a chronic systemic disease of unknown etiology manifested primarily by several inflammatory processes starting symmetrically at the peripheral joints. Its prevalence is 1 to 2%, for women aged more than 65 up to 5%.Genetic disposition may result in an improved susceptibility for inflammation, where immunologic factors and autoantibodies play an important role. Starting with painful joints, in early stages in serum and joint fluid antibodies can be found for the Fc fragment of IgG. Once the disease is correctly diagnosed treatment starts with anti-inflammatory agents, remission-inducing agents (DMARDS, disease modifying anti-rheumatic drugs) and immunosuppressive agents. Until 1985 treatment was merely symptomatic, trying to reduce the pain merely using NSAIDs, whereas after 1985 the DMARDs like sulphasalazine, methotrexate, leflunomide, TNF alpha-blockers like etanercept, infliximab, adalimumab, and interleukin-6- or interleukin-1-receptor-antagonists (anti-cytokines like tocilizumab, anakinra) are used.Clinical effects are measured by means of X-ray imaging of the affected joints or a rating scale like the DAS are instruments in use to quantify the therapeutic effect. Nowadays the ACR 20 is in use: American College of Rheumatology criteria for a 20 percent improvement in measures of disease activity (ACR 20).But all of these instruments are questionnaires and might not fully reflect the actual disease status of the patient. Therefore there is a continuous search for more objective markers of the disease: biomarkers, i.e. indicators for normal or pathogenic biological processes or for pharmacological reactions following pharmacotherapy. A promising approach is actually to test on anti-CCP (autoantibodies to cyclic citrullinated peptides) or on anti-MCV (autoantibodies to modified citrullinated vimentin) alone or combined to IL-6.In this seminar the search for biomarkers for diagnoses and/or for prognoses in rheumatoid arthritis will be discussed and a strategy for therapeutic intervention in this disease will be demonstrated.

Teaching goals:

• to introduce to diagnostic and prognostic tools of RA with focus on the search of RA-biomarkers
• to outline the state of the art of actual pharmacotherapy of RA with focus on TNF alpha-blockers and interleukin-6- and -1-receptor antagonists
• to illustrate the most important biochemical pathways, the pathobiochemistry and the importance of genetic disposition for the disease as well as the susceptibility of pharmacotherapy
• to analyze and assess therapeutic effects and outcomes
• to propose an approach of a holistic care by a RA team involving hospital pharmacists and what duties to assign to them

Learning objectives:

At the end of the seminar, participants will:

• take home the message about approaches, progresses, goals and upcoming innovations in the RA-domain
• recognise the value of hospital pharmacy in the treatment of RA