Counseling Points - December 2008 - (Page 4)

Future Treatments for Rheumatoid Arthritis Novel Treatments for RA Scientists have been working for decades to unravel the complexities involved in autoimmune diseases such as rheumatoid arthritis (RA). As a result, major advances in therapeutic approaches to autoimmune disorders have occurred over the past 20 years, and have accelerated recently due to research focusing on treatment paradigms that target specific molecules. 1 However, despite the fact that there are a number of effective treatments available to help alleviate symptoms and slow or halt the damaging effects of RA, there is still no cure for the disease. 2,3 Currently marketed biologic and nonbiologic diseasemodifying antirheumatic drugs (DMARDs) show efficacy in many patients with RA, but none of these agents leads to response in all patients, and even among responders, symptom and disease improvement is often modest.2,4 It is well recognized that immune cellular components, such as T cells, B cells, and macrophages, play an integral role in the pathogenesis of RA; however, an enormous amount of recent research has been devoted to studying the impact that communicative enzymes, such as cytokines and other proteins, have on the disease process.1,2,4-5 In an effort to find more efficacious RA treatments, a number of new, targeted biologic therapies are being investigated in various stages of clinical trials (Table 1).1,2,4-5 Some of these compounds include inhibitors of specific cytokines, such as tumor necrosis factor (TNF), interleukin-6 (IL-6), and IL-15. Other drugs being studied target B cells or inhibit proteins such Janus kinase (JAK).1,2,4-5 Furthermore, medications such as antibiotics, statins, and bisphosphonates already approved for other inflammatory conditions are being assessed to determine their effectiveness in treating RA.4,5 Certolizumab pegol (Cimzia®), which has been developed by UCB Pharma, and golimumab, manufactured by Centocor, are two new anti-TNF agents. Both of these drugs are being evaluated in phase-3 trials for the treatment of RA.1,3 Certolizumab Certolizumab is a subcutaneous TNF blocker that is currently approved for the treatment of moderate to severe Crohn’s disease.1,6 This compound is a unique agent that Table 1. Novel Compounds for RA Being Investigated in Current Clinical Trials1-5 Drug ACZ885 AMG 714 Atacicept Belimumab Certolizumab CNTO 136 Golimumab Ocrelizumab Ofatumumab INCB018424 SCIO-469 SBI-087 TRU-015 Tocilizumab Class IL-1β antagonist IL-15 receptor antagonist BLyS inhibitor BLyS inhibitor TNF antagonist IL-6 receptor antagonist TNF antagonist B-cell depletion B-cell depletion JAK inhibitor P38 MAP kinase inhibitor B-cell depletion B-cell depletion IL-6 receptor antagonist Administration Subcutaneous Subcutaneous Subcutaneous Intravenous Subcutaneous Subcutaneous Subcutaneous & Intravenous Intravenous Subcutaneous & Intravenous Oral Oral Intravenous Intravenous Intravenous TNF Inhibitors TNF is a pro-inflammatory cytokine produced by macrophages and lymphocytes.2,5 It binds to receptors present on virtually all cells throughout the body and is a critical inflammatory mediator in RA and in a number of other diseases and conditions. Overproduction or inappropriate production of TNF plays an important role in both the pathologic inflammation and joint destruction associated with RA.2,5 COUNSELING POINTS™ 4 BLyS=B-lymphocyte stimulator; IL=interleukin; TNF=tumor necrosis factor; JAK=Janus kinase; MAP=mitogen activated protein.

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Counseling Points - December 2008

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