NATURE REVIEWS | RHEUMATOLOGY VOLUME 7 | NOVEMBER 2011 | 639 Division of Rheumatology, Department of Medicine, Northwestern University Feinberg School of Medicine, 240 East Huron Street, McGaw M300, Chicago, IL 60611, USA. (R. S. Woodrick, E. M. Ruderman) Correspondence to: E. M. Ruderman e-ruderman@ northwestern.edu Safety of biologic therapy in rheumatoid arthritis Robert S. Woodrick and Eric M. Ruderman Abstract | Biologic therapies have revolutionized the treatment of rh eumatic diseases in the past decade. As with any drugs, however , a variety of important safety concer ns affect the choice and use of these agents. Several issues, such as the risk of infection, malignancy , or administration reactions, apply to all of these compounds, although some conditions that affect patient selection and management within these categories seem to be specific to par ticular biologic treatments. Other safety conc erns with biologic agents, such as congestive hear t failure, demyelinating disease, and hyperlipidemia, are associated with individual agents. Despite all these concerns, the therapeutic indice s for biologic agents remain fairly high in relation to non-biologic DMARDs. Available safety data for all biologic agents appr oved for the treatment of rheumatoid arthritis are reviewed in this manuscript. With careful patient selection and appropriate vigilance on the part o f treating physicians and other care providers, these compounds can be safely inte grated into the therapeutic plan. Woodrick, R. S. & Ruderman, E. M. Nat. Rev. Rheumatol. 7, 639–652 (2011); published online 11 October 2011; doi:10.1038/nrrheum.2011.145 Introduction Rheumatic diseases are varied and sometimes vexing in their presentations, and can be accordingly challeng- ing to treat. Recent advances in understanding have led to improved treatments for many of these diseases —perhaps the best known therapeutic advances comprise the development of biologic agents for the treatment of rheumatoid arthritis (RA), juvenile inflammatory arthri- tis (JIA) and spondyloarthropathies (ankylosing spondy- litis and psoriatic arthritis). Blocking sig naling by the proinflammatory cytokine TNF has been, and remains, a major target in tackling the underlying pathology of rheumatic diseases with biologic molecules. Etanercept, a fully humanized TNF antagonist, was the first bio- logic therapy approved for the treatment of RA, which occurred in 1998. Infliximab and adalimumab followed within the next few years, with certolizumab pegol and golimumab approved more recently. Although TNF inhibition has proven to be an effective treatment in RA and other rheumatic conditions, biologic agents that target other pathways involved in inf lamma- tion have also been developed, because a certain per- centage of patients with RA do not respond, or have a suboptimal response, to TNF inhibition. To date, agents targeting IL-1 (anakinra, 2001) and IL-6 p athways (tocili- zumab, 2010), T-cell co-stimulatory pathways (abatacept, 2005) and B cells (r ituximab, 2006) have been approv ed for the treatment of moderate to severe RA, and—in some cases—other rheumatic conditions. The nature and targets of these agents and the anti-TNF biologic therapies are summarized in Figure 1. Although these medications have improved our ability to treat RA and other autoimmune conditions, it is quite clear that there are risks associated with their Competing interests: E. M. Ruderman declares associations with the following companies: Amgen, Abbott, Centocor, Roche, Wyeth/Pfizer and UCB. See the article online for full details of the relationships. R. S. Woodrick, the journal Chief Editor J. Buckland and the CME questions author C. P . Vega declare no competing inter ests. Continuing Medical Education online This activity has been planned and implemented in accordance with the Essential Areas and policies of the Accreditation Council for Continuing Medical Education through the joint sponsorship of Medscape, LLC and Nature Publishing Group. Medscape, LLC is accredited by the ACCME to provide continuing medical education for physicians. Medscape, LLC designates this Journal-based CME activity for a maximum of 1 AMA PRA Category 1 Credit(s) TM . Physicians should claim only the credit commensurate with the extent of their participation in the activity. All other clinicians completing this activity will be issued a certificate of participation. To participate in this journal CME activity: (1) review the learning objectives and author disclosures; (2) study the education content; (3) take the post-test with a 70% minimum passing score and complete the evaluation at http:// www.medscape.org/journal/ nrrheum; (4) view/print certificate. Released: 11 October 2011; Expires: 11 October 2012 Learning objectives Upon completion of this activity, participants should be able to: 1 Evaluate the relationship betw een biologic therapies and the risk for bacterial infections. 2 Distinguish biologic agents associated with a higher risk for tuberculosis infection. 3 Identify types of cancer associated w ith the use of biologic therapies. 4 Assess the interac tion betw een biologic therapies and adverse events related to the immune system. REVIEWS © 2011 Macmillan Publishers Limited. All rights reserved
