Treatment of Rheumatoid Arthritis
Over the past decade, conventional and biological disease modifying antirheumatic drugs (DMARDs) have dramatically improved treatment of patients with rheumatoid arthritis (RA) by minimizing pain and swelling in affected joints, preventing deformity and radiographic damage, controlling extra-articular manifestations, and helping maintain a patient’s quality of life.
Treating To Target
In 2010, the American College of Rheumatology (ACR) and the European League Against Rheumatism (EULAR) issued new clinical classification criteria for RA, with the goal of codifying a strategy to identify patients who would benefit from early, effective treatment to prevent later-stage disease.1
Using these new criteria, a treatment paradigm called treat-to-target (T2T) has been proposed that encourages tight control. T2T utilizes composite measures of disease activity and health-related quality of life, with the appropriate switching of agents (figure 1). Goals of therapy according to T2T are to achieve and maintain a patient’s function and to obtain clinical remission, defined as the absence of signs and symptoms of significant inflammatory disease.2 Low disease activity may be an acceptable treatment goal, particularly in patients with long-standing established disease.2 Other recommendations are to measure disease activity as needed, adjust dosage and medication regimens to meet targets, and share treatment decisions between physicians and patients, including patients’ lifestyle choices and comorbidities in the decision process.2
The T2T paradigm is supported by strong clinical evidence for both early and established disease, and it is now included in several recommendations for the management of RA.3 However, exactly how rheumatologists’ and patients’ behaviors play a role in the implementation of T2T in clinical practice is currently under investigation.
Figure 1: The Treat-to-Target Paradigm2
Therapeutics for RA
Conventional treatment options for RA include synthetic DMARDs (hydroxychloroquine, leflunomide, sulfasalazine, and methotrexate [MTX]), non-steroidal antiinflammatory drugs, glucocorticoids, and non-pharmacological measures, such as physical, occupational, and psychological approaches. MTX is considered the “anchor” DMARD because of extensive positive clinical experience. However, MTX toxicity can limit its use, and many patients do not respond adequately to MTX alone. Advances in the understanding of the pathophysiology of RA have led to the development of several biological DMARDs and small-molecule inhibitors of cytokine signaling, adding to existing options. 4
FDA-approved agents for MTX non-response or intolerance include:
- Interleukin-1 (IL-1) receptor antagonist—anakinra
- Monoclonal antibodies against tumor necrosis factor (TNF) α—infliximab, etanercept, adalimumab, certolizumab pegol, and golimumab
- Monoclonal antibodies against IL-6 receptor—tocilizumab, sarilumab
- Cytotoxic T lymphocyte antigen 4-immunoglobulin G1 (CTLA-4- IgG1) fusion protein (blocker of T-cell co-stimulation)—abatacept
- JAK (Janus kinase) tyrosine-kinase inhibitors—baricitinib, tofacitinib, upadacitinib
Agents that are FDA approved for TNF-inadequate responders include the monoclonal antibody against CD20—rituximab.
The broad range of agents, administration routes (including new oral agents), and mechanisms of action enhance clinical opportunities. Evidence-based guidelines have been developed, and updated recommendations are released periodically based on new clinical evidence (figure 2). The supporting research includes head-to head comparative trials of treatment regimens for different RA patient populations.5,6
Figure 2: Early RA Treatment5
- Aletaha D, Neogi T, Silman AJ, et al. 2010 rheumatoid arthritis classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative. Arthritis Rheum. 2010;62:2569-2581.
- Smolen JS, Aletaha D, Bijlsma JW, et al. Treating rheumatoid arthritis to target: recommendations of an international task force. Ann Rheum Dis. 2010;69:631-637. http://ard.bmj.com/content/early/2010/05/04/ard.2009.126532.full.pdf+html
- Smolen JS. Treat-to-target as an approach in inflammatory arthritis. Curr Opin Rheumatol. 2016;28:297-302.
- Singh JA, Saag KG, Bridges SL Jr, et al. 2015 American College of Rheumatology guideline for the treatment of rheumatoid arthritis. Arthritis Rheumatol. 2016;68:1-26. (Also published in Arthritis Care Res [Hoboken]. 2016;68:1-25.) www.rheumatology.org/Portals/0/Files/ACR%202015%20RA%20Guideline.pdf
- Smolen JS, Landewé R, Breedveld FC, et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2013 update. Ann Rheum Dis. 2014;73:492-509. http://ard.bmj.com/content/early/2013/10/23/annrheumdis-2013-204573.full.pdf+html