2012 Updated Recommendations for Treating Rheumatoid Arthritis
2012 Recommendations for the Use of Disease-Modifying Antirheumatic Drugs and Biologic Agents in the Treatment of Rheumatoid Arthritis, issued by the American College of Rheumatology and coauthored by investigators at the University of Alabama at Birmingham (UAB) Deep South Musculoskeletal Center for Education and Research on Therapeutics (CERT).
By Shelley Norden Barnes
Rheumatoid arthritis (RA) affects about 1.3 million Americans and results in more than 9 million physician visits each year. This chronic condition usually requires lifelong treatment. The most aggressive treatments for RA, namely disease-modifying antirheumatic drugs (DMARDs) and biologic agents, can produce serious side effects or have varying degrees of efficacy. For this reason, the American College of Rheumatology (ACR) published their 2008 guidelines concerning the use of DMARDs and biologic agents as RA treatment.
Since 2008, many developments have occurred that warranted the review and update of the ACR guidelines. Among the developments are U.S. Food and Drug Administration approval of new biologic agents and the emergence of research evidence regarding the pharmacological safety and efficacy of these drugs, the need for more rigorous early intervention and guidelines specific to high-risk patients. The new ACR guidelines, published in 2012, address these and other clinical issues, including indications for using and switching between therapies, using biologic agents in high-risk patients, screening for tuberculosis before using biologic agents, and vaccinating against certain infections before using DMARDs or biologic agents.
The UAB CERT Role in the 2012 Recommendations
"More biologics were introduced since those initial recommendations were published, so much so that the ACR felt it was important to update their recommendations," says Jasvinder A Singh, M.B.B.S., M.P.H., the lead author for the 2012 updated recommendations.
The update was made using scientific evidence and a rigorous evidence-based group consensus process led by Singh and his research team at the University of Alabama at Birmingham Deep South Musculoskeletal Center for Education and Research on Therapeutics (CERT) in conjunction with researchers from the University of California Los Angeles and other academic centers. Based on their previous CERT experience, Singh notes, "The UAB CERT had a critical mass of people with expertise in comparative effectiveness research, systematic reviews, and guidelines development who were available to participate and take a leadership role in developing the revised recommendations."
One of the most significant topics that needed to be addressed in this update was switching between biologics and DMARDs, something that was not covered in the 2008 guidelines, according to Singh.
"The number of available biologics had grown since then," he noted, "and since some patients had failed older biologics, the ACR wanted to address the issue of switching from drugs that cause side effects or are not effective to newer ones that may prove more efficacious." Another significant update, Singh adds, is the recommendation to treat early RA more aggressively. This recommendation is based on new evidence showing that early initiation of treatment can slow disease progression.
The 2012 Update: Significant Changes
The 2012 update is intended to simplify the treatment protocols for patients and providers and give clinicians treatment choices for patients with active RA at all stages of the disease. Significant changes to the 2008 recommendations, which were originally published in the June 2008 issue of Arthritis Care & Research, the official ACR journal, include:
- New indications and timelines for starting or resuming DMARDs and biologic agents, targeting remission or low disease activity, early RA, and established RA. This approach includes adding the non-tumor necrosis factor (TNF) biologic agent tocilizumab and the anti-TNF agents certolizumab pegol and golimumab as therapeutic options when starting or resuming DMARDs and biologic agents.
- The recommendation to switch among or between DMARDs and biologic agents after 3 months for patients with moderate or high disease activity when there is a lack or loss of benefit from the initial therapy and to switch between biologic agents if a patient has an adverse event or when there is a lack or loss of benefit.
- The recommendation to use biologic agents in patients with comorbidities (e.g., hepatitis, malignancy, or congestive heart failure) who qualify for more aggressive treatment, including:
- The potential use of etanercept in patients with RA who also have hepatitis C infection.
- The omission of biologic agents from the RA treatment regimens of patients with untreated chronic hepatitis B infection and treated chronic hepatitis B infection with a Child-Pugh classification of B and higher.
- Starting or resuming any biologic agent in patients who have been treated previously (>5 years) for solid malignancies or for non-melanomatous skin cancer, and using rituximab as a treatment option in patients with malignancies under specific conditions (see the 2012 update).
- Not using anti-TNF biologic agents in patients with congestive heart failure who have a New York Heart Association classification of III or IV and an ejection fraction of 50 percent or less.
- Screening for tuberculosis in patients starting or currently receiving biologic agents as part of their RA therapy.
- Vaccinating for human papillomavirus and herpes zoster in patients starting a DMARD or a biologic agent.
"Our goal was to write the best evidence-based recommendations considering a variety of factors and given the best literature in this area," Singh explains. "These are not intended as proscriptive but rather as effective tools that physicians and patients can use to help make the best treatment decisions."
The full 2012 recommendations (PDF) from the the American College of Rheumatology Web site.
The UAB Deep South Musculoskeletal Center for Education and Research on Therapeutics is one of six nationwide CERTs funded by the Agency for Healthcare Research and Quality. The mission of each CERT is to conduct research and provide education that will advance the optimal use of drugs, medical devices, and biological products; increase awareness of the benefits and risks of therapeutics; and improve quality while cutting the costs of care.