ACR Publishes New Guide for RA Care

On June 15, the ACR published formal recommendations for the use of nonbiologic and biologic disease-modifying antirheumatic drugs (DMARDs) in patients with rheumatoid arthritis (RA). “The ACR is moving toward a formal process for evidence-based [clinical practice] recommendations that is based on the current state of the art of [rheumatology] practice,” says Kenneth G. Saag, MD, MSc, professor of medicine in the division of clinical immunology and rheumatology at the University of Alabama at Birmingham. He co-authored the guidelines, which were published in Arthritis Care & Research, with Daniel Furst, MD, professor of medicine/rheumatology at the University of California, Los Angeles Medical Center.¹

“These are reference standards for the rheumatologist in daily practice; they are not meant to be proscriptive,” Dr. Saag emphasizes. He likewise stresses that the new guidelines are not comprehensive. “There are a large and extensive number of recommendations, but they are not exhaustive,” says Dr. Saag. “There were areas of practice for which the expert panel thought that there was an absence of evidence and consensus,” he says. “Applying these recommendations to clinical practice requires individualized patient assessment and clinical decision making,” write Drs. Saag, Furst, and colleagues in the published article on the guidelines.¹

For the average rheumatologist who treats patients in his or her practice every day—and for those “steeped in current practice”—there are no surprises in the guidelines, Daniel Hal Solomon, MD, MPH, head of the ACR committee that reviewed the guidelines, tells The Rheumatologist. “The last guidelines were issued in 2002, and did not include recommendations for the use of biologic agents, so they needed to be updated. But these recommendations should not be new for doctors in practice who are current,” he says. “Typically, most rheumatologists are likely to find that these recommendations are in keeping with what they are already doing in practice.” says Dr. Solomon, who is associate professor of medicine and associate chief of Harvard Medical School’s division of pharmacoepidemiology and pharmacoeconomics in Boston, and a member of The Rheumatologist’s editorial board.

The value of the guidelines, say Drs. Solomon and Saag, is that all of the information is synthesized into one document. They are also important for nonspecialists who may not have as much experience in managing patients with RA. “The recommendations are meant to be a document that suggests ways to approach the patient in certain stages of the disease and to outline the safe and effective use of DMARDs,” says Dr. Saag.

A Formal Process

The DMARD guidelines are the first published by ACR that follow from a formal group process. Previous ACR guidelines were developed by an informal consensus approach. Dr. Saag explains the first step in development of these formal guidelines was the review of up-to-date scientific evidence to serve as evidence of current established practice. The DMARD guidelines include a review of literature that was available through February 2007. “We reviewed evidence based on the five treatment domains established by ACR for rheumatoid arthritis,” says Dr. Saag. These are: indications for use, screening for tuberculosis (TB) (biologic DMARDs only), monitoring for side effects, assessing clinical response, and roles of cost and patient preferences in decision making (biologic DMARDs only).

“We established a task force panel of international experts that then used a formal development process—the RAND/UCLA Appropriateness Method that has been used in the development of other formal clinical recommendations—to fill in the gaps since the last set of guidelines were published,” says Dr. Saag. “We focus heavily on biologics and where they fit into the treatment paradigm.” A total of 801 full-text articles were considered for review. These included 515 on nonbiologic agents, 226 on biologic DMARDs, and 60 on cost.

Establishing a safety and efficacy profile was a key goal of the guideline process, say its authors. “The two principles of our maximally inclusive search approach were to address indications and therapeutic response to nonbiologic DMARDs and biologic agents for RA, and to address the potential adverse events of nonbiologic and biologic DMARDs, including TB for biologic DMARDs,” say Drs. Saag and Furst.

Additional Areas of Recommendation

In addition to formally recommending the indications for starting or resuming nonbiologic or biologic DMARDs, the task force panel report also made recommendations in these areas:

• Contraindications to the use of nonbiologic and biologic DMARDs. These include contraindications for infectious disease and/or pneumonitis, hematologic and oncologic indications such as a white blood cell count below 3000 mm, liver indications including acute hepatitis B or C and chronic hepatitis B or C, renal indications such as a creatinine clearance less than 30 ml/minute, neurologic indication including multiple sclerosis or demyelinating disorders, pregnancy and breastfeeding, and perioperative infectious risk.
• Safety monitoring, risk surveillance, and preventive immunizations for patients on DMARDs. There are some safety concerns with some biologic DMARD. Early identification of any potential risk or adverse reaction should be the goal of routine laboratory testing. Vaccinations for flu are recommended for patients before they begin DMARD treatment. Hepatitis vaccination is recommended on an individual basis if there is an identified risk.
• TB screening for patients on biologic DMARDs. The goal is to identify any latent infection before starting a course of DMARD therapy.

Feedback and Continuing Review

The ACR’s Guidelines Subcommittee, Quality of Care Committee, and Board of Directors were asked to review the draft guidelines before publication and ACR’s general membership was likewise invited to offer feedback at the 2007 Annual Scientific Meeting. The published guidelines incorporate this feedback. “These guidelines are relatively robust evidence-based guidelines and offer solid evidence of practice for rheumatologists,” says Dr. Solomon. Some rheumatologists have questioned the usefulness of the new guidelines because they do not include all DMARDs currently used in practice. “The guidelines can be used as a reference if the physician has trouble knowing what is the best evidence-based treatment, but they fail to address a number of important questions,” says Joan Bathon, MD, professor of medicine at Johns Hopkins University School of Medicine in Baltimore, who co-authored an editorial that was published in the same issue of Arthritis Care & Research with the guidelines.²

“The current set of guidelines clearly represents an improvement in the methodologic rigor of the ACR guidelines and recommendations process,” write Drs. Bathon and Cohen in their editorial. “However, the strict adherence to the RAND/UCLA method leaves gaps in practice algorithms that could potentially be filled by other methods.” Bathon says this is the main point of disagreement on the value of the new guidelines. “How do we make clinical trial data relevant in daily practice?” she asks. Dr. Bathon says that there are remaining questions for physicians, patients, and payers, but adds that the new evidence-based guidelines do represent “an important tool for reimbursement.” The guidelines protect the patient from insurance carriers who may want to deny coverage for the treatment, because the DMARDs are now identified as sanctioned and endorsed treatments.

“The guidelines should definitely facilitate care for patients,” says Dr. Solomon. “The physician who wants to prescribe DMARDs for a patient no longer should have to justify this use to insurance companies.”

In response to concerns about not including some therapies in these recommendations, Dr. Solomon notes that the ACR task force panel had a defined task and excluding other treatments such as steroids was pragmatic. “Steroid use presents a number of issues and likely requires its own set of guidelines,” he says. Dr. Saag says, “A number of treatments have a low prevalence of use and limited evidence base to demonstrate safety and efficacy. We did not feel that we had sufficient data to provide recommendations in all cases.”

Dr. Saag emphasizes that the guidelines will continue to be updated based on scientific evidence and practice patterns in rheumatology. He adds that the ACR is working with the AMA Physician Consortium for Performance Improvement and the National Committee for Quality Assurance to develop performance measures based in part on the new guidelines. Draft performance measures were available online for public comment through June 27and should be finalized by fall.

Terry Hartnett is a medical journalist based in Pittsburgh.

References

1. Saag KG, Teng GG, Patkar NM, et al. American College of Rheumatology 2008 recommendations for the use of nonbiologic and biologic disease-modifying antirheumatic drugs in rheumatoid arthritis. Arthritis Rheum. 2008; 59(6):762-784.
2. Bathon JM, Cohen SB. The 2008 American College of Rheumatology recommendations for the use of nonbiologic and biologic disease-modifying antirheumatic drugs in rheumatoid arthritis: Where the rubber meets the road. Arthritis Rheum. 2008; 59(6):757-759.