ACR Updates RA Advice on DMARDS, Biologics, Switching Drugs

Janis C. Kelly

April 10, 2012

April 10, 2012 — An American College of Rheumatology (ACR) working group led by Jasvinder A. Singh, MBBS, MPH, has reported 2012 updates to the ACR's 2008 recommendations on the use of disease-modifying antirheumatic drugs (DMARDs) and biologic agents in patients with rheumatoid arthritis (RA).

The new recommendations, published in the May issue of Arthritis Care & Research, include 4 major changes: indications for use and switching of DMARDs and biologics; use of biologic agents in high-risk patients with RA who have hepatitis, cancer, or congestive heart failure; screening for tuberculosis in patients with RA who are starting or receiving biologic drugs; and vaccination (including the new herpes zoster and human papillomavirus vaccines) in patients starting or receiving DMARDS or biologics.

In an accompanying editorial, rheumatologists David I. Daikh, MD, and E. William St. Clair, MD, write, "In the face of a large body of clinical information of widely varying quality, the use of a rigorous, standardized approach that includes a comprehensive, critical review of the literature is essential. This update of ACR RA treatment recommendations uses such an approach, reflecting the importance and value that is placed on quality and validity in the development of all ACR guidelines and recommendations. The authors are also to be congratulated on their efforts to make these recommendations relevant for many patients with RA and to address frequent decision points that will be applicable in most clinical settings."

Tailored for Private Practice Rheumatologists

Dr. Singh, associate professor of rheumatology at the University of Alabama at Birmingham, told Medscape Medical News that the updated recommendations were developed by a process that included a thorough literature review, input from both a nonvoting working group and a core expert panel of clinicians and experts responsible for selecting the topic areas to be considered, and input from a task force panel of 11 internationally recognized expert clinicians, patient representatives, and methodologists with expertise in RA treatment.

Dr. Singh said, "ACR was very cognizant of the need to look at this issue with the private practice rheumatologist in mind, which is why so many of our panelists and reviewers are actually practicing rheumatologists, outside of academia. Consequently, none of these recommendations are likely to come as a surprise to clinicians in North America."

Dr. Singh pointed to 4 major changes from the 2008 ACR recommendations:

  • The 2012 recommendations cover 3 additional biologics (certolizumab, tocilizumab, and golimumab) in addition to adalimumab, etanercept, infliximab, abatacept, and rituximab.

  • For the first time, the recommendations address the question of switching between drugs (both DMARDs and biologics). "This is now a key challenge to treatment of RA patients due to availability of several biologics and was a critical new domain that we addressed," Dr. Singh said.

  • The update provides recommendations regarding use in patients with RA of 2 new vaccines (herpes zoster to prevent shingles and human papillomavirus to prevent cervical cancer), as well as for pneumococcal, influenza, and hepatitis vaccines.

  • The update recommends a treatment target of no disease activity or remission in both early and established RA.

Dr. Singh said, "Current recommendations highlight the need to target low disease or remission in all RA patients. There are updated algorithms that incorporate the new evidence and new biologics for both early and established RA. The recommendations regarding treatment of early RA are quite aggressive because there is an increasing recognition that very effective treatment early on can really reduce disability and limitation for patients with RA."

Guidelines Will Be Updated Frequently

Dr. Singh also warned clinicians to expect shorter cycles for guideline and recommendation updates. "Treatment for RA is evolving so rapidly that one would anticipate frequent updates, and the ACR is preparing to do that much more frequently than in the past," he said.

Emilio B. Gonzalez, MD, who heads the rheumatology program at the University of Texas Medical Branch at Galveston, reviewed the paper for Medscape Medical News. Dr. Gonzalez said, "I think this is well written and relatively comprehensive, although the authors themselves, many of whom I know, state their intention was not to write a comprehensive review on the subject. I agree with 90% of the article's recommendations. I also liked the fact that they clearly stated that these are just recommendations, not specific prescriptions on how to treat individual patients with RA. They unequivocally state that individual treatment decisions are best left up to the patients and their doctors. This is appropriate."

Dr. Gonzalez did, however, disagree with 1 point: the recommendation for the early use of rituximab. Dr. Gonzalez said, "[The recommendations] say that if a patient fails a [tumor necrosis factor] inhibitor agent, the next option would be either abatacept or rituximab. I usually reserve rituximab as the last resort, and I think a lot of practicing rheumatologists do the same. In fact, in their final discussion, the authors themselves mention that their recommendation of rituximab is not evidence-based but, rather, based on expert opinion."

Among the challenges now facing clinicians treating patients with RA are how the various treatment options compare with each other in efficacy and safety, and how to individualize the many options available to provide best care for the particular patient.

More Studies Needed

Dr. Singh said, "We have hardly any direct evidence from studies comparing combinations of commonly used traditional treatments to some of the newer treatments. For example, there are almost no published studies that compare the methotrexate, sulfasalazine, and hydroxychloroquine combination to methotrexate plus a biologic. Such evidence is urgently needed. Currently 2 studies are in progress, but more are needed."

Dr. Singh continued, ""If somebody walks into my office who has RA , who was treated for a lymphoma 6 years ago, and who also has diabetes and is at high risk of infection, can we come up with the best treatment options that will be both effective and safer than other options? Currently, our decisions are based on the very limited evidence we have from otherwise healthy patients in RA randomized controlled trials. It might be helpful to have information from registry data, as well as from traditional randomized studies that include patients with other comorbidities."

Dr. Singh has received consultant fees, speaking fees, and/or honoraria from Allergan, Ardea, Savient, Novartis, and Takeda and research support from Savient and Takeda. Dr. Daikh has disclosed no relevant financial relationships. Dr. St. Clair has received research grants from Genentech and Biogen Idec. Dr. Gonzalez has disclosed no relevant financial relationships.

Arthritis Care Res. 2012;64:625-639, 648-651. Article abstract, Editorial extract


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