BOSTON—Guidelines for the management of rheumatoid arthritis (RA) always spark interest and debate among rheumatologists. A recent glimpse at a draft of the new recommendations for RA treatment was no exception.
On Nov. 16, 2014, in Boston, attendees at the ACR/ARHP Annual Meeting packed a large auditorium, even sitting on the floor in front of the panelists’ table, to read and discuss New ACR Recommendations for the Management of Rheumatoid Arthritis (RA).
Guideline development group members presented a thorough explanation of techniques for gathering and measuring the value of scientific evidence to support the development of treatment recommendations. They also shared a first look at the in-progress guidelines, including emerging approaches to treatment during RA flares and the use of live vaccines in RA patients currently taking biologics. The final guidelines will be jointly published in Arthritis & Rheumatology and Arthritis Care & Research in summer 2015. Since the last RA guidelines update in 2012, new RA therapies, such as tofacitinib, have been approved, driving the need for an update.
GRADE: A Paradigm Shift
The guideline development group began the update project in December 2013. The process used represents a paradigm shift in the approach the ACR uses to develop guidelines, said Timothy McAlindon, MD, MPH, professor of medicine at Tufts University School of Medicine in Boston.
Past ACR RA management guidelines and updates, including those published in 2008 and 2012, used the RAND/UCLA methodology to gather, measure and filter evidence to support recommendations. “But even the RAND/UCLA approach lacked transparency,” he said. For the upcoming 2015 RA guideline, the ACR used GRADE methodology, which incorporates a more “transparent, granular literature review,” he said. GRADE, which stands for Grading of Recommendations, Assessment, Development and Evaluation, incorporates considerations of the quality of evidence, sample sizes, effect sizes and the type of study used. Recommendations may be labeled as strong or conditional depending on these factors, he said.
One of the most important parts of the process in forming the upcoming management recommendations was the development of PICO (population, intervention, comparators, outcomes) questions focusing on RA management issues and treatment approaches, Dr. McAlindon said. Development group members began by generating questions reflecting important clinical scenarios in RA treatment and defining outcomes related to those scenarios. They then gathered and systematically reviewed the available evidence on those topics/outcomes, and subsequently rated the quality of the evidence across outcomes, for each clinical question. The next step was to ask a panel to consider the evidence in light of their own experience and expertise, and draft recommendation statements that could be included in the final guideline. The next step will be to write the guideline paper and submit it to the journals and ACR for approval.
‘The development process was transparent, & our goal was consensus. Transparency is the key for our guidelines.’
Advisory recommendations are not proscriptive, said Jasvinder Singh, MD, MPH, associate professor of medicine at the University of Alabama, Birmingham, and principal investigator for this ACR project. However, they may help improve patient care and should be evidence based, he said.
“The development process was transparent, and our goal was consensus. Transparency is the key for our guidelines,” said Dr. Singh. “In the end, this is really good for our patients because it gives them more options.”
Together, the guideline developers found common ground on key issues in RA treatment, Dr. Singh said. These included disease-modifying antirheumatic drugs (DMARDs) before switching to a new therapy in various scenarios. However, “Arbitrary switching of therapies should not be done if the patient is doing well,” he said.
The guideline developers reviewed the medical literature on several RA-related topics, he added. These include the role of biosimilars in RA therapy, use of biologic drugs and DMARDs during pregnancy and breastfeeding, treatment of RA with interstitial lung disease and biomarker testing.
In the end, a recommendation is considered strong if the benefit of a therapy in a particular scenario outweighs the risks, Dr. Singh said. The ideal target for all of the RA treatment recommendations was low disease activity scores or remission.
Recommendations from the draft guidelines, which remain under review, include:
- An optimal dose of DMARD monotherapy is recommended for the first three months of treatment for patients both with low DAS and moderate to high DAS. Methotrexate is the first-line therapy for most RA patients.
- After three months, if methotrexate or any other DMARD fails, rheumatologists may try dose escalation or switching therapies.
- Short-term glucocorticoids may be given to DMARD-naive RA patients with any disease-activity level who experience a flare.
- DMARD-naive patients with established RA and either low or moderate to high disease activity should also start with DMARD monotherapy. If this fails, rheumatologists should switch to a combination therapy of multiple DMARDs, a TNFα-inhibitor with or without methotrexate, a non-TNF biologic with or without methotrexate, or tofacitinib and methotrexate.
- RA patients, even those in remission, should not discontinue therapy.
Audience members questioned the panel about why tofacitinib was not recommended for early RA and the role of intra-articular glucocorticoids for flares instead of oral drugs.
The guideline development group is continuing to finalize the points and treatments deemed most important to managing RA, with the aim of the final recommendations being published this summer. In the meantime, additional highlights of the draft guidelines can be found in the SessionSelect recording of this session.
Susan Bernstein is a freelance medical journalist based in Atlanta.
If you missed this session, New ACR Recommendations for the Management of Rheumatoid Arthritis, it’s not too late. Catch it on SessionSelect: http://acr.peachnewmedia.com/store/provider/provider09.php.