VIDEO: EULAR guidance on DMARD use in RA made ‘more concise’

LONDON – The European League Against Rheumatism guidelines on the use of disease-modifying antirheumatic drugs for the treatment of rheumatoid arthritis have been updated in line with current evidence and made more concise.

Dr. Josef S. Smolen of the department of rheumatology at the Medical University of Vienna who presented the 2016 guidelines at the European Congress of Rheumatology, noted that they now consist of 12 rather than the 14 recommendations that were included in the 2013 update (Ann Rheum Dis. 2014;73:492-509) and the 15 recommendations that were in the original 2010 version.

These 12 recommendations cover treatment targets and general approaches in the management of rheumatoid arthritis that incorporate disease-modifying antirheumatic drugs (DMARDs) and the use of glucocorticoids, and present treatment options as a hierarchy to help guide clinicians through appropriate procedures when initial and subsequent treatment fails. All DMARDs are considered in the recommendations, from the long-standing conventional synthetic (cs)DMARDs, such as methotrexate, sulfasalazine, and leflunomide, and the newer biologic DMARDs, such as the anti–tumor necrosis factor (TNF)–targeting drugs, to the newer biosimilar DMARDs, and targeted synthetic (ts)DMARDS, such as the Janus kinase (JAK) inhibitors tofacitinib and baricitinib.

The recommendations have been developed in accordance with EULAR’s standard operating procedure for the development of guidelines, Dr. Smolen observed, and involved three systematic literature reviews and expert opinion garnered from a task force of 50 experts and patients.

“This was the largest task force I have ever convened,” Dr. Smolen said, noting that rheumatologists from outside Europe had been invited to contribute their expertise and knowledge for the first time. Altogether 42 rheumatologists, three clinical fellows, two health professionals, and three patients were involved in revising the recommendations.

There are now four rather than three overarching principles, two of which are shared with early inflammatory arthritis recommendations that were also presented at the congress. The first two principles state that shared decision making is key to optimizing care and that rheumatologists should be the primary specialists looking after patients. The third principle recognizes the high burden that RA can have not only on an individual level but also on health care systems and society in general, which rheumatologists should be aware of. The fourth and final principle states that treatment decisions should be based on patients’ disease activity but that other factors, such as patients’ age, risk for progression, coexisting disease, and likely tolerance of treatment should also be kept in mind.

In an interview, Dr. Smolen highlighted that the EULAR recommendations cover three main phases of DMARD treatment: First is the DMARD-naive group of patients, who may be at an early or late stage of their disease. Second is the group in whom initial treatment has failed, and third is the group for whom subsequent treatment has not worked.

“In all these phases, we have some changes,” Dr. Smolen said. As an example, he noted that in the DMARD-naive setting, the use of csDMARDs has always been recommended but that the prior advice to consider combination csDMARD treatment has been edited out.

“We now say methotrexate should be part of the first treatment strategy, and the treatment strategy encompasses the use of additional, at least conventional synthetic, DMARDs.” Glucocorticoids are also more strongly recommended as part of the initial treatment strategy in combination with methotrexate, he said, although there is the proviso to use these for as short a time as possible.

In situations where patients do not respond to methotrexate plus glucocorticoids or they cannot tolerate methotrexate, then the recommendations advise stratifying patients into two groups. Those with poor prognostic factors might be switched to a biologic therapy, such as an anti-TNF agent or a tsDMARD. In regard to the latter, there is now more evidence behind the use of JAK inhibitors, notably tofacitinib, Dr. Smolen observed. Biologic DMARDs should be combined with csDMARDs, but if the latter is not tolerated then there is the option to use an IL-6 pathway inhibitor.

“There is now compelling evidence that all biologic DMARDs, including tocilizumab, convey better clinical, functional, and structural outcomes in combination with conventional synthetic DMARDs, especially methotrexate,” Dr. Smolen observed during his presentation of the recommendations. This may not be the case for the JAK inhibitors based on the current evidence.

When asked how the EULAR recommendations match up to those issued earlier this year by the American College of Rheumatology (Arthritis Care Res. 2016;68:1-25), Dr. Smolen observed that the two had become “much closer.” There remain differences in recommendations on glucocorticoid use, which are “somewhat clearer” in the European than in the American guidelines, and EULAR proposes combining biologic DMARDs with csDMARDs rather than using them as monotherapy. The EULAR recommendations also do not distinguish patients by disease duration but by treatment phase, and use prognostic factors for stratification.