New American College of Rheumatology (ACR) guidelines for treating rheumatoid arthritis (RA) give no guidance on some of the hottest questions in the field, including biosimilar drugs, biomarkers and pregnancy.

“The guidelines can be very insightful, not so much for what they say, but for the things that aren’t said, that aren’t discussed,” says CreakyJoints cofounder Seth Ginsberg.

The ACR published its guidelines for RA November 6 online in the journal Arthritis Care & Research, and presented them in a press conference November 10. It’s the first update to its guidelines since 2012.

Ginsberg is listed in a co-author and participated in key meetings to draw up the guidelines. He was one of two patients on the 26-member committee along with Amye Leong, president and CEO of Healthy Motivation, a health education and advocacy consulting firm.

“I’d like to one more time acknowledge our profound appreciation to the ACR for the inclusion of the patient voice,” Ginsberg said.

 

Searching for Evidence

The committee created its guidelines by reviewing the published research on rheumatoid arthritis to answer the questions it considered most pressing. A panel of experts then voted on recommendations.

For many questions, the committee couldn’t find enough evidence to make a definitive answer. In fact, it made 77 percent of its recommendations “conditional” because the evidence was so weak.

“I think the guideline process is a work in progress,” said Ginsberg. “The need for more evidence is the glaring area where more improvement can be made. think everyone would agree with that.”

The committee considered weighing in on the topic of biosimilars, said Committee Chair Jasvinder Singh, MD, from the University of Alabama at Birmingham.

Biosimilars resemble existing FDA-approved drugs, and are less expensive. But since they are not chemically identical, some experts worry that they might be less effective or cause more adverse reactions.

No biosimilar drugs were approved in the United States at the time of the final rheumatoid arthritis literature review, on September 17, 2014, said Singh. And the ACR does not give guidance on treatments not approved in the United States. So the new guidelines only mention biosimlars in passing. “These were discussed as potential future points to be considered,” Singh said

Since then, the U.S. Food and Drug Administration approved a biosimilar drug for the first time March 6, 2015: filgrastim-sndz (Zarxio, Sandoz), which is analogous to filgrastim (Neupogen, Amgen), for use in cancer. It still has not approved any biosimilars for rheumatoid arthritis.

 

High-Risk Populations

The committee grappled with several other controversies, Singh said. One of the hottest debates centered on the treatment of high-risk populations such as people with rheumatoid arthritis who also have hepatitis B or C or skin cancer.

There is very little evidence on which to base recommendations for these populations, Singh said.

As a result, the committee split on its recommendation in treating patients with a history of non-melanoma skin cancer. The majority thought that disease-modifying anti-rheumatic drugs (DMARDs) should be preferred over biologic drugs because they may be less immunosuppressive.

But one member of the committee argued insistently that the difference in immunosuppressive effects between DMARDS and biologics might not be significant. So the panel decided to recommend DMARDs, but it noted the dissenting opinion in the guidelines.

 

Changes from 2012

The new guidelines differ on several important points from the ACR’s last published guidelines, issued in 2012, said Singh. Among the changes are a strong endorsement of a treat-to-target approach, in which clinicians set specific goals of low disease activity or remission.

There are recommendations for the use of DMARDs and biologic drugs, distinguishing between early and established rheumatoid arthritis, he said.

For the first time, the guidelines address the use of tofacitinib and glucocoricoids.

They also cover the use of vaccines in patients taking DMARDs, screening for tuberculosis in patients taking biologics or tofacitinib (the active ingredient in  Xeljanz and Jakvinus), and laboratory monitoring for traditional DMARDs.

The guidelines are voluntary and should not be used by insurance companies in deciding what treatments they will cover, Singh said. “We have two audiences: physicians and patients.”

 

No Pregnancy Recommendations

Ginsberg he said he had pushed without success for the committee to make recommendations on biosimilars.

In addition, he would have liked the committee to give guidance on treating women who are pregnant or of childbearing age, and on the use of biomarkers in monitoring the disease.

“I spoke up to say, ‘Hey everybody, we’re talking about a disease that affects women of childbearing age. Can someone say the word pregnancy, once?’ And there were a lot of nods and a lot of agreement but unfortunately the ship had sailed.”

There may not be a lot of data to address these subjects, but the committee made recommendations without strong evidence on other topics, Ginsberg pointed out.

“If there is very little data, let’s substitute what the patient wants and needs,” he said.