Early-stage rheumatoid arthritis patients now have another medication choice. The U.S. Food and Drug Administration, or FDA, has expanded the indication of the biologic drug tocilizumab, or Actemra, to include its use in patients who fail to benefit from first-line treatments such as methotrexate and other traditional disease-modifying antirheumatic drugs, or DMARDs.

Tocilizumab, an interleukin-6 receptor, or IL-6, inhibitor, was originally approved by the FDA in 2010 – but only for use in patients who had already failed to benefit from TNF inhibitors, a class of biologics that includes adalimumab, or Humira, certolizumab pegol, or Cimzia, etanercept, or Enbrel, golimumab, or Simponi, and infliximab, or Remicade. By moving up tocilizumab from a third-line treatment to a second line treatment, the FDA’s move effectively puts it on therapeutic par with the TNF inhibitors.

Tocilizumab is the first approved drug to target interleukin-6, a key cytokine, or protein, involved in the excessive inflammatory response seen in rheumatoid arthritis, or RA. Tocilizumab is given by monthly intravenous infusion.

“I think it’s a significant development,” says rheumatologist Jasvinder Singh, MD, an associate professor of medicine at the University of Alabama at Birmingham School of Medicine. “This now allows use of the medication earlier in the disease, which means patients don’t have to fail [TNF inhibitors]. So it offers more options to patients and doctors.”

Dr. Singh says one of the key benefits of the expanded indication is actually financial. While some doctors have already been using tocilizumab as second-line therapy – after a traditional DMARD fails – Dr. Singh says it can sometimes be a struggle to get insurance companies to cover an unapproved indication. “The FDA approval does not directly equate with insurance company coverage,” Dr. Singh says. “But often FDA approvals for additional indications usually make it easier, and insurance companies pay a lot of attention to what the FDA does.”

What’s unclear is whether doctors will choose tocilizumab over TNF inhibitors. TNF inhibitors – also called anti-TNFs – offer certain advantages. Some of them are available as injections that patients can give to themselves at home – as opposed to IV infusions that must be given in a health care setting. Additionally, many clinicians have developed a certain “comfort level” with TNF inhibitors, several of which have been on the market more than 10 years.

“I certainly like to use medications I’m comfortable with using,” says Lin A. Brown, MD, a rheumatologist at the Dartmouth-Hitchcock Medical Center in Lebanon, N.H. “And we now have lots of experience using TNF inhibitors. I view tocilizumab a little like TNF inhibitors with [additional] side effects. It adds a few more things you have to watch for.”

For example, while all biologics increase the risk of infection, tocilizumab appears to increase this risk more. Also, studies have found it can elevate cholesterol and triglycerides levels. And it should be avoided in patients with diverticulitis, as studies have shown it can lead to gastrointestinal perforation.

Dr. Brown also points out that there’s no way to know whether a patient will benefit more from IL-6 inhibition or TNF inhibition. He says that while you can test RA patients for IL-6 and TNF levels, there is no data to suggest that the test provides therapeutically useful information. In other words, just because a patient has high IL-6 blood levels does not necessarily mean tocilizumab would work better than a TNF inhibitor. “You could make that assumption and go with it,” Dr. Brown says, “But it will not necessarily result in better disease control.”

Dr. Singh agrees. “It goes back to the basic question, is one cytokine more important in RA than another, and I don’t think that anybody has answered that question,” he says. “We know that a number of cytokines contribute to this disease. And different patients may respond to different medications. I don’t think that there’s a way to know which patients are going to respond with one drug versus another.”

Dr. Brown says that while she “can’t come up with a great reason why tocilizumab might be used before a TNF inhibitor,” she notes that “it does give patients and doctors choices.”

And, in a disease in which drugs often have a limited term of effectiveness, choice is an important consideration.

“Like every other biologic, this is an important drug for our patients and for us,” Dr. Singh says. “Even though we have nine biologics [approved for RA] we still have patients who need to try several before getting results. And there are always the patients who don’t respond to the first three, four or five drugs we use. So Actemra is an important tool for us and an important option for us to have on hand.”