Even though biologic disease-modifying antirheumatic drugs, or biologic DMARDs, have been around for more than a decade, rheumatologists are still trying to understand how to target the right treatment to the right patient at the right time. And while biologics have been game changers for many patients with rheumatoid arthritis, or RA, the success has not been uniform – some patients don’t respond completely or at all, some stop responding after a while, and some can’t tolerate them. What to do with those patients?

That issue has become a priority for rheumatologists as the gap in outcomes between responders and non-responders grows. A new study has provided some preliminary answers to a key question with which rheumatologists have been grappling: Should a patient who doesn’t improve or respond well to a type of biologic called an anti-tumor necrosis factor drug, or anti-TNF, try a second anti-TNF or another type of biologic altogether? 

The study, published in Arthritis Care & Research, suggests that RA patients who don’t respond to an anti-TNF may get better results if they try a biologic called rituximab, or Rituxan, instead of a second anti-TNF.

The treatment options for new RA patients are relatively well understood up to a point. Typically, a patient newly diagnosed with RA is put on one or a combination of traditional DMARDs, such as methotrexate; hydroxychloroquine, brand name Plaquenil; or leflunomide, brand name Arava. If the patient can’t tolerate or doesn’t respond to traditional DMARDs, he or she is stepped up to a biologic, a complex medication made from living proteins. The American College of Rheumatology, or ACR, guidelines for DMARD therapies, revised in 2012, lists anti-TNFs as the first-line choice among biologics.

Anti-TNFs – also called TNF inhibitors or TNF blockers – work by blocking tumor necrosis factor, a cytokine, or protein, that promotes an inflammatory response. The five anti-TNFs on the market are adalimumab, or Humira; certolizumab pegol, or Cimzia; etanercept, or Enbrel; golimumab, or Simponi; and infliximab, or Remicade.

When an anti-TNF works, it works well, but when it doesn’t, the alternatives are other anti-TNFs or other biologic DMARDs that work via different mechanisms. Rituximab is a selective B-cell inhibitor; anakinra, or Kineret, is an interleukin-1 inhibitor; tocilizumab, or Actemra, is an interleukin-6 inhibitor; and abatacept, or Orencia, is a selective costimulation modulator.

“Our study showed that, overall, the response was slightly better in patients who were switched to rituximab,” says study author Kimme Hyrich, MD, PhD, from the Arthritis Research Epidemiology Unit at the University of Manchester in the United Kingdom.

But she acknowledges that the study findings don’t tell the entire story. “We do not yet have the ability to predict what will be the best treatment for any individual patient, and there may still be circumstances where a second anti-TNF or even a different biologic altogether may be a better choice,” she says.

In the study, researchers analyzed information from a database called the British Society for Rheumatology Biologics Register. They looked at two different subgroups of patients who had “failed” a first anti-TNF treatment (for any reason – either inadequate or no response, loss of response or inability to tolerate) and then switched to either rituximab or another anti-TNF. Because this was a retrospective analysis of existing data, the patients were not randomly assigned to receive a particular second biologic.