SAN FRANCISCO — People who aren’t getting relief from their rheumatoid arthritis (RA) with an anti-tumor necrosis factor (TNF) drug are more likely to do better if they switch to a different type of biologic therapy rather than another anti-TNF, researchers say.
But the researchers also think a test for antidrug antibodies can help figure out which patients will benefit from such a switch.
“This study demonstrated a better effectiveness of a non-TNF-targeted biologic than a second anti-TNF agent for patients who did not respond to their first anti-TNF,” said the lead researcher, Jacques-Eric Gottenberg, MD, PhD from the National Reference Center For Systemic Autoimmune Diseases at Strasbourg University Hospital in France.
“This superiority was consistent throughout the study period and across numerous outcome criteria in a setting nearing common practice, with no significant difference in the safety two treatment strategies evaluated,” he said.
Anti-TNF drugs are a class of drugs that treat inflammatory conditions such as RA. They include Remicade, Enbrel, Humira, Simponi and Simponi Aria. These drugs are often able to reduce inflammation and stop disease progression, but one-third of patients do not find success when taking them to treat RA.
How the Study Was Done
When this happens, rheumatologists often consider one of two strategies: trying a second anti-TNF drug or switching to a non-TNF-targeted biologic. To figure out which works better, researchers from France recently put them to the test in a 48-week randomized study of 292 people.
The researchers randomly assigned participants in the study to either receive a non-TNF-targeted biologic or a second anti-TNF when it was established that the first anti-TNF was not working.
Each participant’s physician chose the second anti-TNF (either Humira, Cimzia, Enbrel or Remicade) or the non-TNF biologic (Orencia, rituximab (the active ingredient in Rituxan, MabThera and Zytux) or Actemra).
Gottenberg’s team followed up with the participants after three, six and 12 months to determine how they were reacting to their new treatment strategies. They used the European League Against Rheumatism criteria to compare such factors as symptoms, swelling and biomarkers.
At three months, 64.2 percent of the non-anti-TNF group and 47.8 percent of the second anti-TNF group achieved a good or moderate response.
At six months, this increased to 69.7 percent for the non-anti-TNF group and 52.1 percent for the second anti-TNF group.
And at 12 months it dropped to 60 percent for the non-anti-TNF group and 43.2 percent for the second anti-TNF group.
The researchers also looked at disease activity scores and noted 40.8 percent of the non-anti-TNF group and 23.5 percent of the second anti-TNF group achieved low disease activity, respectively.
Also 26.9 of the non-anti-TNF group and 13.6 percent of the second anti-TNF group achieved remission.
“However,” Gottenberg pointed out, “at least 40 percent of patients failed to respond to their second-line biologic, which emphasizes the unmet need to continue to increase the number of treatment options and develop personalized medicine for people with RA.”
An Anti-Body Test Might Help
So his team did a second study to see if the presence of anti-drug antibodies would have been helpful in choosing a second biologic.
“Sometimes a person’s immune system can fight against a drug being used to treat a disease,” explained Gottenberg. “This causes the body to create anti-drug antibodies, which may render the drug useless and may even cause side effects. We wanted to see if these antibodies were present in people who weren’t having success with anti-TNF drugs because we believe this knowledge could help a rheumatologist make a better choice for the second treatment strategy.”
In this study, Dr. Gottenberg’s team looked at anti-drug antibodies in 278 patients (pulled from the participants of the first study).
The remains of the anti-TNF medication prevented the researchers from detecting anti-drug antibodies in 19 patients. In another 227 patients, anti-drug antibodies could have been detected but did not show up.
Another 32 patients did have anti-drug antibodies. In these 32 patients, blood levels of the first anti-TNF were very low or undetectable, which might be related to the binding of the first anti-TNF to anti-drug antibodies. And significantly, using a second anti-TNF medication was just as effective as using a non-anti-TNF medication in these patients.
The researchers concluded that the anti-body test could be used in this way: If patients don’t have anti-TNF drug antibodies, that could mean their RA is not TNF-driven. In these patients, the best choice might be to switch to a non-anti-TNF biologic.
If patients do have anti-TNF drug antibodies, the choice of a second anti-TNF might be as successful as a non-anti-TNF biologic.
But Gottenberg says more studies are needed to see how successfully an antibody test can guide such treatment decisions.