Why anti-TNF treatments don’t work the same for everyone

 

INTRODUCTION

Some people who take treatments called anti-TNF drugs for illnesses like rheumatoid arthritis, psoriasis and spondyloarthritides may get less benefit than other people who take the same treatments, because their immune systems stop the drugs working properly.

WHAT DO WE KNOW ALREADY?

Anti-TNF drugs are used to reduce inflammation (for example joint swelling). They can be used to treat illnesses that cause inflammation in the joints, such as rheumatoid arthritis, as well as some bowel and skin conditions. Some names of anti-TNF drugs are infliximab (brand name Remicade), adalimumab (Humira), and etanercept (Enbrel).

Previous studies of people with rheumatoid arthritis and other similar illnesses have shown that anti-TNF drugs can reduce swelling and pain. But some people who take anti-TNF drugs will have less improvement in their symptoms than other people who take the same drugs, or the effect may disappear. Doctors think this happens because, in these people, the immune system fights back against the medicines. The way this happens is that these treatments trigger their immune system, which normally fights infection, to produce proteins called antibodies. These antibodies can be directed against the anti-TNF drugs which then stop working properly.

To find out more, researchers pooled the results from 17 previous studies of 865 people who took infliximab, adalimumab, and etanercept for rheumatoid arthritis, spondyloarthritis, psoriasis, and inflammatory bowel diseases. In these previous studies, people had been given blood tests to see if they produced anti-TNF antibodies. The researchers looked to see if there was a link between how many anti-TNF antibodies people made and how well they did when they had anti-TNF treatment.

WHAT DOES THE NEW STUDY SAY?

The researchers found a link between anti-TNF antibodies and a poorer response to some anti-TNF drugs. Producing anti-TNF antibodies meant it was more likely that a person would not respond to treatment with infliximab or adalimumab.

The researchers also found a link between producing anti-TNF antibodies and how much benefit people got from treatment with an anti-TNF drug. Producing anti-TNF antibodies reduced the benefit from treatment with infliximab or adalimumab.

Anti-TNF drugs didn’t affect the immune system in the same way if people took them along with another treatment that helped stop the immune response (like methotrexate). Fewer people who took this type of combination treatment produced anti-TNF antibodies than people who took anti-TNF drugs on their own (what is called monotherapy).

The researchers didn’t find any link between anti-TNF antibodies and how well etanercept worked. This may have been because the types of studies that were included in the review weren’t designed in a way that showed an effect. Or it may have been because etanercept is less likely than other drugs to cause an antibody reaction.

But it’s not clear from studies whether any one anti-TNF drug works better or has fewer sided effects than any other. ..

HOW RELIABLE ARE THE FINDINGS?

This type of study, which combines the results of previous research, is usually a reliable way to look at the effects of a treatment. But there are a few reasons to be cautious. The 17 studies included in this review used different types of blood tests to look for anti-TNF antibodies, and they varied in length from three to six months. Different blood tests can produce different results, and this could have affected the results of the review. The researchers say that an immune response can take some time to develop. So the results may have been affected by how long the studies were, and whether this was enough time to produce antibodies.

We also need to bear in mind that these were quite small studies that were all designed quite differently. This might also have affected the results. Most of the studies looked at people with rheumatoid arthritis, so we have less information about how far the results apply to other illnesses.

WHAT DOES THIS MEAN FOR ME?

The researchers say these results are promising, as they point toward some ways in which doctors might change the way they use anti-TNF drugs in future. For example, it may be that using higher doses of these treatments produces less of an immune response. So doctors could consider using higher doses so that people benefit

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Date summary prepared: December 2013

Summary based on research article published on: 6 December 2012

From: Garces, S. et al. The immunogenicity of anti-TNF therapy in immune-mediated inflammatory diseases: a systematic review of the literature with a meta-analysis. Ann Rheum Dis. 2013;72:1947-1955 doi:10.1136/annrheumdis-2012-202220

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