TNF Inhibitors and Autoimmune Disease

Megan E.B. Clowse, MD: TNF inhibitors are a class of medications that have now been on the market for 20 years and have really revolutionized the management of inflammatory arthritis. These medications are what we call biologics, which means that they are very specifically targeted to 1 part of your immune system and are delivered in a specific way, which is basically through what looks like an antibody into your body. These are medicines that you take as an injection or an infusion. They’re not pills like you take for a headache. They work in a very unique way. They target the tumor necrosis factor—alpha—TNF-alpha—which is a specific component of your immune system that drives inflammation. It has been shown and was shown for years before these drugs were developed that high levels of TNF-alpha were associated with high levels of inflammation in the joints of patients with rheumatoid arthritis, as well as throughout the body.

When we think about TNF inhibitors, we think about 5 different drugs. The 2 original drugs were etanercept and infliximab. Infliximab is the main one that’s given intravenously. We have adalimumab, which came on to the market a few years later. And then we have golimumab and certolizumab, which both came on to the market last, at about the same time. I think of their effectiveness as basically being the same.

Interestingly, some patients respond to one and not to the other. We don’t really know how to predict which patient is going to do best on one versus another. And intestinally, you can put 1 patient on one drug and see that it doesn’t work. Then, 6 months later, you put them on a different one of the TNF inhibitors and it works great. And then you try them on a third one later and it doesn’t work. So it’s strange to us—we don’t really understand why some people respond and why others don’t. But I think of them, from an effectiveness standpoint, as fairly interchangeable. When you look at the drug trials that have been done, all of them are shown in a similar range to get people into decreased disease activity and into remission.

There are a couple of factors that we think about when we are deciding who gets which therapy. The first consideration is how it’s delivered. As I said, infliximab is an intravenous medication, so if you don’t want to give yourself shots, then infliximab would be a great one to go with. If you don’t want to come in to the office and get an infusion, then you can get shots. Etanercept, adalimumab, golimumab, and certolizumab all are administered via shots that you can do at home.

The next thing that we sort of work from is safety in pregnancy. We look at the data that we have available. They all are thought to be relatively safe in pregnancy, and there have really been no data to suggest that any one of them is unsafe in pregnancy. We know, however, that some of them cross the placenta in the second half of pregnancies. Certolizumab does not do this. Because of the structure of these drugs, adalimumab, golimumab, and infliximab, in particular, move across the placenta into a baby during pregnancy quite rapidly, particularly in the second half of pregnancy. We know, however, that certolizumab, because of its structure, does not cross the placenta. Therefore, some patients feel that this is a safer choice during pregnancy.

All TNF inhibitors really show the same risk profile for patients outside of pregnancy. The main thing we all worry about is that taking a TNF inhibitor will reignite a tuberculosis infection. Doctors will always check your tuberculosis test prior to giving you one of these drugs because it’s a specific infection that can be reignited in your body when you take these medications. The risk of infection from other bugs—the flu, pneumonia, skin infections, or sort of the infections that are a part of normal life—can be more significant and more severe in patients who are taking a TNF inhibitor, so we are more inclined to see if these patients need antibiotics to knock out what started as a cold that everybody else had. Somebody on this medication might end up with a mild pneumonia. So these can worsen infections because your body just isn’t as good at fighting them off.

There are other rare adverse effects that happen very occasionally. The best news is that the data really support that TNF inhibitors do not increase the risk of cancer. That was a very large concern when these first came on to the market, but that really hasn’t borne out in the last 20 years of data collection. We have not seen spikes in the frequency of cancer in our patients who have been taking these medications, which is very reassuring.

One other thing that people often will call about is that they got an injection site reaction. It’s very common, but certainly not all patients get it. When patients give themselves an injection of a TNF inhibitor, sometimes they get a 1-inch-, 2-inch-, or 3-inch-diameter red welt in the area. This happens a day or 2 after they’ve done their injection. It usually goes away by the time the next injection is due. It’s often itchy, and it’s red, and it’s raised, and it looks pretty angry, but then it goes away.

This is a common thing that we see. It doesn’t seem to affect the long-term effectiveness of the drug, so it’s not like you’re making something against the drug that’s going to make it not work. It never turns into a big, all-over-the-body allergic reaction. It’s just a local reaction. And actually—fortunately—sometimes it just eventually goes away. So you’ll have it for a few shots and then it will go away. We treat it with things like topical Benadryl and those [sorts] of things and maybe ice. Although it is one of those things that happens with TNF inhibitors in some patients, it’s certainly not a reason to stop treatment.