Adverse Events of TNF Inhibitors Used to Treat Psoriasis



Mark Lebwohl, MD: Leon, what about the adverse effects of the older drugs. I’ll concentrate perhaps on the really older drugs, which are the TNF [tumor necrosis factor] blockers—malignancies, infections, allergic reactions.

Leon Kircik, MD: It’s interesting. As I was getting ready for this, I looked at the TNF alpha inhibitors’ package insert, vs the IL-17 and IL-23. It’s 101 pages. Just to pick 1, adalimumab, the most commonly used TNF alpha inhibitor; it’s 101 pages. IL-17 is somewhere about 21, 18 pages. The most common one, tildrakizumab, is about 15 pages. The difference is amazing, right?

Given the fact that, as James [Song] mentioned, all the TNF alpha inhibitors tear the package because they came from the factor of the rheumatoid arthritis. They have the IBD [inflammatory bowel disease]. They have so many several other patient populations where they collect all these adverse events in their package insert. Regardless, they are still there, vs all the IL-17s and IL-23s that are directly studied for psoriasis. They have a much cleaner package insert.

But when we talk about adverse events, definitely serious infections, opportunistic infections are there, right, for the TNF [tumor necrosis factor] alpha inhibitors. Tuberculosis is a big 1. With fungal infections, you know we don’t think about it, but I’m in Kentucky, in the Ohio Valley, so histoplasmosis is rapid.

I always check histoplasmosis urine antigen, which is a cheap thing to do. I talked to the infectious disease doctor, she said, “Don’t do an x-ray. Everybody’s lung(?) is do a white(?) count(?) [MB1] and both. But if you do a urine antigen test, it’s easy, it’s cheap, and it is active when they have active disease.

So those are the more common ones. Now malignancies are really tricky. Most of the malignancies in their package insert comes from different populations. For example, lymphomas were seen mostly in kids and young adult males from IBD [inflammatory bowel disease], who were on mercaptopurine or Imuran, right? That’s where the lymphoma population comes, but it’s still there.

Certainly, CHF [congestive heart failure]. But that’s a problem because the drug was studied for CHF and didn’t show any effect, so it got into the label. Well, MS [multiple sclerosis] demyelinating diseases are there. But 1 thing we need to pay attention with the TNF alpha inhibitors is hepatitis B. We don’t think about it, but if somebody has hepatitis B, you should not be giving them TNF alpha inhibitors. That’s really a problem, and we don’t want to miss that, especially when we have other options. In the old days we didn’t, but now we do.

Having said that, there was a very nice article. About a year and a half ago they looked at meta-analysis of all cumulative biologics that patients were on from Europe. It included Israel, Italy, Spain, Ireland, a couple of other European countries. They have a nationalized health care system; they have great data. They took people and they age mixed, gender matched, and even weight matched with a normal population and compared all the malignancies. Actually, it says that there was no risk of cancers, they were not significantly associated with simulative exposures to biologics. Again, given all those things you will find in the package search for patients with psoriasis, the risk is there, but it’s minimal, just like anything else.

Mark Lebwohl, MD: Your discussion of that is fascinating because malignancies are a box warning. As you mentioned, many of the patients were inflammatory bowel disease, around 6 MP [6-mercaptopurine]. We actually assigned some medical students years ago to do a literature review on all of the malignancies reported in any of the patients on a biologic for psoriasis. And we accumulated it: There are a large number of malignancies. Then we looked at what dugs they were on, and it turned out that about two-thirds of them were on combination therapy, usually with a TNF blocker with 6 MP steroids, methotrexate, or some other combinations that you really could pin the malignancy and you couldn’t pin it on the biologic alone. It’s questionable.

But I will say that the black-box warning about malignancies does get me to go to other drugs. You know, the 17s and 23s have some data, and they’re animal data or cell tissue data, suggesting that they might actually be protectives. Whether that’s true or not, and I don’t know that it’s true, it does get me to prescribe that in the dose instead of TNF blockers in patients who have a history of malignancy.

Erin Boh, MD, PhD, FAAD: Mark, you have thousands of patients. I guess I have a lot as well. From a clinical observational standpoint, patients with psoriasis to me—even on the TNF—do not see an increased incidence of malignancy, even though the black-box warning is there. It doesn’t make me not go to the TNF. What you said is exactly on the mark. We tend not to treat with combination therapy for long term as they do in the GI [gastrointestinal] literature. And that’s the key: long-term immunosuppression. Thinking about efalizumab, we saw that that is not the way to go even with monotherapy. But these patients aren’t severely immunosuppressed with the biologics, even the TNFs that we have.

When I say I don’t worry about malignancy, I don’t make that a stopper for me. If a patient needs a TNF, I go to the TNF. I have actually put people back on anti-TNFs—once their malignancy has cleared—if there’s a reason they really have to have it. Again, in conjunction with the oncologists we have many other choices but sometimes we’re limited in what we can do. Malignancies are something we need to keep in the back of our head as a possibility or as a consequence of these TNFs. But it’s a very low risk in general. We just need to be aware that patients who are of certain populations will get malignancies. Age-related screenings are the way to go, and we just need to be up on that and not be scared to use any of these for fear of malignancy.

Mark Lebwohl, MD: I agree with you. Maybe the exception of squamous cell carcinoma of the skin, and people who got PUVA [psoralen–ultraviolet A radiation] a long time ago.

Erin Boh, MD, PhD, FAAD: Right, correct.

Mark Lebwohl, MD: The guy who’s getting 12 is getting 12 squamous cells a year. If he’s on a TNF blocker, he gets 20.

Erin Boh, MD, PhD, FAAD: Absolutely, I would agree with that.

Transcript Edited for Clarity

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