Robert G. Micheletti, MD
: There are some finer points to the use of TNF inhibitors. So, in addition to checking QuantiFERON gold or PPD (purified protein derivative) test for TB (tuberculosis), and following that annually, and talking about risk of infection and so on, we also want to think about some special situations. Occasionally, you have a patient who responds initially to adalimumab or infliximab and then they stop responding. With both of those drugs, one can develop human anti-chimeric antibodies and that can neutralize the drug. In that instance, I found that testing for the antibodies and seeing that they’re there, and then adding something like low-dose methotrexate, has given me useful mileage. I can continue the drug and get continued improvement by trying to neutralize those antibodies. So, that’s one situation that I think is relevant to mention.
The other thing is that, as with psoriasis, if one thing doesn’t work, try the other. Having two TNF inhibitors that have what we think is legitimate efficacy, if one isn’t working or stops working, then trying the other can be useful. And then, I think with hidradenitis, it can be difficult to get control in the first place. So, if I find something that’s working, I tend to leave patients on it, at least for the foreseeable future, because many of these patients with severe disease have many issues that they’re dealing with, and very active inflammatory skin disease. I’m in no hurry to get them off a therapy that I think is working. If I were to start adalimumab in a patient and get the desired result over a period of months, I would tend to leave them on that therapy until I’ve got things as cleaned up as I can get them, and then maybe implement something like some of the lifestyle changes or surgical options, or some of the other things that can be done, smoking cessation, to try ultimately to back them off the therapy. But, again, I’m in no hurry, typically, to get people off a therapy that’s working. Even though many of the studies end at 10 weeks, 12 weeks, we certainly don’t say that after 10 weeks it stops working. So, again, I leave patients on the therapy until I feel like they’re really quiet, and then we can back off as appropriate.
I think the examples that you tend to remember are the most dramatic ones. I had a patient with a very erosive hidradenitis in the axillae and the perineum, and this gentleman was unable to raise his arm really above 90 degrees, significant range of motion issues, and couldn’t sit down. Most of those initial visits, he would actually just stand, so it was really, really a highly impactful disease for him. And so, after getting him onto the appropriate dosing of adalimumab, over time we were able to see that that suppurative inflammatory disease really calmed down. I’m happy to say that, at this point, he has really just a scar left over. He’s been in physical therapy. He’s had some interventions where now he can raise his arm better. There’s much less pain, really very minimal active disease. It did take a while. It’s been months on the drug, but it’s been really miraculous for him when you think about where he’s come from. I have other examples along those lines of patients who have very active disease. They’re requiring even opioids, pain management, because of the disease activity—inflammatory, indurated, suppurative disease that you can see from visit to visit calming down, decreasing in terms of inflammation, and erythema, and suppuration on TNF inhibitors. I think, again, patients like that, they don’t really respond often to the antibiotic combinations as we would want. And so, TNF inhibitors really can make a huge difference for that type of patient.
I think the other patients that also bear mentioning are the ones who don’t have nearly as dramatic of disease, but enough disease that maybe your best efforts at traditional agents don’t quite manage. And so, knowing when to throw in the towel after several months on a good combination regimen and then progress to a TNF inhibitor, that’s also important to know when to make that kind of a change. Often, you can get added benefit from doing so. I think I’ve had good results with both infliximab and adalimumab, and I think there are good results. I tell patients, even with the most severe disease, that I am optimistic that I can get them under control with these agents. It can be a process, certainly, and you have to prepare them for that, but these drugs can make a big difference.
I think the most important thing to think about with side effects of a TNF inhibitor has to do with counseling a patient about infection risk over the long term. So, certainly monitoring for tuberculosis exposure annually, counseling about things like the intramuscular flu vaccine, and other things that we can help manage and prevent, those things are important. But, generally speaking, the drugs themselves are very well tolerated. We’re not having to check regular blood work. We’re not having to worry so much about tolerability. Occasionally, with infliximab, you’ll see things like infusion reactions. I mentioned earlier that you can develop antibodies to these medicines that can sometimes limit efficacy. But, generally, adalimumab is pretty well tolerated. And so, I haven’t seen a lot of side effects. There are some finer points during pregnancy. Obstetricians often will want a patient to come off of TNF therapy, particularly in the third trimester. As always, you want to be communicating with the patient’s other providers, so that everybody is on the same page with what you’re doing. But, I think these are medicines that typically are pretty well tolerated.
Transcript Edited for Clarity