Robert G. Micheletti, MD: I’ve seen patients who come to me with very severe disease and they’re not on appropriate therapy, and also patients who have a mild disease and who are being given too much therapy. It’s important to come up with therapy that matches what you’re seeing clinically. And so, again, the mild, moderate, severe, Hurley staging classification can be useful as we think about this. But, the typical patient who needs a TNF inhibitor is a patient who has multiple inflammatory boils, sinus tracts, possibly an entire anatomic unit that’s involved, and those special cases where you have this erosive very, very inflammatory suppurating disease affecting the axillae or perineum, etc.
So, these patients clearly have more active disease, and often they have more active disease almost from the beginning where they blow right through Hurley stage 1 and right into 2 and 3. And those are the patients where I think it’s useful to recognize that this is more of an acute inflammatory process, and we need an agent that’s going to really address the inflammatory part of this. And so, putting TNF inhibitors to good use for those patients is really important. On the flip side, you sometimes see patients who are sent in with very mild disease with a request to start a TNF inhibitor, and that may not be appropriate, either, because we do have to think about the long-term risks and benefits. But, I think for many patients with moderate or severe disease, a TNF inhibitor can be very appropriate and should be reached for earlier rather than later, particularly if they’re not responding to some of the more traditional agents like clindamycin/rifampin.
There’s a long track record of TNF inhibitor use in medicine, and so I think we understand pretty well the safety profile. These are medicines that generally are well tolerated. Of course, one does have to worry about some atypical infections, like tuberculosis or endemic mycoses, and a rare cancer risk even over the long-term. But, we know that for patients with severe hidradenitis, as with severe other inflammatory conditions in which TNF inhibitors are used, the benefits really far outweigh the risks when you think about quality-of-life impact of the disease.
Adalimumab or infliximab, I think both of them have efficacy in my hands and have some literature to support them. The recent PIONEER 1 and 2 trials, that led to FDA approval of adalimumab, essentially show in patients with pretty moderate or severe disease that about half of those patients had significant improvement compared to a quarter of the placebo patients, roughly speaking. And so, it is a statistically significant difference. Again, these are patients with legitimate disease that oftentimes have failed other therapies. And, again, these are large studies. They had, together, over 600 patients between them, the drug is well tolerated in that group, and the efficacy was there using their scoring criteria.
I think a couple of issues are really important to note about the clinical use of TNF inhibitors. I think the first is that dosing is very important. So, for instance, with infliximab, the typical dosing of 5 mg/kg ultimately every other week, I find that that can be effective, but often it needs to be uptitrated in patients with hidradenitis. Infusions move closer together, dose increased, and it’s the same for adalimumab.
The study that came before PIONEER 1 and 2, that looked at 40 mg weekly versus every other week versus placebo, really showed that the weekly dosing was more effective than every other week. And we think about that with our psoriasis patients if they’re overweight, which many hidradenitis patients are. They really need the higher dosing. So, specifically the dose that was used in the PIONEER 1 and 2 trials is more akin to the Crohn’s disease dosing, where patients would get 160 mg at week 0, 80 mg at week 2, and then 40 mg weekly thereafter, beginning at week 4. And so, that loading dose and then that weekly dosing, I think, is really important to the benefit that you’re seeing in that study and clinically. It is important to note that this is not your regular psoriasis dosing, and it’s important that it got FDA approval because getting access to the medication in that dose was very difficult before that. You’re not going to be able to get a medicine off-label in these higher doses without the data to back it up.
The other thing, I think is worth mentioning, is that we talk about comparative effectiveness research and determining which agent is better, and, really, we don’t have anything like that in hidradenitis. I think if you compare study to study, it’s really apples to oranges; different scoring criteria, different dosing. And so, ultimately, it might be nice to have a head-to-head comparison looking at different, what we think are adequate, dosing regimens, the same scoring criteria, and so on. But, it is tremendously useful to have adalimumab be FDA approved because it lends credence to your efforts to get access to these medicines, either infliximab or adalimumab, from insurance companies for patients who really need them. Like I mentioned earlier, it is a game changer for those patients with more moderate/severe disease.
Transcript Edited for Clarity