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Ginette A. Okoye, MD: Hello. I’m Dr Ginette Okoye. Welcome to the Medscape InDiscussion podcast series on hidradenitis suppurativa (HS). Today we’ll be discussing advanced therapies for difficult-to-treat HS with our guest, Dr Steven Cohen. Dr Cohen serves as director of the Weill Cornell Dermatology Center for HS at Weill Cornell Medicine.
Thank you for joining us today, Dr Cohen, and welcome to the Medscape InDiscussion podcast.
Steven R. Cohen, MD, MPH: And thank you for having me, Dr Okoye. I’m really glad to be here.
Okoye: Can you tell us a little bit about your HS story? What brought you to this subspecialty?
Cohen: That’s a great question because doctors, like patients, have a journey that usually starts when they become seriously engaged with HS. And mine started in 2015. I’ve been doing this for about 10 years, and I realized, like every dermatologist, that it’s very hard to take care of HS.
When I first started, it was a struggle. I didn’t know which medications to use and which order to use them in, and I didn’t know how to evaluate the wide range of HS morphologies and disease severity that I was seeing. It required establishing a mechanism for determining what therapeutic options work best in the different patient presentations. And this is ongoing; it goes on today. I think we’re far more successful now because we have many more therapeutic options. Some of the therapeutic options that were coming online back in 2015, I’m happy to say we explored them and helped develop more effective ways of using those modalities. We’ve been fortunate enough that it’s more on the radar screen of the dermatology and the scientific communities now, and we’re the beneficiaries of new developments that are in the pipeline.
Okoye: Indeed, the landscape is different from what it was 10 years ago, to our patients’ benefit. And speaking of which, we now have three FDA-approved biologics for HS plus, many of the off-label options we use. In your opinion, is there still a role for antibiotics in the management of HS?
Cohen: Antibiotics are a controversial subject. The short answer is yes. When a patient comes to the office, they could be on biologics or they could be on hormone therapy. However, if they’re draining and have culture-positive exudate or drainage from wounds or abscesses that have not been treated with antibiotics, you can be almost certain that the efficacy of any remedies you’re using will be limited. At least that is my experience. We culture all patients at every visit if they have exudate, and we treat them accordingly. Now we have a number of different antimicrobial algorithms, and we use them in different settings. We use single, double, and triple antibiotic approaches. And we use the antibiotics in three different ways.
We use topical, oral, and intravenous modalities. It depends on the severity of the disease and the response to the initial approach. We use minocycline exclusively. We don’t use doxycycline. I think it penetrates tissues better and is absorbed more effectively.
We pretty much rely on that for single therapy, usually for early-stage disease. And then as we get disease above and below the waist, we get a different antimicrobial spectrum. We’re going to use different antibiotic regimens for that. I think you need fluoroquinolones when you’re dealing with disease below the waist, and above the waist, you can use clindamycin or rifampin.
The cultures are important because if we have a patient who has MRSA [methicillin-resistant Staphylococcus aureus] and we’re not recognizing that, we’re not going to get that patient better by giving them an inappropriate antibiotic. To answer your question, in short, we are very strong advocates of antibiotic therapy. I might add to this that we combine antibiotic therapy with antihormonal therapy, antiandrogen therapy, and anti-inflammatory therapy. They go together in patients with advanced disease. And for early-stage disease, we may limit our approach to one or two of these treatment arms.
But for advanced disease, we find that the synergy between these three therapeutic approaches is critical.
Okoye: It makes sense that you’re going after three different pathogenic pathways in the disease: the microbes, the hormones, and the inflammation. I have some more questions about the cultures and your antibiotic choices. Have you noticed trends in the species that you tend to culture above the waist and below?
Cohen: Below the waist, you are often dealing with coliforms, Klebsiella, and Enterobacter. Enterococcus, depending on whether or not you have more superficial or deep disease, you’re going to have more anaerobic involvement or lesser anaerobic involvement. Above the waist, you don’t typically see coliform organisms. You can, but that’s much less common.
You’re more likely to see gram-positive organisms. Any organism could be in any particular site; it depends on how they’re colonized. There is a difference. Similar to what I was saying about the cultures, if I have a patient that has, we’ll say Pseudomonas as an example, which is a very hard organism to treat, the only oral antibiotic we can use for pseudomonas that’s reasonably effective is a fluoroquinolone. Those patients are likely to get either Cipro (ciprofloxacin) or Levaquin (levofloxacin). Whereas we tend to be very specific in terms of what we’re growing. We’re looking at our sensitivities and drafting our treatment regimen based on that. You started by saying, do you even use antibiotics?
And I think the other component of that is, do you culture? If you don’t culture, you might not think antibiotics are important. But when you see the organisms that you get and the sensitivity patterns, you become much more highly motivated to use appropriate antibiotics.
Okoye: This is tough to ask because it depends on the patient and the culture, I realize, but what’s your favorite double antibiotic regimen? And then the same question for the triple antibiotic.
Cohen: That’s a really good question, because we’re in this weird universe where people don’t understand antibiotics, and it is particularly difficult to understand how they work. What I’m going to say is that I have developed my antibiotic preferences based on evidence-based medicine.
It’s not like I decided that I would have some favorites and I would try them. I’ve read the literature. When the French, in particular, introduced levofloxacin, rifampin, metronidazole, they introduced topical therapy with chlorhexidine and clindamycin. I started to rely on that because there was some evidence-based medicine that showed that it worked. To answer your question specifically about my favorites, for early-stage disease, I do use minocycline pretty exclusively. What would early-stage disease be? When people have tender nodules or they have recurrent disease that’s monthly or every other month. And I might start with that and see. Sometimes I can suppress the disease with a few months of therapy, and I’m usually using hormonal therapy at the same time, whether it’s a male or a female patient. And a lot of times, I can stop the antibiotic approach when I have early-stage disease and use the antiandrogen therapy.
When people have a lot of disease, like both axilla, inframammary involvement, or abdominal fold involvement, I’m much more likely to reach for dual antibiotics. That would be clindamycin and rifampin. When there’s a lot of disease below the waist or there are numerous anatomic areas — that would include the suprapubic skin, the inguinal skin, the labia, the scrotum, the perineum, and the buttocks — I’m going to use triple antibiotics. Those triple antibiotics would consist of levofloxacin, rifampin, and metronidazole.
Okoye: Now, not to get too in the weeds here, but this is my opportunity to pick your brain. Dr Cohen, you mentioned clindamycin and rifampin. I remember Dr Revuz — he was French — taking care of HS when no one else was looking at HS, and he had most of the papers and the textbooks. He would use 600 mg of clindamycin three times a day, which is double or triple what we tend to use.
What’s your usual dosing regimen?
Cohen: I use 300 mg twice a day. I like clindamycin and rifampin because they’re both 300-mg pills. Patients can take the two pills (one of each) in the morning and the two pills in the evening. I usually tell them that rifampin is going to turn their urine and all their secretions a little orange or red.
It’s not blood, it’s a dye in the antibiotic, and not to be alarmed about that.
Okoye: It’s good to know that at that lower dose than the European guidelines, you’re still getting efficacy. Now, our colleagues in infectious diseases are sometimes quite concerned about our use of antibiotics, especially since we use relatively long courses, and there’s lots of conversations about using clindamycin and rifampin together, and the fact that because of these CYP interactions, eventually you are on rifampin alone because the rifampin induces the enzymes that break clindamycin down. What are your thoughts on that? Are you worried about that at all?
Cohen: The reason this combination was developed is that clindamycin as a monotherapy has a high risk for colitis and pseudomembranous colitis. That is a nonstarter for using that drug. It became a challenge to have this patient population that might get a good response to clindamycin, but then they’d have to go off the drug because they got colitis. Rifampin has its own problem: If you try to use rifampin alone, you’re going to get a high frequency of drug-resistant staph.
And that’s not a good thing. When you combine these two drugs, clindamycin is very effective at removing the drug-resistant staph. The rifampin is very effective at reducing the tendency to colitis. You have these two drugs working in synergy; they protect each other.
And I never get patients with colitis, ever. I don’t get nearly the degree of drug resistance with clindamycin and rifampin if I try to use them separately. Of course, I never tell patients to do that, but sometimes patients come in and they say, “Oh, I ran out of clindamycin and I’ve been using the rifampin by itself.” They’re flaring and they have some resistant organisms. And that’s the only way I know about that. But I work hard to avoid that.
Okoye: You mentioned IV antibiotics. I assume you’re referring to IV ertapenem. Can you tell me a little bit about your experience with that option?
Cohen: I’m going to tell you about IV drugs rather than IV ertapenem. Ertapenem is another drug the French were very much in the lead in developing — ertapenem therapy. But they had a very different treatment algorithm than what we ultimately wound up using.
They were using IV ertapenem for 6 weeks, and then Join-Lambert was putting the patients on triple antibiotic therapy — levofloxacin, rifampin, and metronidazole — and he reported phenomenal results. I started out doing that and I didn’t get very good results post-treatment. I got great results initially. It’s an amazing drug. It’s an incredible drug. But if you stop in 6 weeks and the patients get their disease back in a few weeks, or a month, it’s like, wow, they spent 6 weeks with a midline or a PICC [peripherally inserted central catheter] line in their arm, and then they wind up with the disease back again. I used to sell that — that in the beginning, they would be getting a little holiday, a reprieve, from their HS.
I decided at some point that maybe we should extend the treatment interval, and we started treating patients for 8 weeks and then 10 weeks and then 12 weeks. In a paper that I reported in JAMA Dermatology a couple of years ago, there were 98 patients who were treated for 12 weeks. And the data itself are remarkable, in terms of efficacy, but I have since extended the treatment interval to 16 weeks. I’m keeping patients on the drug for 16 weeks now.
I said IV antibiotics rather than ertapenem exclusively because ertapenem is a carbapenem antibiotic-class drug. If you have an organism that produces carbapenemase enzymes, they inactivate the carbapenem antibiotic. Ertapenem can be inactivated, for example, by Pseudomonas, which is a big problem.
If you start getting Pseudomonas colonization, you have to do something to fix that. Ertapenem is not great for MRSA; you might want to have patients on linezolid even while they’re on ertapenem. When I have patients with intractable Pseudomonas colonization, I switch their antibiotics out and I put them on a combination drug called ceftazidime-avibactam. This is a significant time investment for the patient.
I think we’ll report some of these data soon. The reason that we don’t like the drug is not because of its efficacy. It’s a great drug. It knocks out the Pseudomonas almost immediately. However, ertapenem is a one-infusion-a-day drug. The infusions take 40 minutes, and it’s pretty easy for the patients to administer as a routine. But now you’re talking about a three-time-a-day drug. For example, if a patient gets admitted to the hospital with HS, they’re going to put them on Zosyn (piperacillin-tazobactam) and vancomycin.
You ask, why don’t we use piperacillin-tazobactam and vancomycin? The reason we don’t is because it’s three times a day, and it’s like an hour-and-a-half infusion. The ceftazidime-avibactam also takes nearly 2 hours. That’s 6 hours a day that people are using these infusions. It depends on how sick they are, and it depends on whether they’re working or not. I have a whole bunch of patients who are on this drug. It’s because it’s effective and they appreciate not having active disease, but it’s a big investment. We’re also using a third IV antibiotic from the tetracycline class, and that’s called omadacycline. Omadacycline is an oral drug. I find that it’s not all that effective, but it’s a once-a-day drug. You can give it as an IV, and if you already have a PICC line in, you can try this. It can be an effective drug in the right patient.
Most of the patients get ertapenem, and when they get to the end of their 16 weeks, they’re in remission, and we transition them back to oral antibiotics. You must use oral antibiotics when you finish. You can be overconfident, as we were initially. We saw how great the patients were doing, and we said, gee, they won’t need antibiotics anymore.
I now tell them from the very first minute they’re going to start on ertapenem, “You’ll be on antibiotics as soon as you’re finished with the ertapenem. Until we have an extended period of remission without any active disease, we might reduce the antibiotic spectrum, the number of drugs we’re giving you, or we may be able to transition you off of antibiotics.”
But I always want people to know that they must go back on antibiotics once the ertapenem is complete. You asked me about the journey associated with taking care of patients with this disease, and ertapenem is one of the more complex therapies to use because you have to have a relationship with interventional radiology. You have to be able to put a PICC line in, and you have to have a relationship with a home infusion service because the patient’s going to do these infusions, for the most part, at home. And they have to go in and they have to service the line, clean up the dressings every month, and make sure that the line is intact.
Learning how to do that is a little complicated. Once you get it down, it’s good. But at first, it’s tough. I think that if our colleagues were able to get more training in getting patients started on this drug, they wouldn’t have to be flummoxed — or shut down by our infectious disease colleagues.
They’re involved in antibiotic stewardship, and they have a very appropriate concern about antibiotic, multidrug resistance. There is a concern about having patients who will not be able to use carbapenem antibiotics; I get that, but we are dealing with patients who don’t have a life. It’s like taking a cancer patient and saying, “We’re not going to use a certain cancer therapy because it’s too toxic,” or “It’s too valuable for another cancer, and we won’t use it for this one.” If you have a life-threatening disease — and I do think HS is life-threatening in its advanced forms; many of our patients are depressed and suicidal — we’re looking at the risk and benefit. Our patients need ertapenem when they have advanced disease. We cannot ignore what they’re going through. At Weill Cornell, where I’m at right now, I have a very good relationship with infectious diseases.
And when my patients get admitted and they’re on ertapenem, they continue their ertapenem while they’re in the hospital. But I didn’t have that at my previous institution. They were very rigid, and they wouldn’t teach me how to do it, and they wouldn’t sanction it. I had to learn on my own, which I did.
It’s worthwhile, if you’re taking care of a lot of HS patients, to become familiar with how to use that therapy.
Okoye: And then to your point, the risk-benefit is worth the legwork and the relationship building that we have to do to put these things in place. I agree with you. Now, Dr Cohen, I have many more questions, but we have a limited amount of time. Do you have any parting words?
Cohen: I will give you some parting words because I want to emphasize, or leave you with, the importance of synergy between therapeutic classes. I think it’s incredibly important to factor antiandrogen therapy into treatment. I can’t give you the mechanism, but we know that this disease begins at puberty. That begins when androgens become active, whether you’re male or female. And we have good antiandrogen therapy that’s not particularly toxic for women. We can use spironolactone, and we can also use finasteride in women.
Birth control pills are great, and these can be very low-estrogen birth control pills. I avoid progesterone. For men, we can give them finasteride as a monotherapy. But I emphasize the importance, for very low risk, of the secondary class of antigens and then anti-inflammatory therapy. It’s very important.
You mentioned right in the beginning about how now we have three drugs that are approved for HS. Adalimumab, secukinumab, and bimekizumab are very important drugs. But I want to leave you with a caveat: that those patients with a high BMI tend to have a much reduced efficacy with fixed-dose treatments.
Having an anti-inflammatory approach, giving patients weight-based therapy, whether it’s infliximab or golimumab or whatever weight-based therapy that you’re doing, is important.
And we did not discuss other things that I want to leave as something to remember after this is over. One is surgery; deroofing and treating abscesses with surgical approaches is incredibly important and incredibly effective. We did not mention that the treatment algorithm is expanding, and it puts a lot of pressure on those of us who are treating HS as a specialty. We have a lot to offer our patients. I emphasize the need for synergy between drugs and early treatment. The earlier you can get a patient on treatment, the better.
And I encourage specialists to think more about surgery when patients are having structural problems with sinus tracts or tunnels, or they have foci that will not be suppressed with conventional medical approaches.
Okoye: You mentioned in passing when you were talking about the antiandrogen therapy, and I love that phrase vs “hormonal therapy” because it’s much more specific. You mentioned that you avoid progesterone. I think this is a really important point to leave our listeners with. Can you end with that?
Cohen: Sure. A lot of the patients, if they’re coming in from a gynecology setting, the gynecology physicians are doing two things: One is that they like progesterone contraceptives because they’re very effective, and they may even be a little bit better tolerated; they tend to have more androgenic effects. If you’re going to take oral contraceptive patches or you’re going to use a hormonal IUD, which is almost pure progesterone, they can aggravate HS. If you want a final parting word, try to avoid progesterone contraceptive measures.
We tend to use low-dose estrogen, the lowest you can use, and it’s very effective. We’re trying to swamp the androgens. And, of course, a lot of the gynecologists now are using continuous therapy to suppress the menstrual cycle, as a way of administering a birth control mechanism that makes women less affected by menstrual irregularities. That poses a problem in of itself because they’re getting progesterone all month long, and it makes it hard for us. I would try to wean patients off that if you can.
Okoye: The good news is that in our next couple of episodes, we’re going to be speaking to a surgeon and we’ll be speaking to an ob/gyn. We are going to delve even deeper into these topics. This was amazing, Dr Cohen. There were many other topics I wanted to cover, but I love the fact that we spent 30 minutes talking about antibiotics because I think that they are becoming a lost art in dermatology.
Today we’ve talked to Dr Cohen about the use of advanced therapies, including advanced approaches to using antibiotics in the management of HS. Thank you for joining us. Please take a moment to download the Medscape app to listen and subscribe to this podcast series on HS. I’m Dr Ginette Okoye for the Medscape InDiscussion podcast.
Resources
Hidradenitis Suppurativa
Efficacy and Safety of Biologics for Hidradenitis Suppurativa: A Network Meta-Analysis of Phase III Trials
Antibiotic, Hormonal/Metabolic, and Retinoid Therapies for Hidradenitis Suppurativa
Hormonal Treatments in Hidradenitis Suppurativa: A Systematic Review
Antiandrogen Therapy in Hidradenitis Suppurativa: Finasteride for Females
Combination Therapy With Clindamycin and Rifampicin for Hidradenitis Suppurativa: A Series of 116 Consecutive Patients
Pharmacokinetic Interaction Between Rifampicin and Clindamycin in Staphylococcal Osteoarticular Infections
Rifampin-Moxifloxacin-Metronidazole Combination Therapy for Severe Hurley Stage 1 Hidradenitis Suppurativa: Prospective Short-Term Trial and 1-Year Follow-Up in 28 Consecutive Patients
Efficacy and Durability of Intravenous Ertapenem Therapy for Recalcitrant Hidradenitis Suppurativa
The Impact of Body Mass Index Upon the Efficacy of Adalimumab in Hidradenitis Suppurativa
Surgical Approach to Hidradenitis Suppurativa