Past President, The American Academy of Dermatology (AAD)
Waldman Professor and Chairman of The Kimberly and Eric J. Waldman Department of Dermatology
Icahn School of Medicine at Mount Sinai
New York, NY
JAK Inhibitors for Dermatologic Indications
The only JAK inhibitor approved for a dermatologic indication, or close to a dermatologic indication, is tofacitinib, which is approved for psoriatic arthritis and has had quite a good impact on that condition. There are, however, numerous publications looking at many other indications, and it looks like JAK inhibitors will have a profound impact on the treatment of alopecia areata, on the treatment of vitiligo, on the treatment of atopic dermatitis, and very close to my heart, on the treatment of psoriasis.
Bristol-Myers Squibb has a TYK2 inhibitor for which they presented superb results in a phase two trial showing dramatic improvement of psoriasis with a very good PASI 75, and even PASI 90 and 100 data for this new drug. And the advantage it has, of course, over the biologics are outstanding in terms of their degree of efficacy, but they’re injectable and there are many patients who don’t want an injection. And being able to take a pill that, at least so far, looks like it’s very safe and will be able to get comparable degrees of clearing is just a blessing to our patients. It’s a real breakthrough.
JAK inhibitors have had a number of uncommon but serious side effects, including thrombotic events. They are regarded as a little immunosuppressive, which is why tofacitinib was not approved for psoriasis. There was an increase in herpes zoster, for example. So, we’re looking at infections, thrombotic events, as comorbidities and, perhaps, even alterations in blood counts. Thrombocytopenia or neutropenia occur with some of the JAK inhibitors.
But the difference that we’re talking about here is that they block different Janus kinases. So, saying something’s a JAK inhibitor doesn’t mean it inhibits all of them. There’s JAK1, 2, and 3, and there’s a tyrosine kinase 2, as I mentioned. So far, the side effect profile of the TYK2 inhibitor looks quite good. I am optimistic that this one will actually reach the market.
The other thing that I didn’t mention is topical JAK inhibitors and there’s a real advantage to having non-topical steroids—something that’s as good as a topical steroid, but isn’t a topical steroid. And those in topical form formulations will represent breakthroughs as well.
Updates in Treatment for Psoriasis
Right now, we’re in great shape with psoriasis from an injectable point of view. We do need more good oral therapies. We need better therapies for psoriatic arthritis. And even with all of the superb treatments we currently have, there are very few drugs that, at their primary endpoint, achieved PASI 100 in the majority of patients. In fact, I would say, until now, there aren’t any. We are looking at a drug called bimekizumab coming out probably in about a year and a half, which indeed, at its primary endpoint, achieved PASI 100 in a majority of patients, at least in one of their studies.
And we are looking at, as you go down further in time, a very high proportion of patients achieving PASI 100. It’s also a dramatically effective treatment for psoriatic arthritis. Until now, we’re lucky to get a drug that achieves 50% improvement in what’s called ACR20. That’s a 20% improvement in psoriatic arthritis scores. And there are some drugs that achieve that. But what about ACR50 and ACR70? Very few drugs achieve anything close to that. Well, it appears as though bimekizumab does. We’re looking at a drug where they’re looking at ACR70s in the majority of patients at week 48 or week 52. It looks like we will have a superb drug both for psoriasis and psoriatic arthritis.
There’s yet another drug that blocks the same things as bimekizumab, which blocks the IL-17A and IL-17F. There’s another drug in development that is a fusion protein bound to serum albumin. And it also blocks 17A and 17F. And at least their initial results in a very early study shows a dramatic proportion of patients achieving PASI 100. So, I think we are looking at a bright future for psoriasis patients.
Identification of Proper Treatment for Psoriatic Patients
The first question we ask is, does the patient have joint pain or psoriatic arthritis? But indeed, the first question we ask is, what’s the patient’s insurance? Because some of them will pay for certain drugs and not for others, and they’re so expensive that we have to be uniquely sensitive to that. Having said that, if costs were not a factor, there are some drugs that are good for psoriatic arthritis and not as good for psoriasis and vice versa. There’s some that are great for psoriasis and not as good for psoriatic arthritis. And then there are some that are good for both.
So, psoriatic arthritis is a big factor. Is the patient obese? Well, there’s some drugs that are better for obese patients and skinny patients. Whereas there are other drugs that are only good in thin patients and not nearly as good in obese patients. Then we look at factors like, does the patient have a history of malignancy? There are some drugs that may predispose to certain cancers. Others don’t. So, there’s a long list of criteria that includes lupus, demyelinating disease, Crohn’s disease, and many other co-morbidities or confounding factors that we have to look at to help us determine what the best drug is for which patient.
We are still stuck with the same topical therapies, so we do indeed need better topical therapies. And there are two of those on the horizon that are not steroids. One of them is called tapinarof. It’s showing us data in psoriasis that is equivalent to a super potent steroid. And the other one is topical roflumilast, which again is showing us data that is equivalent to a super potent topical steroid. And the advantage of these is that we have super potent topical steroids already, but you shouldn’t be using them on places like the face, the axillae, and the groin. They’re areas we don’t want to use topical steroids and we know we’ll get in trouble if we keep using them. And psoriasis is a chronic condition, so we have to keep using them. So, now we have nonsteroidals that are very effective that are going to give us a big advantage for treatment of those areas.
How to Address COVID-19 in the Dermatology Practice
There are number of guidances that have come out about on which systemic therapies should be continued or not, and what you should keep doing for patients. And in general, if you have an infection with COVID-19, the recommendation is to discontinue anything that affects the immune system. That includes biologics, methotrexate, and cyclosporine.
On the other hand, if you don’t have a COVID-19 infection, by and large, the recommendation is to continue current therapy. Now, I will say, if you can get patients off of immunosuppressive therapies, we try to do that, but if that’s not doable, sometimes it’s better to have a patient on an immunosuppressive therapy and then to allow them to become debilitated by their disease, which itself is immunosuppressive in that case. I will say, also, that for some of the biologic therapies like dupilumab, which is used for atopic dermatitis and even some of the psoriasis therapies, there have been suggestions that they might be helpful. And, certainly, I wouldn’t consider discontinuing them unless there is an active infection. So, that’s probably the main reason that touches us.
But there are many circumstances that come up like what do you do if someone on your office staff gets an infection? What do you do if a patient shows up, who proves to have a COVID-19 infection? And we have to make sure that each one of those circumstances is handled very well
Right now, this is affecting New York dermatologists profoundly. It’s going to affect everybody because that virus is out there and it’s spreading. I think everybody should look to New York, see what we’re doing, and try to take best practices from here.
So, first of all, at first, the extent and severity of the infection didn’t hit everyone. And it turns out that every one of us will see COVID-19 patients because we will have no choice. You’re going to pass them in the hall. So, you’re all going to encounter COVID-19 patients and there will be people on your staff who develop symptoms. There’ll be physicians who develop COVID-19 infections. And the bottom line is we’re trying to see as few live patients as possible to minimize exposure. We are doing a tremendous amount of telemedicine. We’ve converted over most of our practices to telemedicine for at least the foreseeable next few weeks, maybe couple of months. And with that comes a financial hitch. You’re not going to make as much money as you did when seeing patients live because you don’t have the procedures and other things that you do in the office.
But we are keeping our offices open with the skeleton staff for emergencies. I’m at Mount Sinai, so most of my staff and nearly all of my residents are either working in the emergency room, or in the hospital wards, or disinfecting hallways and entrances to buildings. But we’re all involved in dealing with this just emergency for humanity. But we are seeing patients here as well when we have to, and there are patients who still develop MRSA infections. I saw one just yesterday. There are patients who have severe infections or bleeding, and things where we have no choice but to see them in the office.
If a patient comes in and is infected, assume that that’s going to happen. You should all be wearing masks–everyone on staff. Hand-washing, masks, and gloves are part of our daily routine here. Disinfecting doorknobs and sink faucets–part of our daily routine. If a staff member develops a COVID-19 infection, everyone on the staff has to assume that they could be an asymptomatic carrier. They have to glove, wear masks, and take their temperature twice a day to see if they develop any symptoms. If they develop symptoms, they’re assumed to have it and they go home and quarantine themselves.
If someone develops a cold, we don’t test them for COVID-19. We assume they have it and we send them home. If we even had enough tests to do, we would still just send them home because about 30% of the tests are false negative. So, you cannot afford to have a staff member with a cold who might have COVID-19 and you don’t know it because their tests came back negative. You don’t want them sitting at your front desk, giving it to every person who comes in the door. We’re learning a lot of this as it happens, but at this point, unfortunately, we have a lot of experience with it.