In this podcast, Erin Boh, MD, PhD, reviews the latest updates in the safety of psoriasis therapies, including tumor necrosis factor inhibitors.
Dr Boh is the Joseph Chastain Clinical Professor of Dermatology and chair of the department of dermatology at Tulane University School of Medicine in New Orleans, LA.
Melissa: Hello, welcome to another podcast with The Dermatologist. I’m Melissa, the associate editor and host of this podcast. Today we’re speaking to Dr Erin Boh, the Joseph Chastain Clinical Professor of Dermatology, and chair of the department of dermatology at Tulane University School of Medicine in New Orleans, Louisiana.
Today, Dr Boh will be reviewing the safety of psoriasis medication, specifically anti‑tumor necrosis factor inhibitors. Thank you for joining us today, Dr Boh. Anti‑TNF inhibitors have been on the market for over a decade and studied pretty closely. Since the first clinical trials and safety assessment, have there been any new safety signals?
Dr Erin Boh: Actually, there have been very few immediately post‑marketing with the TNFs, which was, well over 18 years ago. There were a couple of black box warnings that did come out pretty quickly. One of them was, of course, about reactivation of tuberculosis, or TB, and one of them was also a reactivation of hepatitis B.
Those black box warnings came out within the first one to two years after approval of the first TNFs, and they’ve been in place ever since. But there’s been no new signals since the early days. That portends or supports a very, very, very safe and good profile. What we knew then, in terms of potential problems, is still what we know today, and there have been no new ones.
Now, I will preface by saying that there may be not as robust from a clinical standpoint in terms of with the newer agents, which block very, very selectively or target points right at the pathway. But overall, the durability on the TNFs actually has been remarkably stable.
Again, people do see sometimes potential drop in efficacy, maybe around 5 or 10% of patients, we will see over time that these people may lose some clearance, but I’ve had experience with them with recapturing that response over time.
I think their initial PASI response can be maintained pretty regularly. But again, their PASI responses aren’t as robust in some cases as the newer agents. There are specific situations where the TNFs are superior in terms of their response rates, especially when you get to patients who have both arthritis or other comorbidities along with psoriasis.
Melissa: Going back to the idea that these are really safe drugs, have there been any serious adverse effects that were at first concerning, but are now less concerning?
Dr Boh: The good example to use here would be congestive heart failure. When the TNF drugs came out as a class, one of the safety concerns were in people who had severe or class IV congestive heart failure. Those patients saw worsening of their cardiac status on the TNFs. That was one of the group contraindications, was the severe congestive heart failure.
Nowadays, we’re seeing with patients who have cardiovascular disease that the TNFs are a very good drug, along with some of the newer agents as well. You don’t have to worry as much about just the overall severe congestive heart failure. The guidelines have changed.
Now, if you have treated congestive heart failure, whether it was initially very bad, or you had decompensation, or you had terrible class IV congestive heart failure, once patients are on appropriate treatment and their heart failure improves, you could use these drugs.
That tells us that the drug intrinsically may not cause congestive heart failure. But if you’re not having it treated, it could be significantly problematic.
Similarly, if you think about reactivation of TB, if you take patients in the early trials when they had activation or reactivation of TB, we now know that you just put them on the anti‑TB medicines, wait about a month, and you could restart your TNF.
Again, as long as appropriate treatments are instituted, then some of these potential contraindications that were considered absolute in the past may not be absolute anymore.
If we look at, over time, has that improved? I think yes, it has in terms of our understanding of the medicines. We clearly now say that the anti‑TNFs are very beneficial in cardiovascular disease. Again, we need to make sure that our parameters are defined.
Melissa: Is there any additional research that’s needed to continue to support the long term use of anti‑TNF inhibitors?
Dr Boh: There’s always needs for further research, and possibly, if we look at psoriasis as a multi genetic disease. Meaning that the phenotypes are different and the genotypes are different in people who have psoriasis. There are certain gene mosaicism. Gene mutations that may predispose people to respond better to one class of agents than another.
We don’t know which patients and which genes these patients are expressed. I think research could benefit from seeing what the gene mutation or what the predominant cytokine expression is in a given population or in a given person so that we then can tailor the therapy to that.
Meaning, if a patient has a genetic mutation in a TNF gene, so they have a mutated TNF gene, but still it over functions, then obviously, maybe a blocking of that TNF would be a useful treatment. If the patient has a gene defect in the IL‑23 or the IL‑17 lineage, then one of those classes of drugs would be more appropriate.
As we move into 21st century medicine and into the realm of personalized or tailored medical treatment, we can benefit from research that looks at the genetic defects and see if we can target our therapy to improve what that defect was.
Melissa: What concerns are there regarding the development of drug antibodies among patients with psoriasis?
Dr Boh: Where the drug antibody issues come in, the drug antibodies can form against any of these agents. The ones that have the highest incidence of antibody formation are going to be the ones that are not humanized or not human, ie, infliximab, for instance, is a chimeric antibody, so we would expect more antibodies to that. We do know that that does occur, and many of these antibodies are neutralizing.
Again, you could work around that. Some of the human anti‑TNFs, so the adalimumabs of the world or the etanercept, which is a receptive protein, they still have antibodies forming against. Question is, are they neutralizing or do they impede performance of the drug over time? Maybe to go back to the previous question, that might be where some research is needed.
Because we make antibodies to all of these agents, including the IL‑17s, the IL‑23s. But what is the impact of antibody formation? Yes, we’ve postulated in the past that sometimes antibody levels get really high and that impedes function. But we’ve never actually looked and delved into that to say, without a doubt, that is why you lose efficacy. It could very well be, but we don’t know.
Then we can regain efficacy sometimes, especially with the chimeric antibodies, by adding back an agent such as methotrexate for a few months, that would inhibit for that neutralizing antibody formation. We don’t really know. We postulate that but we not well document, but it certainly is a potential issue and it could contribute to loss of efficacy over time.
Melissa: Obviously, the COVID‑19 pandemic has sparked a lot more focus on the risk of infection associated with these therapies based on the data from clinical trials or the latest updates from registries and other studies. What do we know about the safety of TNF inhibitors during this time?
Dr Boh: In general, what we knew in the beginning of the pandemic, all of us were worried, but yes, this COVID, which is a new kind of virus, we hadn’t seen it before. So there should be theoretically a higher risk of infection with the TNFs because you’re blocking a crucial cytokine fighting off viral infections.
However, the reality is we didn’t see that. As time marched on through COVID, and it’s still marching on, we haven’t seen a super increase in the number of patients on biologics versus on systemic agents that have gotten COVID. It tends to mirror what your area is and the infection rate there.
We did see there was a nice article that was published that actually did show that patients hospitalized, like in areas like in New York, there was not an increased number of patients who were hospitalized for COVID or COVID complications that were on the biologics versus not the biologics.
That tells us maybe that the risks of infections were not overly expressed in patients on the biologics. It even seems that some of the hospitalizations or the severity, especially of pulmonary disease, was somewhat mitigated. Can’t really say that, but you can say that the numbers were down.
Moving forward, what several investigators did was went back and revisited all of the trials in the past that had been published over the years and looked at what was the incidence of viral infections, in general, in those cohorts of patients. They found it wasn’t remarkably different than the general population.
So it gives us a degree of comfort, maybe not as much as we would like or what patients would like, but I think what it’s taught us is that we just need to be careful. These drugs probably immunomodulate a little bit more than remarkably immunosuppress.
We still have to be on our guard, but they can have some beneficial effects, and that is to blunt the response to the virus. Again, this is all speculative, but it certainly is theoretical and it’s what we’ve seen if you take the data of the number of people being hospitalized who are on biologics. We didn’t see a great number of those.
It tells us that maybe the severity of the disease, or that cytokine storm, which people are referring to, may be somewhat blunted in patients who are on immunosuppressives or immunomodulators to a degree.
Again, our cancer patients are the other end of the spectrum where they’re may be remarkably immunosuppressed, and they did have sequally to the COVID. I think the jury’s still out, and so we’re going to proceed with a degree of caution, but it’s a good, positive precaution.
We’ve taken it that we do not tell anybody to stop their biologics at this point in time. We just take care, do judicious hand‑washing, mask, and avoid overcrowded areas, and stay on your biologic.
Melissa: What key takeaways would you like to leave with our audience?
Dr Boh: The key takeaways I’d like to leave with the audience is that we have an incredibly vast choice of options for our patients who have psoriasis. We should not pick a drug for those patients based on the newest and the greatest.
We should not say because one drug gives you 100% clear that that is the best drug. We do really need to look at our patients and see what their comorbidities are and what drugs we’re going to use for that. Taking the patient and their baggage and picking the right drug is the most appropriate thing to do.
What we tend to do as physicians is to go, as soon as we get a new agent out there, that we’re going to jump to that new agent regardless of the prior response of the patient. If patients are doing well on the drugs that they’re on, I recommend you keep them on that drug and see how they are doing in the future.
Melissa: Thank you for listening. If you have any questions for Dr Boh, please submit them in the feedback box below. Thank you.