Mark Lebwohl, MD: The 1 drug that we haven’t spoken about is ustekinumab, and that blocks both IL-12 [interleukin-12] and IL-23. It’s kind of an older version that predated the IL-23s. They block a chemical called p19. Ustekinumab blocks a protein called p40, which contributes to both IL-12 and IL-23. It seems that IL-23 is the pathway we want to block, not the IL-12 pathway.
Ustekinumab has been around for more than 10 years. It is dramatically effective, but not as effective as some of the IL-17 and IL-23 blockers. The advantage of its having been there for 10 years is we know that there are no increases in malignancies or opportunistic infections, so we don’t expect to see those with the new IL-17 and IL-23 blockers either.
In fact, people born with deficiencies in p40, which is what ustekinumab blocks, get only 2 infections. They get salmonella infections, which to the best of my knowledge, have never been seen in patients treated with either ustekinumab or any of the other drugs that we talked about. And the other infection they get are mycobacterial infections. The way those patients often were identified is in a lot of the world they use BCG [Bacillus Calmette-Guerin] vaccinations to protect against tuberculosis [TB]. BCG is a live mycobacterium, and the vaccinations in those patients made the patients ill. That’s how we know that they are deficient in p40. As a result, when we treat patients with any of these drugs, we usually do TB testing annually. If they’re positive, we simply treat them with prophylaxis, so that the latent mycobacterium infection does not evolve into active TB. And that appears to be effective. Certainly in patients who have undergone clinical trials who were PPD [purified protein derivative]-positive, or QuantiFERON-positive, we have not seen any patients progress to develop tuberculosis.
We have so many choices of treatments for psoriasis now that we have to weigh in other factors to help us determine which drug to use for which patient. I will say, and I won’t say this proudly, but probably the biggest impact is what the insurer will allow us to prescribe. Now certainly, we’re not going to prescribe a medication that we think is bad for patients.
For example, if a patient has had a history of a malignancy, a lymphoma, or a lot of skin cancer, I probably wouldn’t go for a TNF [tumor necrosis factor] blocker because they carry that black box warning. There’s certainly evidence showing that they could contribute to the development of squamous cell carcinomas and potentially even lymphomas. So in that setting, I would not use a TNF blocker. And if the insurance company insisted on it, I would simply fight them. This is not a difficult fight. If you simply write a letter, and the American Academy of Dermatology has those letters already written for dermatologists to access—it takes about 30 seconds to generate a letter, which my secretary does for me—we can pretty much get the treatment we want, and we largely base it on the patient’s comorbidities.
In a patient with a malignancy, we wouldn’t go for the TNF blockers. We might go for an IL-17 or IL-23 blocker. If a patient is obese, I would tend to go for some of the stronger medications we have. Some of the medications we have are given according to body weight. Infliximab is one of them, and ustekinumab is another. And certainly, even though the IL-17 and IL-23 blockers are given in fixed doses, they’re so effective that we often use them in obese patients.
If a patient has risk factors for cardiovascular disease, right now the TNF blockers have the most evidence that they’re protective against cardiovascular disease. That evidence comes largely from registries. But as we have experience with the IL-17 and IL-23 blockers, it looks like they’re probably going to be protective as well. If a patient has psoriatic arthritis, they’re going to likely get either a TNF blocker or an IL-17 blocker because those are the most effective drugs for psoriatic arthritis. So there are many factors that we put into the equation when we decide which drug we’re going to prescribe for a particular patient.
Transcript edited for clarity.