Systemic Therapies in Plaque Psoriasis: Biologics

Mark Lebwohl, MD: The other systemic therapies we have are biologics. Nowadays, insurers have recognized that these are very safe and very effective. Some of the older biologic therapies we have, which are called TNF [tumor necrosis factor] blockers—the products there are adalimumab, etanercept, golimumab for psoriatic arthritis, infliximab, and certolizumab—are quite effective. They all carry black box warnings for infection and malignancy, although the risks are very small. In fact, in registries that have followed many thousands of patients with psoriasis treated for 10 years or more, it appears that, on average, patients live longer. There’s a reduction in heart attacks in patients treated with TNF blockers, even though they carry those warnings for infection and malignancy.

Some of the newer drugs are more targeted. They block smaller parts of the immune system—either IL-17 [interleukin-17] or IL-23. They do not have black box warnings for infection or malignancy, and actually don’t have a contraindication to their use in malignancy. They affect very small parts of the immune system. We have examples in nature of patients who are born deficient in some of the molecules that we’re blocking, so we know what to expect in the way of adverse effects.

Patients born with deficiencies in IL-17 develop chronic mucocutaneous candidiasis. They don’t get more cancers. They don’t get more heart attacks. They don’t get other serious opportunistic infections. They get yeast infections, fungal infections. Those are so easy to treat with medications like fluconazole that we don’t have to worry as much about adverse effects. The oldest of those drugs is only on the market for probably a little more than 5 years, or around 5 years. That’s secukinumab. And sure enough, the adverse effect that’s emerged with that has been 1, and that’s yeast infections. And secukinumab blocks IL-17A. Another agent in that class, ixekizumab, also blocks IL-17A. There are different IL-17s, and brodalumab blocks the receptor for all of them. And again, with all 3 of those agents, the adverse effect that’s emerged has just been yeast infections.

There are some new drugs on the horizon that block IL-17A and IL-17F, primarily bimekizumab, and hopefully that will be on the market within 2 years. The data so far look excellent, both in terms of adverse effects and effectiveness. It appears to be highly effective for psoriasis and psoriatic arthritis, and the adverse effect that we’re seeing is yeast infections.

Likewise, the IL-23 molecules are very targeted. When you block IL-23, it appears that IL-23 is necessary to cause a cell, the Th17 cell, to make IL-17. So when you block IL-23, not only are you reducing IL-17, but it seems that those cells actually disappear and it takes a while for them to reconstitute themselves. So by blocking IL-23, we very effectively treat psoriasis. But also, the remissions are quite long. For that reason, the IL-23s can be given as infrequently as every 3 months, which is a big advantage. In fact, it gives patients almost as normal a life as they can get. Every 3 months is 4 injections a year, and patients are clear, virtually, for the entire year.

Those have been a serious breakthrough in psoriasis. They have the drawback in that they’re somewhat slower. It takes a while to get to their peak effect. So when we use the IL-23 blockers, we have to tell patients they peak at around 16 weeks, or even after. But you usually see some benefit within 4 weeks, so they’re not that slow. Once you get there, patients remain clear for years as long as they continue the injections every 2 or 3 months, depending on which drug is being used.

Tildrakizumab is given every 3 months. Risankizumab, every 3 months. Guselkumab is given every 2 months. Those are the 3 drugs that we currently have. There’s one called mirikizumab, which will be coming in hopefully another year or so. With all of these, the adverse effect profiles appear to be excellent. There are no black box warnings for the IL-23 blockers.

Transcript edited for clarity.