Biologic therapies have revolutionized the management of moderate to severe plaque psoriasis, offering the possibility of achieving and maintaining completely clear skin. While the short-term efficacy and safety of biologics have been extensively studied, data evaluating the long-term safety and comparative efficacy are limited.

The studies that led to the US Food and Drug Administration (FDA) approvals of biologics for psoriasis were mostly short-term, so understanding long-term safety data is really important. With time, we observe whether biologics appear to maintain their efficacy and safety, and long-term safety looks good for our biologics for psoriasis, regardless of the agent.

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All of the biologics have some immunomodulatory/immunosuppressive characteristics. For example, TNF-α inhibitors cause the broadest degree of immunosuppression, and there have been reports of serious—including life-threatening—infections and a long-term, faint safety signal for the possible emergence of lymphoma with the use of these agents. I consider this in patients with a history of lymphoma or malignancies, in general. Tuberculosis reactivation is also a concern with this medication class.

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We do not have as much long-term safety data for IL-17 and IL-23 inhibitors because they are newer, but these drugs appear to be quite safe and may be safer than TNF-α inhibitors overall in the long-term. However, IL-17 inhibitors do have a few important safety considerations.

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First, they have been shown to exacerbate and potentially enhance the emergence of inflammatory bowel disease in some trials. It is hard to know whether this is a causal factor, but we have seen it happen. Second, patients taking an IL-17 inhibitor are at an increased risk for candidiasis because IL-17 is part of the innate immune response to candidal infection. This appears to be most strongly observed with the use of bimekizumab, which, of course, does not have as much long-term safety data because it is relatively new to the market.

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Overall, in terms of safety, biologics are designed to be used long-term. Regarding long-term monitoring, we want our patients with plaque psoriasis to be appropriately connected to primary care to ensure good overall health, and basic laboratory tests must be performed to ensure that problems are not emerging. Many of us have a lot of patients who have been using these agents for decades and have been doing well.

TNF-α, IL-17, IL-23, and IL-12/23 inhibitors have been around for quite some time. We know about the serious potential side effects that could occur with the use of these drugs, and it is unlikely that we will discover something new based on emerging information.

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In addition, we know that TNF-α inhibitors have the lowest persistence, IL-17 inhibitors fall in the middle, and IL-23 inhibitors tend to have the highest persistence. That is an advantage of the IL-23 mechanism in a chronic disease such as psoriasis; patients are less likely to lose response or to stop therapy for any reason. We do not want to cycle to another biologic every few years; that is expensive and difficult to manage from a clinical practice standpoint.

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It is still unknown whether these drugs have benefits beyond the skin. There are 2 major areas that we are interested in, in this regard. First, do they lower the risk of heart attack or stroke and related death? And, second, do they prevent patients from developing psoriatic arthritis? Here, the data become murky.

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Observational data and data from small trials evaluating surrogate biomarkers seem to indicate that TNF-α inhibitors may have promise in lowering cardiovascular risk. However, the reality is that we have no large-scale, controlled trials that would enable us to know this for certain. Personally, I do not include the potential for lowering cardiovascular risk in my clinical decision making. I still choose what I think is the best drug for the patient’s skin and joints while ensuring that the patient has proper screening for and management of cardiovascular risk factors such as hypertension, hyperlipidemia, obesity, and diabetes.

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Whether these agents prevent psoriatic arthritis is similarly unclear. Again, most of the data are observational in nature. This question is hard to answer with observational or registry data because the biases are so strong. Having practiced with these drugs for decades, I know that psoriatic arthritis could develop at any point regardless of whether a patient is on a biologic.

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We have to keep being vigilant and use our best judgment. For the field to move forward, we need large-scale studies randomizing people to different biologics at the point of care to see which biologic provides the most benefit and causes the least harm over time.

Dr Gelfand provided a fantastic overview of where we are right now and the road map of where we need to be headed, in terms of thinking about psoriasis not only as a skin disease but also as a systemic disease. Additionally, I think that our patients with psoriasis are extremely savvy when it comes to their questions about medications, more so than patients with other chronic inflammatory skin diseases. They will ask, “Does it work? Is it safe? How long will it work? I know that there are many medications, so how do you know which one works better for longer?” These patients know that this condition is lifelong, and they know that they need to treat it.

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I think that this speaks to our history of having a large treatment armamentarium for psoriasis, with many agents that have been around for quite some time. Some of these medications have open-label extension data, year-long data, and/or even comparative study data out to 2 or more years. We can answer these questions in the world of plaque psoriasis better than we can in other disease states, but there are still gaps, and more information is certainly needed.

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We definitely want more head-to-head data, which now is the standard. Ustekinumab going head-to-head with etanercept in a phase 3 program was groundbreaking. Now it is almost standard to see a comparison trial of a newer biologic vs a TNF-α inhibitor, or even an IL-17 or IL-12/23 inhibitor.