Department of Dermatology, Centro Hospitalar Universitário do Porto
TERMS TO KNOW
- Chemoprophylaxis is the use of drugs to prevent diseases, such as tuberculosis.
- Biologics are a psoriasis treatment that targets parts of the immune system to block the action of specific immune cells or proteins.
- Interleukin 17-A and interleukin 23 are proteins in the immune system that play a significant role in psoriasis.
- One-quarter of the global population is estimated to have latent tuberculosis.
- Current international guidelines recommend screening for tuberculosis before starting biological agents and treating latent tuberculosis if present.
- New psoriasis therapies, such as IL-23 and IL-17 inhibitors, do not pose the same risk of tuberculosis reactivation as previous therapies, like TNF inhibitors.
TIMELINE OF KEY ACHIEVEMENTS
2008: The most recent tuberculosis screening guidelines for biologic treatment patients were published in dermatology literature by the National Psoriasis Foundation and the American Academy of Dermatology.
2009: A type of IL-23 antagonist (ustekinumab) received FDA approval to treat moderate to severe plaque psoriasis.
2010: The Centers for Disease Control and Prevention published updated guidelines on tuberculosis screening for patients using biologic treatment.
2012: The American College of Rheumatology recommended a change in tuberculosis testing to only those who are receiving biologic treatment and live, travel, or work in places where tuberculosis exposure is likely.
2017: The first selective IL-23 antagonist (guselkumab) received FDA approval to treat moderate to severe plaque psoriasis.
Nogueira, M., Warren, R. and Torres, T. (2021), Risk of tuberculosis reactivation with interleukin IL-17 and IL-23 inhibitors in psoriasis – time for a paradigm change. J Eur Acad Dermatol Venereol, 35: 824-834.
Psoriasis and tuberculosis have long gone hand-in-hand. This is especially true in certain parts of the world, where latent tuberculosis continues to be widespread. With one-quarter of the global population estimated to have latent tuberculosis, guidelines to properly screen for and treat tuberculosis in psoriasis patients are critical.
Tiago Torres, MD, PhD, IPC Councilor, and Professor of Dermatology at the Abel Salazar Institute of Biomedical Sciences, University of Porto, in Porto, Portugal, is no stranger to the risk of tuberculosis in psoriasis patients.
“Tuberculosis is still an issue in many countries, including developed European countries, but especially Southern European countries, like Portugal, Spain, Italy, and Greece,” Dr. Torres explains
TUBERCULOSIS AROUND THE WORLD
- The Philippines
- South Africa
The use of immunosuppressive/immunomodulator drugs, particularly tumour necrosis factor (TNF)-a inhibitors, to treat psoriasis has long been recognized to be associated with an increased risk of reactivation of latent tuberculosis. This is why current international guidelines recommend screening for tuberculosis before starting biological agents. They also recommend using chemoprophylaxis if latent tuberculosis is detected, followed by annual screening.
However, routine testing for latent tuberculosis is both costly and, in many cases, offers little clinical value. This can put an unnecessary burden on both providers and psoriasis patients. As for chemoprophylaxis, it can lead to unwanted and dangerous side effects for patients with high toxicity to the treatment.
A paradigm shift in tuberculosis screening
New psoriasis therapies, including interleukin-23 (IL-23) and interleukin-17 (IL-17) inhibitors, don’t pose the same risk of tuberculosis reactivation. According to Dr. Torres, this may warrant a change in tuberculosis screening guidelines.
In his article published in The Journal of the European Academy of Dermatology and Venereology in August 2020, Dr. Torres reviews the available data on tuberculosis reactivation after treating psoriasis with IL-23 and IL-17 inhibitors. Along with co-authors M. Nogueira and R.B. Warren, he explores these new therapies and their possible impact on the current management of latent tuberculosis infection before or after starting treatment.
Here are three things to know about new psoriasis therapies IL-23 and IL-17 inhibitors and their implications on tuberculosis management.
1. THE RISKS OF TREATING LATENT TUBERCULOSIS ARE WELL-KNOWN.
Many patients require both psoriasis treatment and tuberculosis treatment. “We have been treating these patients for latent tuberculosis for a long time,” says Dr. Torres. “We know the risks that they face.”
Old psoriasis treatments, such as anti-TNF agents (or (TNF)-α inhibitors), have a well-documented risk of reactivating latent tuberculosis. This means that treating latent tuberculosis becomes warranted and necessary.
Due to specific comorbidities, medications, or lifestyle habits, some patients have a higher risk of toxicity to the treatment of tuberculosis. “This is something that we deal with every day,” he says.
2. NEW PSORIASIS THERAPIES LIKELY DON'T INCREASE THE RISK OF REACTIVATION OF TUBERCULOSIS.
Fortunately, new psoriasis treatments are available. In clinical trials and real-world studies, many patients with treated and non-treated latent tuberculosis were exposed to IL-23 and IL-17 inhibitors. The data is clear — there is no increased risk of tuberculosis reactivation.
“There is an opportunity that, for some patients, we can avoid using anti-TNF agents and treating their latent tuberculosis by using these new agents — IL-17- and IL-23 inhibitors,” says Dr. Torres.
With the development of new treatments with no risk of reactivation, psoriasis management may change for the better.
“I don’t say we should not screen patients for latent tuberculosis. But at least for patients with a higher risk of toxicity to anti-tuberculosis drugs, we can treat them with other psoriatic drugs and not treat them for latent tuberculosis,” Dr. Torres says.
This means less risk for the patient — a welcome prospect for psoriasis management. “I’m not exposing my patients to a risk that can be avoided,” he says. “The risk is the treatment of latent tuberculosis.”
3. THERE ARE MINIMAL DOWNSIDES TO THESE NEW THERAPIES.
The evidence shows that IL-23 and IL-17 treatment is better than anti-TNF agents. “There are no downsides to this — only good things,” says Dr. Torres.
According to Dr. Torres, the only downside may be the cost. “I will use better drugs, but they are more expensive than anti-TNF agents,” he says.
Of course, costs vary by country. In Dr. Torres’s country, Portugal, medications are paid for by the government. In other countries, like the United States, Canada, and some European countries, they are often paid for by insurance.
Dermatologists may need to explain why using a more expensive but better treatment is essential. “This explanation — that a patient faces a higher risk of toxicity being treated for latent tuberculosis — is a good argument,” Dr. Torres explains.
Another way to bolster this argument is by incorporating this new evidence into screening guidelines, something he says may be forthcoming.
The present and future of tuberculosis screening guidelines in psoriasis patients
As Dr. Torres says, “Our reality is changing.” He already sees a change in his daily practice.
Dermatologists can use this knowledge to treat psoriasis patients in the near term. “I still screen all patients for latent tuberculosis, as recommended by current guidelines. But patients that have a high risk of toxicity to latent tuberculosis treatment because of age, comorbidities, or other medications — I am not treating them for that. I am not using anti-TNF agents to treat them. As a first-line treatment, I am using IL-23 and IL-17 agents,” he explains.
In the longer term, tuberculosis screening guidelines must be revisited. Currently, the guidelines for screening and treating latent tuberculosis are based on old biological treatments like (TNF)-α inhibitors. “With new evidence, guidelines have to be changed,” he explains.
“It should be stated that, for patients using IL-23 and IL-17 agents, we don’t need to treat latent tuberculosis if they are positive for that,” he says. “A step further would be, if a patient has latent tuberculosis, they should not use anti-TNF agents, and they should use new agents — IL-23 and IL-17 inhibitors.”
The connection between psoriasis and tuberculosis will always remain, but with new therapies come new opportunities to care for psoriasis patients using the most effective and safest approaches.
To learn more about new psoriasis therapies IL-23 and IL-17 inhibitors, refer to Dr. Torres’s article, “Risk of tuberculosis reactivation with interleukin IL-17 and IL-23 inhibitors in psoriasis – time for a paradigm change.”