Prescreening patients with psoriasis for tuberculosis (TB) before they start taking a biologic to treat their disease has been baked into the science of dermatologic practice, but a new position statement from two leading medical societies states that the testing is not needed with the newer interleukin (IL)-17 and IL-23 inhibitors.

The requirement, and existing label recommendation, for prescreening for TB before prescribing the IL-17 and IL-23 inhibitors for psoriasis is a holdover from when TNF inhibitors were first approved, Andrew Blauvelt, MD, MBA, medical board chair of the National Psoriasis Foundation (NPF) and lead author of the statement, told Medscape Dermatology. The statement was published online on November 17 in the Journal of the American Academy of Dermatology.

“The scientific basis for testing of TB for IL-17 and -23 blockers has always been weak from the beginning. Because of the history of testing for patients on TNF blockers, the original biologic, there was this carryover to the newer biologics,” said Blauvelt, a dermatologist and owner of Blauvelt Consulting in Annapolis, Maryland.

Evidence Points to No Link

The joint statement from the NPF Medical Board and the International Psoriasis Council cited 13 clinical trials and real-world studies, which found that IL-17 inhibitors do not increase the risk for reactivation of latent TB and 17 publications supporting the same conclusion for IL-23 inhibitors, along with laboratory studies that found no link.

The statement’s analysis also included an investigation of the FDA Adverse Event Reporting System, which found no cases of extrapulmonary internal-organ TB of disseminated TB associated with these biologics.

The product information for all of the approved therapies that were the focus of the statement — the IL-17 inhibitors secukinumab, ixekizumab, brodalumab, and bimekizumab; and the IL-23 inhibitors guselkumab, tildrakizumab, and risankizumab — currently recommend TB prescreening before initiating therapy. Blauvelt said he hopes the statement will lead to a label change that eliminates this requirement.

The statement acknowledged the requirement for TB prescreening with these drugs had been based on three 2010 preclinical studies that implicated IL-17 and T helper17 cells in TB and “on historic precedent with older biologic therapies,” and called the evidence supporting the practice “weak.”

Despite what the labels state, Blauvelt said that this statement gives dermatologists and other prescribers cover to discontinue TB prescreening before prescribing these IL-inhibitors in most patients. “I’ve been practicing in that manner for years without any issues,” he said. “Yes, I think it can open the possibility a little bit for medicolegal action by not doing TB testing. However, in reality I don’t think that will ever become an issue.”

“Doctors can utilize this paper to back their decision not to do testing.” 

Removing Barriers and Exceptions

Eliminating the requirement for TB prescreening removes some barriers to use of these treatments. “It will help decrease unnecessary testing and decrease healthcare costs,” Blauvelt said. In addition, “it will help expedite care of patients” with these treatments and “and avoid unnecessary delays.”

It may also alleviate some patient hesitancy about taking these treatments, who may think twice about going on a treatment that could reactivate TB, he said.

But situations exist where prescreening for TB would be indicated for patients starting IL-17 or IL-23 inhibitor therapy, Blauvelt noted.

“Whenever a doctor wants to know the TB status of the patient, they can always check it,” he said. “If patients are on concomitant immunosuppressive drugs in addition to IL-17 or IL-23 blockers, then they should be tested for tuberculosis.”

The statement noted that prescreening should continue in regions of the world where TB is endemic. It also called for experts to make similar position statements for the use of IL-17 and IL-23 inhibitors to treat patients with other types immune-mediated inflammatory diseases, such as psoriatic arthritis, ankylosing spondylitis, hidradenitis suppurativa, and inflammatory bowel disease.

“This is going to take time to take hold in the clinical community because dermatologists have tested for TB for over 20 years,” Blauvelt said.

Starting the Discussion

“Position statements like this don’t necessarily change what we’re doing immediately, but they start the discussion and allow for an expert group to present a unified opinion about this,” said Jeffrey M. Cohen, MD, MPH, director of the Psoriasis Treatment Program at Yale School of Medicine, New Haven, Connecticut.

The integrity of granulomas in the lungs of people who have latent TB is the key to preventing reactivation of the disease, Cohen told Medscape Dermatology. One of the early preclinical studies the statement cited found that IL-17A played a key role in the prevention of TB by inducing mature granuloma formation in the lung, but mice without the IL-17A gene did not develop mature granulomas. The statement cited four publications that support the concept that TNF inhibitors can inhibit granuloma formation.

“Fast forward, we still use those TNF inhibitors, but the IL-17 and IL-23 inhibitors are much more targeted,” said Cohen, who was not an author of the position statement. “It turns out that those targets are not as relevant to granuloma integrity and therefore are not necessarily so relevant when we think about tuberculosis reactivation.”

Cohen added, “It’s important to note that none of us take this lightly; but at the same time, we want to be doing the best we can for our patients and for the healthcare system by making sure we’re being as rational and evidence-based as possible with recommending some of this testing.”

Blauvelt reported financial relationships with AbbVie, Acelyrin, Almirall, Alumis, Amgen, AnaptysBio, Apogee, Arcutis, Boehringer Ingelheim, Bristol Myers Squibb, Celltrion, Corvus, Dermavant, Eli Lilly, Galderma, GlaxoSmithKline, Immunovant, Incyte, IQVIA, Janssen, Leo, Lipidio, Merck, Novartis, Oruka, Paragon, Pfizer, Regeneron, Sanofi, Spherix Global Insights, Sun Pharma, Syncona, Takeda, UCB, Union, and Lipidio. Other statement authors had disclosures related to multiple pharmaceutical companies; three authors had no relevant disclosures. Cohen reported serving on the data and safety monitoring board for Advarra and as a consultant for Novartis, GlaxoSmithKline, Takeda and Sanofi.

Richard Mark Kirkner is a medical journalist based in Philadelphia.