Why the TB Testing Statement Stops Short of Ustekinumab and TYK2 Inhibitors

A joint position statement from the National Psoriasis Foundation (NPF) and the International Psoriasis Council (IPC) on tuberculosis (TB) testing focuses specifically on interleukin (IL)-17 and IL-23 inhibitors. In the third segment of this HCPLive Special Report, 2 of the statement’s co-authors explained why other drug classes were left out and how the statement may lead to label changes. They were Andrew Blauvelt, MD, MBA, adjunct professor in the Department of Dermatology at the University of Maryland School of Medicine, and Joseph F. Merola, MD, MMSc, chair of the Department of Dermatology at UT Southwestern Medical Center.

Why Were IL-12/23 Inhibitors Excluded From the Statement?

Blauvelt noted that ustekinumab targets p40, a subunit shared by IL-12 and IL-23, whereas IL-23 inhibitors selectively block the p19 subunit. The IL-12 pathway drives T helper 1 (Th1) immunity, which is believed to be important for forming and controlling granulomas. Inhibiting that pathway could therefore impair granulomas in theory. The biology differs from that of tumor necrosis factor (TNF), however, which plays a central role in controlling TB within tissue. Some cases of TB reactivation have been reported with ustekinumab. The risk appears lower than with TNF inhibitors but is still present, which is why the authors chose not to include the drug.

Could TYK2 Inhibitors Follow the Same Path?

The same question now applies to tyrosine kinase 2 (TYK2) inhibitors. These include deucravacitinib and 2 newer agents on the way. They inhibit both IL-12 and IL-23 and work somewhat like an oral version of ustekinumab. Blauvelt said the NPF has been asked to review TB data for the class. In his view, though, the case for dropping testing is not as strong as it is for IL-17 and IL-23 inhibitors. Merola agreed. He added that TYK2 inhibition also affects type 1 interferon signaling and that the science does not yet support extending the statement to this class.

How Might FDA Labels Change?

Several years ago, before the paper was written, Blauvelt met with the FDA alongside NPF representatives and Mark Lebwohl, MD. They raised the issue of TB testing with IL-17 and IL-23 inhibitors, and the agency was open to label changes based on data. Each manufacturer, however, must start such a change by petitioning the FDA. Blauvelt called the nonmandatory TB testing language in the icotrokinra label a success for the NPF and IPC effort, and he suggested future agents in these classes may follow suit. Merola said that if the statement shapes how future studies are designed, it could also support company-driven label changes for existing drugs.