Position Statement: Routine TB Testing for IL-17 and IL-23 Inhibitors

For decades, screening for latent tuberculosis (TB) infection (LTBI) has been a non-negotiable step before initiating biologic therapy for psoriasis. That practice was shaped by the well-documented association between tumor necrosis factor (TNF) inhibitors and reactivation of latent Mycobacterium tuberculosis. TNF is critical for granuloma integrity, and its inhibition can dismantle the immune architecture that keeps TB in check. As a result, clinicians grew accustomed to ordering baseline and periodic interferon-gamma release assays or tuberculin skin tests for nearly all patients receiving biologics, including those receiving newer biologics such as IL-17 or IL-23 inhibitors. 

But not all biologics behave the same. A newly released joint position statement from the National Psoriasis Foundation (NPF) Medical Board and the International Psoriasis Council (IPC) now challenges this long-standing reflex. After a comprehensive review of preclinical, clinical trial, real-world, and pharmacovigilance data, 87.5% of experts from the 2 organizations agreed on a striking conclusion: Routine testing for LTBI is not required for psoriasis patients treated with IL-17 or IL-23 inhibitors. This recommendation marks a meaningful departure from current labeling language and clinical convention, and it is rooted in an increasingly robust evidence base. 

What Biology Shows 

The historic rationale for TB screening comes almost entirely from experience with TNF inhibitors. TNF plays a central role in granuloma formation, macrophage activation, and containment of intracellular pathogens. Blocking TNF dismantles these defenses, leading to rapid reactivation of latent TB, often within the first year of therapy and frequently with extrapulmonary or disseminated disease. 

IL-17 and IL-23 are central to psoriasis pathogenesis, but their roles in TB immunity differ fundamentally from TNF. Animal models demonstrate that mice deficient in TNF rapidly succumb to M. tuberculosis, while selective inhibition of IL-17A, IL-17F, IL-17RA, or IL-22 does not impair control of infection. In human microgranuloma models, secukinumab-mediated IL-17 blockade does not reverse TB dormancy, whereas ustekinumab (IL-12/23 blockade) and adalimumab (TNF blockade) do. 

Similarly, while IL-23 participates in host defense, control of TB infection is dominated by IL-12-driven Th1 responses and interferon-γ signaling. Therapeutic inhibition of IL-23 via p19- selective agents, such as guselkumab, tildrakizumab, and risankizumab, is partial, reversible, and context-dependent, in contrast to the complete genetic deficiencies associated with susceptibility to TB. Yet despite their distinct mechanisms of action, IL-17 and IL-23 inhibitors inherited the TB testing paradigm of TNF blockers primarily by precedent rather than evidence. 

Clinical Trials: No Signal for Reactivation 

Across thousands of patient-years of exposure, clinical trials of IL-17 and IL-23 inhibitors have produced essentially no evidence of TB reactivation. 

For IL-17 inhibitors, hundreds of trial participants with LTBI were enrolled after receiving preventive therapy, and none developed active TB. Notably, 6 patients treated with ixekizumab seroconverted to LTBI positivity during trials, continued therapy without TB prophylaxis, and did not develop active disease. 

For IL-23 inhibitors, pooled analyses are equally reassuring. Among 4399 guselkumab-treated patients (10,787 patient-years), 1413 tildrakizumab-treated patients, and 2072 risankizumab-treated patients (7927 patient-years), there were no cases of progression from latent to active TB. Similar findings have been reported in trials for psoriatic arthritis, Crohn’s disease, and ulcerative colitis. 

Several trials even included patients who did not receive preventive therapy. In the IMMhance risankizumab study, 31 LTBI-positive patients were treated for 55 weeks without prophylaxis and none developed TB. 

Real-World Evidence: Hundreds of Untreated Patients, Almost No TB 

Real-world data remove the confounding effect of mandatory prophylaxis. Across multiple observational cohorts, hundreds of LTBI-positive patients were treated with IL-17 or IL-23 inhibitors without TB preventive therapy because of liver disease, drug interactions, comorbidities, or patient choice. 

Among these patients, only 1 case of active TB has been reported, and it occurred 14 months after starting an IL-17 inhibitor. This is well beyond the high-risk window seen with TNF inhibitors and within the background lifetime risk of TB reactivation (5%–10%). 

This pattern stands in sharp contrast to TNF inhibitors, where reactivation often occurs early and disproportionately involves extrapulmonary disease. 

FAERS: A Pharmacovigilance Reality Check 

To further examine safety, the authors searched the US Food and Drug Administration Adverse Event Reporting System (FAERS) for extrapulmonary internal-organ TB, which serves as a specific indicator of immunosuppression-related disease. 

Among 96,351 US safety reports for IL-17 and IL-23 inhibitors, there were 0 cases of extrapulmonary internal-organ TB or disseminated TB. By contrast, among 139,825 reports for TNF inhibitors, 26 cases of extrapulmonary TB were identified, including 8 disseminated cases. 

After nearly a decade of real-world use, the absence of a pharmacovigilance signal for IL-17 and IL-23 inhibitors is striking. 

The Joint Position Statement 

Based on this convergence of biologic plausibility, clinical trial experience, real-world data, and FAERS surveillance, the NPF Medical Board and the IPC voted to formally adopt the following statement: Routine testing for LTBI is not required prior to or during treatment of psoriasis patients with IL-17 or IL-23 inhibitors. 

Eighty-seven and a half percent of respondents endorsed this recommendation. Most dissenters practiced in TB-endemic regions, where clinicians remain understandably cautious. 

Practical Implications for Clinical Practice 

This position statement is more than just an academic exercise; it has real-world consequences, such as lowering burden and costs, reducing false positives, and enabling faster treatment start. TB screening adds time, expense, and administrative hurdles to psoriasis management. Eliminating unnecessary testing simplifies access to therapy. Additionally, interferon-gamma release assays are not perfect. False positives can cause anxiety, unnecessary imaging, hepatotoxic prophylaxis, and delays in treatment. Removing TB testing as a barrier helps speed up care for patients with moderate-to-severe psoriasis. 

However, the statement is not absolute. Continued testing may be prudent in selected scenarios, including patients living in TB-endemic regions, patients receiving concomitant immunosuppressive therapies such as systemic corticosteroids, and individuals with known high-risk exposures or evolving epidemiologic risks. Clinical judgment remains essential. 

A Turning Point in Psoriasis Care 

For years, dermatology has operated under a one-size-fits-all biologic safety framework driven by experience with TNF inhibitors. The NPF Medical Board/IPC joint position statement acknowledges what the data show: IL-17 and IL-23 inhibitors are fundamentally different. 

Requiring routine LTBI testing in this context is no longer evidence based. Updating practices to reflect contemporary science can reduce unnecessary barriers, improve efficiency, and deliver faster, safer care to patients living with psoriasis.

Reference 
Blauvelt A, Strober BE, Eakin GS, et al. Joint position statement from the National Psoriasis Foundation Medical Board and the International Psoriasis Council on routine testing for latent tuberculosis infection prior to and during treatment of psoriasis patients with interleukin 17 or interleukin 23 inhibitors. J Am Acad Dermatol. 2025:S0190-9622(25)03232-3. doi:10.1016/j.jaad.2025.11.033