Assessing tuberculosis risk in Crohn’s disease patients receiving biologic therapies: real-world insights from Japan

In the past 20 years, advances in therapy have significantly improved the management of inflammatory bowel disease, allowing for better achievement of remission [1]. While these new treatment strategies, including biologic agents, are effective in alleviating symptoms and modifying disease progression, their strong immunosuppressive action poses a risk for opportunistic infections [2]. Among these opportunistic infections, tuberculosis (TB) is one of the most clinically significant concerns [3].

In the current issue of Intestinal Research, Fujimoto et al. [4] reported valuable real-world evidence on the risk of TB in Crohn’s disease (CD) patients receiving biologic therapies in Japan using a large-scale medical claims database. According to this study, tumor necrosis factor alpha (TNF-α) inhibitors were associated with increased risk of active TB development (hazard ratio 3.66). However, no TB cases were observed among the patients with ustekinumab (UST) and vedolizumab (VDZ) during the follow-up period. It is consistent with previous results from Western and Asian studies [5,6].

Since the incidence of TB is influenced not only by the intrinsic risk of the biologic agent but also by the regional prevalence of TB, this study is meaningful in that it evaluates TB risk using a large-scale, population-based database representative of the Japanese population. This large sample size allows the capture of rare events such as TB, which remains a critical concern in immunosuppressed populations. Importantly, the authors employed a time-dependent Cox proportional hazard model to better reflect the real-world timing of biologic initiation and TB onset, enhancing the validity of the observed associations.

Despite these strengths, several considerations should be taken into account when interpreting the results of this study. As the authors noted, the database lacks clinical variables, such as tuberculin skin test and interferon-gamma release assay. To address this limitation, they attempted to exclude patients who received isoniazid monotherapy, thereby removing cases with latent TB infection undergoing prophylaxis. However, according to the previous study [7], the risk of TB reactivation remains even among patients who receive prophylactic therapy upon initiation of biologic agents. Therefore, an accurate evaluation of TB risk requires more detailed analyses including latent TB infection patients with prophylaxis [8]. Furthermore, comprehensive data such as regimen and duration of TB prophylaxis and the methods used for TB surveillance would also be helpful.

In summary, this study offers important real-world evidence that TNF-α inhibitors increase the risk of active TB in Japanese CD patients. This study reinforces the importance of TB risk assessment prior to initiating TNF-α inhibitors [9]. It also highlights the potential utility of alternative agents like UST and VDZ in patients at high risk for active TB or those with latent TB. Nevertheless, firm conclusions about the comparative safety of newer biologics must await further prospective, registry-based evaluations because UST/VDZ have had shorter periods of availability and relatively fewer users in this dataset. Continued pharmacovigilance and individualized treatment approaches remain essential in the evolving landscape of CD management.