Risankizumab efficacy and safety in psoriatic patients with latent tuberculosis infection: A multicentric real‐world study

According to current guidelines for the treatment of psoriasis, screening for tuberculosis infection (TBI) is performed before starting any biological drug, using interferon-gamma (IFN-γ) release assay (Quantiferon TB test), or clinical and radiographic examination when needed, to rule out an active form (aTBI).1 TNF-α inhibition exposes patients to an augmented risk of latent tuberculosis (LTBI) reactivation.2, 3 However, interleukin (IL)-17 and IL-23 pathways do not interfere with the control of the latent bacterial infection, and data from clinical trials and many real-world reports demonstrate a greater safety profile of anti-IL agents in psoriatic patients with LTBI.4-8 Nevertheless, TB chemoprophylaxis should be undertaken before starting biologic therapy.1 Many TB treatment schemes are approved, such as isoniazid monotherapy long-course regimen (6–9 months) or rifamycin short-course one (3 months). Anti-TB drugs are linked to multiple and sometimes severe adverse reactions and are frequently associated with numerous drug interactions.9 Psoriatic patients with LTBI and a high risk of developing secondary complications due to TB chemoprophylaxis require a personalized approach. The safety information on risankizumab is generally reassuring: many individuals with LTBI were exposed to the IL-23 inhibitor in clinical trials, and aTBI has never been documented.4, 5, 10 We proposed to determine, in a real-world clinical setting, the rate of TBI reactivation in psoriatic patients with previously or newly diagnosed LTBI, treated with risankizumab over a follow-up period of 52 weeks, comparing those who had undergone TB chemoprophylaxis with those who had not. A multicentric, real-life, retrospective observational cohort study was conducted. Adult psoriatic patients who initiated risankizumab between April 2019 and December 2022 were included. Enrolled patients (n. 297) were selected by 10 Italian tertiary care centres, details in Table 1. Before starting risankizumab all enrolled patients undertook a Quantiferon TB test, and 39/297 (13%) had LTBI (Table 2). In addition, a baseline chest X-ray was carried out on each LTBI patient. LTBI was defined as a positive Quantiferon TB test result without clinical symptoms or signs of an aTBI. The mean of absolute values (ESAT-6 and CFP-10) was 3.37 IU/mL (range: 0.8–10; cut off < 0.35) for TB1 (CD4); 3.74 IU/mL (range: 0.6–10; cut off < 0.35) for TB2 (CD4/CD8); 9 IU/mL (range: 6.6–10; cut off > 0.5) for positive control. Chest X-rays excluded aTBI, reporting clear lungs and a clearly outlined chest cavity. Patients were classified as “no TB-prophylaxis” if they did not take chemoprophylaxis or if they did not complete at least 1 month of chemoprophylaxis treatment. According to infectious disease or pneumologist specialist consultations, chemoprophylaxis was prescribed having considered the National guidelines, the patient's comorbidities and compliance, and possible contraindications (Table 2). Of 39 LTBI psoriatic patients, 24 (61.5%) received anti-TB therapy, whereas 15 (38.4%) didn't receive anti-TB drugs before starting risankizumab. The latter group included LTBI psoriatic patients (n. 2) who started anti-TB therapy but did not complete it due to the occurrence of anti-TB drug-induced adverse events (hepatotoxicity and intense nausea). At week 52, all enrolled LTBI patients repeated the Quantiferon TB test and chest X-ray. No cases of aTBI were reported both in the TB-prophylaxis (n. 24) and no TB-prophylaxis group (n. 15). Risankizumab showed the same high profile of efficacy and safety in psoriatic patients with LTBI, even in those with untreated LTBI (PASI100-90-75 response rate at W52 was 63%, 89%, and 100%, respectively, in overall LTBI patients). Limitations of the current investigation are the retrospective design, the small sample size of the population of interest (untreated LTBI psoriatic patient), the limited follow-up period and the fact that the evaluation was limited to a single biologic drug. However, this study, and future ones, could address concerns around the long-term management of the psoriatic patient. The authors thank Doctor Giancarmine Pastore, who has supported the collection of data for the study. This paper was not funded. The authors declare no conflicts of interest. The study was conducted following the principles of the 1975 Declaration of Helsinki and its amendments, the International Conference of Harmonization Good Clinical Practice and all applicable laws and regulations. Informed consent from patients was not required because the analysis was anonymous. Since the study was retrospective and all the procedures were part of routine clinical practice, ethical approval was not required. The data supporting this study's findings are available from the corresponding author upon request.