Guselkumab Safety in Patients With Latent Tuberculosis: Analysis of 11 Studies in Psoriatic Disease.

Certain psoriatic disease treatments, including tumor necrosis factor-α inhibitors (TNFi), increase tuberculosis (TB) risk. Testing for latent TB infection (LTBI) before initiating systemic therapy has been standard practice for psoriasis (PsO) patients; however, updated consensus states routine testing is not required before initiating interleukin (IL)-17 or IL-23 inhibitors. This analysis reports safety outcomes in LTBI+ patients with moderate-to-severe PsO or active psoriatic arthritis (PsA) who received guselkumab for up to 5 years. Data were pooled from 11 phase 2/3 studies (7 PsO, 4 PsA). Guselkumab 100 mg was generally administered at Week 0, Week 4, then every 8 weeks (PsO studies) or every 4 or 8 weeks (PsA studies). Placebo-randomized patients crossed over to guselkumab at Week 16 and Week 24 in PsO and PsA studies, respectively. Patients with active TB or a history of active TB were excluded. LTBI+ patients could participate if LTBI treatment was initiated before/with the first dose of study drug or if LTBI treatment was completed within 5 years before the first dose of study drug. Among 5 255 randomized patients, 374 (7.1%) had LTBI and received preventive treatment, most commonly isoniazid (82.1%) and rifampicin (11.8%). No new-onset TB or LTBI reactivation occurred in any guselkumab-treated patient. Through Year 1, liver transaminase elevations were more common in LTBI+ vs. LTBI- patients; ≤ 2% of LTBI+ patients had CTCAE Grade 3 elevations vs. 0.5% of LTBI- patients (no LTBI+ patients had Grade 4 elevations). From Year 1-5 (after ~98% of LTBI+ patients completed preventive treatment), transaminase elevations were generally similar among LTBI+ and LTBI- patients. The absence of observed TB risk in guselkumab-treated patients suggests IL-23 inhibitors may be better treatment options than TNFi in high-risk patients, including those in TB-endemic regions.