P68 Safety in patients with latent tuberculosis who received concomitant anti-tuberculosis medications: analysis of 11 studies of guselkumab in psoriatic disease

Abstract Treatments for psoriatic disease, including TNF inhibitors (TNFi), increase the risk of latent tuberculosis infection (LTBI) activation, and TB screening before initiating systemic therapy is recommended. Safety outcomes in LTBI+ patients with moderate-to-severe psoriasis (PsO) or active psoriatic arthritis (PsA) on guselkumab for up to 5 years were pooled from 11 Phase 2/3 studies (7 PsO, 4 PsA). Guselkumab was generally administered as 100 mg subcutaneous injections at Week (W)0, W4, then every 8 weeks (q8w) in PsO studies and W0, W4, then every 4 weeks (q4w) or q8w in PsA studies. Patients randomized to placebo crossed over to guselkumab at W16 (in PsO) or W24 (in PsA). Patients with active TB at screening were excluded. LTBI+ patients were eligible if appropriate LTBI treatment was initiated before/with the first study-drug administration or appropriate treatment was completed within 5 years. Safety was reported annually during the placebo-controlled period, and through the end of follow-up (PsO ≤5 years; PsA ≤2 years). LTBI+ patients were from Asia-Pacific − 10.0%(70/697), Western Europe − 7.3%(51/698), Eastern Europe − 7.3%(179/2453), and North America − 5.3%(74/1407). LTBI treatment initiated before [88.2% (330/374)], with [6.1% (23/374)], or after [5.6% (21/374)] first study drug dose [median −8.0 days (interquartile range, IQR, −20.0 to −2.0)]. LTBI treatments included isoniazid (82.1%), rifampicin (11.8%), and other medications (17.4%); 89.8% received monotherapy. No new-onset TB or LTBI activation was observed in any guselkumab-treated patient. Adverse events (AEs) and serious AEs rates were similar for guselkumab- and placebo-treated patients in LTBI+ and LTBI− groups during the placebo-controlled period; cumulative rates were comparable between guselkumab-treated LTBI+ and LTBI− patients through the end of follow-up. Through Year 1, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) elevations were more common in LTBI+ vs. LTBI− group; ≤2% of LTBI+ patients had Grade 3 elevations (no Grade 4) vs. 0.5% of LTBI− patients. From Years 1–5 [after ∼98% of LTBI+ patients completed prophylaxis (median 185 days, IQR 124–274)], the proportions of LTBI+ and LTBI− patients with elevated ALT/AST were similar. No cases of new-onset TB or LTBI activation were observed in up to 5 years of guselkumab treatment and safety was generally similar in LTBI+ and LTBI− patients. Consistent with the known safety of LTBI medications, ALT/AST elevations were more common in LTBI+ vs. LTBI− patients through Year 1; however, ALT/AST elevation rates were generally similar post-LTBI treatment. The absence of observed TB risk in guselkumab-treated patients suggests guselkumab may be a better treatment option than TNFi in high-risk patients, including those in TB-endemic regions.