Long-Term Safety of Tildrakizumab Through Week 208 in Patients with Psoriatic Arthritis: Results from the Phase 2B Open-Label Extension Study

Objectives Tildrakizumab is an anti-IL-23 p19 monoclonal antibody approved for the treatment of adults with moderate-to-severe plaque psoriasis. In a Phase 2b trial in patients with active psoriatic arthritis (PsA; NCT02980692 ), tildrakizumab treatment significantly improved joint and skin symptoms and was well tolerated for up to 52 weeks.[1] Our objective is to report safety results through Week (W)208 of an open-label long-term extension (LTE) of the trial. Methods Patients who completed treatment in the parent study, achieved ACR20 response at W52, and had sufficient clinical benefit per the investigator were eligible for the LTE. Patients received tildrakizumab 200 mg every 4 weeks, 200 mg every 12 weeks (Q12W), or 100 mg Q12W until parent study database lock (≥52 weeks of treatment), after which all patients received tildrakizumab 100 mg Q12W through W208. Safety was assessed in all patients who entered the LTE and received ≥1 dose of tildrakizumab based on frequency and severity of adverse events (AEs); frequency of serious AEs (SAEs), AEs of special interest (AESIs) and clinical interest (AECIs); and presence of antidrug antibodies (ADAs) to tildrakizumab. Analyses were based on the treatment received. Results Of 281 patients who entered the LTE, 205 completed treatments through W208. Any AEs, treatment-related AEs (TRAEs), SAEs, and treatment-related SAEs occurred in 224/281 (79.7%), 55/281 (19.6%), 40/281 (14.2%), and 2/281 (0.7%) patients, respectively (Table). The most common TRAEs were upper respiratory tract infection (3.2%) and nasopharyngitis (2.5%). Overall, 17/281 (6.0%) and 7/281 (2.5%) patients discontinued the study due to AEs and TRAEs, respectively, chiefly infections and infestations. AESIs were reported in 13/281 (4.6%) patients and included infections and infestations (1.8%); cardiac disorders (1.1%; not treatment related); malignancies (n = 2; 0.7%); respiratory, thoracic, and mediastinal disorders (n = 2; 0.7%); and vascular disorders (n = 1; 0.4%). Only 1 AECI occurred during the LTE. Two patients died due to AEs (1 aortic dissection and 1 metastatic adenocarcinoma, neither treatment related). Non-treatment-emergent (TE) and TE ADAs were detected in 2.8% and 1.1% and non-TE and TE neutralizing ADAs in 0.7% and 0.4% of patients, respectively. Patients’ ADA status was not associated with AEs of hypersensitivity or injection-site reactions, AESIs, or AECIs. Table. Summary of AEs in the LTE study Conclusion The safety profile of tildrakizumab was maintained through extension W208 in patients with PsA. These data support continued development of tildrakizumab to treat patients with active PsA. References [1.] Mease PJ. Ann Rheum Dis 2021;13:1147-57.