OP0230 EFFICACY AND SAFETY OF TILDRAKIZUMAB, A HIGH-AFFINITY ANTI–INTERLEUKIN-23P19 MONOCLONAL ANTIBODY, IN PATIENTS WITH ACTIVE PSORIATIC ARTHRITIS IN A RANDOMISED, DOUBLE-BLIND, PLACEBO-CONTROLLED, MULTIPLE-DOSE, PHASE 2B STUDY

Abstract

Background:Tildrakizumab (TIL), a high-affinity anti–interleukin-23p19 monoclonal antibody, is approved to treat moderate to severe plaque psoriasis and is under investigation for treatment of psoriatic arthritis (PsA).1Objectives:To evaluate efficacy and safety of TIL up to week (W)52 in a randomised, double-blind, placebo-controlled, multiple-dose, phase 2b study in PsA (NCT02980692).Methods:Patients (pts) ≥18 years with active PsA2were randomised 1:1:1:1:1 to TIL 200 mg every 4 weeks (Q4W) to W52, TIL 200 mg Q12W to W52, TIL 100 mg Q12W to W52, TIL 20 mg Q12W until W24 then TIL 200 mg Q12W to W52, or placebo (PBO) Q4W until W24 then TIL 200 mg Q12W to W52. Efficacy assessments included ACR20/50/70, 75%/90%/100% improvement in Psoriasis Area and Severity Index (PASI), proportion of pts with residual minimal disease activity (MDA) response; and mean change from baseline (BL) in HAQ-DI, Leeds Dactylitis Index (LDI, pts with BL LDI ≥1), and Leeds Enthesitis Index (LEI, pts with BL LEI ≥1) to W52. Treatment-emergent adverse events (TEAEs) were monitored.Results:Of 500 pts screened, 391 were randomised and received ≥1 dose of drug. Proportions of ACR20/50/70 responders were superior with TIL vs PBO through W24; after W24 rates of responses further increased for TIL 20→200 mg Q12W and PBO→200 mg Q12W through W52 (Figure 1, 2). Other efficacy results are shown in Table. Overall from BL→W24/W25→W52, 50.4%/39.9% and 2.3%/1.0% of pts experienced a TEAE and serious AE, respectively. From BL→W24, 1 case of pyelonephritis and urinary tract infection was reported in the TIL 100 mg Q12W arm and 1 case of chronic tonsillitis was reported in the TIL 20 mg→200 mg Q12W arm. During W25→W52, 1 malignancy (intraductal proliferative breast lesion) was reported with TIL 20 mg→200 mg Q12W. No deaths or major adverse cardiac events occurred.Table.W52 clinical efficacyTIL 200 mg Q4Wn=78TIL 200 mg Q12Wn=79TIL 100 mg Q12Wn=77TIL 20→200 mg Q12Wn=78PBO→TIL 200 mg Q12Wn=79HAQ-DI, BLa1.0 ± 0.61.0 ±0.61.0 ± 0.71.1 ± 0.61.2 ± 0.6 W52b−0.5 ± 0.5−0.5 ± 0.6−0.5 ± 0.6−0.5 ± 0.5−0.5 ± 0.5LEI, BLa,c1.9 ± 2.01.5 ± 1.92.2 ± 2.12.2 ± 2.01.5 ± 1.9 W52b−1.3 ± 1.9−1.0 ± 1.6−1.7 ± 2.1−1.2 ± 1.8−1.2 ± 1.8LDI, BLa,d32.8 ± 32.961.3 ± 73.593.8 ± 146.571.4 ± 118.599.6 ± 170.7 W52b,d−21.4 ± 37.1−42.1 ± 76.7−41.6 ± 89.3−56.5 ± 123.4−81.5 ± 173.0 BL, W52 mediand21.8, 7.428.3, 3.232.1, 20.028.6, 034.0, 5.6MDAe56.964.445.047.142.0PASI 100e54.044.443.947.535.0PASI 90e72.080.658.555.050.0PASI 75e82.094.482.975.067.5aBL mean ± SD.bMean change from BL ± SD.cPts with BL LEI ≥1 will be presented at EULAR.dPts with BL LDI ≥1 (n = 27, 21, 21, 19, 25) using nonresponder imputation.e% at W52Missing data not imputed.SD, standard deviation.Conclusion:TIL was well tolerated and improved joint and skin manifestations of PsA through W52.