Maintenance of efficacy and safety of ustekinumab in patients with active psoriatic arthritis despite prior conventional nonbiologic and anti-TNF biologic therapy: 1 yr results of the psummit 2 trial

Background Ustekinumab (UST)has demonstrated efficacy in pts with active psoriatic arthritis (PsA) at wk24 in the Phase 3, multicenter, PBO-controlled PSUMMIT2 trial. Results through wk52 PSUMMIT 2 are presented herein. Methods 312 adults with active PsA were randomized to UST 45mg or 90mg at wk0, wk4, and q12w or PBO at wks0, 4, and 16 followed by crossover to UST 45mg at wk24, wk28, and wk40. Randomization was stratified by site, weight (≤100kg, >100kg) and baseline MTX use, and pts previously treated with biologic anti-TNF agents were eligible. At wk16, pts with <5% improvement in both tender/swollen joint counts entered blinded early escape (PBO→UST 45mg, 45mg→90mg, 90mg→90mg). The primary endpoint was ACR20 at wk24. Secondary endpoints were HAQ-DI, ACR50, ACR70, and ≥75% improvement in the Psoriasis Area and Severity Index (PASI75). Results Anti-TNF-experienced pts had more active disease at baseline than anti-TNF-naïve pts. More UST (43.8%>combined, 43.7%>45mg, 43.8%>90mg) than PBO (20.2%) treated pts had ACR20 at wk24 (all P<0.001). Significant differences were observed for ACR50 and PASI75 response at wk24 (table). Efficacy was sustained through wk52. At wk52, 51% and 44% of pts who were and were not, respectively, receiving MTX at baseline had ACR20. UST efficacy at wk52 was more robust in anti-TNF-naïve (ACR20 59-73%) than anti-TNF-experienced (37-41%) pts and pts who had previously received 1 (50-55%) vs. 2 (13-39%) or ≥3 (13-30%) anti-TNF agents. UST was generally well tolerated, with no deaths or TB and similar rates of AEs (78.6%>45mg, 77.9%>90mg), SAEs (5.8%>45mg, 5.8%>90mg), and AEs leading to discontinuation (5.8%>45mg, 3.8%>90mg) reported across doses through wk60. 2 pts, both anti-TNF-experienced, had malignancies (breast-45mg, squamous cell carcinoma-90mg); 2/287 (0.7%) of UST-treated pts (both 90mg) had serious infections. 3 pts (2-45mg, 1-90mg) had MACE (myocardial infarctions) through wk60, all had multiple CV risk factors and prior anti-TNF experience. Conclusions Both UST doses (45/90 mg q12w) yielded significant and sustained improvements in PsA signs/symptoms with favorable and comparable safety profiles. UST was effective in both anti-TNF-naïve and anti-TNF-experienced pts, with greater efficacy in anti-TNF naïve pts and anti-TNF-experienced pts previously treated with 1 or 2 anti-TNF agents. (Figure Presented).