Objectives To report the safety of ustekinumab (UST) from the psoriatic arthritis (PsA) development program.
Methods Safety data through up to 2yrs of follow-up were pooled from Ph3 for the analysis of overall safety endpoints. Data were pooled from Ph2 (n=146) and Ph3 for AEs of interest. In Ph3, adult PsA pts (PSUMMIT I [n=615], PSUMMIT II [n=312]) with active disease (≥5 SJC and ≥5 TJC; CRP≥0.3mg/dL [ULN 1.0 mg/dL]) despite DMARD and/or NSAID or previously treated with DMARD and/or NSAID, and prior anti-TNFα therapy (PSUMMIT II only) were randomized to UST45mg, 90mg, or PBO at wks 0, 4, and q12wks; at wk16, pts with <5% improvement in SJC & TJC entered blinded EE (PBO→UST45mg; UST45mg→90mg; 90mg→90mg). PBO pts crossed over to UST45mg at wks24 and 28 and q12wk dosing. No concomitant DMARDs except MTX (approx 50% in each Ph3 study) were permitted. The PBO-controlled period was 12wks and 16wks for the Ph2 and Ph3 trials, respectively. AEs were reported as the number of events /100 pt-yrs of follow-up (PY). All pts who received ≥1 dose of treatment were included.
Results 379 and 1018 pts were treated with PBO and UST, resp, for up to 2yrs (duration of follow-up: Ph2 36wks, PSUMMIT1 108wks, and PSUMMIT2 60wks) with 145 PY and 1403 PY overall for the PBO and UST grps, resp. At baseline, 96.8% were white, 52.2% male, mean age 47.6yrs (SD 11.8). Mean BMI was 30.9 kg/m2(SD 7.1), mean PsA and PsO duration was 7.2 yrs (SD 7.7) and 15.8yrs (SD 12.6), resp. Safety outcomes are detailed in Table 1. Event rates of overall AEs, infections, and SAEs, were comparable among PBO and UST during the PBO-controlled period; rates remained comparable through 2yrs of follow-up. Rates of AEs leading to d/c were higher in PBO. Overall AE rates were not impacted by baseline MTX or prior anti-TNF usage. 1 squamous cell carcinoma (90mg), 1 serious infection (PBO) and 1 MI (PBO) were reported during PBO-controlled period. With up to 2yrs of follow-up, rate of infections was similar in 90mg vs 45mg grps; serious infections were numerically greater in the 90mg vs 45 mg grp (2.1/100PY [95% CI:1.1,3.5] vs 0.5/100PY [95% CI: 0.1,1.3], resp), and included 2 pts in the 90mg grp with multiple events (most were single events without apparent trend). 4 non-melanoma skin cancers (NMSC)(0.64/100PY) occurred in the 90mg grp and no NMSCs occurred in the 45mg grp. 3 malignancies (0.4/100PY), other than NMSC, occurred in 45mg grp and none in 90mg grp. Major adverse cardiovascular event (MACE) rates were low and no dose effects were observed (1.15 vs 0.24 for 45mg and 90mg, resp). No cases of active TB or serious opportunistic infections, RPLS, demyelination, anaphylaxis or serum sickness-like reactions were reported.
Conclusions Pooled safety data show that UST was well tolerated at both doses with up to 2yrs of follow-up without new safety signals. The safety profile of UST in the PsA clinical development program was generally comparable to that observed in the psoriasis population.
Disclosure of Interest A. Kavanaugh Grant/research support from: AbbVie, Amgen, Janssen, and UCB., I. McInnes Grant/research support from: AbbVie, BMS, Janssen, Pfizer, Roche, Merck/Schering-Plough, and UCB., C. Ritchlin Grant/research support from: Amgen, Janssen, and UCB, Consultant for: AbbVie, Amgen, Janssen, Regeneron, Roche, and UCB., P. Rahman Grant/research support from: AbbVie, Amgen, Janssen, Pfizer, and Novartis., L. Puig Grant/research support from: AbbVie, Amgen, Boehringer, Celgene, Eli Lilly, Janssen, Leo-Pharma, Merck/Schering-Plough, Merck-Serono, Novartis, Pfizer, Sandoz, and VBL., A. Gottlieb Grant/research support from: Amgen, AbbVie, Celgene, Coronado, Eli Lilly, Janssen, Levia, Merck, and Pfizer, Consultant for: AbbVie, Actelion, Akros, Amgen, Astellas, Bristol Myers Squibb, Canfite, Catabasis, Celegene, CSL Behring Biotherapies for Life, Coronado, Dermipsor, Eli Lilly, GlaxoSmithKline, Incyte, Janssen, Karyopharm, Novartis, Novo Nordisk, Pfizer, Sanofi Aventix, UCB, Vertex, and Xenoport., M. Song Employee of: Janssen R&D, LLC., B. Randazzo Employee of: Janssen R&D, LLC., S. Li Employee of: Janssen R&D, LLC., Y. You Employee of: Janssen R&D, LLC., A. Mendelsohn Employee of: Janssen R&D, LLC.