Ustekinumab Safety in Psoriasis, Psoriatic Arthritis, and Crohn’s Disease:an integrated analysis of Phase II/III Clinical Development Programs

IntroductionTheoretical risks of biologic agents remain under study.ObjectiveThe aim of this study was to integrate 1-year safety data from 12 ustekinumab registrational trials.MethodsPatients had moderate-to-severe plaque psoriasis, active psoriatic arthritis (PsA) (± methotrexate), or moderate-to-severe Crohn's disease (CD; failed/intolerant of immunomodulators/corticosteroids). Psoriatic patients received subcutaneous ustekinumab 45/90 mg or placebo, generally at week 0, week 4, then every 12 weeks thereafter, while those with CD received a single intravenous ustekinumab dose (130 mg or weight range-based dosing of approximately 6 mg/kg) or placebo induction dose at week 0, followed by subcutaneous ustekinumab 90 mg at week 8 and every 8/12 weeks thereafter. The incidence rates of a priori-defined safety events were integrated post hoc (adjusted for duration of follow-up, reported per 100 patient-years [PYs]).ResultsAmong 6280 enrolled patients, 5884 ustekinumab-treated patients (psoriasis: 3117; PsA: 1018; CD: 1749) contributed 4521 PYs versus 674 PYs in placebo-treated patients through year 1 (829 PYs and 385 PYs during 8- to 16-week controlled periods). Combined across diseases among ustekinumab- versus placebo-treated patients, respective incidences/100 PYs (95% confidence intervals) of infections were 125.4 (122.2-128.7) versus 129.4 (120.9-138.3) through year 1, and not meaningfully increased in patients who did versus those who did not receive methotrexate (92.5 [84.2-101.5] vs. 115.3 [109.9-121.0]), or significantly increased in patients who did versus those who did not receive corticosteroids (116.3 [107.3-125.9] vs. 107.3 [102.0-112.8]) at baseline. Major adverse cardiovascular events (0.5 [0.3-0.7] vs. 0.3 [0.0-1.1]), malignancies (0.4 [0.2-0.6] vs. 0.2 [0.0-0.8]), and deaths (0.1 [0.0-0.3] vs. 0.0 [0.0-0.4]) were rare across indications.ConclusionsUstekinumab demonstrated a favorable and consistent safety profile across registrational trials in approved indications.Trial registrationsClinicalTrials.gov identifier: NCT00320216, NCT00267969, NCT00307437, NCT00454584, NCT00267956, NCT01009086, NCT01077362, NCT00265122, NCT00771667, NCT01369329, NCT01369342, and NCT01369355

Pooled safety results through 1 year of 2 phase iii trials of guselkumab in patients with psoriatic arthritis

Objective: Evaluate the safety of guselkumab (monoclonal antibody targeting interleukin [IL]-23p19) in patients with psoriatic arthritis (PsA) through 1 year (1Y) of the phase III DISCOVER-1 and DISCOVER-2 trials. Methods: Patients with active PsA (n = 1120; biologic-naïve except 118 patients treated with tumor necrosis factor inhibitors in DISCOVER-1) were randomized to subcutaneous guselkumab 100 mg every 4 weeks (Q4W) or at Week 0, Week 4, then every 8 weeks (Q8W); or placebo. At Week 24, patients in the placebo group switched to guselkumab 100 mg Q4W. Treatment continued through 1Y and 2 years for DISCOVER-1 and DISCOVER-2, respectively. In this pooled analysis, patients with ≥ 1 adverse event (AE) through 1Y were standardized for 100 patient-years [100 PYs] of follow-up. Results: Through Week 24, adverse events (AEs) were consistent between patients treated with placebo and guselkumab (Q4W + Q8W). AEs were 142.8/100 PYs and 150.6/100 PYs, serious AEs were 7.1/100 PYs and 4.4/100 PYs, and AEs leading to study agent discontinuation were 4.1/100 PYs and 3.8/100 PYs, respectively. Through 1Y in patients treated with guselkumab, no uveitis, active tuberculosis, opportunistic infections, or inflammatory bowel disease were observed, and low rates of malignancy and major adverse cardiovascular (CV) events were observed. Injection-site reactions occurred in 1.7%, and antibodies to guselkumab in 4.5% of patients treated with guselkumab through 1Y; the vast majority of antibodies to guselkumab were nonneutralizing. Serum hepatic transaminase elevations (more common with Q4W than Q8W dosing) and decreased neutrophil counts were generally mild, transient, and did not require treatment discontinuation, with minimal change from Week 24 to 1Y. Conclusion: Guselkumab 100 mg Q4W and Q8W were well tolerated in patients with PsA, with no new safety concerns through 1Y of the phase III DISCOVER trials. Guselkumab safety through 1Y in patients with PsA is consistent with that established in patients with psoriasis who were treated with guselkumab. [ClinicalTrials.gov: NCT03162796 and NCT03158285]

Correction to: Ustekinumab Safety in Psoriasis, Psoriatic Arthritis, and Crohn's Disease: An Integrated Analysis of Phase II/III Clinical Development Programs.

In the original publication of this article, the following correction should be noted in Table 5

Correction to:Ustekinumab Safety in Psoriasis, Psoriatic Arthritis, and Crohn's Disease: An Integrated Analysis of Phase II/III Clinical Development Programs

In the original publication of this article, the following correction should be noted in Table 5

Pooled Safety Results Through One Year of Two Phase-3 Trials of Guselkumab in Patients with Psoriatic Arthritis.

OBJECTIVE: Evaluate safety of guselkumab (monoclonal antibody targeting IL-23p19) in psoriatic arthritis (PsA) patients through 1year (1Y) of the Phase-3 DISCOVER-1&2 trials. METHODS: Patients with active PsA (N=1120; biologic-naïve except the118 TNFi-treated DISCOVER-1 patients) were randomized to subcutaneous guselkumab 100 mg every 4 weeks (Q4W) or at Week 0, Week4, then Q8W; or placebo. At Week24, placebo patients switched to guselkumab 100 mg Q4W. Treatment continued through 1Y and 2Y for DISCOVER-1&2, respectively. In this pooled analysis, patients with ≥1 adverse event (AE) through 1Y were standardized for 100 patient-years of follow-up [100PY]). RESULTS: Through Week24, AEs were consistent between placebo- and guselkumab (Q4W+Q8W)-treated patients: AEs 143/100PY and 151/100PY; serious AEs 7.1/100PY and 4.4/100PY; AEs leading to study agent discontinuation 4.1/100PY and 3.8/100PY, respectively. Through 1Y, no active tuberculosis, opportunistic infections, or inflammatory bowel disease, and low rates of malignancy and major adverse cardiovascular events, were observed in guselkumab-treated patients. Injection-site reactions occurred in 1-2%, and antibodies to guselkumab in 4.5% of guselkumab-treated patients through 1Y; the vast majority of antibodies to guselkumab were non-neutralizing. Serum hepatic transaminase elevations (more common with Q4W than Q8W) and decreased neutrophil counts were generally mild, transient, and did not require treatment discontinuation, with minimal change from Week24 to 1Y. CONCLUSION: Guselkumab 100 mg Q4W and Q8W were well tolerated in PsA patients, with no new safety concerns through 1Y of the Phase-3 DISCOVER trials. Guselkumab safety through 1Y in PsA patients is consistent with that established in guselkumab-treated psoriasis patients