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

Drug Saf. 2019 Jun;42(6):751-768. doi: 10.1007/s40264-019-00797-3.

Abstract

Introduction: Theoretical risks of biologic agents remain under study.

Objective: The aim of this study was to integrate 1-year safety data from 12 ustekinumab registrational trials.

Methods: Patients 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]).

Results: Among 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.

Conclusions: Ustekinumab demonstrated a favorable and consistent safety profile across registrational trials in approved indications.

Trial registrations: ClinicalTrials.gov identifier: NCT00320216, NCT00267969, NCT00307437, NCT00454584, NCT00267956, NCT01009086, NCT01077362, NCT00265122, NCT00771667, NCT01369329, NCT01369342, and NCT01369355.

Publication types

  • Clinical Trial, Phase II
  • Clinical Trial, Phase III
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antibodies, Monoclonal / adverse effects
  • Antibodies, Monoclonal / therapeutic use
  • Arthritis, Psoriatic / drug therapy*
  • Crohn Disease / drug therapy*
  • Female
  • Humans
  • Male
  • Methotrexate / adverse effects
  • Methotrexate / therapeutic use
  • Middle Aged
  • Psoriasis / drug therapy*
  • Severity of Illness Index
  • Treatment Outcome
  • Ustekinumab / adverse effects*
  • Ustekinumab / therapeutic use*

Substances

  • Antibodies, Monoclonal
  • Ustekinumab
  • Methotrexate

Associated data

  • ClinicalTrials.gov/NCT00454584
  • ClinicalTrials.gov/NCT00771667
  • ClinicalTrials.gov/NCT00320216
  • ClinicalTrials.gov/NCT01077362
  • ClinicalTrials.gov/NCT00265122
  • ClinicalTrials.gov/NCT01369329
  • ClinicalTrials.gov/NCT00267956
  • ClinicalTrials.gov/NCT00307437
  • ClinicalTrials.gov/NCT01369342
  • ClinicalTrials.gov/NCT00267969
  • ClinicalTrials.gov/NCT01369355
  • ClinicalTrials.gov/NCT01009086