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

Subrata Ghosh, Lianne S Gensler, Zijiang Yang, Chris Gasink, Soumya D Chakravarty, Kamyar Farahi, Paraneedharan Ramachandran, Elyssa Ott, Bruce E Strober, Subrata Ghosh, Lianne S Gensler, Zijiang Yang, Chris Gasink, Soumya D Chakravarty, Kamyar Farahi, Paraneedharan Ramachandran, Elyssa Ott, Bruce E Strober

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.

Conflict of interest statement

Contributors

All authors had full access to the study data, were involved in data interpretation, participated in manuscript preparation, and approved the final version for submission. In addition, SG planned the initial draft of the manuscript; ZY assisted with data analyses; and BS, CG, EO, and SG were involved in study conduct and data acquisition.

Conflicts of interest

Subrata Ghosh has received consulting honoraria from AbbVie, Boehringer-Ingelheim, Bristol Myers Squibb, Gilead, Janssen, Pfizer, and Takeda, and research grant support from AbbVie and GlaxoSmithKline. Lianne S. Gensler has received consulting honoraria from Janssen and Novartis, and research grant support from AbbVie, Amgen, and UCB. Zijiang Yang and Paraneedharan Ramachandran are employed by Janssen Research & Development, LLC, and Chris Gasink, Soumya D. Chakravarty, Kamyar Farahi, and Elyssa Ott are employed by Janssen Scientific Affairs, LLC, both wholly owned subsidiaries of Johnson & Johnson (J&J), and own stock/stock options in J&J. Bruce E. Strober discloses the following relationships: consultant and member of the advisory board for AbbVie, Almirall, Amgen, AstraZeneca, Boehringer Ingelheim, Celgene, Cutanea-Maruho, Dermira, Eli Lilly, Janssen, Leo, Medac, Novartis, Pfizer Inc, Sun Pharma, UCB, and Valeant (honoraria for all); investigator for AbbVie, Amgen, Boehringer Ingelheim, Celgene, Eli Lilly, Galderma, GlaxoSmithKline, Janssen, Merck, Novartis, Pfizer Inc, Sun Pharma (payments to the University of Connecticut, not to Bruce Strober, MD, PhD); scientific director for CORRONA Psoriasis Registry (consulting fee); and grant support to the University of Connecticut for Fellowship Program from AbbVie, Janssen (payments to the University of Connecticut, not to Bruce Strober, MD, PhD).

Figures

Fig. 1
Fig. 1
Incidence rates/100 PYs of AEs, SAEs, and infections among ustekinumab- and placebo-treated patients through up to year 1 in phase II/III studies of a psoriasis, b psoriatic arthritis, c Crohn’s disease, and d combined across all indications. PYs patient-years, AEs adverse events, SAEs serious adverse events

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