B0379 - Active Tuberculosis and Opportunistic Infections: Pooled Safety Analysis of Ustekinumab Through up to 5 Years Across All Approved Indications

Monday, October 24, 2022

10:00 AM – 12:00 PM ET

Location: Crown Ballroom

Has Audio

Presenting Author(s)

EL

Edward V. Loftus, Jr., MD, FACG

Mayo Clinic College of Medicine and Science
Rochester, Minnesota

Edward V. Loftus, MD, FACG¹, Millie Long, MD, MPH, FACG², Elyssa Ott, MPH³, Christopher Gasink, MD³, Thomas Baker, MD⁴, Bridget Goodwin, MD³, Ye Miao, MS⁴, Subrata Ghosh, MD⁵
¹Mayo Clinic College of Medicine and Science, Rochester, MN; ²UNC Chapel Hill, Chapel Hill, NC; ³Janssen Scientific Affairs, LLC, Horsham, PA; ⁴Janssen Research & Development, LLC, Spring House, PA; ⁵College of Medicine and Health, University College, Cork, Cork, Ireland

Introduction: Ustekinumab (UST) is an approved treatment for adults with inflammatory bowel disease (IBD: Crohn’s disease [CD] and ulcerative colitis [UC]), psoriasis (PsO), and psoriatic arthritis (PsA). Here, we present pooled safety analyses in these approved indications of patients (pts) with active tuberculosis (TB) and opportunistic infections (OIs) through 5 years (yrs) of UST treatment.

Methods: Pooled data included 13 Phase 2/3 UST studies through 5 yrs of CD and PsO, 2 yrs of UC, and 1 yr of PsA. OIs were identified by clinician review. Herpes zoster (HZ) was evaluated separately. Event rates per 100 pt yrs (PYs) are presented. Concomitant immunomodulators/corticosteroids were permitted in IBD and PsA pts. All pts who received ≥1 UST dose were included. In IBD, placebo (PBO) pts included data up to the first UST dose for pts initially treated with PBO, or >16 weeks after the last UST dose for UST pts who switched to PBO.

Results: Across all approved indications, 19 OIs including TB were reported, with rates in PBO of 0.40 and UST of 0.10 through 5 yrs in 13807 PYs of follow-up (Table 1); rates of HZ were 1.21 and 0.63, respectively. Of 19 OIs, 18 were in IBD pts and 1 in a PsO pt. Overall, 14/16 pts (12/13 UST) with OIs excluding TB were also receiving confounding concomitant medications. A total of 3 active TB cases (2 pts with CD and 1 pt with UC) were reported in PBO (n=2; 1 in a CD pt 10 months after receiving UST 130 mg IV) and UST pts (n=1) (Table 1). One active TB case was reported in an asymptomatic South African CD pt treated with UST who had a positive QuantiFERON^®-TB Gold test on routine screening and bronchial brushings positive for M. tuberculosis. Both CD pts completed TB treatment with disease resolution. The most common OIs were esophageal candidiasis (UST n=3; PBO n=2) and cytomegalovirus colitis (UST n=3; PBO n=1).

Discussion: Rates of OIs, including active TB, in UST-treated pts were low across approved indications through up to 5 years with 13807 PYs of follow-up and not higher in UST pts vs PBO, suggesting no increased risk of OI with long-term UST treatment.

	Inflammatory Bowel Disease Indications^a		Psoriatic Indications^a		All Approved Indications Pooled
	Placebo^b (n=1389)	Ustekinumab^c (n=2575)	Placebo^d (n=1112)	Ustekinumab^e (n=4135)	Placebo^b,d (n=2501)	Ustekinumab^c.e (n=6710)
Total PYs of follow-up	916	3960	327	9847	1244	13807
Average duration of follow-up (weeks)	34.31	79.97	15.30	123.83	25.86	107.00
All OIs, event rates per 100 PYs [n]	0.55 [5]	0.33 [13]	0.00 [0]	0.01[1]	0.40 [5]	0.10 [14]
OIs excluding TB	0.33 [3]	0.30 [12]	0.00 [0]	0.01 [1]	0.24 [3]	0.09 [13]
TB	0.22 [2]	0.03 [1]	0.00 [0]	0.00 [0]	0.16 [2]	0.01 [1]
^aPsoriatic (PsO and PsA) trials evaluated subcutaneous ustekinumab (UST) 45/90 mg or placebo (PBO), generally at week 0 and 4, then every 12 weeks (q12w). IBD (CD and UC) trials generally evaluated a single intravenous UST dose (130 mg or weight range-based dosing of ~6 mg/kg) or PBO induction dose at week 0, followed by subcutaneous UST 90 mg at week 8, then q8w or q12w. ^bCD and UC: includes data up to the first UST dose for patients who were initially treated with PBO; includes data at or after 16 weeks from the first UST dose onward, up to the dose adjustment if patients had a dose adjustment, for patients who crossed-over or re-randomized to PBO maintenance ^cCD and UC: includes data up to 16 weeks from the first UST dose for patients who crossed-over or re-randomized to PBO maintenance, and from the dose adjustment onward if patients had a dose adjustment from subcutaneous PBO to subcutaneous UST 90 mg q8w ^d Psoriatic diseases: includes data up to the time of early escape or crossover ^e Psoriatic diseases: includes data from the first UST dose onward for patients who early escaped or crossed-over from PBO

Table: Table 1. Opportunistic infections (OIs) and active tuberculosis (TB) in Inflammatory Bowel Disease (CD, UC) and Psoriatic studies (PsO, PsA) through up to 5 yrs; numbers of events per 100 patient-years (PYs) of follow-up

Disclosures:

Edward Loftus: AbbVie – Consultant, Grant/Research Support. Amgen – Consultant, Grant/Research Support. Arena Pharmaceuticals – Consultant. Boehringer Ingelheim – Consultant. Bristol-Myers Squibb – Consultant, Grant/Research Support. Calibr – Consultant. Celgene – Consultant, Grant/Research Support. Eli Lilly – Consultant. Genentech – Consultant, Grant/Research Support. Gilead – Consultant, Grant/Research Support. Iterative Scopes – Consultant. Janssen – Consultant, Grant/Research Support. Morphic – Consultant. Ono Pharma – Consultant. Pfizer – Consultant, Grant/Research Support. Protagonist – Consultant. Receptos – Grant/Research Support. Robarts Clinical Trials – Grant/Research Support. Scipher Medicine – Consultant. Sun Pharma – Consultant. Surrozen – Consultant. Takeda – Consultant, Grant/Research Support. Theravance – Grant/Research Support. UCB – Consultant, Grant/Research Support.

Millie Long: AbbVie – Consultant. Bristol Myers Squibb – Consultant. Calibr – Consultant. Eli Lilly – Consultant. Genentech – Consultant. Janssen – Consultant. Pfizer – Consultant, Grant/Research Support. Prometheus – Consultant. Roche – Consultant. Salix – Consultant. Takeda – Consultant, Grant/Research Support. Target RWE – Consultant. Theravance – Consultant.

Elyssa Ott: Janssen – Employee, Stock-publicly held company(excluding mutual/index funds).

Christopher Gasink: Janssen – Employee, Stock-publicly held company(excluding mutual/index funds).

Thomas Baker: Janssen – Employee, Stock-publicly held company(excluding mutual/index funds).

Bridget Goodwin: Janssen Pharmaceutical Companies of Johnson and Johnson – Employee, Stock-publicly held company(excluding mutual/index funds).

Ye Miao: Janssen Research & Development, LLC – Employee, Stock-publicly held company(excluding mutual/index funds).

Subrata Ghosh: AbbVie – Advisory Committee/Board Member, steering committee, Speakers Bureau. Boehringer Ingelheim – steering committee. Bristol Myers Squibb – steering committee. Celgene – steering committee. Celltrion – Speakers Bureau. Eli Lilly – Advisory Committee/Board Member. Ferring – Speakers Bureau. Gilead – Advisory Committee/Board Member, steering committee. Janssen – Advisory Committee/Board Member, steering committee, Speakers Bureau. Pfizer – Advisory Committee/Board Member, Speakers Bureau. Roche – Advisory Committee/Board Member. Takeda – Advisory Committee/Board Member, Speakers Bureau.

Edward V. Loftus, MD, FACG¹, Millie Long, MD, MPH, FACG², Elyssa Ott, MPH³, Christopher Gasink, MD³, Thomas Baker, MD⁴, Bridget Goodwin, MD³, Ye Miao, MS⁴, Subrata Ghosh, MD⁵. B0379 - Active Tuberculosis and Opportunistic Infections: Pooled Safety Analysis of Ustekinumab Through up to 5 Years Across All Approved Indications, ACG 2022 Annual Scientific Meeting Abstracts. Charlotte, NC: American College of Gastroenterology.