P1654 - Analysis of Infections of Interest in Patients Treated with Tofacitinib in the Ulcerative Colitis Clinical Program

Monday, October 25, 2021

10:30 AM – 4:15 PM PT

Location: Shoreline Exhibit Hall

Has Audio

Presenting Author(s)

CH

Christina Ha, MD, FACG

Inflammatory Bowel Disease Center, Cedars-Sinai Medical Center
Los Angeles, CA, United States

Michael V. Chiorean, MD¹, Christina Ha, MD, FACG², Alessandro Armuzzi, MD, PhD³, Nervin Lawendy, PharmD⁴, Rajiv Mundayat, MSc⁵, Leonardo Salese, MD⁴, John C. Woolcott, PhD⁴, Chinyu Su, MD⁴, Iris Dotan, MD⁶
¹Swedish Medical Center, Seattle, WA; ²Inflammatory Bowel Disease Center, Cedars-Sinai Medical Center, Los Angeles, CA; ³Fondazione Policlinico Universitario A. Gemelli IRCCS – Università Cattolica del Sacro Cuore, Rome, Lazio, Italy; ⁴Pfizer Inc., Collegeville, PA; ⁵Pfizer Inc., New York, NY; ⁶Rabin Medical Center, Sackler Faculty of Medicine, Tel Aviv University, Ramat Aviv, Tel Aviv, Israel

Introduction: Tofacitinib is an oral, small molecule JAK inhibitor for the treatment of UC. We present an update on infections data from the tofacitinib UC clinical program, including final data from the open-label, long-term extension (OLE) study (as of Aug 24, 2020).

Methods: Infections were evaluated in a Phase 2 induction study (NCT00787202), two Phase 3 induction studies (NCT01465763; NCT01458951), a Phase 3 maintenance study (NCT01458574), and an OLE study (NCT01470612), as three cohorts: Induction (Phase 2 and Phase 3; placebo [PBO] or tofacitinib 10 mg BID), Maintenance (Phase 3; PBO, tofacitinib 5 or 10 mg BID), and Overall (patients [pts] receiving tofacitinib 5 or 10 mg BID in Phase 2/Phase 3/OLE studies; by predominant dose [5 or 10 mg BID based on average daily dose < 15 mg or ≥ 15 mg, respectively]). Proportions and incidence rates (IRs; unique pts with events per 100 pt-years [PY] of exposure; censored at time of event) were evaluated for infections (all), herpes zoster (HZ; including HZ events adjudicated as opportunistic infections [OIs]), OIs (independently adjudicated; including non-HZ OIs and HZ events adjudicated as OIs), and serious infections (SIs).

Results: 1,157 pts received ≥ 1 dose of tofacitinib 5 or 10 mg BID (83% predominantly 10 mg BID), with 2,814.4 PY of exposure (up to 7.8 years). Infection events in the Induction and Maintenance Cohorts were previously reported (Table).¹ Overall, 92 pts had HZ (non-serious and serious; IR 3.38 [95% confidence interval (CI) 2.73, 4.15]), of which 7 pts had serious HZ. IRs were similar between doses and stable over time. OIs were infrequent (30 pts; IR 1.05 [95% CI 0.71, 1.50]), most OIs were HZ (25/30 pts; IR 0.88 [95% CI 0.57, 1.29]; mostly cutaneous), and there was one new non-HZ OI (cytomegalovirus infection) vs the previous data cut.¹ Overall Cohort SI IR was 1.72 [95% CI 1.28, 2.27], similar between doses and stable over time. No SIs resulted in death.

Discussion: In the Overall Cohort, IRs of HZ, a recognized risk with tofacitinib treatment, were similar between doses and remained stable over time. Most HZ events were non-serious. Non-HZ OIs were rare. The SI IR for tofacitinib was similar between doses, remained stable over time, and was similar to that in pts with UC treated with biologics.²

References:

1. Winthrop et al. Am J Gastroenterol 2020;115(S):644.

2. Curtis et al. Inflamm Bowel Dis 2020;Epub ahead of print

	Induction Cohort (8 weeks)^a		Maintenance Cohort (52 weeks)^a			Overall Cohort, Aug 2020 (≤7.8 years)^a
	PBO (N=282; 44.8 PY)	Tofacitinib 10 mg BID (N=938; 156.2 PY)	PBO (N=198; 100.4 PY)	Tofacitinib 5 mg BID (N=198; 146.2 PY)	Tofacitinib 10 mg BID (N=196; 154.3 PY)	PD tofacitinib 5 mg BID (N=201; 776.4 PY)	PD tofacitinib 10 mg BID (N=956; 2,038.0 PY)	Tofacitinib All (N=1,157; 2,814.4 PY)
Infections (all) n (%), IR [95% CI]	43 (15.2), 93.23 [67.47, 125.57]	196 (20.9), 134.25 [116.11, 154.42]	48 (24.2) 58.16 [42.88, 77.12]	71 (35.9), 62.54 [48.85, 78.89]	78 (39.8), 72.82 [57.56, 90.88]	136 (67.7), 40.79 [34.22, 48.25]	504 (52.7), 50.48 [46.17, 55.08]	640 (55.3), 48.05 [44.40, 51.92]
SIs^b n (%), IR [95% CI]	0 (0), 0.00 [0.00, 7.30]	8 (0.9), 4.83 [2.09, 9.52]	2 (1.0), 1.94 [0.23, 7.00]	2 (1.0), 1.35 [0.16, 4.87]	1 (0.5), 0.64 [0.02, 3.54]	10 (5.0), 1.26 [0.60, 2.31]	40 (4.2), 1.90 [1.36, 2.59]	50 (4.3), 1.72 [1.28, 2.27]
OIs^c n (%), IR [95% CI]	0 (0), 0.00 [0.00, 9.13]^d	3 (0.3), 1.89 [0.39, 5.53]^e	1 (0.5), 0.97 [0.02, 5.42]	2 (1.0), 1.36 [0.16, 4.92]	4 (2.0), 2.60 [0.71, 6.65]	8 (4.0), 1.04 [0.45, 2.05]	22 (2.4), 1.05 [0.66, 1.60]^f	30 (2.7),^g 1.05 [0.71, 1.50]^h
Non-HZ OIs^c,i n (%) IR [95% CI]	0 (0), 0.00 [0.00, 9.13]^d	1 (0.1), 0.63 [0.02, 3.51]^e	0 (0), 0.00 [0.00, 3.57]	0 (0), 0.00 [0.00, 2.48]	0 (0), 0.00 [0.00, 2.35]	1 (0.5), 0.13 [0.00, 0.70]	4 (0.4), 0.19 [0.05, 0.48]^f	5 (0.4), 0.17 [0.06, 0.40]^h
All HZ (non-serious and serious)^j n (%), IR [95% CI]	1 (0.4), 1.98 [0.05, 11.05]	6 (0.6), 3.62 [1.33, 7.88]	1 (0.5), 0.97 [0.02, 5.42]	3 (1.5), 2.05 [0.42, 6.00]	10 (5.1), 6.64 [3.19, 12.22]	22 (10.9), 3.02 [1.89, 4.58]	70 (7.3), 3.51 [2.74, 4.44]	92 (8.0), 3.38 [2.73, 4.15]
	SIs^b by time interval, in the Overall Cohort (N=1,157; 2,814.4 PY)				HZ (non-serious and serious) by time interval, in the Overall Cohort (N=1,157; 2,814.4 PY)
Time (months) 0–6 >6–12 >12–18 >18–24 >24–30 >30	N 1,157 780 679 606 554 507	n (%) 15 (1.3) 6 (0.8) 5 (0.7) 3 (0.5) 4 (0.7) 17 (3.4)	IR 3.02 1.66 1.57 1.03 1.51 1.45	95% CI 1.69, 4.98 0.61, 3.62 0.51, 3.67 0.21, 3.02 0.41, 3.86 0.85, 2.32	N 1,157 768 654 577 519 471	n (%) 22 (1.9) 14 (1.8) 14 (2.1) 10 (1.7) 5 (1.0) 27 (5.7)	IR 4.46 3.98 4.58 3.66 2.02 2.57	95% CI 2.79, 6.75 2.17, 6.67 2.51, 7.69 1.76, 6.73 0.66, 4.72 1.70, 3.75

Table: Table. Summary of Incidence of Treatment-emergent Infections (All Causality) in the Induction, Maintenance, and Overall Cohorts, and Incidence of SIs and HZ Over Time in the Overall Cohort. Overall Cohort data includes final data from the OLE study, as of Aug 2020. For the Overall Cohort, pts were categorized based on the average daily dose of tofacitinib (PBO exposure was not included): PD tofacitinib 5 mg BID (average total daily dose < 15 mg) and PD tofacitinib 10 mg BID (average total daily dose ≥ 15 mg)
a.Only pts with events occurring within 28 days after the last dose are included in this table; b.Infections meeting serious adverse event reporting criteria (any adverse event that results in death, persistent or significant disability/incapacity or congenital anomaly/birth defect, is life-threatening, or requires hospitalization or prolongation of existing hospitalization); c.OIs were adjudicated by an independent committee; calculated as percentage (%), based on the number of pts in the studies in which adjudication was performed; excludes Phase 2 pts; excludes tuberculosis and HZ with 2 adjacent dermatomes; d.N1=234; e.N1=905; f.N1=923; g.Of the 30 pts with OIs in the Overall Cohort: HZ (25; HZ OIs were either multidermatomal [non-adjacent or > 2 adjacent dermatomes; 18 pts] or disseminated [any of: diffuse rash > 6 dermatomes, HZ meningitis (encephalitis), pneumonia, other non-skin organ involvement; 7 pts]; other organ involvement: keratitis [1], ophthalmic HZ [1], HZ meningitis [encephalitis] [1]); h.N1=1,124; i.Non-HZ OIs included CMV hepatitis (1), CMV colitis (1; based on a colonic biopsy showing a positive polymerase chain reaction test for CMV), CMV infection (1), histoplasmosis (1; with pulmonary involvement), and pulmonary mycosis (1; cryptococcosis); there were no events of new EBV infection reported; one event of lymphoma in an EBV-positive pt was reported; j.Four pts with HZ had post-herpetic neuralgia.
BID, twice daily; CI, confidence interval; CMV, cytomegalovirus; EBV, Epstein-Barr virus; HZ, herpes zoster; IR, incidence rate (unique pts with events per 100 PY of exposure); N, number of pts treated in the treatment group; N1, number of pts in the studies in which adjudication was performed; n, number of unique pts with a particular adverse event; OI, opportunistic infection; OLE, open-label, long-term extension; PBO, placebo; PD, predominant dose; pts, patients; PY, pt-years; SI, serious infection

Disclosures:
Michael Chiorean: AbbVie – Consultant, Other Financial or Material Support, speaker fees. Arena – Consultant. Bristol-Myers Squibb – Consultant. Janssen – Other Financial or Material Support, speaker fees. Lilly – Advisory Committee/Board Member. Medtronic – Consultant, Other Financial or Material Support, speaker fees. Pfizer Inc – Consultant, Other Financial or Material Support, speaker fees. Prometheus – Consultant. Takeda – Consultant, Other Financial or Material Support, speaker fees.
Christina Ha: AbbVie – Other Financial or Material Support, personal fees. Bristol Myers Squibb – Advisory Committee/Board Member. Eli Lilly – Advisory Committee/Board Member. Genentech – Other Financial or Material Support, personal fees. InDex Pharmaceuticals – Advisory Committee/Board Member. Janssen – Other Financial or Material Support, personal fees. Pfizer Inc – Grant/Research Support, Other Financial or Material Support, personal fees. Takeda – Other Financial or Material Support, personal fees.
Alessandro Armuzzi: AbbVie – Consultant, Other Financial or Material Support, lecture fees. Allergan – Consultant. Amgen – Consultant, Other Financial or Material Support, lecture fees. Arena – Consultant. Biogen – Consultant, Other Financial or Material Support, lecture fees. Bristol-Myers Squibb – Consultant, Other Financial or Material Support, lecture fees. Celgene – Consultant. Celltrion – Consultant. Chiesi – Other Financial or Material Support, lecture fees. Eli Lilly – Consultant. Ferring Pharmaceuticals – Consultant, Other Financial or Material Support, lecture fees. Gilead Sciences – Consultant, Other Financial or Material Support, lecture fees. Janssen – Consultant, Other Financial or Material Support, lecture fees. Mitsubishi Tanabe Pharma – Other Financial or Material Support, lecture fees. MSD – Consultant, Grant/Research Support, Other Financial or Material Support, lecture fees. Mylan – Consultant. Nikkiso – Other Financial or Material Support, lecture fees. Novartis – Other Financial or Material Support, lecture fees. Pfizer Inc – Consultant, Grant/Research Support, Other Financial or Material Support, lecture fees. Roche – Consultant, Other Financial or Material Support, lecture fees. Samsung Bioepis – Consultant, Other Financial or Material Support, lecture fees. Sandoz – Consultant, Other Financial or Material Support, lecture fees. Takeda – Consultant, Grant/Research Support, Other Financial or Material Support, lecture fees. TiGenix – Other Financial or Material Support, lecture fees.
Nervin Lawendy: Pfizer Inc – Employee, Stockholder/Ownership Interest (excluding diversified mutual funds).
Rajiv Mundayat: Pfizer Inc – Employee, Stockholder/Ownership Interest (excluding diversified mutual funds).
Leonardo Salese: Pfizer Inc – Employee, Stockholder/Ownership Interest (excluding diversified mutual funds).
John Woolcott: Pfizer Inc – Employee, Stockholder/Ownership Interest (excluding diversified mutual funds).
Chinyu Su: Pfizer Inc – Employee, Stockholder/Ownership Interest (excluding diversified mutual funds).
Iris Dotan: Abbott – Other Financial or Material Support, personal fees. AbbVie – Other Financial or Material Support, lecture fees and personal fees. Altman Research – Other Financial or Material Support, personal fees. Arena – Other Financial or Material Support, personal fees. Athos – Other Financial or Material Support, personal fees. Cambridge Healthcare – Other Financial or Material Support, lecture fees. Celgene/Bristol-Myers Squibb – Other Financial or Material Support, personal fees. Celltrion – Other Financial or Material Support, lecture fees and personal fees. Dr. Falk Pharma – Other Financial or Material Support, lecture fees and personal fees. DSM – Other Financial or Material Support, personal fees. Ferring Pharmaceuticals – Other Financial or Material Support, lecture fees and personal fees. Food Industries Organisation – Other Financial or Material Support, personal fees. Genentech/Roche – Other Financial or Material Support, lecture fees and personal fees. Gilead Sciences – Other Financial or Material Support, personal fees. Iterative scopes – Advisory Committee/Board Member. Janssen – Other Financial or Material Support, lecture fees and personal fees. Materia Prima – Other Financial or Material Support, lecture fees. MSD – Other Financial or Material Support, lecture fees and personal fees. Neopharm – Other Financial or Material Support, personal fees. Nestlé – Other Financial or Material Support, lecture fees and personal fees. Pfizer Inc – Other Financial or Material Support, lecture fees and personal fees. Rafa Laboratories – Other Financial or Material Support, lecture fees and personal fees. Sandoz – Other Financial or Material Support, lecture fees and personal fees. Sangamo – Other Financial or Material Support, personal fees. Sublimity – Other Financial or Material Support, personal fees. Takeda – Other Financial or Material Support, personal fees. Wild Biotech – Other Financial or Material Support, personal fees.

Michael V. Chiorean, MD¹, Christina Ha, MD, FACG², Alessandro Armuzzi, MD, PhD³, Nervin Lawendy, PharmD⁴, Rajiv Mundayat, MSc⁵, Leonardo Salese, MD⁴, John C. Woolcott, PhD⁴, Chinyu Su, MD⁴, Iris Dotan, MD⁶. P1654 - Analysis of Infections of Interest in Patients Treated with Tofacitinib in the Ulcerative Colitis Clinical Program, ACG 2021 Annual Scientific Meeting Abstracts. Las Vegas, Nevada: American College of Gastroenterology.