P3632 - Tofacitinib for the Treatment of Ulcerative Colitis: Up to 9.2 Years of Safety Data from the Global Clinical Program

Tuesday, October 24, 2023

10:30 AM – 4:00 PM PT

Location: Exhibit Hall

Has Audio

Presenting Author(s)

Remo Panaccione, MD

University of Calgary
Calgary, AB, Canada

Julian Panés, MD, PhD¹, Geert R. D’Haens, PhD², Bruce E. Sands, MD, MS, FACG³, Siew C. Ng, ⁴, Nervin Lawendy, ⁵, Nicole Kulisek, ⁵, Xiang Guo, ⁵, Joseph Wu, PhD⁶, Ivana Vranic, ⁷, Remo Panaccione, MD⁸, Séverine Vermeire, MD, PhD⁹
¹Hospital Clínic de Barcelona, IDIBAPS, CIBERehd, Barcelona, Catalonia, Spain; ²Amsterdam University Medical Center, Amsterdam, Drenthe, Netherlands; ³Icahn School of Medicine at Mount Sinai, New York, NY; ⁴Li Ka Shing Institute of Health Sciences, Chinese University of Hong Kong, Hong Kong, Hong Kong; ⁵Pfizer Inc., Collegeville, PA; ⁶Pfizer Inc., Cambridge, MA; ⁷Pfizer Inc., Tadworth, England, United Kingdom; ⁸University of Calgary, Calgary, AB, Canada; ⁹UZ Leuven, Leuven, Vlaams-Brabant, Belgium

Introduction: Tofacitinib is an oral small molecule Janus kinase inhibitor for the treatment of ulcerative colitis (UC). The safety of tofacitinib was evaluated in the Overall Cohort, which consisted of 6 studies: 4 randomized, placebo-controlled Phase (P)2/3 studies (NCT00787202; NCT01465763; NCT01458951; NCT01458574), an open-label, long-term extension study (NCT01470612), and a randomized P3b/4 study (NCT03281304). We report final safety analyses from the tofacitinib UC clinical program of ≤ 9.2 years of tofacitinib exposure (cut-off date: April 18, 2022).

Methods: This analysis included 1,157 patients (pts) receiving tofacitinib 5 or 10 mg twice daily (BID; predominant dose [PD]) in the Overall Cohort and a previously reported 52-week Maintenance Cohort.^1,2 Proportions and incidence rates (IRs; unique pts with events/100 pt-years of exposure) were evaluated for deaths and adverse events of special interest (AESI): serious infections; herpes zoster (HZ), non-serious and serious; opportunistic infections (OIs); malignancies (excluding non-melanoma skin cancer [NMSC]); NMSC; major adverse cardiovascular events (MACE); deep vein thrombosis (DVT); pulmonary embolism (PE); and gastrointestinal (GI) perforations.

Results: In the Overall Cohort, 1,157 pts received ≥ 1 dose of tofacitinib 5 or 10 mg BID; 938 (81.1%) received a PD of 10 mg BID; 552 (47.7%) pts had received tofacitinib for ≥ 2 years. Median treatment duration was 1.7 years (mean 2.8; range 0.0–9.2). IRs (95% CI) for all tofacitinib in the Overall Cohort (Table): deaths 0.24 (0.10, 0.48); serious infections 1.80 (1.37, 2.32); HZ (non-serious and serious) 3.24 (2.63, 3.94); serious HZ 0.24 (0.10, 0.48); OIs 0.96 (0.65, 1.36); malignancies (excluding NMSC) 0.88 (0.59, 1.26); NMSC 0.71 (0.45, 1.07); MACE 0.27 (0.12, 0.52); DVT 0.06 (0.01, 0.22); PE 0.18 (0.07, 0.40); and GI perforations 0.09 (0.02, 0.27).

Discussion: IRs for AESI remained stable over an extended period of time (≤ 9.2 years) with the inclusion of the P3b/4 final data and were consistent with prior Overall Cohort analyses (≤ 7.8 years).^1,2 The safety profile of tofacitinib in the UC clinical program was consistent with that observed in other indications.^3,4
References
1. Sandborn et al. Clin Gastroenterol Hepatol 2019;17:1541–50
2. Sandborn et al. J Crohns Colitis 2023;17:338–51
3. Cohen et al. RMD Open 2020;6:e001395
4. Burmester et al. Drug Saf 2020;43:379–92

	Maintenance Cohort^[1],[2] (52 weeks)				Overall Cohort (≤ 9.2 years)
	Placebo (N=198; 100.4 PY)	Tofacitinib 5 mg BID (N=198; 146.2 PY)	Tofacitinib 10 mg BID (N=196; 154.3 PY)	Tofacitinib all (N=394; 300.5 PY)	PD tofacitinib 5 mg BID (N=219; 902.3 PY)	PD tofacitinib 10 mg BID (N=938; 2,299.7 PY)	Tofacitinib all (N=1,157; 3,202.0 PY)
Baseline demographics and clinical characteristics
Age (yrs), mean (SD)^[a]	43.4 (14.0)	41.9 (13.7)	43.0 (14.4)	42.5 (14.0)	44.0 (14.4)	40.6 (13.7)	41.3 (13.9)
TMS, mean (SD)^[b],[c]	3.3 (1.8)	3.3 (1.8)	3.4 (1.8)	3.4 (1.8)	7.9 (2.4)	8.8 (1.8)	8.6 (2.0)
Disease duration (yrs), mean (SD)^[b]	8.8 (7.5)	8.3 (7.2)	8.7 (7.0)	8.5 (7.1)	8.3 (6.6)	8.2 (7.1)	8.2 (7.0)
Prior TNFi failure, n (%)^[d]	89 (44.9)	83 (41.9)	92 (46.9)	175 (44.4)	93 (42.5)	490 (54.1)	583 (51.9)
CS use at baseline, n (%)^[b]	100 (50.5)	101 (51.0)	86 (43.9)	187 (47.5)	89 (40.6)	434 (46.3)	523 (45.2)
AEs
Pts with AEs, n (%)	149 (75.3)	143 (72.2)	156 (79.6)	299 (75.9)	205 (93.6)	789 (84.1)	994 (85.9)
Pts with serious AEs, n (%)	13 (6.6)	10 (5.1)	11 (5.6)	21 (5.3)	46 (21.0)	208 (22.2)	254 (22.0)
Deaths, n (%), IR [95% CI]^[e]	0 (0.0), 0.00 [0.00, 3.57]	0 (0.0), 0.00 [0.00, 2.48]	0 (0.0), 0.00 [0.00, 2.35]	0 (0.0), 0.00 [0.00, 1.21]	0 (0.0), 0.00 [0.00, 0.40]	8 (0.9), 0.34 [0.14, 0.66]	8 (0.7),^[f]0.24 [0.10, 0.48]
Infections, n (%), IR [95% CI]^[g]
SIs^[h]	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]	3 (0.8), 0.98 [0.20, 2.87]	10 (4.6), 1.08 [0.52, 1.99]	49 (5.2), 2.07 [1.53, 2.74]	59 (5.1), 1.80 [1.37, 2.32]
All HZ (non-serious and serious)	1 (0.5), 0.97 [0.02, 5.42]	3 (1.5),^[i]2.05 [0.42, 6.00]	10 (5.1),^[i]6.64 [3.19, 12.22]	13 (3.3),^[i]4.38 [2.33, 7.50]	23 (10.5), 2.71 [1.72, 4.06]	76 (8.1), 3.44 [2.71, 4.31]	99 (8.6), 3.24 [2.63, 3.94]
Serious HZ	0 (0.0), 0.00 [0.00, 3.57]	0 (0.0), 0.00 [0.00, 2.48]	0 (0.0), 0.00 [0.00, 2.35]	0 (0.0), 0.00 [0.00, 1.21]	1 (0.5), 0.11 [0.00, 0.60]	7 (0.7), 0.29 [0.12, 0.61]	8 (0.7), 0.24 [0.10, 0.48]
OIs^[d],[j],[k]	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]	6 (1.5), 1.99 [0.73, 4.34]	8 (3.7), 0.89 [0.39, 1.76]	23 (2.5), 0.99 [0.63, 1.48]	31 (2.8), 0.96 [0.65, 1.36]
HZ OIs^[j]	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]	6 (1.5), 1.99 [0.73, 4.34]	7 (3.2), 0.78 [0.31, 1.61]	19 (2.1), 0.81 [0.49, 1.27]	26 (2.3), 0.80 [0.53, 1.18]
Malignancies, n (%), IR [95% CI]^[d],[e],[j]
Malignancies (excluding NMSC)	1 (0.5),^[l]0.97 [0.02, 5.39]	0 (0.0), 0.00 [0.00, 2.48]	0 (0.0), 0.00 [0.00, 2.35]	0 (0.0), 0.00 [0.00, 1.21]	5 (2.3), 0.54 [0.18, 1.26]	24 (2.7), 1.01 [0.65, 1.51]	29 (2.6),^[m]0.88 [0.59, 1.26]
NMSC	1 (0.5), 0.97 [0.02, 5.40]	0 (0.0), 0.00 [0.00, 2.48]	3 (1.5), 1.91 [0.39, 5.59]	3 (0.8), 0.98 [0.20, 2.87]	6 (2.7), 0.66 [0.24, 1.43]	17 (1.9), 0.73 [0.43, 1.17]	23 (2.0), 0.71 [0.45, 1.07]
MACE, n (%), IR [95% CI]^[d],[e],[j]	0 (0.0), 0.00 [0.00, 3.57]	1 (0.5),^[n]0.68 [0.02, 3.77]	1 (0.5),^[o] 0.64 [0.02, 3.54]	2 (0.5), 0.66 [0.08–2.37]	4 (1.8), 0.44 [0.12, 1.12]	5 (0.6), 0.21 [0.07, 0.49]	9 (0.8),^[p]0.27 [0.12, 0.52]
VTE, n (%), IR [95% CI]^[g],[j]
DVT	1 (0.5), 0.97 [0.02, 5.39]	0 (0.0), 0.00 [0.00, 2.48]	0 (0.0), 0.00 [0.00, 2.35]	0 (0.0), 0.00 [0.00, 1.21]	0 (0.0), 0.00 [0.00, 0.40]	2 (0.2), 0.08 [0.01, 0.30]	2 (0.2),^[q]0.06 [0.01, 0.22]
PE	1 (0.5), 0.98 [0.02, 5.44]	0 (0.0), 0.00 [0.00, 2.48]	0 (0.0), 0.00 [0.00, 2.35]	0 (0.0), 0.00 [0.00, 1.21]	0 (0.0), 0.00 [0.00, 0.40]	6 (0.6), 0.25 [0.09, 0.55]	6 (0.5),^[r]0.18 [0.07, 0.40]
GI perforations, n (%), IR [95% CI]^{[d],[g],[j],[s]}	1 (0.5), 0.97 [0.02, 5.39]	0 (0.0), 0.00 [0.00, 2.48]	0 (0.0), 0.00 [0.00, 2.35]	0 (0.0), 0.00 [0.00, 1.21]	1 (0.5), 0.11 [0.00, 0.60]	2 (0.2), 0.08 [0.01, 0.30]	3 (0.3), 0.09 [0.02, 0.27]

Disclosures:

Julian Panés: AbbVie – Grant/Research Support, Personal fees. Arena – Consultant. Athos – Consultant. Atomwise – Consultant. Boehringer Ingelheim – Consultant. Celgene – Consultant. Celltrion – Consultant. Ferring – Consultant, Speakers Bureau. Galapagos – Consultant. Genentech/Roche – Consultant. GlaxoSmithKline – Consultant. Immunic – Personal fees. Janssen – Consultant, payment for development of educational presentations. Mirum – Consultant. Morphic – Consultant. Origo – Consultant. Pandion – Consultant. Pfizer Inc – Grant/Research Support, payment for development of educational presentations. Progenity – Consultant. Revolo – Consultant. Takeda – payment for development of educational presentations. Theravance – Consultant. Wasserman – Consultant.

Geert D’Haens: AbbVie – Advisor or Review Panel Member, Speakers Bureau. Agomab Therapeutics – Advisor or Review Panel Member. Alimentiv – Advisor or Review Panel Member. Applied Molecular Therapeutics – Advisor or Review Panel Member. AstraZeneca – Advisor or Review Panel Member. Boehringer Ingelheim – Advisor or Review Panel Member. Bristol Myers Squibb – Advisor or Review Panel Member, Speakers Bureau. Celltrion – Advisor or Review Panel Member. Cytoki – Advisor or Review Panel Member. Eli Lilly – Advisor or Review Panel Member, Speakers Bureau. Exeliom – Advisor or Review Panel Member. Ferring – Advisor or Review Panel Member. Galapagos – Advisor or Review Panel Member, Speakers Bureau. GlaxoSmithKline – Advisor or Review Panel Member. Gossamer Bio – Advisor or Review Panel Member. Immunic – Advisor or Review Panel Member. Johnson & Johnson – Advisor or Review Panel Member, Speakers Bureau. Pfizer – Advisor or Review Panel Member, Speakers Bureau. Polpharma – Advisor or Review Panel Member. ProciseDx – Advisor or Review Panel Member. Progenity – Advisor or Review Panel Member. Prometheus Biosciences – Advisor or Review Panel Member. Prometheus Laboratories – Advisor or Review Panel Member. Protagonist Therapeutics – Advisor or Review Panel Member. Seres – Advisor or Review Panel Member. Takeda – Advisor or Review Panel Member, Speakers Bureau. Tillotts – Advisor or Review Panel Member, Speakers Bureau. Versant – Advisor or Review Panel Member.

Bruce Sands: AbbVie – Consultant. Abivax – Consultant, Speaker’s fees. Adiso Therapeutics – Consultant. Alimentiv – Consultant. Amgen – Consultant. Arena pharmaceuticals – Consultant. Artizan Biosciences – Consultant. Artugen Therapeutics – Consultant. AstraZeneca – Consultant. Bacainn Therapeutics – Consultant. Biora Therapeutics – Consultant. Boehringer Ingelheim – Consultant. Boston Pharmaceuticals – Consultant. Bristol Myers Squibb – Consultant, Grant/Research Support, speaking fees and other support. Calibr – Consultant. Celltrion – Consultant. ClostraBio – Consultant. Connect Biopharm – Consultant. Cytoki Pharma – Consultant. Eli Lilly – Consultant, speaking fees and other support. Enthera – Consultant. Evommune – Consultant. Ferring – Consultant. Fresenius Kabi – Consultant. Galapagos – Consultant. Genentech – Consultant. Gilead Sciences – Consultant. GlaxoSmithKline – Consultant. Gossamer Bio – Consultant. HMP Acquisition – Consultant. Imhotex – Consultant. Immunic – Consultant. InDex Pharmaceuticals – Consultant. Innovation Therapeutics – Consultant. Inotrem – Consultant. Ironwood Pharmaceuticals – Consultant. Janssen – Grant/Research Support, consulting and speaking fees and other support. Johnson & Johnson – Consultant. Kaleido Biosciences – Consultant. Kallyope – Consultant. Merck – Consultant. MiroBio – Consultant. Morphic Therapeutics – Consultant. MRM Health – Consultant. OSE Immunotherapeutics – Consultant. Pfizer Inc – Consultant, Grant/Research Support, speaking fees and other support. Progenity – Consultant. Prometheus Biosciences – Consultant. Prometheus Laboratories – Consultant. Protagonist Therapeutics – Consultant. Q32 Bio – Consultant. RedHill Biopharma – Consultant. Sun Pharma – Consultant. Surrozen – Consultant. Synlogic Operating Company – Consultant. Takeda – Grant/Research Support, consulting and speaking fees and other support. Target RWE – Consultant. Theravance Biopharma – Consultant, Grant/Research Support. TLL Pharmaceutical – Consultant. USWM Enterprises – Consultant. Ventyx Biosciences – Consultant, personal fees and stock options for consulting. Viela Bio – Consultant.

Siew Ng: AbbVie – Advisory Committee/Board Member, Grant/Research Support, Speakers Bureau. Ferring – Advisory Committee/Board Member, Grant/Research Support, Speakers Bureau. GenieBiome – Scientific co-founder Shareholder. Janssen – Advisory Committee/Board Member, Grant/Research Support, Speakers Bureau. Menarini – Speakers Bureau. Microbiota I-Center – Directorship. Olympus – Grant/Research Support. Pfizer Inc – Advisory Committee/Board Member, Speakers Bureau. Takeda – Speakers Bureau. Tillotts – Speakers Bureau.

Nervin Lawendy: Pfizer Inc – Employee, Shareholder.

Nicole Kulisek: Pfizer Inc – Employee, Shareholder.

Xiang Guo: Pfizer Inc – Employee, Shareholder.

Joseph Wu: Pfizer Inc – Employee, Stock Options.

Ivana Vranic: Pfizer Inc – Employee, Shareholder.

Remo Panaccione: Abbivax – Consultant. Abbott – Consultant. AbbVie – Consultant. Alimentiv – Consultant. Amgen – Consultant. Arena – Consultant. AstraZeneca – Consultant. Biogen – Consultant. Boehringer Ingelheim – Consultant. Bristol Myers Squibb – Consultant. Celgene – Consultant. Celltrion – Consultant. Cosmos Technology – Consultant. Eisai – Consultant. Elan – Consultant. Eli Lilly – Consultant. Ferring – Consultant. Fresenius Kabi – Consultant. Galapagos – Consultant. Genentech – Consultant. Gilead Sciences – Consultant. GlaxoSmithKline – Consultant. JAMP Bio – Consultant. Janssen – Consultant. Merck – Consultant. Mylan – Consultant. Novartis – Consultant. Oppilan Pharma – Consultant. Organon – Consultant. Pandion Pharma – Consultant. Pendopharm – Consultant. Pfizer Inc – Consultant. Progenity – Consultant. Prometheus – Consultant. Protagonist Therapeutics – Consultant. Roche – Consultant. Sandoz – Consultant. Satisfai Health – Consultant. Shire – Consultant. Sublimity Therapeutics – Consultant. Takeda Pharmaceuticals – Consultant. Theravance Biopharma – Consultant. Trellus – Consultant. UCB – Consultant. Ventyx – Consultant. Viatris – Consultant.

Séverine Vermeire: AbbVie – Consultant, Grant/Research Support. AbolerIS Pharma – Grant/Research Support. AgomAb – Grant/Research Support. Alimentiv – Consultant. Arena Pharmaceuticals – Consultant. AstraZeneca – Consultant. Avaxia Biologics – Consultant. Boehringer Ingelheim – Consultant. Bristol Myers Squibb – Consultant. Celgene – Consultant. CVasThera – Consultant, Speakers Bureau. Cytoki Pharma – Consultant, Speakers Bureau. Dr. Falk Pharma – Consultant, Speakers Bureau. Eli Lilly – Consultant, Speakers Bureau. Ferring Pharmaceuticals – Consultant, Speakers Bureau. Galapagos – Consultant, Grant/Research Support, Speakers Bureau. Genentech/Roche – Consultant, Speakers Bureau. Gilead – Consultant, Speakers Bureau. GSK – Consultant, Speakers Bureau. Hospira – Consultant, Speakers Bureau. IMIDomics – Consultant, Speakers Bureau. Janssen Pharmaceuticals – Consultant, Speakers Bureau. Johnson & Johnson – Consultant, Grant/Research Support, Speakers Bureau. Materia Prima – Consultant, Speakers Bureau. MiroBio – Consultant, Speakers Bureau. Morphic – Consultant, Speakers Bureau. MRM Health – Consultant, Speakers Bureau. MSD – Consultant, Speakers Bureau. Mundipharma – Consultant, Speakers Bureau. Pfizer – Consultant, Grant/Research Support, Speakers Bureau. ProDigest – Consultant, Speakers Bureau. Progenity – Consultant, Speakers Bureau. Prometheus – Consultant, Speakers Bureau. Robarts Clinical Trials – Consultant, Speakers Bureau. Second Genome – Consultant, Speakers Bureau. Shire – Consultant, Speakers Bureau. Surrozen – Consultant, Speakers Bureau. Takeda – Consultant, Grant/Research Support, Speakers Bureau. Theravance Biopharma – Consultant, Speakers Bureau. Tillotts Pharma – Consultant, Speakers Bureau. Zealand Pharma – Consultant, Speakers Bureau.

Julian Panés, MD, PhD¹, Geert R. D’Haens, PhD², Bruce E. Sands, MD, MS, FACG³, Siew C. Ng, ⁴, Nervin Lawendy, ⁵, Nicole Kulisek, ⁵, Xiang Guo, ⁵, Joseph Wu, PhD⁶, Ivana Vranic, ⁷, Remo Panaccione, MD⁸, Séverine Vermeire, MD, PhD⁹. P3632 - Tofacitinib for the Treatment of Ulcerative Colitis: Up to 9.2 Years of Safety Data from the Global Clinical Program, ACG 2023 Annual Scientific Meeting Abstracts. Vancouver, BC, Canada: American College of Gastroenterology.