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Abstract Number: 1941

The Risk of Venous Thromboembolic Events in Patients with RA Aged ≥ 50 Years with ≥ 1 Cardiovascular Risk Factor: Results from a Phase 3b/4 Randomized Safety Study of Tofacitinib vs TNF Inhibitors

Christina Charles-Schoeman1, Roy Fleischmann2, Eduardo Mysler3, Maria Greenwald4, Cunshan Wang5, All-shine Chen5, Carol A Connell5, John C Woolcott6, Sujatha Menon5, Yan Chen7, Kristen Lee7 and Zoltan Szekanecz8, 1Department of Medicine, University of California, Los Angeles, Los Angeles, CA, 2Metroplex Clinical Research Center and University of Texas Southwestern Medical Center, Dallas, TX, 3Organización Médica de Investigación, Buenos Aires, Argentina, 4Desert Medical Advances, Palm Desert, CA, 5Pfizer Inc, Groton, CT, 6Pfizer Inc, Collegeville, PA, 7Pfizer Inc, New York, NY, 8Division of Rheumatology, University of Debrecen, Faculty of Medicine, Debrecen, Hungary

Meeting: ACR Convergence 2021

Keywords: Anti-TNF Drugs, Cardiovascular, clinical trial, Disease-Modifying Antirheumatic Drugs (Dmards), rheumatoid arthritis

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Session Information

Date: Tuesday, November 9, 2021

Session Title: Abstracts: RA – Treatments I: Safety & Harms (1939–1942)

Session Type: Abstract Session

Session Time: 4:30PM-4:45PM

Background/Purpose: ORAL Surveillance (NCT02092467) was a randomized, open-label, non-inferiority, Phase 3b/4 study that assessed the relative risk of major adverse cardiovascular (CV) events (MACE) and malignancies with tofacitinib 5 and 10 mg twice daily (BID) vs TNF inhibitors (TNFi) in patients (pts) with active, moderate to severe RA, who had an inadequate response to MTX and a high risk of MACE (age ≥ 50 yrs; ≥ 1 additional CV risk factor). This analysis assessed the risk of venous thromboembolic events (VTE; including deep vein thrombosis [DVT] and pulmonary embolism [PE]) in ORAL Surveillance.

Methods: Pts were randomized 1:1:1 to receive tofacitinib 5 or 10 mg BID or a TNFi (etanercept 50 mg every week or adalimumab 40 mg every 2 weeks) with background MTX. A 2019 review by the Tofacitinib Rheumatology Data Safety Monitoring Board observed a statistically and clinically important difference in the occurrence of PE within the tofacitinib 10 mg BID treatment arm, compared with the TNFi control arm, resulting in a dose switch from tofacitinib 10 to 5 mg BID for the rest of the trial. All data are reported per randomized treatment. Incidence rates (IRs; pts with events/100 pt-yrs [PY]) were reported for adjudicated VTEs, DVT, and PE, and nominal p values comparing treatment arms were generated post hoc. The probability of not having an adjudicated event was assessed by Kaplan-Meier plots. Numbers Needed to Harm (NNH) were calculated post hoc. Multivariate Cox regression models were used post hoc to identify overall independent baseline (BL) risk factors for PE using backward model selection.

Results: This analysis included 1,455, 1,456, and 1,451 pts receiving tofacitinib 5 mg BID, 10 mg BID, and TNFi, respectively; BL pt characteristics were similar across treatment groups, with high mean disease activity (Clinical Disease Activity Index score, 39.7–39.9) and mean/median age of 61.2/60.0 yrs. In pts with VTE (n=66), mean age was 62.9–66.5 yrs across treatment groups. IRs for VTE, DVT, and PE were < 1.0 across treatment groups (Figure 1a); VTE, DVT, and PE IRs and probability of event were higher with tofacitinib 10 vs 5 mg BID, and higher for both tofacitinib doses vs TNFi (Figure 1a, Figure 2). NNH for tofacitinib 5 and 10 mg BID, respectively, vs TNFi were 763 and 198 PY for VTE, 1,347 and 589 PY for DVT, and 870 and 229 PY for PE. Across treatment groups, VTE, DVT, and PE IRs were higher in pts with vs without a history of VTEs (Figure 1b–c). Identified overall independent risk factors for PE across treatment groups included history of VTE; BL use of oral contraceptives or HRT; BL BMI ≥ 30 kg/m2; age ≥ 65 yrs; and history of hypertension (Figure 3).

Conclusion: VTE, DVT, and PE IRs were higher for tofacitinib (10 > 5 mg BID) vs TNFi, and were < 1.0 across treatment groups. IRs were generally consistent with ranges reported for tofacitinib and biologic DMARDs among pts at a high risk of a CV event;1 PE IR with tofacitinib 10 mg BID in ORAL Surveillance was higher than those reported in tofacitinib or biologic DMARD clinical trial or registry data.1

1. Mease P et al. Ann Rheum Dis 2020; 79: 1400-13

Acknowledgments: Study sponsored by Pfizer Inc. Medical writing support was provided by AG McCluskey, CMC Connect, funded by Pfizer Inc.


Disclosures: C. Charles-Schoeman, AbbVie, 2, 5, Bristol-Myers Squibb, 5, Pfizer Inc, 2, 5, Gilead Sciences, 2, Sanofi-Regeneron, 2; R. Fleischmann, AbbVie, 2, 5, Amgen, 2, 5, Bristol-Myers Squibb, 2, 5, Celltrion, 2, 5, Eli Lilly, 2, 5, Genentech, 2, 5, Janssen, 2, 5, Novartis, 2, 5, Pfizer Inc, 2, 5, Sanofi-Aventis, 2, 5, UCB, 2, 5, GSK, 2, 5, AstraZeneca, 2, 5, Bayer, 2, 5, Biogen, 5, Flexion, 2, 5, Galapagos, 5, Galvani, 2, 5, Gilead Sciences, 2, 5, Horizon, 5, Noven, 5, Samumed, 5, Scipher, 5, Selecta, 5, Teva Pharmaceuticals, 5, Viela, 5, Vorso, 5; E. Mysler, Eli Lilly, 5, 6, Pfizer Inc, 5, 6, Roche, 5, 6, AbbVie, 6, Bristol-Myers Squibb, 6, Janssen, 6, Sanofi, 6; M. Greenwald, AbbVie, 5, Eli Lilly, 5, Galapagos, 5, Gilead Sciences, 5, Novartis, 5, Pfizer Inc, 5; C. Wang, Pfizer Inc, 3, 11; A. Chen, Pfizer Inc, 3, 11; C. Connell, Pfizer Inc, 3, 11; J. Woolcott, Pfizer Inc, 3, 11; S. Menon, Pfizer Inc, 3, 11; Y. Chen, Pfizer Inc, 3, 11; K. Lee, Pfizer Inc, 3, 11; Z. Szekanecz, AbbVie, 1, 2, 6, Eli Lilly, 1, 2, 6, Gedeon Richter, 1, Pfizer Inc, 1, 2, 5, 6, Roche, 1, 2, 6, Sanofi, 2, 6, Novartis, 1, 2, 6.

To cite this abstract in AMA style:

Charles-Schoeman C, Fleischmann R, Mysler E, Greenwald M, Wang C, Chen A, Connell C, Woolcott J, Menon S, Chen Y, Lee K, Szekanecz Z. The Risk of Venous Thromboembolic Events in Patients with RA Aged ≥ 50 Years with ≥ 1 Cardiovascular Risk Factor: Results from a Phase 3b/4 Randomized Safety Study of Tofacitinib vs TNF Inhibitors [abstract]. Arthritis Rheumatol. 2021; 73 (suppl 9). https://acrabstracts.org/abstract/the-risk-of-venous-thromboembolic-events-in-patients-with-ra-aged-%e2%89%a5-50-years-with-%e2%89%a5-1-cardiovascular-risk-factor-results-from-a-phase-3b-4-randomized-safety-study-of-tofacitinib-vs-tn/. Accessed February 5, 2023.
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