Phase 4
Completed N=4,372
Safety Study Of Tofacitinib Versus Tumor Necrosis Factor (TNF) Inhibitor In Subjects With Rheumatoid Arthritis
Arthritis, Rheumatoid
Source: ClinicalTrials.gov NCT02092467 ↗
Enrolled (actual)
4,372
Serious AEs
26.0%
Results posted
Aug 2021
Primary outcomePrimary: Incidence Rate of Adjudicated Malignancies Excluding Non-melanoma Skin Cancers (NMSC) — 1.13; 1.13; 1.13; 0.77 participants with event/100 PY
◆ Published Evidence
Emerging
15citations · ~8 / year
Risk of extended major adverse cardiovascular event endpoints with tofacitinib versus TNF inhibitors in patients with rheumatoid arthritis: a post hoc analysis of a phase 3b/4 randomised safety study.
Summary
This post-marketing study is designed to compare the safety of tofacitinib versus TNF inhibitor with respect to major cardiovascular adverse events and malignancies, excluding non-melanoma skin cancers when given to subjects with rheumatoid arthritis. Other safety events, including non-melanoma skin cancers, hepatic events, infections, and efficacy parameters will be collected and evaluated in the study.
Linked Publications (5)
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Risk of extended major adverse cardiovascular event endpoints with tofacitinib versus TNF inhibitors in patients with rheumatoid arthritis: a post hoc analysis of a phase 3b/4 randomised safety study.
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Use of statins and its association with major adverse cardiovascular events with tofacitinib vs TNF inhibitors in patients with rheumatoid arthritis with and without atherosclerotic cardiovascular disease.
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Machine learning prediction and explanatory models of serious infections in patients with rheumatoid arthritis treated with tofacitinib.
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Cardiovascular Events, Malignancies, and Efficacy Outcomes in Latin American Patients With Rheumatoid Arthritis Receiving Tofacitinib or Tumor Necrosis Factor Inhibitors: A Post Hoc Analysis of the ORAL Surveillance Study.
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Geographical Differences in the Safety and Efficacy of Tofacitinib Versus TNFi: A Post Hoc Analysis of ORAL Surveillance.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Incidence Rate of Adjudicated Malignancies Excluding Non-melanoma Skin Cancers (NMSC) |
1.13; 1.13; 1.13; 0.77 | — |
| PRIMARY Incidence Rate of Adjudicated Major Adverse Cardiovascular Events (MACE) |
0.91; 1.05; 0.98; 0.73 | — |
| SECONDARY Incidence Rate of Non-fatal Stroke |
0.27; 0.33; 0.34 | — |
| SECONDARY Incidence Rate of Non-fatal Myocardial Infarction |
0.37; 0.33; 0.16 | — |
| SECONDARY Incidence Rate of Adjudicated Opportunistic Infection Events Including Tuberculosis |
0.76; 0.91; 0.42 | — |
| SECONDARY Incidence Rate of Adjudicated Hepatic Events |
0.90; 1.51; 0.70 | — |
| SECONDARY Incidence Rate of Adjudicated Cardiovascular Events Other Than Major Adverse Cardiovascular Events (MACE) |
1.21; 1.45; 1.05 | — |
| SECONDARY Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) |
1333; 1344; 1308; 373; 420; 339 | — |
| SECONDARY Number of Participants With Clinically Significant Abnormal Laboratory Parameters |
238; 252; 167 | — |
| SECONDARY Incidence Rate of Adjudicated All-Cause Deaths |
0.50; 0.80; 0.34; 0.08; 0.18; 0.06 | — |
| SECONDARY Number of Participants With Reasons For Permanent or Temporary Discontinuation of Study Medication |
210; 304; 210; 665; 736; 576 | — |
| SECONDARY Change From Baseline in Disease Activity Score 28-4 (DAS28-4) C-reactive Protein (CRP) at Month 2, 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, 48, 51, 54, 57, 60 and 63 |
-2.00; -2.14; -1.89; -2.28; -2.42; -2.19 | — |
| SECONDARY Change From Baseline in Simplified Disease Activity Index (SDAI) Score at Month 2, 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, 48, 51, 54, 57, 60 and 63 |
-22.95; -23.84; -22.24; -25.73; -26.81; -25.26 | — |
| SECONDARY Change From Baseline in Clinical Disease Activity Index (CDAI) Score at Month 2, 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, 48, 51, 54, 57, 60 and 63 |
-21.99; -22.84; -21.30; -24.76; -25.77; -24.29 | — |
| SECONDARY Percentage of Participants Who Achieved Observed American College of Rheumatology-European League Against Rheumatism (ACR-EULAR) Boolean Remission Criteria |
3.83; 4.99; 3.22; 5.73; 7.72; 6.10 | — |
| SECONDARY Percentage of Participants With Simplified Disease Activity Index (SDAI) Less Than or Equal to (<=) 3.3 |
4.62; 7.03; 4.15; 9.19; 11.14; 7.84 | — |
| SECONDARY Percentage of Participants With Clinical Disease Activity Index (CDAI) <=2.8 |
4.70; 7.40; 4.36; 9.26; 11.06; 7.76 | — |
| SECONDARY Percentage of Participants With Simplified Disease Activity Index (SDAI) <=11 |
30.76; 35.02; 28.08; 41.47; 45.00; 37.99 | — |
| SECONDARY Percentage of Participants With Clinical Disease Activity Index (CDAI) <=10 |
29.47; 34.25; 26.92; 40.07; 43.90; 35.99 | — |
| SECONDARY Percentage of Participants With Disease Activity Score 28-4 (DAS28-4) C-reactive Protein (CRP) <=3.2 |
31.55; 35.57; 28.36; 41.68; 46.05; 37.54 | — |
| SECONDARY Number of Participants With an American College of Rheumatology 20 Percent (%) (ACR20) Response |
832; 867; 812; 979; 992; 923 | — |
| SECONDARY Number of Participants With an American College of Rheumatology 50% (ACR50) Response |
402; 452; 336; 528; 561; 460 | — |
| SECONDARY Number of Participants With an American College of Rheumatology 70% (ACR70) Response |
152; 193; 113; 253; 268; 199 | — |
| SECONDARY Change From Baseline in Health Assessment Questionnaire - Disability Index (HAQ-DI) at Months 2, 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, 48, 51, 54, 57, 60 and 63 |
-0.42; -0.45; -0.38; -0.45; -0.48; -0.42 | — |
Eligibility Criteria
Inclusion Criteria
- Moderate to severe rheumatoid arthritis
- Taking methotrexate without adequate control of symptoms
- Have at least one cardiovascular risk factor (eg, current smoker, high blood pressure, high cholesterol levels, diabetes mellitus, history of heart attack, family history of coronary heart disease, extra-articular RA disease)
Exclusion Criteria
- Current or recent infection
- Clinically significant laboratory abnormalities
- Pregnancy
Data sourced from ClinicalTrials.gov (NCT02092467) and the linked publication. Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.