Tofacitinib (Xeljanz) Special Investigation for Rheumatoid Arthritis

XELJANZ (REGISTERED) TABLETS 5MG SPECIAL INVESTIGATION (ALL-CASES SURVEILLANCE)

The objective of this Surveillance is to verify the following subject matters concerning Tofacitinib (Xeljanz) under general practice.

1) Occurrence of adverse reactions, factors that may potentially affect safety and efficacy 2） Long-term safety (particularly, malignant tumors and serious infections) and efficacy

Occurrences of malignant tumors and serious infections will be compared with a control group.

Study Overview

• Status: Completed
• Conditions: Rheumatoid Arthritis
• Intervention / Treatment: Drug: Tofacitinib (Xeljanz); Drug: Etanercept, other Biologics, Disease-modifying antirheumatic drugs (DMARDs), etc

Detailed Description

All the patients whom an investigator prescribes the Xeljanz or Standard of Care for rheumatoid arthritis should be registered consecutively until the number of subjects reaches target number in order to extract patients enrolled into the investigation at random.

• Study Type: Observational
• Enrollment (Actual): 9968

Contacts and Locations

Study Locations

• Japan
  • Tokyo, Japan

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 second and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

Adult patients with moderately to severely active rheumatoid arthritis who have had an inadequate response or intolerance to over 8 mg Methotrexate for 3 months treatment.

Description

Inclusion Criteria:

• All patients receiving Tofacitinib (Xeljanz)

Exclusion Criteria:

Not Applicable

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Tofacitinib (Xeljanz); Tablets 5 mg BID	Drug: Tofacitinib (Xeljanz); 5 mg Tablet BID
Standard of Care; Standard of Care for Rheumatoid Arthritis	Drug: Etanercept, other Biologics, Disease-modifying antirheumatic drugs (DMARDs), etc; Etanercept: 10 to 25 mg twice weekly, or 25 to 50 mg once weekly

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Treatment-related Adverse Events or Serious Treatment-related Adverse Events in Participants Who Received XELJANZ	An adverse drug reaction (ADR) was any untoward medical occurrence attributed to XELJANZ in a participant who received XELJANZ. A serious adverse event/adverse drug reaction (SADR) was a treatment-related adverse event resulting in any of the following outcomes or deemed significant for any other reason: death; life-threatening experience (immediate risk of dying); initial or prolonged inpatient hospitalization; persistent or significant disability/incapacity; congenital anomaly. Relatedness to XELJANZ was assessed by the physician.	36 months
Change in Disease Activity Based on Simplified Disease Activity Index (SDAI)	The SDAI is the numerical sum of five outcome parameters: tender joint count (TJC) and swollen joint count (SJC) based on a 28-joint assessment, patient global assessment (PtGA) and physician global assessment (PGA) assessed on 0-10 cm VAS, and C-reactive protein (CRP) (mg/dL). SDAI is defined as follows: ≤3.3, disease remission; >3.3 to ≤11, low disease activity, >11 to ≤26, moderate disease activity; and >26, high disease activity. SDAI was assessed at each evaluation time point and mean change from the start of XELJANZ was calculated with the 95% CI.	Baseline, 1, 6, 12, 24, 36 months
Change in Disease Activity Score Based on 28-joints Count (DAS28)	DAS28 is the numerical sum of 4 outcome parameters: tender joint count (TJC) and swollen joint count (SJC) based on a 28-joint assessment, PtGA assessed on 0-10 cm VAS, and the erythrocyte sedimentation rate (ESR) (millimeters per hour [mm/hour]). DAS28 is defined as follows: <2.6, disease remission; ≥2.6 to <3.2, low disease activity, ≥3.2 to ≤5.1, moderate disease activity; and >5.1, high disease activity. DAS28 was assessed at each evaluation time point and mean change from the start of XELJANZ was calculated with the 95% CI.	Baseline, 1, 6, 12, 24, 36 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Occurrence of Serious Infection Events	Comparison of time to serious infection between XELJANZ group and control group. Hazard ratio (unadjusted): Baseline characteristics are unadjusted Hazard ratio (adjusted 1): Adjusted by propensity score estimated by logistic regression Hazard ratio (adjusted 2): Adjusted by propensity score estimated by random forest Hazard ratio (adjusted 3): Adjusted by propensity score estimated by logistic regression (with upper limit of weighting) Hazard ratio (adjusted 4): Adjusted by propensity score estimated by random forest (with upper limit of weighting)	12 months
Occurrence of Malignancy	Comparison of time to malignancy between XELJANZ group and control group. The standard incidence ratio (SIR) was calculated using the general Japanese population as the reference population. Hazard ratio (unadjusted): Baseline characteristics are unadjusted Hazard ratio (adjusted 1): Adjusted by propensity score estimated by logistic regression Hazard ratio (adjusted 2): Adjusted by propensity score estimated by random forest Hazard ratio (adjusted 3): Adjusted by propensity score estimated by logistic regression (with upper limit of weighting) Hazard ratio (adjusted 4): Adjusted by propensity score estimated by random forest (with upper limit of weighting)	36 months
Occurrence of Death	Comparison of time to death between XELJANZ group and control group. The standardized mortality ratio (SMR) was calculated using the general Japanese population as the reference population. Hazard ratio (unadjusted): Baseline characteristics are unadjusted	36 months

Collaborators and Investigators

• Sponsor: Pfizer
• Investigators: Study Director: Pfizer CT.gov Call Center, Pfizer

Publications and helpful links

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start (Actual): July 26, 2013
• Primary Completion (Actual): August 24, 2021
• Study Completion (Actual): August 24, 2021

Study Registration Dates

• First Submitted: July 30, 2013
• First Submitted That Met QC Criteria: August 27, 2013
• First Posted (Estimated): August 30, 2013

Study Record Updates

• Last Update Posted (Actual): October 26, 2024
• Last Update Submitted That Met QC Criteria: July 30, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Keywords: Rheumatoid Arthritis; Xeljanz; Tofacitinib; Regulatory Post Marketing Commitment Plan; Good Post Marketing Study Practice
• Additional Relevant MeSH Terms: Musculoskeletal Diseases; Joint Diseases; Rheumatic Diseases; Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Arthritis; Arthritis, Rheumatoid; Janus Kinase Inhibitors; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Inflammatory Agents; Peripheral Nervous System Agents; Gastrointestinal Agents; Enzyme Inhibitors; Sensory System Agents; Protein Kinase Inhibitors; Analgesics, Non-Narcotic; Analgesics; Anti-Inflammatory Agents, Non-Steroidal; Etanercept; Tofacitinib; Antirheumatic Agents
• Other Study ID Numbers: A3921194

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.