Methotrexate (Rheumatrex) High Dose Special Investigation (Regulatory Post Marketing Commitment Plan)

Rheumatrex High Dose Special Investigation (Regulatory Post Marketing Commitment Plan)

This Investigation is to be performed for the purpose of assessing the following information in the long-term post-marketing daily medical practice in the patients who receive REUMATOLEX 2 mg Capsule for the treatment of Rheumatoid Arthritis (RA) at the dose higher than 8 mg/week.

1. Condition of occurrence of ADRs
2. Factors considered to affect safety
3. Verification of efficacy

Study Overview

• Status: Completed
• Conditions: Arthritis; Rheumatoid; High Dose
• Intervention / Treatment: Drug: Methotrexate (MTX)

Detailed Description

Implemented as a Special Investigation by Central Registration System

• Study Type: Observational
• Enrollment (Actual): 2860

Contacts and Locations

Study Locations

• Japan
  • Fukuoka-ken
    • Kitakyushu-shi, Fukuoka-ken, Japan
      • University of Occupational and Environmental Health Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 17 years to 99 years (ADULT, OLDER_ADULT, CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Patients who receive the MTX Preparation at the dose higher than 8 mg/week for the treatment of Rheumatoid Arthritis.

Description

Inclusion Criteria:

• Patients need to be administered Rheumatrex in order to be enrolled in the survey
• Patients who receive the Rheumatrex at the dose higher than 8 mg/week for the treatment of Rheumatoid Arthritis

Exclusion Criteria:

• Patients who have been treated with Rheumatrex at the dose higher than 8 mg/week since the days when the high dose therapy for RA was not approved
• Patients who have been treated MTX other than Rheumatrex administered Rheumatrex

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

Methotrexate (MTX); Patients who receive the MTX Preparation at the dose higher than 8 mg/week for the treatment of Rheumatoid Arthritis.

Drug: Methotrexate (MTX); Methotrexate should be administered at the weekly dose of 6 mg orally once a week or twice or three times a week by subdividing the weekly dose into the relevant number of portions. When administering the subdivided doses, MTX should be administered at the interval of 12 hours on Day 1 to Day 2. When the weekly dose is subdivided into two portions, suspend the administration for the remaining 6 days. When the weekly dose is subdivided into three portions, suspend the administration on the remaining 5 days. Repeat this weekly cycle. The dose should be adjusted as appropriate depending on the age, symptom, tolerability, and response to the MTX Preparation in individual patients. The weekly dose should not be higher than 16 mg.; Other Names: Rheumatrex

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Treatment-Related Adverse Events	A treatment-related adverse event was any untoward medical occurrence attributed to methotrexate in a participant who received methotrexate.	24 Weeks
Disease Activity Score (DAS28)-4ESR	Disease activity score based on 28-joint count and erythrocyte sedimentation rate (4 variables) (DAS28-4 [ESR]) was calculated from swollen joint count (SJC) and tender joint count (TJC) using 28 joints count, ESR (mm/hour) and visual analogue scale (VAS) of general health assessed by participant or investigator. Higher score indicated more disease activity. The total scale range of DAS28-4 (ESR) , minimum is 0.0 and maximum can not be specified. DAS28-4 (ESR) >5.1 indicated high disease activity, ?3.2 to ?5.1 indicated moderate disease activity, <3.2 indicated low disease activity, and <2.6 indicated remission.	Baseline and 24 Weeks
Disease Activity Score (DAS28)-4CRP	Disease activity score based on 28-joint count and C-reactive protein (4 variables) (DAS28-4 [CRP]) was calculated from swollen joint count (SJC) and tender joint count (TJC) using 28 joints count, C-reactive protein (CRP, mg/dL) and VAS of general health. The total scale range of DAS28-4 (ESR) , minimum is 0.0 and maximum can not be specified. DAS28-4 (CRP) >4.1 indicated high disease activity, ≥2.7 to 4.1 indicated moderate disease activity, <2.7 indicated low disease activity, and <2.3 indicated remission.	Baseline and 24 Weeks
Change From Baseline in Disease Activity Score (DAS28)-4ESR	Disease activity score based on 28-joint count and erythrocyte sedimentation rate (4 variables) (DAS28-4 [ESR]) was calculated from swollen joint count (SJC) and tender joint count (TJC) using 28 joints count, ESR (mm/hour) and visual analogue scale (VAS) of general health assessed by participant or investigator. Mean change from baseline in the DAS28-4 (ESR) at Week 24 is calculated. The total scale range can not be specified.	Baseline and 24 Weeks
Change From Baseline in Disease Activity Score (DAS28)-4CRP	Disease activity score based on 28-joint count and C-reactive protein (4 variables) (DAS28-4 [CRP]) was calculated from swollen joint count (SJC) and tender joint count (TJC) using 28 joints count, C-reactive protein (CRP, mg/dL) and VAS of general health. Mean change from baseline in the DAS28-4 (CRP) at Week 24 is calculated. The total scale range can not be specified.	Baseline and 24 Weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Treatment-Related Serious Adverse Events	A treatment-related adverse event was any untoward medical occurrence attributed to methotrexate in a participant who received methotrexate. A treatment-related serious adverse event was a treatment-related adverse event resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; lifethreatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Relatedness to methotrexate was assessed by the investigator.	24 Weeks
Number of Participants With Treatment Related Pre-specified Important Serious Adverse Events	Pre-specified important adverse events were 1) Interstitial pneumonia, 2) Pulmonary fibrosis, 3) Hepatic impairment, 4) Renal impairment, 5) Hematopoietic disorder, 6) Infection, and 7) Lymphoma. A treatment-related adverse event was any untoward medical occurrence attributed to methotrexate in a participant who received methotrexate. A treatment-related serious adverse event was a treatment-related adverse event resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; lifethreatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Relatedness to methotrexate was assessed by the investigator.	24 Weeks
Clinical Efficacy Rate	Clinical efficacy rate, which was defined as the percentage of participants who achieved clinical effectiveness over the total number of assesable effectiveness analysis population, was presented along with the corresponding 2-sided 95% CI. Clinical effectiveness of methotrexate was assessed as "effective" or "ineffective" by the investigator. The assessment was based on the baseline condition of disease control and degree of alleviation from baseline in clinical symptoms and laboratory data.	24 Weeks

Collaborators and Investigators

• Sponsor: 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): May 1, 2011
• Primary Completion (ACTUAL): March 1, 2014
• Study Completion (ACTUAL): March 1, 2014

Study Registration Dates

• First Submitted: August 9, 2011
• First Submitted That Met QC Criteria: August 9, 2011
• First Posted (ESTIMATE): August 11, 2011

Study Record Updates

• Last Update Posted (ACTUAL): August 6, 2018
• Last Update Submitted That Met QC Criteria: November 8, 2017
• Last Verified: November 1, 2017

More Information

Terms related to this study

• Keywords: High Dose; Rheumatrex
• Additional Relevant MeSH Terms: Joint Diseases; Musculoskeletal Diseases; Arthritis; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antirheumatic Agents; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Dermatologic Agents; Reproductive Control Agents; Abortifacient Agents, Nonsteroidal; Abortifacient Agents; Folic Acid Antagonists; Methotrexate
• Other Study ID Numbers: B3211003