Study Comparing Etanercept and Methotrexate vs. Methotrexate Alone in Rheumatoid Arthritis

A 24-Month,Randomized,Double-Blind,Two-Period Study to Evaluate the Efficacy and Safety of the Combination of Etanercept and Methotrexate and Methotrexate Alone in Subjects With Early Rheumatoid Arthritis

To compare the effects of the combination of ETN and MTX to MTX alone on radiographic change and clinical disease activity in subjects with early RA over 12 months.

Study Overview

• Status: Completed
• Conditions: Rheumatoid Arthritis
• Intervention / Treatment: Drug: Etanercept; Drug: Methotrexate; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 542
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Colorado
    • Denver, Colorado, United States, 80230

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Satisfies the 1987 ACR Revised Criteria for Rheumatoid Arthritis
• Has RA greater than or equal to 3 months and less than or equal to 2 years

Exclusion Criteria:

• Received any previous treatment with MTX
• Received any previous treatment with ETN or other tumour necrosis factor antagonist

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: 1a; Etanercept + Methorexate for Period 1 (first 12 months) and Period 2 (Second 12 months)	Drug: Etanercept; Group 1a: Etanercept 50 mg SC injections weekly + oral Methotrexate weekly for Period 1 & 2 Group 1b: Etanercept 50 mg SC injections weekly + oral Methotrexate weekly for Period 1 then Etanercept 50 mg SC injections weekly + Placebo weekly for Period 2 Group 2a: Oral Methotrexate weekly + Placebo for Period 1, then Etanercept 50 mg SC injections weekly + oral Methotrexate weekly for Period 2; Drug: Methotrexate; Group 1a: Etanercept 50 mg SC injections weekly + oral Methotrexate weekly for Period 1 & 2 Group 1b: Etanercept 50 mg SC injections weekly + oral Methotrexate weekly for Period 1 then Etanercept 50 mg SC injections weekly + Placebo weekly for Period 2 Group 2a: Oral Methotrexate weekly + Placebo for Period 1, then Etanercept 50 mg SC injections weekly + oral Methotrexate weekly for Period 2 Group 2b: Oral Methotrexate weekly for both Periods 1 and 2
Active Comparator: 1b; Etanercept + Methotrexate for Period 1 (First 12 months) and Etanercept alone for Period 2 (Second 12 months)	Drug: Etanercept; Group 1a: Etanercept 50 mg SC injections weekly + oral Methotrexate weekly for Period 1 & 2 Group 1b: Etanercept 50 mg SC injections weekly + oral Methotrexate weekly for Period 1 then Etanercept 50 mg SC injections weekly + Placebo weekly for Period 2 Group 2a: Oral Methotrexate weekly + Placebo for Period 1, then Etanercept 50 mg SC injections weekly + oral Methotrexate weekly for Period 2; Drug: Methotrexate; Group 1a: Etanercept 50 mg SC injections weekly + oral Methotrexate weekly for Period 1 & 2 Group 1b: Etanercept 50 mg SC injections weekly + oral Methotrexate weekly for Period 1 then Etanercept 50 mg SC injections weekly + Placebo weekly for Period 2 Group 2a: Oral Methotrexate weekly + Placebo for Period 1, then Etanercept 50 mg SC injections weekly + oral Methotrexate weekly for Period 2 Group 2b: Oral Methotrexate weekly for both Periods 1 and 2; Drug: Placebo; Group 1b: Etanercept 50 mg SC injections weekly + oral Methotrexate weekly for Period 1 then Etanercept 50 mg SC injections weekly + Placebo weekly for Period 2 Group 2a: Oral Methotrexate weekly + Placebo for Period 1, then Etanercept 50 mg SC injections weekly + oral Methotrexate weekly for Period 2
Active Comparator: 2a; Methotrexate alone in Period 1 (First 12 months) and etanercept + Methotrexate in Period 2 (Second 12 months)	Drug: Etanercept; Group 1a: Etanercept 50 mg SC injections weekly + oral Methotrexate weekly for Period 1 & 2 Group 1b: Etanercept 50 mg SC injections weekly + oral Methotrexate weekly for Period 1 then Etanercept 50 mg SC injections weekly + Placebo weekly for Period 2 Group 2a: Oral Methotrexate weekly + Placebo for Period 1, then Etanercept 50 mg SC injections weekly + oral Methotrexate weekly for Period 2; Drug: Methotrexate; Group 1a: Etanercept 50 mg SC injections weekly + oral Methotrexate weekly for Period 1 & 2 Group 1b: Etanercept 50 mg SC injections weekly + oral Methotrexate weekly for Period 1 then Etanercept 50 mg SC injections weekly + Placebo weekly for Period 2 Group 2a: Oral Methotrexate weekly + Placebo for Period 1, then Etanercept 50 mg SC injections weekly + oral Methotrexate weekly for Period 2 Group 2b: Oral Methotrexate weekly for both Periods 1 and 2; Drug: Placebo; Group 1b: Etanercept 50 mg SC injections weekly + oral Methotrexate weekly for Period 1 then Etanercept 50 mg SC injections weekly + Placebo weekly for Period 2 Group 2a: Oral Methotrexate weekly + Placebo for Period 1, then Etanercept 50 mg SC injections weekly + oral Methotrexate weekly for Period 2
Active Comparator: 2b; Methotrexate alone in Period 1 (First 12 months) and Methotrexate alone in Period 2 (Second 12 months)	Drug: Methotrexate; Group 1a: Etanercept 50 mg SC injections weekly + oral Methotrexate weekly for Period 1 & 2 Group 1b: Etanercept 50 mg SC injections weekly + oral Methotrexate weekly for Period 1 then Etanercept 50 mg SC injections weekly + Placebo weekly for Period 2 Group 2a: Oral Methotrexate weekly + Placebo for Period 1, then Etanercept 50 mg SC injections weekly + oral Methotrexate weekly for Period 2 Group 2b: Oral Methotrexate weekly for both Periods 1 and 2

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Number of Participants Achieving Remission As Measured by a Disease Activity Score for 28 Joints (DAS 28) < 2.6.	Effects of the combination of etanercept and methotrexate to methotrexate alone on clinical disease activity. DAS28 scale 0 - 10, 3.2 or lower showing controlled disease while 5.1 implies active disease.	12 months
Year 1 Participants Having an Annualized Modified Total Sharp Score (mTSS) < 0.5.	The (van der Heijde) modified total Sharp score (mTSS) is the sum of scores for erosions (range 0-280) and joint space narrowings (range 0-168) and thus has a total range of (0 - 448 ), where zero is the best score , indicating no damage.	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety Measured by Number of Participants Reporting a Serious Adverse Event That Led to Death	Safety report for entire trial where participants reported a serious adverse event that led to death.	12 and 24 months

Collaborators and Investigators

• Sponsor: Wyeth is now a wholly owned subsidiary of Pfizer

Publications and helpful links

General Publications

• Gallo G, Brock F, Kerkmann U, Kola B, Huizinga TW. Efficacy of etanercept in combination with methotrexate in moderate-to-severe rheumatoid arthritis is not dependent on methotrexate dosage. RMD Open. 2016 Apr 21;2(1):e000186. doi: 10.1136/rmdopen-2015-000186. eCollection 2016.
• Fleischmann RM, van der Heijde D, Gardiner PV, Szumski A, Marshall L, Bananis E. DAS28-CRP and DAS28-ESR cut-offs for high disease activity in rheumatoid arthritis are not interchangeable. RMD Open. 2017 Jan 30;3(1):e000382. doi: 10.1136/rmdopen-2016-000382. eCollection 2017.
• Zhang W, Sun H, Emery P, Sato R, Singh A, Freundlich B, Anis AH. Does achieving clinical response prevent work stoppage or work absence among employed patients with early rheumatoid arthritis? Rheumatology (Oxford). 2012 Feb;51(2):270-4. doi: 10.1093/rheumatology/ker189. Epub 2011 Jun 29.
• Emery P, Breedveld FC, Hall S, Durez P, Chang DJ, Robertson D, Singh A, Pedersen RD, Koenig AS, Freundlich B. Comparison of methotrexate monotherapy with a combination of methotrexate and etanercept in active, early, moderate to severe rheumatoid arthritis (COMET): a randomised, double-blind, parallel treatment trial. Lancet. 2008 Aug 2;372(9636):375-82. doi: 10.1016/S0140-6736(08)61000-4. Epub 2008 Jul 16.

Study record dates

Study Major Dates

• Study Start: November 1, 2004
• Primary Completion (Actual): March 1, 2008
• Study Completion (Actual): March 1, 2008

Study Registration Dates

• First Submitted: September 13, 2005
• First Submitted That Met QC Criteria: September 13, 2005
• First Posted (Estimate): September 19, 2005

Study Record Updates

• Last Update Posted (Estimate): September 5, 2012
• Last Update Submitted That Met QC Criteria: August 1, 2012
• Last Verified: August 1, 2012

More Information

Terms related to this study

• Keywords: Rheumatoid Arthritis
• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Arthritis; Arthritis, Rheumatoid; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Gastrointestinal Agents; Dermatologic Agents; Reproductive Control Agents; Abortifacient Agents, Nonsteroidal; Abortifacient Agents; Folic Acid Antagonists; Etanercept; Methotrexate
• Other Study ID Numbers: 0881A-101548