A Study to Determine the Effect of Methotrexate (MTX) Dose on Clinical Outcome and Ultrasonographic Signs in Subjects With Moderately to Severely Active Rheumatoid Arthritis (RA) Treated With Adalimumab (MUSICA)

NCT01185288 | Completed Phase 4 Results

• 1 other identifier: M12-071
• Study Type: interventional
• Target: 309
• Locations: 2 countries
• Sites: 49

Brief Summary

This study will investigate the efficacy of both low and high doses of methotrexate (MTX) in combination with open-label adalimumab (ADA) in patients who have had an inadequate response to high dose of MTX. The study will also evaluate the pharmacokinetics and safety of the two regimens of MTX in combination with ADA in participants with rheumatoid arthritis (RA).

Conditions

Rheumatoid Arthritis

Keywords

Rheumatoid Arthritis

Outcome Measures

Primary Outcomes (1)

• Disease Activity Score for 28 Joints Based on C-reactive Protein (DAS28[CRP]) at Week 24

  The DAS28(CRP) score includes 28 tender joint counts, 28 swollen joint counts, C-reactive protein, and participant's global assessment of disease activity. Scores on the DAS28(CRP) range from 0 to 10. A DAS28(CRP) score ≥ 5.1 indicates high disease activity, and a DAS28(CRP) score \< 2.6 indicates clinical remission. Least squares means and 95% CI were from 2-way ANCOVA model with effects for baseline DAS28(CRP) value, treatment group, and prior methotrexate dose group.

  Week 24

Secondary Outcomes (5)

• Percentage of Participants With Power Doppler Ultrasound (PD U/S) Score for Synovial Vascularity Improvement by 30% at Week 24

  Baseline, 24 weeks

• Percentage of Participants With American College of Rheumatology 50% (ACR50) Criteria Response at Week 24

  Baseline, 24 weeks

• Percentage of Participants With American College of Rheumatology 70% (ACR70) Criteria Response at Week 24

  Baseline, 24 weeks

• Percentage of Participants With a Change From Baseline in Health Assessment Questionnaire - Disability Index (HAQ-DI) ≤ -0.22 at Week 24

  Baseline, 24 weeks

• Percent Change From Baseline in Medical Outcomes Study Version II (MOS) Sleep Problem Index 9 at Week 24

  Baseline, 24 weeks

Other Outcomes (1)

• Serum Adalimumab Trough Concentrations at Week 24

  Week 24

Study Arms (2)

Adalimumab + Low Dose Methotrexate

EXPERIMENTAL

Open-label adalimumab (40 mg subcutaneous every other week) plus blinded, low dose methotrexate (7.5 mg orally once weekly).

Biological: Adalimumab; Drug: Methotrexate

Adalimumab + High Dose Methotrexate

ACTIVE COMPARATOR

Open-label adalimumab (40 mg subcutaneous every other week) plus blinded, high dose methotrexate (20 mg orally once weekly).

Biological: Adalimumab; Drug: Methotrexate

Interventions

Adalimumab BIOLOGICAL

Adalimumab in pre-filled syringes

Also known as: ABT-D2E7, Humira

Adalimumab + High Dose Methotrexate; Adalimumab + Low Dose Methotrexate

Methotrexate DRUG

Methotrexate capsule

Adalimumab + High Dose Methotrexate; Adalimumab + Low Dose Methotrexate

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adult subjects with moderately to severely active rheumatoid arthritis
• Subjects must have a DAS28(CRP) (Disease Activity Score using C-Reactive Protein) greater than or equal to 3.2 at baseline (there is no minimum CRP score required to qualify)
• Subjects must have at least 5/68 tender joints plus 5/66 swollen joints assessed at screening or baseline
• Subject must treated with and MTX (methotrexate) dose (oral and/or injectable) of 15 mg or more per week (no upper limit on dose) for at least 12 weeks prior to screening
• Subject is either biologic-naïve or has only one prior biologic disease-modifying antirheumatic drug (i.e. abatacept, anakinra, certolizumab, etanercept, golimumab, infliximab, or tocilizumab)

You may not qualify if:

• Previous exposure to adalimumab (Humira), rituximab (Rituxan), natalizumab (Tysabri), efalizumab (Raptiva)
• Subject has been treated with intra-articular or parenteral administration of corticosteroids within 4 weeks of screening
• Subject has diagnosis or history of gout or pseudogout
• Subject has undergone joint surgery within 12 weeks of screening (at joints to be assessed by ultrasound)
• Subject has history of chronic arthritis diagnosed before age 16 years

Sponsors & Collaborators

• AbbVie (prior sponsor, Abbott): lead

Study Sites (49)

Site Reference ID/Investigator# 38982

Huntsville, Alabama, 35801, United States

Location

Site Reference ID/Investigator# 38686

Tuscaloosa, Alabama, 35406, United States

Location

Site Reference ID/Investigator# 42044

Mesa, Arizona, 85202, United States

Location

Site Reference ID/Investigator# 37983

Phoenix, Arizona, 85031, United States

Location

Site Reference ID/Investigator# 44823

Little Rock, Arkansas, 72205, United States

Location

Site Reference ID/Investigator# 37981

Hemet, California, 92543, United States

Location

Site Reference ID/Investigator# 40208

Long Beach, California, 90822, United States

Location

Site Reference ID/Investigator# 38423

Sacramento, California, 95816, United States

Location

Site Reference ID/Investigator# 38204

Victorville, California, 92395, United States

Location

Site Reference ID/Investigator# 40762

Walnut Creek, California, 94598, United States

Location

Site Reference ID/Investigator# 43049

Danbury, Connecticut, 06810, United States

Location

Site Reference ID/Investigator# 38687

Jacksonville, Florida, 32209, United States

Location

Site Reference ID/Investigator# 40105

Miami, Florida, 33169, United States

Location

Site Reference ID/Investigator# 38083

Sarasota, Florida, 34239, United States

Location

Site Reference ID/Investigator# 38688

Lawrenceville, Georgia, 30045, United States

Location

Site Reference ID/Investigator# 38689

Meridian, Idaho, 83642, United States

Location

Site Reference ID/Investigator# 38085

Rock Island, Illinois, 61201, United States

Location

Site Reference ID/Investigator# 40128

Springfield, Illinois, 62704, United States

Location

Site Reference ID/Investigator# 38981

Bowling Green, Kentucky, 42101, United States

Location

Site Reference ID/Investigator# 38086

Covington, Louisiana, 70433, United States

Location

Site Reference ID/Investigator# 40125

Fall River, Massachusetts, 02720, United States

Location

Site Reference ID/Investigator# 65490

Las Vegas, Nevada, 89102, United States

Location

Site Reference ID/Investigator# 40124

Clifton, New Jersey, 07012, United States

Location

Site Reference ID/Investigator# 38978

Freehold, New Jersey, 07728, United States

Location

Site Reference ID/Investigator# 40123

Voorhees Township, New Jersey, 08043, United States

Location

Site Reference ID/Investigator# 38264

Smithtown, New York, 11787, United States

Location

Site Reference ID/Investigator# 38983

The Bronx, New York, 10467, United States

Location

Site Reference ID/Investigator# 38263

Asheville, North Carolina, 28803, United States

Location

Site Reference ID/Investigator# 38261

Greenville, North Carolina, 27834, United States

Location

Site Reference ID/Investigator# 39024

Mayfield Village, Ohio, 44143, United States

Location

Site Reference ID/Investigator# 40127

Oklahoma City, Oklahoma, 73104, United States

Location

Site Reference ID/Investigator# 38202

Bend, Oregon, 97701, United States

Location

Site Reference ID/Investigator# 39023

Eugene, Oregon, 97401, United States

Location

Site Reference ID/Investigator# 38265

Duncansville, Pennsylvania, 16635, United States

Location

Site Reference ID/Investigator# 38082

Jackson, Tennessee, 38305, United States

Location

Site Reference ID/Investigator# 37980

Dallas, Texas, 75231, United States

Location

Site Reference ID/Investigator# 44888

Dallas, Texas, 75246, United States

Location

Site Reference ID/Investigator# 43050

Houston, Texas, 77074, United States

Location

Site Reference ID/Investigator# 43735

San Antonio, Texas, 78229, United States

Location

Site Reference ID/Investigator# 44344

Richmond, Virginia, 23294, United States

Location

Site Reference ID/Investigator# 40210

Seattle, Washington, 98101, United States

Location

Site Reference ID/Investigator# 38084

Seattle, Washington, 98122, United States

Location

Site Reference ID/Investigator# 38542

Seattle, Washington, 98133, United States

Location

Site Reference ID/Investigator# 38424

Spokane, Washington, 99204, United States

Location

Site Reference ID/Investigator# 38203

Tacoma, Washington, 98405, United States

Location

Site Reference ID/Investigator# 38087

Franklin, Wisconsin, 53132, United States

Location

Site Reference ID/Investigator# 60850

San Juan, 00936-5067, Puerto Rico

Location

Site Reference ID/Investigator# 38691

San Juan, 00936-8344, Puerto Rico

Location

Site Reference ID/Investigator# 60851

Vega Baja, 00694-0764, Puerto Rico

Location

Related Publications (6)

• Kaeley GS, MacCarter DK, Pangan AL, Wang X, Kalabic J, Ranganath VK. Clinical Responses and Synovial Vascularity in Obese Rheumatoid Arthritis Patients Treated with Adalimumab and Methotrexate. J Rheumatol. 2018 Dec;45(12):1628-1635. doi: 10.3899/jrheum.171232. Epub 2018 Sep 1.

  PMID: 30173153 DERIVED

• Kaeley GS, MacCarter DK, Goyal JR, Liu S, Chen K, Griffith J, Kupper H, Garg V, Kalabic J. Similar Improvements in Patient-Reported Outcomes Among Rheumatoid Arthritis Patients Treated with Two Different Doses of Methotrexate in Combination with Adalimumab: Results From the MUSICA Trial. Rheumatol Ther. 2018 Jun;5(1):123-134. doi: 10.1007/s40744-018-0105-7. Epub 2018 Mar 24.

  PMID: 29574622 DERIVED

• Burmester GR, Kaeley GS, Kavanaugh AF, Gabay C, MacCarter DK, Nash P, Takeuchi T, Goss SL, Rodila R, Chen K, Kupper H, Kalabic J. Treatment efficacy and methotrexate-related toxicity in patients with rheumatoid arthritis receiving methotrexate in combination with adalimumab. RMD Open. 2017 Sep 17;3(2):e000465. doi: 10.1136/rmdopen-2017-000465. eCollection 2017.

  PMID: 28955494 DERIVED

• Burmester GR, Landewe R, Genovese MC, Friedman AW, Pfeifer ND, Varothai NA, Lacerda AP. Adalimumab long-term safety: infections, vaccination response and pregnancy outcomes in patients with rheumatoid arthritis. Ann Rheum Dis. 2017 Feb;76(2):414-417. doi: 10.1136/annrheumdis-2016-209322. Epub 2016 Jun 23.

  PMID: 27338778 DERIVED

• Kaeley GS, Evangelisto AM, Nishio MJ, Goss SL, Liu S, Kalabic J, Kupper H. Methotrexate Dosage Reduction Upon Adalimumab Initiation: Clinical and Ultrasonographic Outcomes from the Randomized Noninferiority MUSICA Trial. J Rheumatol. 2016 Aug;43(8):1480-9. doi: 10.3899/jrheum.151009. Epub 2016 Jun 15.

  PMID: 27307526 DERIVED

• Kaeley GS, Nishio MJ, Goyal JR, MacCarter DK, Wells AF, Chen S, Kupper H, Kalabic J. Changes in Ultrasonographic Vascularity Upon Initiation of Adalimumab Combination Therapy in Rheumatoid Arthritis Patients With an Inadequate Response to Methotrexate. Arthritis Rheumatol. 2016 Nov;68(11):2584-2592. doi: 10.1002/art.39751. Epub 2016 Sep 29.

  PMID: 27214046 DERIVED

Related Links

• Related Info

MeSH Terms

Conditions

Arthritis, Rheumatoid

Interventions

Adalimumab; Methotrexate

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Global Medical Services
• Organization: AbbVie (prior sponsor, Abbott)

800-633-9110

Study Officials

• Dawn Carlson, MD

  AbbVie

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 18, 2010
• First Posted: August 19, 2010
• Study Start: September 1, 2010
• Primary Completion: January 1, 2013
• Study Completion: January 1, 2013
• Last Updated: March 18, 2014
• Results First Posted: March 18, 2014

Record last verified: 2014-01

Locations

US (46); PR (3)