Clinical trial NCT01185288: 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)
Official title: A Multicenter, Double-Blind, Randomized, Parallel-Arm Study to Determine the Effect of Methotrexate Dose on Clinical Outcome and Ultrasonographic Signs in Subjects With Moderately to Severely Active Rheumatoid Arthritis Treated With Adalimumab (MUSICA)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Rheumatoid Arthritis
Keywords: Rheumatoid Arthritis
Lead sponsor: AbbVie
Sponsor class: INDUSTRY
First posted: 2010-08-19
Enrollment: 309
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).


Eligibility criteria: Inclusion Criteria:

* 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)

Exclusion Criteria:

* 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

Primary outcomes:
measure: Disease Activity Score for 28 Joints Based on C-reactive Protein (DAS28[CRP]) at Week 24
timeFrame: Week 24
Secondary outcomes:
measure: Percentage of Participants With Power Doppler Ultrasound (PD U/S) Score for Synovial Vascularity Improvement by 30% at Week 24
timeFrame: Baseline, 24 weeks
measure: Percentage of Participants With American College of Rheumatology 50% (ACR50) Criteria Response at Week 24
timeFrame: Baseline, 24 weeks
measure: Percentage of Participants With American College of Rheumatology 70% (ACR70) Criteria Response at Week 24
timeFrame: Baseline, 24 weeks
measure: Percentage of Participants With a Change From Baseline in Health Assessment Questionnaire - Disability Index (HAQ-DI) ≤ -0.22 at Week 24
timeFrame: Baseline, 24 weeks
measure: Percent Change From Baseline in Medical Outcomes Study Version II (MOS) Sleep Problem Index 9 at Week 24
timeFrame: Baseline, 24 weeks
Other outcomes:
measure: Serum Adalimumab Trough Concentrations at Week 24
timeFrame: Week 24
Locations:
city: Huntsville
country: United States
facility: Site Reference ID/Investigator# 38982
state: Alabama
city: Tuscaloosa
country: United States
facility: Site Reference ID/Investigator# 38686
state: Alabama
city: Mesa
country: United States
facility: Site Reference ID/Investigator# 42044
state: Arizona
city: Phoenix
country: United States
facility: Site Reference ID/Investigator# 37983
state: Arizona
city: Little Rock
country: United States
facility: Site Reference ID/Investigator# 44823
state: Arkansas
city: Hemet
country: United States
facility: Site Reference ID/Investigator# 37981
state: California
city: Long Beach
country: United States
facility: Site Reference ID/Investigator# 40208
state: California
city: Sacramento
country: United States
facility: Site Reference ID/Investigator# 38423
state: California
city: Victorville
country: United States
facility: Site Reference ID/Investigator# 38204
state: California
city: Walnut Creek
country: United States
facility: Site Reference ID/Investigator# 40762
state: California
city: Danbury
country: United States
facility: Site Reference ID/Investigator# 43049
state: Connecticut
city: Jacksonville
country: United States
facility: Site Reference ID/Investigator# 38687
state: Florida
city: Miami
country: United States
facility: Site Reference ID/Investigator# 40105
state: Florida
city: Sarasota
country: United States
facility: Site Reference ID/Investigator# 38083
state: Florida
city: Lawrenceville
country: United States
facility: Site Reference ID/Investigator# 38688
state: Georgia
city: Meridian
country: United States
facility: Site Reference ID/Investigator# 38689
state: Idaho
city: Rock Island
country: United States
facility: Site Reference ID/Investigator# 38085
state: Illinois
city: Springfield
country: United States
facility: Site Reference ID/Investigator# 40128
state: Illinois
city: Bowling Green
country: United States
facility: Site Reference ID/Investigator# 38981
state: Kentucky
city: Covington
country: United States
facility: Site Reference ID/Investigator# 38086
state: Louisiana
city: Fall River
country: United States
facility: Site Reference ID/Investigator# 40125
state: Massachusetts
city: Las Vegas
country: United States
facility: Site Reference ID/Investigator# 65490
state: Nevada
city: Clifton
country: United States
facility: Site Reference ID/Investigator# 40124
state: New Jersey
city: Freehold
country: United States
facility: Site Reference ID/Investigator# 38978
state: New Jersey
city: Voorhees
country: United States
facility: Site Reference ID/Investigator# 40123
state: New Jersey
city: Bronx
country: United States
facility: Site Reference ID/Investigator# 38983
state: New York
city: Smithtown
country: United States
facility: Site Reference ID/Investigator# 38264
state: New York
city: Asheville
country: United States
facility: Site Reference ID/Investigator# 38263
state: North Carolina
city: Greenville
country: United States
facility: Site Reference ID/Investigator# 38261
state: North Carolina
city: Mayfield Village
country: United States
facility: Site Reference ID/Investigator# 39024
state: Ohio
city: Oklahoma City
country: United States
facility: Site Reference ID/Investigator# 40127
state: Oklahoma
city: Bend
country: United States
facility: Site Reference ID/Investigator# 38202
state: Oregon
city: Eugene
country: United States
facility: Site Reference ID/Investigator# 39023
state: Oregon
city: Duncansville
country: United States
facility: Site Reference ID/Investigator# 38265
state: Pennsylvania
city: Jackson
country: United States
facility: Site Reference ID/Investigator# 38082
state: Tennessee
city: Dallas
country: United States
facility: Site Reference ID/Investigator# 37980
state: Texas
city: Dallas
country: United States
facility: Site Reference ID/Investigator# 44888
state: Texas
city: Houston
country: United States
facility: Site Reference ID/Investigator# 43050
state: Texas
city: San Antonio
country: United States
facility: Site Reference ID/Investigator# 43735
state: Texas
city: Richmond
country: United States
facility: Site Reference ID/Investigator# 44344
state: Virginia
city: Seattle
country: United States
facility: Site Reference ID/Investigator# 40210
state: Washington
city: Seattle
country: United States
facility: Site Reference ID/Investigator# 38084
state: Washington
city: Seattle
country: United States
facility: Site Reference ID/Investigator# 38542
state: Washington
city: Spokane
country: United States
facility: Site Reference ID/Investigator# 38424
state: Washington
city: Tacoma
country: United States
facility: Site Reference ID/Investigator# 38203
state: Washington
city: Franklin
country: United States
facility: Site Reference ID/Investigator# 38087
state: Wisconsin
city: San Juan
country: Puerto Rico
facility: Site Reference ID/Investigator# 60850
city: San Juan
country: Puerto Rico
facility: Site Reference ID/Investigator# 38691
city: Vega Baja
country: Puerto Rico
facility: Site Reference ID/Investigator# 60851
Study officials:
affiliation: AbbVie
name: Dawn Carlson, MD
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.