Methotrexate Dosage Reduction Upon Adalimumab Initiation: Clinical and Ultrasonographic Outcomes from the Randomized Noninferiority MUSICA Trial.
To examine the clinical and ultrasonographic (US) outcomes of reducing methotrexate (MTX) dosage upon initiating adalimumab (ADA) in MTX-inadequate responders with moderately to severely active rheumatoid arthritis (RA).



MUSICA (NCT01185288) was a double-blind, randomized, parallel-arm study of 309 patients with RA receiving MTX ≥ 15 mg/week for ≥ 12 weeks before screening. Patients were randomized to high dosage (20 mg/week) or low dosage (7.5 mg/week) MTX; all patients received 40 mg open-label ADA every other week for 24 weeks. The primary endpoint was Week 24 mean 28-joint Disease Activity Score based on C-reactive protein (DAS28-CRP) to test for noninferiority of low-dosage MTX using a 15% margin. US images were scored using a 10-joint semiquantitative system incorporating OMERACT definitions for pathology, assessing synovial hypertrophy, vascularity, and bony erosions.



Rapid improvement in clinical indices was observed in both groups after addition of ADA. The difference in mean DAS28-CRP (0.37, 95% CI 0.07-0.66) comparing low-dosage (4.12, 95% CI 3.88-4.34) versus high-dosage MTX (3.75, 95% CI 3.52-3.97) was statistically significant and non-inferiority was not met. Statistically significant differences were not detected for most clinical, functional, and US outcomes. Pharmacokinetic and safety profiles were similar.



In MUSICA, Week 24 mean DAS28-CRP, the primary endpoint, did not meet non-inferiority for the low-dosage MTX group. Although the differences between the 2 MTX dosage groups were small, our study findings did not support routine MTX reduction in MTX inadequate responders initiating ADA.
From the University of Florida College of Medicine, Jacksonville, Florida; Arthritis, Rheumatic and Back Disease Associates, Voorhees, New Jersey; Diablo Clinical Research, Walnut Creek, California; AbbVie Inc., North Chicago, Illinois, USA; AbbVie Deutschland GmbH and Co. KG., Ludwigshafen, Germany.G.S. Kaeley, MBBS, MRCP, University of Florida College of Medicine; A.M. Evangelisto, MD, Arthritis, Rheumatic and Back Disease Associates; M.J. Nishio, MD, Diablo Clinical Research; S.L. Goss, PhD, AbbVie Inc.; S. Liu, PhD, AbbVie Inc.; J. Kalabic, MD, AbbVie Inc.; H. Kupper, MD, AbbVie Deutschland GmbH and Co. KG. Gurjit.Kaeley@jax.ufl.edu.
Gurjit S
GS
Kaeley
From the University of Florida College of Medicine, Jacksonville, Florida; Arthritis, Rheumatic and Back Disease Associates, Voorhees, New Jersey; Diablo Clinical Research, Walnut Creek, California; AbbVie Inc., North Chicago, Illinois, USA; AbbVie Deutschland GmbH and Co. KG., Ludwigshafen, Germany.G.S. Kaeley, MBBS, MRCP, University of Florida College of Medicine; A.M. Evangelisto, MD, Arthritis, Rheumatic and Back Disease Associates; M.J. Nishio, MD, Diablo Clinical Research; S.L. Goss, PhD, AbbVie Inc.; S. Liu, PhD, AbbVie Inc.; J. Kalabic, MD, AbbVie Inc.; H. Kupper, MD, AbbVie Deutschland GmbH and Co. KG.
Amy M
AM
Evangelisto
From the University of Florida College of Medicine, Jacksonville, Florida; Arthritis, Rheumatic and Back Disease Associates, Voorhees, New Jersey; Diablo Clinical Research, Walnut Creek, California; AbbVie Inc., North Chicago, Illinois, USA; AbbVie Deutschland GmbH and Co. KG., Ludwigshafen, Germany.G.S. Kaeley, MBBS, MRCP, University of Florida College of Medicine; A.M. Evangelisto, MD, Arthritis, Rheumatic and Back Disease Associates; M.J. Nishio, MD, Diablo Clinical Research; S.L. Goss, PhD, AbbVie Inc.; S. Liu, PhD, AbbVie Inc.; J. Kalabic, MD, AbbVie Inc.; H. Kupper, MD, AbbVie Deutschland GmbH and Co. KG.
Midori J
MJ
Nishio
From the University of Florida College of Medicine, Jacksonville, Florida; Arthritis, Rheumatic and Back Disease Associates, Voorhees, New Jersey; Diablo Clinical Research, Walnut Creek, California; AbbVie Inc., North Chicago, Illinois, USA; AbbVie Deutschland GmbH and Co. KG., Ludwigshafen, Germany.G.S. Kaeley, MBBS, MRCP, University of Florida College of Medicine; A.M. Evangelisto, MD, Arthritis, Rheumatic and Back Disease Associates; M.J. Nishio, MD, Diablo Clinical Research; S.L. Goss, PhD, AbbVie Inc.; S. Liu, PhD, AbbVie Inc.; J. Kalabic, MD, AbbVie Inc.; H. Kupper, MD, AbbVie Deutschland GmbH and Co. KG.
Sandra L
SL
Goss
From the University of Florida College of Medicine, Jacksonville, Florida; Arthritis, Rheumatic and Back Disease Associates, Voorhees, New Jersey; Diablo Clinical Research, Walnut Creek, California; AbbVie Inc., North Chicago, Illinois, USA; AbbVie Deutschland GmbH and Co. KG., Ludwigshafen, Germany.G.S. Kaeley, MBBS, MRCP, University of Florida College of Medicine; A.M. Evangelisto, MD, Arthritis, Rheumatic and Back Disease Associates; M.J. Nishio, MD, Diablo Clinical Research; S.L. Goss, PhD, AbbVie Inc.; S. Liu, PhD, AbbVie Inc.; J. Kalabic, MD, AbbVie Inc.; H. Kupper, MD, AbbVie Deutschland GmbH and Co. KG.
Shufang
S
Liu
From the University of Florida College of Medicine, Jacksonville, Florida; Arthritis, Rheumatic and Back Disease Associates, Voorhees, New Jersey; Diablo Clinical Research, Walnut Creek, California; AbbVie Inc., North Chicago, Illinois, USA; AbbVie Deutschland GmbH and Co. KG., Ludwigshafen, Germany.G.S. Kaeley, MBBS, MRCP, University of Florida College of Medicine; A.M. Evangelisto, MD, Arthritis, Rheumatic and Back Disease Associates; M.J. Nishio, MD, Diablo Clinical Research; S.L. Goss, PhD, AbbVie Inc.; S. Liu, PhD, AbbVie Inc.; J. Kalabic, MD, AbbVie Inc.; H. Kupper, MD, AbbVie Deutschland GmbH and Co. KG.
Jasmina
J
Kalabic
From the University of Florida College of Medicine, Jacksonville, Florida; Arthritis, Rheumatic and Back Disease Associates, Voorhees, New Jersey; Diablo Clinical Research, Walnut Creek, California; AbbVie Inc., North Chicago, Illinois, USA; AbbVie Deutschland GmbH and Co. KG., Ludwigshafen, Germany.G.S. Kaeley, MBBS, MRCP, University of Florida College of Medicine; A.M. Evangelisto, MD, Arthritis, Rheumatic and Back Disease Associates; M.J. Nishio, MD, Diablo Clinical Research; S.L. Goss, PhD, AbbVie Inc.; S. Liu, PhD, AbbVie Inc.; J. Kalabic, MD, AbbVie Inc.; H. Kupper, MD, AbbVie Deutschland GmbH and Co. KG.
Hartmut
H
Kupper
D000068879:Adalimumab / Q000627:therapeutic use*; D000328:Adult; D000368:Aged; D018501:Antirheumatic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000000981:diagnostic imaging / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D050823:Hand Joints / Q000000981:diagnostic imaging; D006801:Humans; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage / Q000627:therapeutic use*; D008875:Middle Aged; D016896:Treatment Outcome; D014463:Ultrasonography
D018501:Antirheumatic Agents; D000068879:Adalimumab; D008727:Methotrexate
ADALIMUMAB; COMBINATION DRUG THERAPY; METHOTREXATE; RHEUMATOID ARTHRITIS; ULTRASONOGRAPHY