Gurjit S Kaeley1, Amy M Evangelisto2, Midori J Nishio2, Sandra L Goss2, Shufang Liu2, Jasmina Kalabic2, Hartmut Kupper2. 1. 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. 2. 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.
Abstract
OBJECTIVE: 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). METHODS: 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. RESULTS: 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. CONCLUSION: 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.
RCT Entities:
OBJECTIVE: 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). METHODS: 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. RESULTS: 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. CONCLUSION: 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.
Entities:
Keywords:
ADALIMUMAB; COMBINATION DRUG THERAPY; METHOTREXATE; RHEUMATOID ARTHRITIS; ULTRASONOGRAPHY
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