Efficacy and safety of ascending methotrexate dose in combination with adalimumab: the randomised CONCERTO trial
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Open Access
- 18 February 2014
- journal article
- research article
- Published by BMJ in Annals Of The Rheumatic Diseases
- Vol. 74 (6), 1037-1044
- https://doi.org/10.1136/annrheumdis-2013-204769
Abstract
CONCERTO was a randomised, double-blind, parallel-armed study of methotrexate (MTX) in combination with adalimumab to assess whether an increasing trend of efficacy and decreased safety exists when increasing MTX dose in patients with early rheumatoid arthritis (RA). Early, biologic and MTX-naive RA patients (N=395) were evenly randomised to open-label adalimumab (40 mg every other week) plus weekly blinded 2.5, 5, 10 or 20 mg MTX for 26 weeks. Clinical, radiographic and functional outcomes were analysed using two-sided linear trend tests or one-way analysis of covariance. Statistically significant increasing trends were observed in the proportion of patients achieving the primary endpoint, 28-joint count disease activity score with C reactive protein (DAS28(CRP)) <3.2 (42.9%, 44.0%, 56.6% and 60.2% for 2.5, 5, 10 or 20 mg/week MTX, respectively), DAS28(CRP) <2.6 and American College of Rheumatology 50/70/90 responses with increasing doses of MTX in combination with adalimumab. No statistical differences in minimal clinically important differences in physical function were detected. Statistically significant trends for achieving low disease activity and remission were demonstrated with increasing MTX dose by validated clinical indices; differences comparing 10 and 20 mg MTX were minimal. Adalimumab serum concentrations increased with ascending dose up to 10 mg MTX. More patients experienced infectious adverse events with increasing MTX dose. Increasing doses of MTX in combination with adalimumab demonstrated a statistically significant trend in improved clinical outcomes that mimicked the adalimumab pharmacokinetic profile. In early RA patients initiating adalimumab combination therapy, efficacy of 10 and 20 mg/week MTX appeared equivalent.Keywords
This publication has 33 references indexed in Scilit:
- Efficacy and safety of certolizumab pegol in a broad population of patients with active rheumatoid arthritis: results from the REALISTIC phase IIIb studyRheumatology, 2012
- Induction therapy with adalimumab plus methotrexate for 24 weeks followed by methotrexate monotherapy up to week 48 versus methotrexate therapy alone for DMARD-naïve patients with early rheumatoid arthritis: HIT HARD, an investigator-initiated studyAnnals Of The Rheumatic Diseases, 2012
- Clinical, functional and radiographic consequences of achieving stable low disease activity and remission with adalimumab plus methotrexate or methotrexate alone in early rheumatoid arthritis: 26-week results from the randomised, controlled OPTIMA studyAnnals Of The Rheumatic Diseases, 2012
- 2012 Update of the 2008 American College of Rheumatology recommendations for the use of disease‐modifying antirheumatic drugs and biologic agents in the treatment of rheumatoid arthritisArthritis Care & Research, 2012
- The effects of golimumab on radiographic progression in rheumatoid arthritis: Results of randomized controlled studies of golimumab before methotrexate therapy and golimumab after methotrexate therapyArthritis & Rheumatism, 2011
- Multinational evidence-based recommendations for the use of methotrexate in rheumatic disorders with a focus on rheumatoid arthritis: integrating systematic literature research and expert opinion of a broad international panel of rheumatologists in the 3E InitiativeAnnals Of The Rheumatic Diseases, 2008
- Comparison of the clinical efficacy and safety of subcutaneous versus oral administration of methotrexate in patients with active rheumatoid arthritis: Results of a six‐month, multicenter, randomized, double‐blind, controlled, phase IV trialArthritis & Rheumatism, 2007
- Measuring function in rheumatoid arthritis: Identifying reversible and irreversible componentsArthritis & Rheumatism, 2006
- Course of radiographic damage over 10 years in a cohort with early rheumatoid arthritisAnnals Of The Rheumatic Diseases, 2003
- The american rheumatism association 1987 revised criteria for the classification of rheumatoid arthritisArthritis & Rheumatism, 1988