Predictors of disease activity and structural progression after treatment with adalimumab plus methotrexate or continued methotrexate monotherapy in patients with early rheumatoid arthritis and suboptimal response to methotrexate
Josef S Smolen, Ronald F van Vollenhoven, Stefan Florentinus, Su Chen, Jessica L Suboticki, Arthur Kavanaugh, Josef S Smolen, Ronald F van Vollenhoven, Stefan Florentinus, Su Chen, Jessica L Suboticki, Arthur Kavanaugh
Abstract
Objectives: Methotrexate is considered to be first-line therapy for rheumatoid arthritis (RA). However, a substantial proportion of treated patients do not achieve the desired goals of therapy. This analysis aimed to identify predictors of insufficient response to methotrexate in patients with early RA.
Methods: The Optimal Protocol for Treatment Initiation with Methotrexate and Adalimumab (OPTIMA) and PREMIER studies in patients with RA for <1 and <3 years, respectively, examined the efficacy of methotrexate and adalimumab in methotrexate-naive patients. This post hoc analysis included patients for whom initial methotrexate monotherapy was not successful after 6 months. Candidate predictors of insufficient response and clinically relevant radiographic progression (CRRP) included demographics, baseline disease characteristics and time-averaged disease variables over a 12-week interval. In OPTIMA, adalimumab was added to therapy after insufficient treatment response; in PREMIER, initial methotrexate therapy was continued; clinical, functional and radiologic outcomes were assessed after 1 year.
Results: Baseline 28-joint Disease Activity Score based on C-reactive protein (DAS28(CRP)) and time-averaged DAS28(CRP) over 4, 8 and 12 weeks were the strongest predictors of insufficient response to methotrexate and CRRP. Addition of adalimumab to methotrexate therapy was associated with better clinical, functional and radiographic outcomes after 1 year compared with continuing on methotrexate monotherapy.
Conclusions: In patients with early RA, baseline disease characteristics and early disease activity can predict response to methotrexate treatment and radiographic progression at 6 months. The addition of adalimumab at 6 months after methotrexate failure is associated with improved outcomes. These results support treatment-to-target strategies and timely adaptation of therapy in patients with early RA.
Trial registration number: NCT00420927, NCT00195663; Post-results.
Keywords: anti-TNF; methotrexate; rheumatoid arthritis.
Conflict of interest statement
Competing interests: JSS and AK provided remunerated expert advice to and received grant/research support for his institution from AbbVie. RFvV has received grants and research support from AbbVie, Amgen, Bristol-Myers Squibb, GlaxoSmithKline, Pfizer, Roche and UCB; and consulting fees and honoraria from AbbVie, AstraZeneca, Biotest, Bristol-Myers Squibb, Celgene, Crescendo, GlaxoSmithKline, Janssen, Lilly, Merck, Novartis, Pfizer, Roche, UCB and Vertex. SF, SC and JLS are employees of AbbVie and may hold stock or stock options.
© Author(s) (or their employer(s)) 2018. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.
Figures
![Figure 1](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/6225797/bin/annrheumdis-2018-213502f01.jpg)
Figure 2
Backward logistic regression analysis of…
Figure 2
Backward logistic regression analysis of baseline and postbaseline predictors, including DAS28(CRP), of insufficient…
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- Singh JA, Saag KG, Bridges SL, et al. . 2015 American college of rheumatology guideline for the treatment of rheumatoid arthritis. Arthritis Rheumatol 2016;68:1–26. - PubMed
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- Rezaei H, Saevarsdottir S, Forslind K, et al. . In early rheumatoid arthritis, patients with a good initial response to methotrexate have excellent 2-year clinical outcomes, but radiological progression is not fully prevented: data from the methotrexate responders population in the SWEFOT trial. Ann Rheum Dis 2012;71:186–91. 10.1136/annrheumdis-2011-200038 - DOI - PubMed
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- van der Heijde D, Klareskog L, Rodriguez-Valverde V, et al. . Comparison of etanercept and methotrexate, alone and combined, in the treatment of rheumatoid arthritis: two-year clinical and radiographic results from the TEMPO study, a double-blind, randomized trial. Arthritis Rheum 2006;54:1063–74. 10.1002/art.21655 - DOI - PubMed
- Randomized Controlled Trial
- Research Support, Non-U.S. Gov't
- Adalimumab / therapeutic use*
- Aged
- Antirheumatic Agents / therapeutic use*
- Arthritis, Rheumatoid / diagnostic imaging
- Arthritis, Rheumatoid / drug therapy*
- Disease Progression
- Double-Blind Method
- Drug Therapy, Combination
- Female
- Humans
- Male
- Methotrexate / therapeutic use*
- Middle Aged
- Retreatment
- Severity of Illness Index*
- Treatment Failure
- Antirheumatic Agents
- Adalimumab
- Methotrexate
- ClinicalTrials.gov/NCT00420927
- ClinicalTrials.gov/NCT00195663
- Full Text Sources
- Other Literature Sources
- Medical
- Research Materials
- Miscellaneous
![Figure 2](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/6225797/bin/annrheumdis-2018-213502f02.jpg)
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Source: PubMed