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Treatment efficacy and methotrexate-related toxicity in patients with rheumatoid arthritis receiving methotrexate in combination with adalimumab

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Burmester GR1, Kaeley GS2, Kavanaugh AF3, Gabay C4, MacCarter DK5, Nash P6, Takeuchi T7, Goss SL8, Rodila R8, Chen K8, Kupper H9, Kalabic J9. RMD Open. 2017 Sep 17;3(2):e000465. doi: 10.1136/rmdopen-2017-000465. eCollection 2017.


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1 Department of Rheumatology and Clinical Immunology, Charité University Hospital, Berlin, Germany.

2 Department of Rheumatology, University of Florida College of Medicine, Jacksonville, Florida, USA.

3 Division of Rheumatology, Allergy and Immunology, University of California San Diego, San Diego, California, USA.

4 Department of Rheumatology, Geneva University Hospitals, University of Geneva, Geneva, Switzerland.

5 North Valley Hospital, Whitefish, Montana, USA.

6 Department of Medicine, University of Queensland, Brisbane, Queensland, Australia.

7 Division of Rheumatology, Department of Internal Medicine, Keio University, Tokyo, Japan.

8 AbbVie, North Chicago, Illinois, USA.

9 AbbVie Deutschland, Ludwigshafen, Germany.


BACKGROUND: Treatment of rheumatoid arthritis (RA) with a combination of methotrexate (MTX)+adalimumab (ADA) is more effective than ADA monotherapy. We assessed the toxicity of different doses of MTX and treatment efficacy of ADA+MTX in two trials.

METHODS: Data originated from CONCERTO, in patients with early RA initiating ADA+ 2.5, 5, 10 or 20 mg/week MTX for 26 weeks; and MUSICA, in patients with an inadequate response to MTX initiating ADA+ 7.5 or 20 mg/week MTX for 24 weeks. Efficacy was assessed by the American College of Rheumatology 50 (ACR50). Patient-reported MTX-related toxicity information was collected at each visit on 18 prespecified MTX-related adverse events (AE) in the MTX label.

RESULTS: In CONCERTO, ACR50 rates increased over time, ranging from 54% to 68% at week 26, while AE rates remained steady, ranging from 2.4% to 17.8% at week 26. Of 395 patients, 113 (28.6%) reported 345 MTX-related AEs, including one serious AE (SAE, excessive fatigue and/or malaise); 10 AEs (in two patients) led to study discontinuation. In MUSICA, ACR50 rates increased over time, and were 32.3% and 37.5% at week 24, while MTX-related AE rates remained steady and were 6.5% at week 24. Of 309 patients, 71 (23%) reported 185 MTX-related AEs, including 5 SAEs (four infections and one fever/chills); six AEs (in four patients) led to study discontinuation.

CONCLUSION: In patients with RA initiating ADA+MTX combination, treatment efficacy was achieved and increased throughout both trials, while rates of MTX-related AEs remained steady. MTX-related AEs were observed in up to 30% of patients and most were mild. MTX was discontinued by 0.5%-1.3% of patients.