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Rheumatoid arthritis
Original article
Treatment efficacy and methotrexate-related toxicity in patients with rheumatoid arthritis receiving methotrexate in combination with adalimumab
  1. Gerd R Burmester1,
  2. Gurjit S Kaeley2,
  3. Arthur F Kavanaugh3,
  4. Cem Gabay4,
  5. Daryl K MacCarter5,
  6. Peter Nash6,
  7. Tsutomu Takeuchi7,
  8. Sandra L Goss8,
  9. Ramona Rodila8,
  10. Kun Chen8,
  11. Hartmut Kupper9 and
  12. Jasmina Kalabic9
  1. 1 Department of Rheumatology and Clinical Immunology, Charité University Hospital, Berlin, Germany
  2. 2 Department of Rheumatology, University of Florida College of Medicine, Jacksonville, Florida, USA
  3. 3 Division of Rheumatology, Allergy and Immunology, University of California San Diego, San Diego, California, USA
  4. 4 Department of Rheumatology, Geneva University Hospitals, University of Geneva, Geneva, Switzerland
  5. 5 North Valley Hospital, Whitefish, Montana, USA
  6. 6 Department of Medicine, University of Queensland, Brisbane, Queensland, Australia
  7. 7 Division of Rheumatology, Department of Internal Medicine, Keio University, Tokyo, Japan
  8. 8 AbbVie, North Chicago, Illinois, USA
  9. 9 AbbVie Deutschland, Ludwigshafen, Germany
  1. Correspondence to Dr Gerd R Burmester; gerd.burmester{at}charite.de

Abstract

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.

Trial registration number MUSICA (NCT01185288), CONCERTO (NCT01185301), Post results.

  • adalimumab
  • methotrexate
  • rheumatoid arthritis
  • combination treatment
  • toxicity
  • efficacy

This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/

https://doi.org/10.1136/rmdopen-2017-000465

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    Footnotes

    • Contributors GRB, GSK, AK, CG, DKM, PN, TT, SLG, HK and JK contributed to the design, review and interpretation of data. KC and RR contributed to the data analyses and interpretation. In accordance with ICMJE authorship criteria, all authors are responsible for the development of this manuscript, and have reviewed and approved the final version.

    • Funding AbbVie funded the clinical trials (NCT01185301 and NCT01185288).

    • Competing interests GRB has received research grants and consulting fees or other remuneration from, and served on speakers’ bureaus on behalf of AbbVie, Bristol-Myers Squibb, Merck, Roche, Pfizer and UCB. GSK is a consultant for AbbVie. AK has received grant/research and/or provided expert advice to AbbVie, Amgen, Astra-Zeneca, BMS, Celgene, Centocor-Janssen, Pfizer, Roche and UCB. CG has received research grants and/or provided expert advice to AbbVie, Amgen, BMS, MSD, Pfizer, Roche, Celgene, Sanofi, Debiopharm, AB2 Bio and Regeneron. DKM has served on speakers' bureaus and is a consultant for AbbVie. PN received funding for clinical trials, research grants, and honoraria for lectures and advice from AbbVie, BMS, Roche, Pfizer, Janssen, Amgen, Sanofi-Aventis, UCB, Eli Lilly, Novartis and Celgene. TT has received grants from Astellas, AbbVie GK, Asahi Kasei Pharma, BMS KK, Chugai, Daiichi Sankyo, Eisai, Mitsubishi Tanabe, Pfizer Japan, Santen Pharmaceutical, SymBio Pharmaceuticals, Taisho Toyama, Takeda Pharmaceutical, Teijin Pharma; speaking fees from Astellas, AbbVie GK, Asahi Kasei Pharma, BMS KK, Chugai, Daiichi Sankyo, Eisai, Mitsubishi Tanabe, Pfizer Japan, Santen Pharmaceutical, SymBio Pharmaceuticals, Taisho Toyama, Takeda and Teijin Pharma; and consultant fees from AbbVie GK, Asahi Kasei Medical KK, Astra-Zeneca, Bristol-Myers KK, Daiichi Sankyo, Eli Lilly Japan, Mitsubishi Tanabe, Nippon Kayaku and Novartis KK. SLG, RR, KC, HK and JK are employees of AbbVie and may own stock/options of AbbVie.

    • Ethics approval Institutional review boards of participating study centres.

    • Provenance and peer review Not commissioned; externally peer reviewed.

    • Data sharing statement Qualified researchers may request access to the study data sets from AbbVie via the process defined on AbbVie.com under Clinical Trial Data and Information Sharing.