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

Gerd R. Burmester, Gurjit S. Kaeley, Arthur F. Kavanaugh, Cem Gabay, Daryl K. MacCarter, Peter Nash, Tsutomu Takeuchi, Sandra L. Goss, Ramona Rodila, Kun Chen, Hartmut Kupper, Jasmina Kalabic

Research output: Contribution to journalArticle

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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.

Original languageEnglish
Article numbere000465
JournalRMD Open
Volume3
Issue number2
DOIs
Publication statusPublished - 2017 Sep 1

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Methotrexate
Rheumatoid Arthritis
Adalimumab
Rheumatology
Chills
Fatigue
Fever

Keywords

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

ASJC Scopus subject areas

  • Rheumatology
  • Immunology and Allergy
  • Immunology

Cite this

Burmester, G. R., Kaeley, G. S., Kavanaugh, A. F., Gabay, C., MacCarter, D. K., Nash, P., ... Kalabic, J. (2017). Treatment efficacy and methotrexate-related toxicity in patients with rheumatoid arthritis receiving methotrexate in combination with adalimumab. RMD Open, 3(2), [e000465]. https://doi.org/10.1136/rmdopen-2017-000465

Treatment efficacy and methotrexate-related toxicity in patients with rheumatoid arthritis receiving methotrexate in combination with adalimumab. / Burmester, Gerd R.; Kaeley, Gurjit S.; Kavanaugh, Arthur F.; Gabay, Cem; MacCarter, Daryl K.; Nash, Peter; Takeuchi, Tsutomu; Goss, Sandra L.; Rodila, Ramona; Chen, Kun; Kupper, Hartmut; Kalabic, Jasmina.

In: RMD Open, Vol. 3, No. 2, e000465, 01.09.2017.

Research output: Contribution to journalArticle

Burmester, GR, Kaeley, GS, Kavanaugh, AF, Gabay, C, MacCarter, DK, Nash, P, Takeuchi, T, Goss, SL, Rodila, R, Chen, K, Kupper, H & Kalabic, J 2017, 'Treatment efficacy and methotrexate-related toxicity in patients with rheumatoid arthritis receiving methotrexate in combination with adalimumab', RMD Open, vol. 3, no. 2, e000465. https://doi.org/10.1136/rmdopen-2017-000465
Burmester, Gerd R. ; Kaeley, Gurjit S. ; Kavanaugh, Arthur F. ; Gabay, Cem ; MacCarter, Daryl K. ; Nash, Peter ; Takeuchi, Tsutomu ; Goss, Sandra L. ; Rodila, Ramona ; Chen, Kun ; Kupper, Hartmut ; Kalabic, Jasmina. / Treatment efficacy and methotrexate-related toxicity in patients with rheumatoid arthritis receiving methotrexate in combination with adalimumab. In: RMD Open. 2017 ; Vol. 3, No. 2.
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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.",
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author = "Burmester, {Gerd R.} and Kaeley, {Gurjit S.} and Kavanaugh, {Arthur F.} and Cem Gabay and MacCarter, {Daryl K.} and Peter Nash and Tsutomu Takeuchi and Goss, {Sandra L.} and Ramona Rodila and Kun Chen and Hartmut Kupper and Jasmina Kalabic",
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T1 - Treatment efficacy and methotrexate-related toxicity in patients with rheumatoid arthritis receiving methotrexate in combination with adalimumab

AU - Burmester, Gerd R.

AU - Kaeley, Gurjit S.

AU - Kavanaugh, Arthur F.

AU - Gabay, Cem

AU - MacCarter, Daryl K.

AU - Nash, Peter

AU - Takeuchi, Tsutomu

AU - Goss, Sandra L.

AU - Rodila, Ramona

AU - Chen, Kun

AU - Kupper, Hartmut

AU - Kalabic, Jasmina

PY - 2017/9/1

Y1 - 2017/9/1

N2 - 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.

AB - 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.

KW - adalimumab

KW - combination treatment

KW - efficacy

KW - methotrexate

KW - rheumatoid arthritis

KW - toxicity

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