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The effect of methotrexate versus other disease-modifying anti-rheumatic drugs on serum drug levels and clinical response in patients with rheumatoid arthritis treated with tumor necrosis factor inhibitors

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Abstract

To investigate the effect of concomitant conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) with adalimumab or infliximab on maintaining serum drug and clinical outcomes after the first year of treatment in patients with rheumatoid arthritis (RA). Second, to assess the influence of methotrexate (MTX) dose on these outcomes. Ninety-two patients with RA starting infliximab (n = 67) or adalimumab (n = 25) tumor necrosis factor inhibitor (TNFi) with available drug levels and clinical improvement assessment (European League Against Rheumatism [EULAR] response) after 12 months were included. Patients were grouped according to concomitant csDMARD use: (i) TNFi monotherapy; (ii) TNFi+MTX; (iii) TNFi with csDMARDs other than MTX (TNFi+OD). Patients receiving MTX were also classified by dose as < 15 mg/week (TNFi+MTX<15) and ≥ 15 mg/week (TNFi+MTX≥15). Logistic regression analyses were employed. More TNFi+MTX patients had circulating serum TNFi at 12 months (71% TNFi+MTX vs. 20% TNFi+OD vs. 9% TNFi monotherapy). Of these, the probability of maintaining serum TNFi levels was twice (OR 2.3; p = 0.06) than that of patients without MTX. However, statistically significant results were observed only for the highest MTX dose (OR 4.9; p = 0.02). Most patients achieving good EULAR response were treated with TNFi+MTX (81%). The probability of achieving this response was three times higher in patients within the TNFi+MTX group (OR 3.4; p = 0.03); however, no differences were found with regard to MTX dose. The persistence of serum TNFi and the probability of achieving clinical response are influenced by MTX but not by OD in patients with RA treated with infliximab or adalimumab.

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Acknowledgements

Chamaida Plasencia-Rodríguez has received speaking fees or funding for research projects from Pfizer, Lilly, Novartis, and Roche. Victoria Navarro-Compán has received speaking fees or funding for research projects and attending congresses from AbbVie, BMS, Lilly, MSD, Novartis, Pfizer, Roche, and UCB; Dora Pascual-Salcedo has received speaking fees of Abbvie, Pfizer, Takeda, Menarini, and Grifols. Alejandro Balsa has received unrestricted grants from Pfizer, Roche, and AbbVie and speaker fees from Pfizer, Janssen, AbbVie, MSD, BMS, UCB, Nordic, Sandoz, and Roche.

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Authors and Affiliations

  1. Immuno-Rheumatology Group, Hospital La Paz Institute for Health Research (IdiPAZ), Paseo de la Castellana 261, 28046, Madrid, Spain

    Ana Martínez-Feito, Chamaida Plasencia-Rodríguez, Victoria Navarro-Compán, Borja Hernández-Breijo, Dora Pascual-Salcedo & Alejandro Balsa

  2. Immunology Unit, University Hospital La Paz, La Paz, Spain

    Ana Martínez-Feito, María Ángeles González & Pilar Nozal

  3. Rheumatology Department, University Hospital La Paz, La Paz, Spain

    Chamaida Plasencia-Rodríguez, Victoria Navarro-Compán, Irene Monjo, Laura Nuño & Alejandro Balsa

Authors
  1. Ana Martínez-Feito
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  2. Chamaida Plasencia-Rodríguez
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  3. Victoria Navarro-Compán
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  4. Borja Hernández-Breijo
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  5. María Ángeles González
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  6. Irene Monjo
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  7. Laura Nuño
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  8. Pilar Nozal
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  9. Dora Pascual-Salcedo
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  10. Alejandro Balsa
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Corresponding author

Correspondence to Ana Martínez-Feito.

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The study was approved by the La Paz University Hospital Ethics Committee and all the patients signed an informed consent document.

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Electronic supplementary material

ESM 1

Flowchart of the study population.Description of study population according to the different concomitant use of csDMARDs at baseline.RA: rheumatoid arthritis; TNFi: TNF inhibitor; csDMARDs: conventional synthetic disease-modifying anti-rheumatic drugs; MTX:methotrexate; OD:other csDMARDs. (JPG 84 kb)

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Martínez-Feito, A., Plasencia-Rodríguez, C., Navarro-Compán, V. et al. The effect of methotrexate versus other disease-modifying anti-rheumatic drugs on serum drug levels and clinical response in patients with rheumatoid arthritis treated with tumor necrosis factor inhibitors. Clin Rheumatol 38, 949–954 (2019). https://doi.org/10.1007/s10067-018-4355-0

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  • DOI: https://doi.org/10.1007/s10067-018-4355-0

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