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How to treat patients with rheumatoid arthritis when methotrexate has failed? The use of a multiple propensity score to adjust for confounding by indication in observational studies
  1. Sytske Anne Bergstra1,
  2. Lai-Ling Winchow2,
  3. Elizabeth Murphy3,
  4. Arvind Chopra4,
  5. Karen Salomon-Escoto5,
  6. João Eurico Fonseca6,
  7. Cornelia F Allaart1,
  8. Robert B M Landewé7,8
  1. 1 Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands
  2. 2 Department of Rheumatology, University of the Witwatersrand, Johannesburg, South Africa
  3. 3 Department of Rheumatology, University Hospital Wishaw, Wishaw, Scotland
  4. 4 Center for Rheumatic Diseases, Pune, India
  5. 5 University of Massachusetts Medical School, Rheumatology Center, UMass Memorial Medical Center, Worcester, Massachusetts, USA
  6. 6 Serviço de Reumatologia e Doenças Ósseas Metabólicas, Hospital de Santa Maria, CHLN, Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Centro Académico de Medicina de Lisboa, Lisboa, Portugal
  7. 7 Amsterdam Rheumatology & Immunology Center, Amsterdam, The Netherlands
  8. 8 Zuyderland Medical Center, Heerlen, The Netherlands
  1. Correspondence to Sytske Anne Bergstra, Leiden University Medical Center, Leiden RC 2300, The Netherlands; s.a.bergstra{at}


Objectives To compare consecutive disease modifying antirheumatic drug (DMARD)-treatment regimes in daily practice in patients with rheumatoid arthritis (RA) who failed on initial methotrexate, while using a multiple propensity score (PS) method to control for the spurious effects of confounding by indication.

Methods Patients with newly diagnosed RA who had failed initial treatment with methotrexate were selected from METEOR, an international, observational registry. Subsequent DMARD-treatment regimens were categorised as: (1) conventional synthetic DMARD(s) (csDMARD(s)) only (143 patients), (2) csDMARD(s)+glucocorticoid (278 patients) and (3) biological DMARD (bDMARD)±csDMARD(s) (89 patients). Multiple PS that reflect the likelihood of treatment with each treatment-regime were estimated per patient using multinomial regression. Linear mixed model analyses were performed to analyse treatment responses per category (Disease Activity Score (DAS)) after a maximum follow-up duration of 6 and 12 months, and results were presented with adjustment for the multiple PS.

Results After 6 months, follow-up PS-adjusted treatment responses yielded a change in DAS per year (95%  CI) of −2.00 (−2.65 to −1.36) if patients received a bDMARD; of −0.96 (−1.33 to −0.59) if patients received csDMARD(s)+glucocorticoids and of −0.73 (−1.21 to −0.25) if patients received csDMARDs only. These changes were −0.91 (−1.23 to −0.60); −0.43 (−0.62 to −0.23) and −0.39 (−0.66 to −0.13), respectively after 1  year of follow-up.

Conclusions In this analysis of worldwide common practice data with adjustment for multiple PS, patients with RA who had failed initial treatment with methotrexate monotherapy had a better DAS-response after a subsequent switch to a bDMARD-containing treatment regimen than to a regimen with csDMARD(s) only, with or without glucocorticoids.

  • rheumatoid arthritis
  • methotrexate
  • disease activity
  • treatment

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  • Handling editor Josef S Smolen

  • Contributors SAB, CFA and RBML contributed to the design, analysis and interpretation of the data. L-LW, EM, AC, KS-E, JEF and CFA contributed to the acquisition of data. SAB drafted the work. All authors revised the manuscript and read and approved the final version of the document.

  • Competing interests SAB, L-LW, AC, KS-E, CFA, RBML: none declared. EM: received support from AbbVie and UCB to attend meetings and has received support from Roche to audit work on behalf of the Scottish Society for Rheumatology. JEF: received unrestricted research grants or acted as a speaker for Abbvie, Ache, Amgen, BIAL, Biogen, BMS, Janssen, Lilly, MSD, Novartis, Pfizer, Roche, Sanofi, UCB.

  • Patient consent Not required.

  • Ethics approval The METEOR registry contains completely anonymised data which was gathered during daily practice. Treatment, timing of follow-up visits and measurements were non-protocolled. Therefore, medical ethics board approval was not required.

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

  • Data sharing statement The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.