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Adding baseline protein biomarkers to clinical predictors does not enhance prediction of treatment response to a methotrexate strategy in early rheumatoid arthritis
  1. Xavier M Teitsma1,
  2. Johannes W G Jacobs1,
  3. Pascal H P de Jong2,
  4. Johanna M W Hazes2,
  5. Angelique E A M Weel2,3,
  6. Paco M J Welsing1,
  7. Attila Pethö-Schramm4,
  8. Michelle E A Borm5,
  9. Jacob M van Laar1,
  10. Johannes W J Bijlsma1,
  11. Floris P J G Lafeber1
  1. 1 Department of Rheumatology & Clinical Immunology, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands
  2. 2 Department of Rheumatology, University Medical Center Rotterdam, Rotterdam, The Netherlands
  3. 3 Department of Rheumatology, Maasstad Hospital, Rotterdam, The Netherlands
  4. 4 F Hoffman-La Roche, Basel, Switzerland
  5. 5 Roche Nederland BV, Woerden, The Netherlands
  1. Correspondence to Xavier M Teitsma, Department of Rheumatology & Clinical Immunology, University Medical Center Utrecht, Utrecht 85500, The Netherlands; x.m.teitsma{at}

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Recently, we identified baseline higher disease activity score assessing 28 joints, current smoking and no alcohol consumption as predictors of inadequate response (IR) to methotrexate (MTX), used with or without other conventional synthetic disease modifying anti-rheumatic drugs, here designated as ‘MTX+’, in new-onset rheumatoid arthritis (RA).1 For those with a predicted IR to ‘MTX+’, a more intensive treatment strategy could be initiated, if prediction would be reliable. Therefore, we investigated, within the same patient population, protein biomarkers for additive predictive value to these clinical predictors.

A model was developed using data from patients with RA in the U-Act-Early trial ( number NCT01034137) treated with a step-up MTX strategy (n=106) and was validated in patients who received MTX therapy (n=80) in the treatment in the Rotterdam Early Arthritis Cohort trial (tREACH, ISRCTN26791028).2,3 IR to ‘MTX+’ therapy was defined as the need to initiate a biological within the first treatment year. In baseline serum, 85 proteins were analysed in 2014 using multiplex Luminex profiling; seven candidate proteins, identified by partial least square discriminant analyses, were remeasured in 2018.

Clinical baseline characteristics of the patients in both studies are shown in table 1. Of the proteins identified in the development cohort, in the …

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  • Handling editor Prof Josef S Smolen

  • Contributors All authors were involved with drafting the article or revising it critically and approved the final draft to be published and agree to be accountable for all aspects. Study conception or design: XMT, JWGJ, PMJW, PHPdJ, FPJGL, JWJB. Acquisition of data: XMT, JWGJ, PMJW, PHPdJ, AP-S and MEAB. Analysis or interpretation of data: all authors.

  • Funding The U-Act-Early trial was funded by Roche Nederland BV and the work within the tREACH trial was supported by an unrestricted grant from Pfizer.

  • Competing interests The department of the authors who included patients (JWGJ and JWJB) in the U-Act-Early trial received reimbursements from Roche Nederland BV. JWJB reported grants and fees from Roche, AbbVie, Bristol-Myers Squibb, Merck Sharp & Dohme, Pfizer and UCB. JMvL received fees from Arthrogen, MSD, Pfizer, Eli Lilly and BMS and research grants from Astra Zeneca and Roche-Genentech. FPJGL reports grants from Roche. AP-S is an employee of F Hoffmann-La Roche, and MEAB is an employee of Roche Nederland BV.

  • Patient consent Obtained.

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