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Predictors of response to methotrexate in early DMARD naïve rheumatoid arthritis: results from the initial open-label phase of the SWEFOT trial
  1. Saedis Saevarsdottir1,2,
  2. Helena Wallin1,
  3. Maria Seddighzadeh1,
  4. Sofia Ernestam1,
  5. Pierre Geborek3,
  6. Ingemar F Petersson4,
  7. Johan Bratt1,
  8. Ronald F van Vollenhoven1,
  9. for the SWEFOT Trial Investigators Group
  1. 1Rheumatology Unit, Department of Medicine, The Karolinska Institute and Karolinska University Hospital, Stockholm, Sweden
  2. 2Institute of Environmental Medicine, The Karolinska Institute, Stockholm, Sweden
  3. 3Department of Rheumatology, Lund University Hospital, Lund, Sweden
  4. 4Department of Orthopedics, South Sweden Musculoskeletal Research Centre, Lund University Hospital, Lund, Sweden
  1. Correspondence to Dr Saedis Saevarsdottir, Rheumatology Unit, Department of Medicine, Karolinska University Hospital, 17176 Stockholm, Sweden; saedis.saevarsdottir{at}


Objective To identify predictors of response to methotrexate (MTX) in early rheumatoid arthritis (RA).

Methods In the SWEFOT trial, patients with RA with symptom duration <1 year started MTX monotherapy (20 mg/weekly) and 405/487 continued until the 3–4- month visit. The primary outcome measure was the DAS28-based European League against Rheumatism (EULAR) response criteria. Multivariate logistic regression was used to study the association between response and the following baseline characteristics: gender, age, symptom duration, cigarette smoking habits, autoantibody status, Health Assessment Questionnaire (HAQ) score, concurrent prednisolone and treatment with non-steroidal anti-inflammatory drugs. Secondary response and remission measures were the American College of Rheumatology and the Simple Disease Activity Index and Clinical Disease Activity Index (SDAI/CDAI)-derived criteria.

Results After 3–4 months of MTX treatment, the frequency of EULAR good/moderate/no response was 34%/41%/25%, respectively. Parameters associated with a decreased likelihood of EULAR response were female gender (adjusted OR (adj OR) 0.50, 95% CI 0.31 to 0.81), symptom duration (adj OR per month increase 0.93, 95% CI 0.88 to 0.99), current smoking (adj OR 0.35, 95% CI 0.20 to 0.63) and higher HAQ (adj OR 0.56, 95% CI 0.40 to 0.80). Parameters associated with an increased likelihood of EULAR response were higher age (adj OR per 10-year increase 1.30, 95% CI 1.11 to 1.51) and prednisolone treatment (adj OR 2.84, 95% CI 1.43 to 5.63). The findings were similar when patients on prednisolone were excluded and other response criteria tested, although current smoking was the only significant predictor using all response criteria, while HAQ was the only significant predictor of all the remission criteria used. A matrix showed up to ninefold differences between subgroups stratified by the main predictors.

Conclusion Current smoking, female sex, longer symptom duration and younger age predict a worse response to MTX in patients with new-onset RA.

TrialRegNo NCT00764725

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  • NCT00764725 (

  • SWEFOT Trial Investigators Group Lars Cöster, Linköping; Eva Waltbrand, Borås; Agneta Zickert, Stockholm; Jan Theander, Kristianstad; Åke Thörner, Eskilstuna; Helena Hellström, Falun; Annika Teleman, Halmstad; Christina Dackhammar, Mölndal; Finn Akre, Örebro; Kristina Forslind, Helsingborg; Lotta Ljung, Umeå; Rolf Oding, Västerås; Katerina Chatzidionysiou, Stockholm; Margareta Wörnert, Stockholm.

  • Funding The study was supported in part by a grant from the Swedish Rheumatism Association. SS, RvV and SE were supported by clinical research funds from Stockholm county (ALF funds). An annual unrestricted grant was provided by Schering-Plough Sweden that was used to support the study coordinator (MW) and a medical monitor.

  • Competing interests None.

  • Patient consent All patients were provided with oral and written information prior to inclusion and consented to participate by signing the informed consent document.

  • Ethics approval This study was conducted with the approval of the regional ethical committees of the participating clinics in Sweden.

  • Provenance and peer review Commissioned; externally peer-reviewed.