title: Conventional combination treatment versus biological treatment in methotrexate-refractory early rheumatoid arthritis: 2 year follow-up of the randomised, non-blinded, parallel-group Swefot trial.
abstract: BACKGROUND
  Analysis of the Swedish Farmacotherapy (Swefot) trial at 12 months showed that the addition of an anti-tumour-necrosis-factor agent gave an improved clinical outcome compared with the addition of conventional disease-modifying antirheumatic drugs in patients with methotrexate-refractory early rheumatoid arthritis. Here we report the 2 year follow-up assessment.
  
  
  METHODS
  In this randomised, non-blinded, parallel-group trial, we enrolled adult patients older than 18 years with rheumatoid arthritis and a symptom duration of less than 1 year from 15 rheumatology units in Sweden between December, 2002 and December, 2006. All patients were started on methotrexate. After 3-4 months, those who failed treatment were randomly assigned (1:1) to group A (conventional treatment; additional sulfasalazine and hydroxychloroquine) or group B (biological treatment; additional infliximab). Randomisation was done with a computer-generated sequence. We analysed clinical outcomes at months 18 and 24 by the response criteria of the American College of Rheumatology and the European League Against Rheumatism, and radiographs of patients' hands and feet at months 12 and 24 using the Van der Heijde modification of the Sharp score. Analysis was by intention to treat. This trial is registered with www.ClinicalTrials.gov, number NCT00764725.
  
  
  RESULTS
  Of 493 screened individuals, we enrolled 487, of whom 258 were randomly allocated to treatment. The proportion of patients in group B who received a EULAR-defined good response was non-significantly greater than it was in group A at 18 months (49 of 128 [38%] vs 38 of 130 [29%]) and at 24 months (49 of 128 [38%] vs 40 of 130 [31%]; p=0·204). After 24 months, radiological disease progression was greater in patients in group A than it was in those in group B (mean 7·23 [SD 12·72] vs 4·00 [10·0]; p=0·009). We recorded three serious adverse events: an extended generalised illness in group A, an extended febrile episode in group B, and a generalised illness in group B.
  
  
  CONCLUSIONS
  Additional biological treatment is a valid option for patients who fail initial methotrexate treatment. However, improved clinical outcomes after 12 months and better radiographical results after 24 months should be weighed against the absence of a convincing clinical difference at 24 months and substantially higher costs. Therefore, for many patients who fail initial methotrexate treatment, add-on treatment with disease-modifying antirheumatic drugs is an appropriate treatment option.
  
  
  BACKGROUND
  Swedish Rheumatism Association, Stockholm County, and Schering-Plough/Merck Sharp and Dohme.
authors.affiliation: Unit for Clinical Therapy Research, Inflammatory Diseases, Karolinska Institute, Stockholm, Sweden. ronald.van.vollenhoven@ki.se
authors.forename: Ronald F
authors.initials: RF
authors.lastname: van Vollenhoven
authors.forename: Pierre
authors.initials: P
authors.lastname: Geborek
authors.forename: Kristina
authors.initials: K
authors.lastname: Forslind
authors.forename: Kristina
authors.initials: K
authors.lastname: Albertsson
authors.forename: Sofia
authors.initials: S
authors.lastname: Ernestam
authors.forename: Ingemar F
authors.initials: IF
authors.lastname: Petersson
authors.forename: Katerina
authors.initials: K
authors.lastname: Chatzidionysiou
authors.forename: Johan
authors.initials: J
authors.lastname: Bratt
mesh_terms: D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D018501:Antirheumatic Agents / Q000008:administration & dosage*; D001172:Arthritis, Rheumatoid / Q000000981:diagnostic imaging / Q000188:drug therapy*; D001691:Biological Therapy; D004351:Drug Resistance; D004359:Drug Therapy, Combination; D005260:Female; D005529:Foot Bones / Q000000981:diagnostic imaging; D050276:Hand Bones / Q000000981:diagnostic imaging; D006801:Humans; D006886:Hydroxychloroquine / Q000008:administration & dosage; D000069285:Infliximab; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use*; D008875:Middle Aged; D011859:Radiography; D012460:Sulfasalazine / Q000008:administration & dosage; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
chemical_list: D000911:Antibodies, Monoclonal; D018501:Antirheumatic Agents; D014409:Tumor Necrosis Factor-alpha; D012460:Sulfasalazine; D006886:Hydroxychloroquine; D000069285:Infliximab; D008727:Methotrexate