title: Adalimumab alone and in combination with disease-modifying antirheumatic drugs for the treatment of rheumatoid arthritis in clinical practice: the Research in Active Rheumatoid Arthritis (ReAct) trial.
abstract: OBJECTIVE
  To evaluate the safety and effectiveness of adalimumab alone or in combination with standard disease-modifying antirheumatic drugs (DMARDs) for the treatment of rheumatoid arthritis (RA).
  
  
  METHODS
  Patients with active RA despite treatment with DMARDs or prior treatment with a tumour necrosis factor antagonist participated in a multicentre, open-label clinical study of adalimumab 40 mg every other week for 12 weeks with an optional extension phase. Patients were allowed to continue with pre-existing traditional DMARDs. Long-term safety results are reported for all patients (4210 patient-years (PYs) of adalimumab exposure). The observed effectiveness results at week 12 are reported using American College of Rheumatology (ACR) and European League Against Rheumatism (EULAR) response criteria.
  
  
  RESULTS
  Among the 6610 treated patients, adalimumab was generally well tolerated. Serious infections occurred in 3.1% of patients (5.5/100 PYs, including active tuberculosis, 0.5/100 PYs). Demyelinating disease (0.06%) and systemic lupus erythematosus (0.03%) were rare serious adverse events. The standardised incidence ratio of malignancy was 0.71 (95% CI 0.49 to 1.01). The standardised mortality ratio was 1.07 (95% CI 0.75 to 1.49). At week 12, 69% of patients achieved an ACR20 response, 83% a moderate, and 33% a good EULAR response. Adalimumab was effective in combination with a variety of DMARDs. The addition of adalimumab to antimalarials was comparably effective to the combination of adalimumab and methotrexate.
  
  
  CONCLUSIONS
  Considering the limitations of an open-label study, adalimumab alone or in combination with standard DMARDs appeared to be well tolerated and effective in 6610 difficult-to-treat patients with active RA treated in clinical practice.
authors.affiliation: Department of Rheumatology and Clinical Immunology, Charité-University Medicine Berlin, Charitéplatz 1, 10117 Berlin, Germany. gerd.burmester@charite.de
authors.forename: Gerd R
authors.initials: GR
authors.lastname: Burmester
authors.forename: Xavier
authors.initials: X
authors.lastname: Mariette
authors.forename: Carlomaurizio
authors.initials: C
authors.lastname: Montecucco
authors.forename: Indalecio
authors.initials: I
authors.lastname: Monteagudo-Sáez
authors.forename: Michel
authors.initials: M
authors.lastname: Malaise
authors.forename: Athanasios G
authors.initials: AG
authors.lastname: Tzioufas
authors.forename: Johannes W J
authors.initials: JW
authors.lastname: Bijlsma
authors.forename: Kristina
authors.initials: K
authors.lastname: Unnebrink
authors.forename: Sonja
authors.initials: S
authors.lastname: Kary
authors.forename: Hartmut
authors.initials: H
authors.lastname: Kupper
mesh_terms: D000068879:Adalimumab; D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009894:Opportunistic Infections / Q000209:etiology; D010352:Patient Dropouts; D012720:Severity of Illness Index; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents; D014409:Tumor Necrosis Factor-alpha; D000068879:Adalimumab