title: Induction therapy with adalimumab plus methotrexate for 24 weeks followed by methotrexate monotherapy up to week 48 versus methotrexate therapy alone for DMARD-naive patients with early rheumatoid arthritis: HIT HARD, an investigator-initiated study.
abstract: OBJECTIVE
  To investigate the long-term effects of induction therapy with adalimumab (ADA) plus methotrexate (MTX) in comparison with placebo (PBO) plus MTX in DMARD-naïve patients with active early rheumatoid arthritis (RA).
  
  
  METHODS
  Patients with active early RA (disease duration of ≤12 months) were randomly assigned to receive 40 mg ADA subcutaneously every other week (eow) plus MTX 15 mg/week subcutaneously or PBO plus MTX subcutaneously at 15 mg/week over 24 weeks. Thereafter, all patients received MTX monotherapy up to week 48. The primary outcome was the Disease Activity Score 28 (DAS28) at week 48. Secondary outcomes included proportions of patients in remission (DAS28<2.6), ACR responses, Health Assessment Questionnaire (HAQ) score and radiographic progression.
  
  
  RESULTS
  87 patients were assigned to ADA/MTX and 85 patients to PBO/MTX. At baseline, DAS28 was 6.2±0.8 in the ADA/MTX and 6.3±0.9 in the PBO/MTX groups. At week 24, treatment with ADA/MTX compared with PBO/MTX resulted in a greater reduction in DAS28 (3.0±1.2 vs 3.6±1.4; p=0.009) and other secondary outcomes such as DAS28 remission rate (47.9% vs 29.5%; p=0.021) and HAQ (0.49±0.6 vs 0.72±0.6; p=0.0014). At week 48, the difference in clinical outcomes between groups was not statistically significant (DAS28: 3.2±1.4 vs 3.4±1.6; p=0.41). Radiographic progression at week 48 was significantly greater in patients administered PBO/MTX (Sharp/van der Heijde score: ADA/MTX 2.6 vs PBO/MTX 6.4; p=0.03, Ratingen score: 1.7 vs 4.2; p=0.01).
  
  
  CONCLUSIONS
  A greater reduction in radiographic progression after initial combination therapy with ADA and MTX was seen at week 48, even after discontinuation of ADA treatment at week 24. This sustained effect was not found at the primary endpoint (DAS28 reduction).
authors: Department of Rheumatology and Clinical Immunology, Charité-Universitätsmedizin Berlin, Berlin, Germany. jacqueline.detert@charite.de
authors: Jacqueline
authors: J
authors: Detert
authors: Hans
authors: H
authors: Bastian
authors: Joachim
authors: J
authors: Listing
authors: Anja
authors: A
authors: Weiß
authors: Siegfried
authors: S
authors: Wassenberg
authors: Anke
authors: A
authors: Liebhaber
authors: Karin
authors: K
authors: Rockwitz
authors: Rieke
authors: R
authors: Alten
authors: Klaus
authors: K
authors: Krüger
authors: Rolf
authors: R
authors: Rau
authors: Christina
authors: C
authors: Simon
authors: Eva
authors: E
authors: Gremmelsbacher
authors: Tanja
authors: T
authors: Braun
authors: Bettina
authors: B
authors: Marsmann
authors: Vera
authors: V
authors: Höhne-Zimmer
authors: Karl
authors: K
authors: Egerer
authors: Frank
authors: F
authors: Buttgereit
authors: Gerd-R
authors: GR
authors: Burmester
mesh_terms: D000068879:Adalimumab; D000328:Adult; D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage*; D018501:Antirheumatic Agents / Q000008:administration & dosage*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D018450:Disease Progression; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D061345:Early Medical Intervention; D005260:Female; D006801:Humans; D060828:Induction Chemotherapy / Q000379:methods; D060046:Maintenance Chemotherapy / Q000379:methods; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage*; D008875:Middle Aged; D016896:Treatment Outcome
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents; D000068879:Adalimumab; D008727:Methotrexate