title: A randomised trial evaluating anakinra in early active rheumatoid arthritis.
abstract: OBJECTIVE
  The effectiveness of anakinra (interleukin-1 receptor antagonist) in early rheumatoid arthritis (RA) is unknown. We evaluated the efficacy of anakinra (combined with methotrexate) in a randomised clinical trial of early active RA patients.
  
  
  METHODS
  The Combination Anti-Rheumatic Drugs in Early RA-2 (CARDERA-2) trial was a randomised trial of early (duration <1 year) active RA. Patients were randomised to 12 months of: (1) methotrexate or (2) anakinra-methotrexate. Follow-up lasted 2 years. The primary outcome was erosive progression (changes from baseline in modified Larsen scores). Secondary outcomes were changes from baseline in disease activity score on a 28-joint count (DAS28), health assessment questionnaire (HAQ), and quality of life (EQ-5D) scores alongside ACR responder rates.
  
  
  RESULTS
  154 patients received the allocated intervention (from 259 screened). Similar Larsen score progression was seen at 12 and 24 months in patients receiving anakinra-methotrexate (mean changes from baseline of 2.50 and 5.10, respectively) and methotrexate monotherapy (mean changes from baseline of 4.16 and 5.20, respectively). Lower improvements in DAS28 and HAQ scores were seen at all time-points in anakinra-methotrexate treated patients; these were significantly less at 24 months (DAS28 p=0.04; HAQ P=0.02). Significantly lower EQ-5D score increases were seen at 12 months with anakinra-methotrexate (p=0.03). Anakinra-methotrexate was associated with more serious adverse events compared with methotrexate monotherapy (11 vs. 6 patients), although this was not significant (p=0.59).
  
  
  CONCLUSIONS
  Anakinra (combined with methotrexate) is not effective in early, active RA. It provided no clinical benefits beyond methotrexate monotherapy.
authors: Department of Medical and Molecular Genetics, King's College London, Guy's Hospital, London; and Academic Department of Rheumatology, Centre for Molecular and Cellular Biology of Inflammation, King's College, London, UK. ian.scott@kcl.ac.uk.
authors: Ian C
authors: IC
authors: Scott
authors: Department of Rheumatology, Weston Education Centre, King's College Hospital, London, UK.
authors: Fowzia
authors: F
authors: Ibrahim
authors: Department of Rheumatology, Weston Education Centre, King's College Hospital, London, UK.
authors: Gemma
authors: G
authors: Simpson
authors: Department of Rheumatology, Weston Education Centre, King's College Hospital, London, UK.
authors: Anna
authors: A
authors: Kowalczyk
authors: King's Clinical Trials Unit at KHP, Institute of Psychiatry, Psychology and Neuroscience, King's College, London, UK.
authors: Beverley
authors: B
authors: White-Alao
authors: Department of Rheumatology, Haywood Hospital, Stoke-on-Trent, Staffordshire, UK.
authors: Andrew
authors: A
authors: Hassell
authors: Department of Rheumatology, James Cook University Hospital, Middlesbrough, UK.
authors: Michael
authors: M
authors: Plant
authors: Department of Rheumatology, Poole Hospital, Poole, UK.
authors: Selwyn
authors: S
authors: Richards
authors: Department of Rheumatology, Freeman Hospital, Newcastle upon Tyne, UK.
authors: David
authors: D
authors: Walker
authors: Department of Rheumatology, Weston Education Centre, King's College Hospital, London, UK.
authors: David L
authors: DL
authors: Scott
mesh_terms: D000328:Adult; D000368:Aged; D018501:Antirheumatic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000175:diagnosis / Q000188:drug therapy* / Q000276:immunology; D004185:Disability Evaluation; D018450:Disease Progression; D004359:Drug Therapy, Combination; D004739:England; D005260:Female; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use; D008875:Middle Aged; D011788:Quality of Life; D012074:Remission Induction; D012720:Severity of Illness Index; D011795:Surveys and Questionnaires; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D018501:Antirheumatic Agents; D053590:Interleukin 1 Receptor Antagonist Protein; D008727:Methotrexate