Targan 2007.
Methods | A phase III, randomized, double‐blind, placebo‐controlled , multi‐center (114 sites), 12 week induction trial Permitted concurrent therapies for Crohn’s disease: stable doses of 5‐ASA, prednisone or an equivalent corticosteroid (20 mg/day), budesonide (6 mg/day), AZA, 6‐MP, MTX, and antibiotics, were permitted Exclusion criteria: short‐bowel syndrome, an ostomy, total colectomy, a stricture with obstructive symptoms, draining fistulas, an abdominal abscess, anti‐TNF‐α therapy within the previous 12 weeks, previous natalizumab therapy |
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Participants | 509 patients with moderate to severely active Crohn's disease (CDAI ≥220 and ≤ 450) and evidence of active inflammation (CRP > 2.87 mg/L) Patients were randomized 1:1 to treatment with natalizumab or placebo infusions at weeks 0, 4, and 8 Efficacy and safety assessments were performed at weeks 4, 8, and 12 |
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Interventions | Three infusions of intravenous natalizumab (300 mg, n = 259) or placebo (n = 250) at weeks 0, 4, and 8 | |
Outcomes | The primary outcome variable was response by week eight which was defined as a reduction of > 70 points in the CDAI score from baseline that sustained through week twelve Secondary outcome variables included the proportion of patients achieving response at week twelve, a clinical remission (defined as a CDAI score of less than 150) by week eight sustained to week twelve, and the proportion of patients with remission at week 12 Tertiary outcomes included proportion achieving a > 100‐point CDAI score decrease at weeks eight and twelve, achieving clinical response or remission at weeks four and eight, response at week eight, time to clinical remission, mean change in baseline CDAI, platelets and CRP at weeks four, eight and twelve, and to evaluate the effects of natalizumab on quality of life (IBDQ and SF‐36) at week twelve |
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Notes | Industry support: Funded by Elan Pharmaceuticals, Inc and Biogen Idec. Various authors acted as paid consultants or employees for Elan or Biogen Idec | |
Risk of bias | ||
Bias | Authors' judgement | Support for judgement |
Random sequence generation (selection bias) | Low risk | Centrally stratified |
Allocation concealment (selection bias) | Low risk | Centrally randomized |
Blinding (performance bias and detection bias) All outcomes | Low risk | Double‐blind: the patients, site staff, and study investigators were all blinded to treatment assignment |
Incomplete outcome data (attrition bias) All outcomes | Low risk | Patient withdrawals were reported as failures and were evenly distributed across treatment groups |
Selective reporting (reporting bias) | Unclear risk | Most expected outcomes were reported Although the mean change in SF‐36 and its components (a secondary outcome) was not reported the authors did report on the mean change in IBDQ from baseline |
Other bias | Low risk | The study appears to be free of other sources of bias |
CDAI: Crohn's disease activity index
AZA: azathioprine
6‐MP: 6‐mercaptopurine
MTX: methotrexate
CYA: cyclosporine
ID: investigational drug
CRP: C‐reactive protein
IBDQ: Inflamatory Bowel Disease Questionnaire
5‐ASA: 5‐aminosalicylic acid
TAC: tacrolimus
ESR: erythrocyte sedimentation rate
anti‐TNF‐α: anti‐tumour necrosis factor‐alpha
SF‐36: 36‐Item Short Form Health Survey