Mannon 2004.
| Methods | Randomized, double‐blind, placebo‐controlled, multi‐center trial in the USA, Germany, and the Netherlands Patients were randomized 1:2:2 to placebo or one of the two dosages of briakinumab |
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| Participants | Participants with clinically active Crohn's disease (N = 79) Inclusion criteria: CDAI 220‐450, age ≥18 years Exclusion criteria: recently started Crohn's related medication, infections, history of malignancies, moderate to severe asthma, pregnancy/lactation, intestinal obstruction, stricture, ostomy, short bowel syndrome or probable operation in the near future |
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| Interventions | Briakinumab was given at two different dosages: 1 mg/kg body weight subcutaneously (n = 31) or 3 mg/kg body weight subcutaneously (n = 32) Patients were enrolled into two cohorts with different dosing regimens (week 0, 4, 5, 6, 7, 8, 9 or week 0, 1, 2, 3, 4, 5, 6) with the first forty patients being enrolled in the former dosing regimen Each dosing cohort included a placebo group with 8 patients |
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| Outcomes | Primary outcome: adverse events Secondary outcomes: clinical response (CDAI decrease ≥ 100), clinical remission (CDAI < 150), anti‐drug antibodies, histologic response (subgroup, modified D'Haens score, only partially reported), cytokine secretion by lamina propria mononuclear cells (subgroup, only partially reported) Endoscopic relapse / remission and quality of life were not assessed |
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| Duration of follow‐up | ˜27 weeks after last injection (i.e. 5 to 6 months after randomisation) | |
| Notes | For the purpose of this review the two different dosing regimens were combined for each dosage of briakinumab Different dosages were assessed separately The respective control groups were split evenly |
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| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | Computer generated randomization (as per investigator) |
| Allocation concealment (selection bias) | Low risk | Telephone interactive voice response system for treatment allocation (as per investigator) |
| Blinding (performance bias and detection bias) All outcomes | Low risk | Blinding of patients and investigators: The placebo was the same isotonic solution as the antibody |
| Incomplete outcome data (attrition bias) clinical relapse / remission | Low risk | Last observation carried forward for incomplete data Drop‐outs were balanced across interventions with similar reasons for withdrawal |
| Incomplete outcome data (attrition bias) adverse events | Low risk | Participants who discontinued the study were included in the safety analysis unless lost to follow‐up Drop‐outs were balanced across interventions with similar reasons for withdrawal |
| Selective reporting (reporting bias) | Unclear risk | Pre‐specified primary and secondary outcomes (safety and efficacy) were reported Histology and laboratory scores were only reported for the treatment group |
| Other bias | Low risk | The study appears to be free of other sources of bias |