Summary of findings 3. Prophylaxis regimen versus on‐demand treatment.
| Prophylaxis regimen compared with on‐demand treatment for previously treated individuals with haemophilia A or B | ||||||
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Patient or population: children and adults with haemophilia A or B Settings: outpatient Intervention: secondary prophylaxis Comparison: on‐demand treatment | ||||||
| Outcomes | Illustrative comparative risks* (95% CI) | Relative effect (95% CI) | No of Participants (studies) | Certainty of the evidence (GRADE) | Comments | |
| Assumed risk | Corresponding risk | |||||
| On‐demand treatment | Prophylaxis regimen | |||||
| Number of joint bleeding episodes or joint bleeding frequency Follow‐up: 12 months |
The mean number of joint bleeding episodes in the on‐demand treatment group was 34 | The mean number of joint bleeding episodes in the prophylaxis regimen group was 30.34 lower (46.95 lower to 13.73 lower) | MD ‐30.34 (‐46.95 to ‐13.73) | 164 (2 trials) |
⊕⊕⊝⊝ lowa,b | The data from the A‐LONG trial suggests the same; however, these data were reported with medians, hence could not be included in the analysis. |
| Number of total bleeds per year or bleeding frequency Follow‐up: 12 months |
The mean number of total bleeds in the on‐demand treatment group was 44 | The mean number of total bleeds in the prophylaxis regimen group was 40.24 lower (64.04 lower to 16.44 lower) | MD ‐40.24 (‐64.04 to ‐16.44) | 164 (2 trials) |
⊕⊕⊝⊝
lowa,b |
The data from the A‐LONG trial suggests the same effect; however, these data were reported with medians, hence could not be included in the analysis (A‐LONG 2014). When comparing the overall bleeding frequency in 9 participants in the Aronstam cross‐over trial, there was a significant reduction in the overall bleeding frequency in the prophylaxis group |
| Any reported adverse events Follow‐up: 12 months |
415 per 1000 (27 per 65) | 712 per 1000 (47 per 66) The number of participants with adverse events in the prophylaxis regimen group was 1.71 times higher (1.24 times higher to 2.37 times higher) |
RR 1.71 (1.24 to 2.37) |
131 (2 trials) |
⊕⊕⊕⊝ moderatea | The 2 trials were open‐label trials with unclear risk of bias for randomised sequence generation (A‐LONG 2014; SPINART 2013). The LEOPOLD II trial did not give the distribution of adverse events across groups, but there were 3 reported treatment‐related adverse events while no participant developed an inhibitor during the course of treatment (LEOPOLD II 2015). In the 1976 Aronstam trial, one participant developed antigen‐negative hepatitis and was removed from the remaining duration of the trial (Aronstam 1976). |
| *Th\e basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% CI) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: confidence interval; RR: risk ratio; MD: mean difference | ||||||
| GRADE Working Group grades of evidence High certainty: further research is very unlikely to change our confidence in the estimate of effect. Moderate certainty: further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate. Low certainty: further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate. Very low certainty: we are very uncertain about the estimate. | ||||||
a. Downgraded once due to high risk of bias due to performance and detection bias attributed to open‐label studies. b. Downgraded once due to high levels of heterogeneity across trials.