Summary of findings for the main comparison. Deferasirox compared to deferoxamine in people with transfusion‐dependent thalassemia.
| Deferasirox compared to deferoxamine in people with transfusion‐dependent thalassemia | ||||||
| Patient or population: people with transfusion‐dependent thalassemia Setting: outpatient care Intervention: deferasirox Comparison: deferoxamine | ||||||
| Outcomes | Anticipated absolute effects* (95% CI) | Relative effect (95% CI) | № of participants (studies) | Quality of the evidence (GRADE) | Comments | |
| Risk with deferoxamine | Risk with deferasirox | |||||
| Mortality at any time point | Study population | RR 0.48 (0.09 to 2.63) | 1170 (8 RCTs) | ⊕⊕⊝⊝ LOW 1 2 | ||
| 7 per 1.000 | 3 per 1.000 (1 to 18) | |||||
| Responder analysis II (responder: LIC 1 to less than 7 mg Fe/g dw) | Study population | RR 0.80 (0.69 to 0.92) | 553 (1 RCT) | ⊕⊕⊕⊝ MODERATE 1 3 4 | ||
| 664 per 1.000 | 531 per 1.000 (458 to 611) | |||||
| Serum ferritin (ng/mL): mean change from baseline and at end of study | MD 454.42 higher (337.13 higher to 571.71 higher) | ‐ | 1002 (6 RCTs) 5 | ⊕⊕⊕⊝ MODERATE 1 3 4 | ||
| LIC (mg Fe/g dw) evaluated by biopsy or SQUID: mean change from baseline | MD 2.37 higher (1.68 higher to 3.07 higher) | ‐ | 541 (1 RCT) | ⊕⊕⊕⊝ MODERATE 1 3 4 | ||
| Satisfaction with treatment (very satisfied or satisfied): participants previously treated with DFO assessed with: questionnaire follow up: mean 52 weeks | Study population | RR 2.20 (1.89 to 2.57) | 571 (1 RCT) | ⊕⊕⊕⊝ MODERATE 1 | ||
| 1.330 per 1.000 | 1000 per 1.000 (1.000 to 1.000) | |||||
| Adherence: discontinuations | Study population | RR 0.95 (0.60 to 1.50) | 1211 (8 RCTs) | ⊕⊕⊝⊝ LOW 1 6 | ||
| 54 per 1.000 | 52 per 1.000 (33 to 82) | |||||
| AE: investigations ‐ isolated serum creatinine increase above ULN | Study population | RR 2.57 (1.88 to 3.51) | 657 (2 RCTs) | ⊕⊕⊝⊝ LOW 1 7 | ||
| 137 per 1.000 | 353 per 1.000 (258 to 482) | |||||
| *The risk in the intervention group (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). AE: adverse events; CI: confidence interval; DFO:deferiprone; dw: dry weight; FE: iron LIC: liver iron concentration; MD: mean difference; RR: risk ratio; SQUID: superconducting quantum interference device; ULN: upper limit of normal. | ||||||
| GRADE Working Group grades of evidence High quality: we are very confident that the true effect lies close to that of the estimate of the effect Moderate quality: we are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different Low quality: our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect Very low quality: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect | ||||||
1 Serious risk of bias: studies that carry large weight for the overall effect estimate rated as high risk of bias due to lack of blinding and selective reporting. 2 Serious imprecision: wide confidence interval including both clinically relevant benefit as well as harm. 3 Serious inconsistency: differing ratio of drugs between subgroups of one study. 4 Upgrade due to dose‐response gradient: observed for both drugs. Effects therefore depending on ratio of drugs used in comparisons. 5 A sensitivity analysis without the results from four studies which were calculated according to Wan 2014 showed similar results. 6 Serious imprecision: Wide confidence interval, including less discontinuations with deferoxamine treatment. 7 Serious indirectness: Surrogate of creatinine used for patient‐important outcome of kidney failure.