Table 1.
Comparative effects of erythropoiesis‐stimulating agents on clinical outcomes in chronic kidney disease
| Outcomes / interventions | Comparators (treatment estimate (OR (95% CI)) | |||||
| Epoetin alfa | Epoetin beta | Darbepoetin alfa | Methoxy polyethylene‐glycol epoetin beta | Biosimilar ESA | Placebo | |
| Blood transfusion | ||||||
| Epoetin alfa | ‐‐ | 2.04 (0.38‐11.0) | 1.06 (0.35‐3.29) | 1.14 (0.27‐4.97) | 0.66 (0.19‐2.28) | 0.18 (0.05‐0.59) |
| Epoetin beta | Not estimable | ‐‐ | 0.52 (0.10‐2.67) | 0.56 (0.11‐3.00) | 0.33 (0.04‐2.60) | 0.09 (0.02‐0.38) |
| Darbepoetin alfa | 2.31 (1.34‐3.97) | Not estimable | ‐‐ | 1.08 (0.38‐3.04) | 0.62 (0.12‐3.30) | 0.17 (0.05‐0.57) |
| Methoxy polyethylene‐glycol epoetin beta |
Not estimable | 0.83 (0.17‐4.15) | 0.94 (0.45‐1.95) | ‐‐ | 0.58 (0.09‐3.92) | 0.15 (0.03‐0.70) |
| Biosimilar ESA | 0.72 (0.42‐1.22) | Not estimable | Not estimable | Not estimable | ‐‐ | 0.27 (0.05‐1.47) |
| Placebo | 0.07 (0.01‐0.84) | 0.07 (0.03‐0.21) | 0.53 (0.46‐0.63) | Not estimable | Not estimable | ‐‐ |
| All‐cause mortality | ||||||
| Epoetin alfa | ‐‐ | 1.53 (0.77‐3.03) | 1.17 (0.68‐2.05) | 1.08 (0.54‐2.15) | 0.95 (0.62‐1.44) | 1.25 (0.71‐2.21) |
| Epoetin beta | Not estimable | – | 0.77 (0.43‐1.38) | 0.71 (0.35‐1.42) | 0.62 (0.29‐1.37) | 0.82 (0.45‐1.48) |
| Darbepoetin alfa | 1.12 (0.59‐2.14) | 0.89 (0.38‐2.09) | ‐‐ | 0.91 (0.60‐1.40) | 0.81 (0.41‐1.61) | 1.06 (0.91‐1.24) |
| Methoxy polyethylene‐glycol epoetin beta | Not estimable | 0.81 (0.12‐5.35) | 0.90 (0.59‐1.40) | ‐‐ | 0.88 (0.40‐1.97) | 1.16 (0.74‐1.82) |
| Biosimilar ESA | 1.04 (0.53‐2.01) | 0.34 (0.04‐2.82) | Not estimable | Not estimable | ‐‐ | 1.31 (0.65‐2.62) |
| Placebo | 0.99 (0.14‐6.86) | 0.61 (0.17‐2.15) | 1.06 (0.91‐1.24) | Not estimable | Not estimable | ‐‐ |
| Fatigue | ||||||
| Epoetin alfa | ‐‐ | Not estimable | Not estimable | Not estimable | Not estimable | Not estimable |
| Epoetin beta | Not estimable | ‐‐ | Not estimable | Not estimable | Not estimable | Not estimable |
| Darbepoetin alfa | 0.94 (0.57‐1.55) | Not estimable | ‐‐ | Not estimable | Not estimable | Not estimable |
| Methoxy polyethylene‐glycol epoetin beta | Not estimable | Not estimable | Not estimable | ‐‐– | Not estimable | Not estimable |
| Biosimilar ESA | 0.18 (0.01‐3.91) | Not estimable | Not estimable | Not estimable | ‐‐ | Not estimable |
| Placebo | Not estimable | Not estimable | Not estimable | Not estimable | Not estimable | ‐‐ |
| Breathlessness | ||||||
| Epoetin alfa | ‐‐ | Not estimable | Not estimable | Not estimable | Not estimable | Not estimable |
| Epoetin beta | Not estimable | ‐‐ | Not estimable | Not estimable | Not estimable | Not estimable |
| Darbepoetin alfa | 0.71 (0.46‐1.10) | Not estimable | ‐‐ | Not estimable | Not estimable | Not estimable |
| Methoxy polyethylene‐glycol epoetin beta | Not estimable | Not estimable | Not estimable | ‐‐ | Not estimable | Not estimable |
| Biosimilar ESA | 0.68 (0.37‐1.25) | Not estimable | Not estimable | Not estimable | ‐‐ | Not estimable |
| Placebo | Not estimable | Not estimable | Not estimable | Not estimable | Not estimable | ‐‐ |
| Cardiovascular mortality | ||||||
| Epoetin alfa | ‐‐ | 2.12 (0.34‐13.1) | 1.48 (0.28‐7.96) | 1.02 (0.16‐6.48) | 0.55 (0.22‐1.38) | 1.56 (0.29‐8.37) |
| Epoetin beta | Not estimable | ‐‐ | 0.70 (0.12‐4.10) | 0.48 (0.07‐3.31) | 0.26 (0.04‐1.51) | 0.74 (0.13‐4.28) |
| Darbepoetin alfa | 2.15 (0.31‐14.9) | Not estimable | ‐‐ | 0.69 (0.32‐1.48) | 0.37 (0.06‐2.20) | 1.05 (0.87‐1.26) |
| Methoxy polyethylene‐glycol epoetin beta | Not estimable | Not estimable | 0.69 (0.32‐1.48) | ‐‐ | 0.54 (0.08‐3.74) | 1.52 (0.69‐3.34) |
| Biosimilar ESA | 0.53 (0.20‐1.35) | 0.34 (0.04‐2.82) | Not estimable | Not estimable | ‐‐ | 2.81 (0.47‐16.7) |
| Placebo | Not estimable | 0.45 (0.06‐3.75) | 1.05 (0.87‐1.26) | Not estimable | Not estimable | ‐‐ |
| Major adverse cardiovascular events | ||||||
| Epoetin alfa | ‐‐ | Not estimable | Not estimable | Not estimable | Not estimable | Not estimable |
| Epoetin beta | Not estimable | ‐‐ | Not estimable | Not estimable | Not estimable | Not estimable |
| Darbepoetin alfa | 0.20 (0.01‐4.17) | Not estimable | ‐‐ | Not estimable | Not estimable | Not estimable |
| Methoxy polyethylene‐glycol epoetin beta | Not estimable | Not estimable | Not estimable | ‐‐ | Not estimable | Not estimable |
| Biosimilar ESA | 0.49 (0.17‐1.47) | Not estimable | Not estimable | Not estimable | ‐‐ | Not estimable |
| Placebo | Not estimable | Not estimable | 1.08 (0.95‐1.24) | Not estimable | Not estimable | ‐‐ |
| Myocardial infarction | ||||||
| Epoetin alfa | ‐‐ | Not estimable | 1.04 (0.35‐3.11) | 0.55 (0.05‐5.69) | 1.18 (0.47‐3.02) | 1.00 (0.32‐3.09) |
| Epoetin beta | Not estimable | ‐‐ | Not estimable | Not estimable | Not estimable | Not estimable |
| Darbepoetin alfa | 0.87 (0.20‐3.81) | Not estimable | ‐‐ | 0.53 (0.07‐4.18) | 1.14 (0.27‐4.83) | 0.97 (0.75‐1.25) |
| Methoxy polyethylene‐glycol epoetin beta | Not estimable | Not estimable | 0.47 (0.06‐3.65) | ‐‐ | 2.17 (0.17‐27.1) | 1.83 (0.18‐19.1) |
| Biosimilar ESA | 1.23 (0.49‐3.12) | Not estimable | Not estimable | Not estimable | ‐‐ | 0.84 (0.20‐3.65) |
| Placebo | 3.46 (0.12‐100.51) | Not estimable | 0.97 (0.75‐1.25) | Not estimable | Not estimable | ‐‐ |
| Stroke | ||||||
| Epoetin alfa | ‐‐ | 4.56 (0.29‐71.8) | 1.39 (0.38‐5.16) | 2.36 (0.24‐23.6) | 0.92 (0.39‐2.16) | 2.74 (0.71‐10.5) |
| Epoetin beta | Not estimable | ‐‐ | 0.31 (0.02‐4.55) | 0.52 (0.02‐14.0) | 0.20 (0.01‐3.61) | 0.60 (0.04‐8.88) |
| Darbepoetin alfa | 1.44 (0.37‐5.54) | Not estimable | ‐‐ | 1.70 (0.26‐11.2) | 0.66 (0.14‐3.14) | 1.96 (1.40‐2.75) |
| Methoxy polyethylene‐glycol epoetin beta | Not estimable | Not estimable | 1.33 (0.17‐10.49) | ‐‐ | 0.38 (0.03‐4.50) | 1.16 (0.17‐7.90) |
| Biosimilar ESA | 0.92 (0.39‐2.15) | Not estimable | Not estimable | Not estimable | ‐‐ | 2.99 (0.61‐14.8) |
| Placebo | Not estimable | 0.33 (0.01‐8.21) | 1.97 (1.40‐2.76) | Not estimable | Not estimable | ‐‐ |
| Hypertension | ||||||
| Epoetin alfa | ‐‐ | 0.90 (0.41‐1.95) | 1.26 (0.81‐1.96) | 1.18 (0.64‐2.18) | 1.95 (0.97‐3.94) | 2.31 (1.27‐4.23) |
| Epoetin beta | Not estimable | ‐‐ | 1.41 (0.70‐2.82) | 1.31 (0.63‐2.72) | 2.18 (0.76‐6.22) | 2.57 (1.23‐5.39) |
| Darbepoetin alfa | 0.94 (0.62‐1.43) | 1.18 (0.38‐3.69) | ‐‐ | 0.93 (0.60‐1.45) | 1.55 (0.68‐3.55) | 1.83 (1.05‐3.21) |
| Methoxy polyethylene‐glycol epoetin beta | Not estimable | 1.38 (0.62‐3.09) | Not estimable | ‐‐ | 1.66 (0.65‐4.21) | 1.96 (0.98‐3.92) |
| Biosimilar ESA | 1.77 (1.02‐3.09) | Not estimable | Not estimable | Not estimable | ‐‐ | 1.18 (0.47‐2.99) |
| Placebo | 4.10 (2.16‐7.76) | 2.95 (1.19‐7.26) | 1.14 (0.99‐1.32) | Not estimable | Not estimable | ‐‐ |
| End‐stage kidney disease | ||||||
| Epoetin alfa | ‐‐ | Not estimable | Not estimable | Not estimable | Not estimable | Not estimable |
| Epoetin beta | Not estimable | ‐‐ | Not estimable | Not estimable | Not estimable | Not estimable |
| Darbepoetin alfa | 2.17 (0.37‐12.74) | Not estimable | ‐ | Not estimable | Not estimable | Not estimable |
| Methoxy polyethylene‐glycol epoetin beta | Not estimable | Not estimable | 1.83 (0.66‐5.09) | ‐‐ | Not estimable | Not estimable |
| Biosimilar ESA | Not estimable | Not estimable | Not estimable | Not estimable | ‐‐ | Not estimable |
| Placebo | Not estimable | Not estimable | 1.04 (0.88‐1.23) | Not estimable | Not estimable | ‐‐ |
| Vascular access thrombosis | ||||||
| Epoetin alfa | ‐‐ | 0.93 (0.28‐3.10) | 1.22 (0.78‐1.91) | 1.04 (0.48‐2.25) | 1.26 (0.45‐3.36) | 1.72 (0.58‐5.16) |
| Epoetin beta | Not estimable | ‐‐ | 1.30 (0.42‐4.04) | 1.11 (0.38‐3.24) | 1.35 (0.29‐6.34) | 1.85 (0.61‐5.63) |
| Darbepoetin alfa | 1.15 (0.73‐1.82) | Not estimable | ‐‐ | 0.86 (0.45‐1.61) | 1.04 (0.35‐3.05) | 1.42 (0.50‐4.03) |
| Methoxy polyethylene‐glycol epoetin beta | Not estimable | 1.74 (0.49‐6.24) | 0.76 (0.39‐1.47) | ‐‐ | 1.21 (0.35‐4.22) | 1.66 (0.54‐5.08) |
| Biosimilar ESA | 1.71 (0.30‐10.00) | Not estimable | Not estimable | Not estimable | ‐‐ | 1.37 (0.32‐5.93) |
| Placebo | 6.40 (0.80‐51.50) | 1.09 (0.28‐4.34) | 1.34 (0.30‐6.01) | Not estimable | Not estimable | ‐‐ |
Treatment estimates for pairwise meta‐analyses are shown in italics