Change from baseline in markers of iron metabolism and iron overload at week 24 and week 96 in patients with PK deficiency in ACTIVATE and the LTE study
| Marker . | All patients . | |||||
|---|---|---|---|---|---|---|
| Baseline . | Change from baseline at week 24 . | Change from baseline at week 96 . | ||||
| M/M N = 40 . | P/M N = 40 . | M/M N = 40 . | P/M N = 40 . | M/M N = 40 . | P/M N = 40 . | |
| Hepcidin, mean (SD) (95% CI), ng/L∗ | 25 920 (27 900) n = 40 | 29 989 (18 044) n = 40 | 4770 (18 347) (−1532 to 11 072) n = 35 | −3282 (14 735) (−8687 to 2123) n = 31 | 6009 (23 135) (−2791 to 14 809) n = 29 | 9935 (23 580) (−262 to 20 132) n = 23 |
| Erythroferrone, mean (SD) (95% CI), ng/L∗ | 21 080 (16 029) n = 40 | 20 380 (13 096) n = 40 | −9835 (13 081) (−14 328 to −5 341) n = 35 | −2133 (6 278) (−4 436 to 170) n = 31 | −12 635 (13 019) (−17 587 to 7 683) n = 29 | −10 720 (6729) (−13 630 to −7810) n = 23 |
| sTfR, mean (SD) (95% CI), nmol/L∗ | 187 (76) n = 40 | 174 (69) n = 40 | −56 (83) (−85 to −27) n = 34 | −2 (17) (−9 to 5) n = 28 | −60 (85) (−93 to −27) n = 28 | −31 (41) (−48 to −13) n = 25 |
| Erythropoietin, mean (SD) (95% CI), IU/L∗ | 74 (60) n = 39 | 74 (57) n = 40 | −33 (62) (−55 to −11) n = 34 | 7 (38) (−7 to 21) n = 30 | −32 (71) (−59 to −4) n = 28 | −31 (54) (−53 to −9) n = 26 |
| Reticulocyte percentage, mean (SD) (95% CI), %∗ | 37.1 (24.1) n = 40 | 40.1 (22.2) n = 40 | −10.7 (10.9) (−14.5 to −7.0) n = 35 | −0.4 (9.9) (−3.9 to 3.0) n = 34 | −9.6 (11.6) (−14.5 to −4.7) n = 24 | −9.5 (14.6) (−15.6 to −3.5) n = 25 |
| Ferritin, mean (SD) (95% CI), μg/L∗ | 748 (1116) n = 39 | 688 (605) n = 38 | 39 (285) (−57 to 136) n = 36 | −50 (217) (−130 to 29) n = 31 | 25 (188) (−48 to 98) n = 28 | 59 (393) (−100 to 218) n = 26 |
| LIC assessment by MRI, mg Fe/g dw† | n = 38 | n = 39 | n = 31 | n = 31 | n = 22 | n = 23 |
| Mean (SD) (95% CI) | 7.6 (10.8) | 6.1 (8.0) | 1.7 (15.7) (−4.1 to 7.5) | 1.4 (12.4) (−3.2 to 5.9) | −2.0 (6.2) (−4.8 to 0.8) | −1.8 (6.0) (−4.4 to 0.8) |
| Median (Q1, Q3)‡ | 3.05 (1.70, 6.50) | 3.40 (2.00, 6.30) | −0.40 (−1.10, 0.70) | 0.30 (−0.30, 1.20) | −0.85 (−1.90, −0.10) | −0.30 (−1.30, 0.70) |
| Marker . | All patients . | |||||
|---|---|---|---|---|---|---|
| Baseline . | Change from baseline at week 24 . | Change from baseline at week 96 . | ||||
| M/M N = 40 . | P/M N = 40 . | M/M N = 40 . | P/M N = 40 . | M/M N = 40 . | P/M N = 40 . | |
| Hepcidin, mean (SD) (95% CI), ng/L∗ | 25 920 (27 900) n = 40 | 29 989 (18 044) n = 40 | 4770 (18 347) (−1532 to 11 072) n = 35 | −3282 (14 735) (−8687 to 2123) n = 31 | 6009 (23 135) (−2791 to 14 809) n = 29 | 9935 (23 580) (−262 to 20 132) n = 23 |
| Erythroferrone, mean (SD) (95% CI), ng/L∗ | 21 080 (16 029) n = 40 | 20 380 (13 096) n = 40 | −9835 (13 081) (−14 328 to −5 341) n = 35 | −2133 (6 278) (−4 436 to 170) n = 31 | −12 635 (13 019) (−17 587 to 7 683) n = 29 | −10 720 (6729) (−13 630 to −7810) n = 23 |
| sTfR, mean (SD) (95% CI), nmol/L∗ | 187 (76) n = 40 | 174 (69) n = 40 | −56 (83) (−85 to −27) n = 34 | −2 (17) (−9 to 5) n = 28 | −60 (85) (−93 to −27) n = 28 | −31 (41) (−48 to −13) n = 25 |
| Erythropoietin, mean (SD) (95% CI), IU/L∗ | 74 (60) n = 39 | 74 (57) n = 40 | −33 (62) (−55 to −11) n = 34 | 7 (38) (−7 to 21) n = 30 | −32 (71) (−59 to −4) n = 28 | −31 (54) (−53 to −9) n = 26 |
| Reticulocyte percentage, mean (SD) (95% CI), %∗ | 37.1 (24.1) n = 40 | 40.1 (22.2) n = 40 | −10.7 (10.9) (−14.5 to −7.0) n = 35 | −0.4 (9.9) (−3.9 to 3.0) n = 34 | −9.6 (11.6) (−14.5 to −4.7) n = 24 | −9.5 (14.6) (−15.6 to −3.5) n = 25 |
| Ferritin, mean (SD) (95% CI), μg/L∗ | 748 (1116) n = 39 | 688 (605) n = 38 | 39 (285) (−57 to 136) n = 36 | −50 (217) (−130 to 29) n = 31 | 25 (188) (−48 to 98) n = 28 | 59 (393) (−100 to 218) n = 26 |
| LIC assessment by MRI, mg Fe/g dw† | n = 38 | n = 39 | n = 31 | n = 31 | n = 22 | n = 23 |
| Mean (SD) (95% CI) | 7.6 (10.8) | 6.1 (8.0) | 1.7 (15.7) (−4.1 to 7.5) | 1.4 (12.4) (−3.2 to 5.9) | −2.0 (6.2) (−4.8 to 0.8) | −1.8 (6.0) (−4.4 to 0.8) |
| Median (Q1, Q3)‡ | 3.05 (1.70, 6.50) | 3.40 (2.00, 6.30) | −0.40 (−1.10, 0.70) | 0.30 (−0.30, 1.20) | −0.85 (−1.90, −0.10) | −0.30 (−1.30, 0.70) |
| . | Patients with iron overload at baseline who received mitapivat§ N = 43 . | ||
|---|---|---|---|
| Baseline . | Change from baseline at week 24 . | Change from baseline at week 96 . | |
| LIC assessment by MRI, mg Fe/g dw† | n = 43 | n = 37 | n = 20 |
| Mean (SD) (95% CI) | 11.7 (13.1) | −0.8 (18.2) (−6.9 to 5.3) | −3.3 (6.6) (−6.4 to −0.3) |
| Median (Q1, Q3)‡ | 6.50 (4.10, 15.60) | −0.90 (−2.50, 0.40) | −1.95 (−4.85, −0.70) |
| . | Patients with iron overload at baseline who received mitapivat§ N = 43 . | ||
|---|---|---|---|
| Baseline . | Change from baseline at week 24 . | Change from baseline at week 96 . | |
| LIC assessment by MRI, mg Fe/g dw† | n = 43 | n = 37 | n = 20 |
| Mean (SD) (95% CI) | 11.7 (13.1) | −0.8 (18.2) (−6.9 to 5.3) | −3.3 (6.6) (−6.4 to −0.3) |
| Median (Q1, Q3)‡ | 6.50 (4.10, 15.60) | −0.90 (−2.50, 0.40) | −1.95 (−4.85, −0.70) |
Patients in the M/M arm started mitapivat treatment at baseline; patients in the P/M arm started mitapivat treatment at week 24.
95% CI was calculated based on t-distribution.
The baseline is defined as the average of all screening assessments within 45 (42 + 3) days before randomization for patients randomized and not dosed, or before the start of study treatment for patients randomized and dosed. Assessments collected within 61 days after a transfusion were excluded from the baseline derivation.
The baseline for LIC by MRI is defined as the last assessment before randomization for patients randomized and not dosed, or the last assessment before the start of study treatment for patients randomized and dosed.
Median (Q1, Q3) was reported for LIC by MRI in addition to mean (SD) [95% CI] because of 2 incorrectly reported values, which were included in the analysis. These 2 outlier values for LIC limit the interpretation of the summaries of mean change in LIC from baseline to week 24; data for mean change from baseline to week 96 were not affected.
Patients were considered to have iron overload at baseline if they met at least 1 of 3 criteria: baseline ferritin of >1000 μg/L, baseline LIC of >3 mg Fe/g dw, and/or chelation therapy within the last year before start of treatment with mitapivat.