Comparative effectiveness of pegcetacoplan versus ravulizumab in patients with paroxysmal nocturnal hemoglobinuria previously treated with eculizumab: a matching-adjusted indirect comparison

Figures & data

Table 1. Comparison of endpoint definitions.

Endpoint	PEGASUS study	ALXN1210-PNH-302 study
Clinical and hematological
Transfusion avoidance	Proportion of patients with transfusion avoidance through Week 16	Proportion of participants who remained transfusion free and did not require a transfusion per protocol-specified guidelines through Week 26
Transfusion requirements	Total number of units of PRBCs transfused from baseline to Week 16	Total number of units of PRBCs transfused from baseline to Week 26
Hemoglobin level stabilization	Proportion of patients with avoidance of a ≥ 2 g/dL decrease in Hb level in the absence of transfusion from baseline through Week 16	Proportion of patients with avoidance of a ≥ 2 g/dL decrease in Hb level in the absence of transfusion from baseline through Week 26
LDH level	Week 16 change from baseline in LDH level	Week 16 change from baseline in LDH level^a
LDH level normalization	Proportion of patients with LDH level ≤ 1× ULN (226 U/L) in the absence of transfusions from baseline through Week 16^b	Proportion of patients with LDH level ≤ 1× ULN (246 U/L) from baseline through Week 16^c
Fatigue and quality of life
Fatigue	Week 16 change from baseline in FACIT-Fatigue score	Week 26 change from baseline in FACIT-Fatigue score
Global health status	Week 16 change from baseline in global health status EORTC QLQ-C30 score	Week 26 change from baseline in global health status EORTC QLQ-C30 score
Physical functioning	Week 16 change from baseline in physical functioning EORTC QLQ-C30 score	Week 26 change from baseline in physical functioning EORTC QLQ-C30 score
Fatigue symptoms	Week 16 change from baseline in fatigue symptoms EORTC QLQ-C30 score	Week 26 change from baseline in fatigue symptoms EORTC QLQ-C30 score

Abbreviations. EORTC QLQ-C30, European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30; FACIT, Functional Assessment of Chronic Illness Therapy; g/dL, grams/deciliter; Hb: hemoglobin; LDH, lactate dehydrogenase; PRBC, packed red blood cells; U/L: units/Liter; ULN, upper limit of normal.

Notes.

^aChange from baseline in LDH level was examined for Week 16 (Day 113) for the ALXN1210-PNH-302 study. Baseline mean and SD for LDH level were reported in Table 1 of the Kulasekararaj et al.¹⁰ publication. Week 16 (Day 113) mean and 95% CI for LDH level were extracted from Supplemental Figure S3 of the Kulasekararaj et al.¹⁰ publication. The SD for LDH level at Week 16 (Day 113) was calculated using the following equation: √(N)*(upper limit of CI - lower limit of CI)/3.92.

^bLDH level normalization is defined as the proportion of patients who achieved LDH level ≤1× ULN (226 U/L) in the absence of transfusions from baseline through the end of follow-up.

^cLDH level normalization is defined as the proportion of patients who achieved LDH level ≤1× ULN (246 U/L), with or without transfusions (i.e. patients were not excluded if they experienced transfusions during follow-up). Week 16 (Day 113) mean and 95% CI for the proportion of patients with LDH level normalization in the ALXN1210-PNH-302 study were extracted from Figure 2 of the Kulasekararaj et al.¹⁰ publication.

Table 2. Overview of study baseline characteristics before and after matching (clinical and hematological endpoints).

Characteristic	PEGASUS study (before matching)		PEGASUS study (after matching^a)		ALXN1210-PNH-302 study (as reported)
	Pegcetacoplan (N = 36)	Eculizumab (N = 32)	Pegcetacoplan (N = 36)	Eculizumab (N = 32)	Ravulizumab (N = 97)	Eculizumab (N = 98)
Sex, %
Male	30.6	40.6	51.5	49.0	51.5	49.0
Female^b	69.4	59.4	48.5	51.0	48.5	51.0
Age at first infusion of study drug^b, mean (SD), year	49.0 (16.8)	48.8 (14.0)	46.4 (15.5)	48.8 (12.0)	46.4 (14.4)	48.8 (14.0)
Race, %
White^b	58.3	65.6	51.5	62.2	51.5	62.2
Asian^b	13.9	15.6	23.7	19.4	23.7	19.4
African American	5.6	0.0	11.1	0.0	5.2	3.1
Other/multiple races	0.0	3.1	0.0	9.2	3.1	1.0
Not reported/unknown	22.2	15.6	13.7	9.2	16.5	14.3
Weight, mean (SD), kg	75.2 (19.6)	73.2 (14.2)	81.8 (27.1)	79.1 (10.8)	72.4 (16.8)	73.4 (14.6)
Height, mean (SD), cm	167.1 (9.7)	168.8 (7.4)	170.3 (12.6)	169.6 (7.9)	168.3 (10.1)	168.8 (9.9)
Time on eculizumab before first study infusion, mean (SD), y	5.4 (4.4)	5.1 (3.8)	5.1 (4.5)	5.8 (3.9)	6.0 (3.5)	5.6 (3.5)
History of transfusions within 1 year before first dose, %	72.2	71.9	66.7	72.9	13.4	12.2
Age at PNH diagnosis, mean (SD), y	40.5 (17.0)	35.7 (13.4)	38.6 (15.6)	36.0 (12.0)	34.1 (14.4)	36.8 (14.1)
Time from PNH diagnosis to consent, mean (SD), y	8.5 (7.1)	13.0 (9.8)	7.8 (7.4)	12.8 (9.8)	12.4 (8.4)	11.9 (9.4)
LDH^b, mean (SD), U/L	229.0 (57.2)	203.5 (35.5)	228.0 (50.9)	235.2 (30.7)	228.0 (48.7)	235.2 (49.7)
Hemoglobin, mean (SD), g/dL	8.7 (1.1)	8.7 (0.8)	8.7 (1.1)	8.6 (0.7)	11.1 (1.8)	10.9 (1.8)
History of major adverse vascular events, %	25.0	18.8	19.9	9.6	28.9	22.4
History of aplastic anemia^b, %	27.8	18.8	35.1	39.8	35.1	39.8

Abbreviations. cm, centimeter; g/dL, grams/deciliter; kg: kilogram; LDH, lactate dehydrogenase; PNH, paroxysmal nocturnal hemoglobinuria; SD, standard deviation; U/L, units/Liter; y: year.

Notes.

^aFollowing matching procedures, the effective sample size was 24 and 12 for pegcetacoplan and eculizumab patients, respectively.

^bIndicates variable included in matching procedures.

Table 3. Overview of study baseline characteristics before and after matching (fatigue and quality of life endpoints).

Characteristic	PEGASUS Study (before matching)		PEGASUS Study (after matching^a)		ALXN1210-PNH-302 Study (as reported)
	Pegcetacoplan (N = 36)	Eculizumab (N = 32)	Pegcetacoplan (N = 36)	Eculizumab (N = 32)	Ravulizumab (N = 97)	Eculizumab (N = 98)
Sex, %
Male	30.6	40.6	25.0	57.7	51.5	49.0
Female	69.4	59.4	75.0	42.3	48.5	51.0
Age at first infusion of study drug^b, mean (SD), y	49.0 (16.8)	48.8 (14.0)	46.4 (16.6)	48.8 (12.1)	46.4 (14.4)	48.8 (14.0)
Race, %
White	58.3	65.6	56.7	53.8	51.5	62.2
Asian	13.9	15.6	14.3	34.4	23.7	19.4
African American	5.6	0.0	5.0	0.0	5.2	3.1
Other/multiple races	0.0	3.1	0.0	6.1	3.1	1.0
Not reported/unknown	22.2	15.6	23.9	5.7	16.5	14.3
Weight^b, mean (SD), kg	75.2 (19.6)	73.2 (14.2)	72.4 (17.4)	73.4 (11.8)	72.4 (16.8)	73.4 (14.6)
Height, mean (SD), cm	167.1 (9.7)	168.8 (7.4)	166.0 (8.8)	169.1 (7.5)	168.3 (10.1)	168.8 (9.9)
Time on eculizumab before first study infusion, mean (SD), y	5.4 (4.4)	5.1 (3.8)	5.7 (4.6)	6.2 (3.7)	6.0 (3.5)	5.6 (3.5)
History of transfusions within 1 year before first dose, %	72.2	71.9	74.8	71.1	13.4	12.2
Age at PNH diagnosis, mean (SD), y	40.5 (17.0)	35.7 (13.4)	37.7 (16.5)	36.0 (11.5)	34.1 (14.4)	36.8 (14.1)
Time from PNH diagnosis to consent, mean (SD), y	8.5 (7.1)	13.0 (9.8)	8.6 (7.2)	12.8 (9.4)	12.4 (8.4)	11.9 (9.4)
LDH^b, mean (SD), U/L	229.0 (57.2)	203.5 (35.5)	228.0 (61.6)	235.2 (35.8)	228.0 (48.7)	235.2 (49.7)
Hemoglobin, mean (SD), g/dL	8.7 (1.1)	8.7 (0.8)	8.8 (1.1)	8.7 (0.8)	11.1 (1.8)	10.9 (1.8)
History of major adverse vascular events, %	25.0	18.8	23.8	11.9	28.9	22.4
History of aplastic anemia^b, %	27.8	18.8	35.1	39.8	35.1	39.8

Abbreviations. cm, centimeter; g/dL: grams/deciliter; kg: kilogram; LDH, lactate dehydrogenase; PNH, paroxysmal nocturnal hemoglobinuria; SD, standard deviation; U/L, units/Liter; y: year.

Notes.

^aFollowing matching procedures, the effective sample size was 34 and 9 for pegcetacoplan and eculizumab patients, respectively.

^bIndicates variable included in matching procedures.

Figure 1. Anchored comparisons of clinical and hematological endpoints through Week 16 (PEGASUS study) and Week 26 (ALXN1210-PNH-302 study) after matching^a. Abbreviations. CI: confidence interval; LDH, lactate dehydrogenase; SD, standard deviation. Notes. ^aThe following baseline characteristics were matched on: age at first infusion of study drug, female, White, Asian, history of aplastic anemia, and LDH. ^bChange from baseline in LDH level was examined for Week 16 (Day 113) for the ALXN1210-PNH-302 study. Baseline mean and SD for LDH level were reported in Table 1 of the Kulasekararaj et al.¹⁰ publication. Week 16 (Day 113) mean and 95% CI for LDH level were extracted from Supplemental Figure S3 of the Kulasekararaj et al.¹⁰ publication. The SD for LDH level at Week 16 (Day 113) was calculated using the following equation: √(N)*(upper limit of CI – lower limit of CI)/3.92. During follow-up, LDH level was available at Week 16 (Day 113) for 94 patients who received ravulizumab and 96 patients who received eculizumab in the ALXN1210-PNH-302 study. ^cIn the PEGASUS study, LDH level normalization is defined as the proportion of patients who achieved LDH level ≤1× ULN (226 U/L) in the absence of transfusions from baseline through the end of follow-up. In the ALXN1210-PNH-302 study, LDH level normalization is defined as the proportion of patients who achieved LDH level ≤1× ULN (246 U/L), with or without transfusions. Week 16 (Day 113) mean and 95% CI for the proportion of patients with LDH level normalization in the ALXN1210-PNH-302 study were extracted from Figure 2 of the Kulasekararaj et al. ¹⁰ publication.

Figure 2. Anchored comparisons of fatigue and quality of life endpoints through Week 16 (PEGASUS study) and Week 26 (ALXN1210-PNH-302 study) after matching^a. Abbreviations. CI, confidence interval; EORTC QLQ-C30, European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30; FACIT, Functional Assessment of Chronic Illness Therapy; LDH, lactate dehydrogenase. Notes. ^aThe following baseline characteristics were matched on: age at first infusion of study drug, weight, history of aplastic anemia, and LDH. ^bData were available for 67 of 68 patients in the PEGASUS study.

Kulasekararaj AG, Hill A, Rottinghaus ST, et al. Ravulizumab (ALXN1210) vs eculizumab in C5-inhibitor-experienced adult patients with PNH: the 302 study. Blood. 2019;133(6):540–549.

 PubMed Web of Science ®Google Scholar

Data availability statement

For data requests, please contact Rachel H. Bhak ([email protected]).