Hereditary transthyretin amyloidosis: baseline characteristics of patients in the NEURO-TTR trial

Figures & data

Table 1. Demographics and baseline characteristics by region, disease onset and prior treatment with TTR Stabilizers.

		Region			Disease onset			Prior treatment
	Total (n = 172)	US (n = 82)	Europe (n = 60)	SA (n = 30)	Early (n = 56)	Late (n = 116)	Stabilizers (n = 99)	Naïve (n = 73)
Age, yrs
Mean (SD)	59.2 (13.0)	64.6 (8.7)	57.0 (13.8)	48.6 (13.9)	43.8 (9.3)	66.6 (6.3)	59.8 (13.2)	59.7 (13.0)
Min–Max	27–81	40–78	27–81	28–73	27–70	53–81	28–81	27–78
Sex
Male, n (%)	118 (69%)	61 (74%)	39 (65%)	18 (60%)	33 (59%)	85 (73%)	65 (66%)	53 (73%)
mBMI^a, kg/m^2 g/L
Mean (SD)	1025 (228)	1050 (245)	1008 (210)	986 (213)	989 (235)	1041 (224)	1034 (222)	1012 (238)
Min–Max	573–1752	573–1752	685–1687	669–1405	669–1710	573–1752	573–1752	630–1710
BP, mm Hg
Mean, SBP / DBP	121 / 76	122 / 76	123 / 78	116 / 72	115 / 74	124 / 77	123 / 77	118 / 74
TTR, mg/dL
Mean (SD)	21.5 (5.6)	20.5 (5.4)	21.7 (5.4)	23.7 (6.3)	22.0 (5.7)	21.2 (5.6)	22.5 (4.9)	20.1 (6.2)
Min–Max	8.6–39.7	9.6–35.3	8.6–33.4	11.8–39.7	11.8–39.7	8.6–33.4	9.8–35.3	8.6–39.7
TTR Mutation, n (%)
Val30Met	89 (52%)	21 (26%)	40 (67%)	28 (93%)	40 (71%)	49 (42%)	52 (53%)	37 (51%)
Prior Treatment, n (%)
Tafamidis	53 (31%)	3 (4%)	43 (72%)	7 (23%)	28 (50%)	25 (22%)	53 (54%)	0 (0%)
Diflunisal	49 (28%)	41 (50%)	6 (10%)	2 (7%)	6 (11%)	43 (37%)	49 (49%)	0 (0%)
None	73 (42%)	39 (48%)	13 (22%)	21 (70%)	22 (39%)	51 (44%)	0 (0%)	73 (100%)
Disease stage^b, n (%)
Stage 1	116 (67%)	57 (70%)	38 (63%)	21 (70%)	44 (79%)	72 (62%)	68 (69%)	48 (66%)
Stage 2	56 (33%)	25 (30%)	22 (37%)	9 (30%)	12 (21%)	44 (38%)	31 (31%)	25 (34%)
Disease onset^c, n (%)
Early	56 (33%)	13 (16%)	24 (40%)	19 (63%)	56 (100%)	0 (0%)	34 (34%)	22 (30%)
Duration of symptoms^d, yrs
Mean (SD)	5.3 (4.4)	5.7 (5.7)	5.3 (2.7)	4.3 (2.4)	6.6 (5.4)	4.7 (3.7)	5.9 (4.3)	4.6 (4.4)
Presence of CM^e,  n (%)	108 (63%)	63 (77%)	34 (57%)	11 (37%)	20 (36%)	88 (76%)	60 (61%)	48 (66%)
NYHA^f, n (%)
I	111 (65%)	55 (67%)	33 (55%)	23 (77%)	45 (80%)	66 (57%)	67 (68%)	44 (60%)
II	61 (35%)	27 (33%)	27 (45%)	7 (23%)	11 (20%)	50 (43%)	32 (32%)	29 (40%)
NT-proBNP, pg/mL
Mean (SD)	910 (1916)	1023 (1470)	1027 (2693)	362 (467)	354 (569)	1181 (2256)	665 (1103)	1254 (2640)
Min–Max	11–19084	31–7198	11–19,084	21–1743	11–2499	21–19,084	11–7387	21–19,084
mNIS +7
Mean (SD)	78 (38)	71 (36)	88 (33)	76 (47)	79 (38)	77 (37)	81 (36)	73 (39)
(Min–Max)	(11–175)	(11–175)	(30–169)	(13–160)	(13–160)	(11–175)	11–175	13–165
NSC^g, n (%)
W-P-S-A	120 (70%)	55 (67%)	46 (77%)	19 (63%)	40 (71%)	80 (69%)	68 (69%)	52 (71%)
W-S-P	18 (10%)	10 (12%)	5 (8%)	3 (10%)	6 (11%)	12 (10%)	15 (15%)	3 (4%)
W-P-A	11 (6%)	6 (7%)	3 (5%)	2 (7%)	1 (2%)	10 (9%)	3 (3%)	8 (11%)
W-S-A	5 (3%)	2 (2%)	2 (3%)	1 (3%)	3 (5%)	2 (2%)	3 (3%)	2 (3%)
S-P-A	3 (2%)	0 (0%)	2 (3%)	1 (3%)	2 (4%)	1 (1%)	1 (1%)	2 (3%)
Other	15 (9%)	9 (11%)	2 (3%)	4 (13%)	4 (7%)	11 (9%)	9 (9%)	6 (8%)
PND, n (%)
I	55 (32%)	35 (43%)	10 (17%)	10 (33%)	16 (29%)	39 (34%)	26 (26%)	29 (40%)
II	61 (35%)	22 (27%)	28 (47%)	11 (37%)	28 (50%)	33 (28%)	42 (42%)	19 (26%)
III	45 (26%)	21 (26%)	18 (30%)	6 (20%)	9 (16%)	36 (31%)	28 (28%)	17 (23%)
IV	11 (6%)	4 (5%)	4 (7%)	3 (10%)	3 (5%)	8 (7%)	3 (3%)	8 (11%)

^a Modified BMI (mBMI) adjusts for serum albumin

^b Stage I does not require assistance with ambulation, Stage II requires assistance with ambulation

^c Disease symptoms before age 50 (calculated by age minus years with symptoms).

^d Duration of symptoms calculated as time between symptom onset and ICF date.

^e Presence of cardiomyopathy was defined by a diagnosis of TTR cardiomyopathy at study entry and/or by the following criteria: interventricular wall thickness of ≥13 mm on transthoracic ECHO at baseline as ascertained by a central reader, no known history of persistent hypertension ≥150 mmHg within 12 months prior to screening.

^f Study excluded NYHA III and higher

^g Neuropathy Symptom and Change (NSC) domain categories: Muscle Weakness (W), Sensory Loss (S), Positive Neuropathy Sensory Symptoms (P), Autonomic (A). Other includes combinations of 2 domains (P-A, W-A, W-P, S-P) or a single domains (A).

Table 2. Baseline characteristics by TTR mutation (> =5% prevalence in NEURO-TTR).

	Total (n = 172)	Val30Met (n = 89)	Non-Val30Met (n = 83)	Thr60Ala (n = 22)	Leu58His (n = 10)	Ser77Tyr (n = 9)	Phe64Leu (n = 8)
Region^a
United States	82 (48%)	21 (24%)	61 (73%)	19 (86%)	10 (100%)	2 (22%)	7 (88%)
Europe	60 (35%)	40 (45%)	20 (24%)	2 (9%)	0 (0%)	6 (67%)	1 (13%)
South America	30 (17%)	28 (31%)	2 (2%)	1 (5%)	0 (0%)	1 (11%)	0 (0%)
Age, yrs
Mean (SD)	59.2 (13.0)	55.5 (15.2)	63.1 (8.8)	65.8 (6.5)	65.3 (7.8)	62.4 (4.0)	69.4 (4.7)
Min–Max	27–81	27–81	40–78	52–78	52–75	55–68	59–74
Sex
Male, n (%)	118 (69%)	63 (71%)	55 (66%)	17 (77%)	6 (60%)	5 (6%)	8 (100%)
mBMI^b, kg/m^2 g/L
Mean (SD)	1025 (228)	1003 (209)	1047 (246)	1081 (305)	1206 (177)	1005 (205)	1036 (157)
Min–Max	573–1752	573–1687	630–1752	630–1710	883–1450	817–1388	775–1257
BP, mmHg
Mean, SBP/DBP	121 / 76	120 / 75	123 / 76	123 / 76	133 / 81	122 / 80	123 / 78
TTR, mg/dL
Mean (SD)	21.5 (5.6)	22.9 (5.3)	20.0 (5.6)	20.3 (5.8)	24.2 (5.8)	19.4 (4.9)	18.9 (3.4)
Min–Max	8.6–39.7	11.8–39.7	8.6–35.3	9.6–30.1	15.2–35.3	10.6–26.4	13.5–23.7
Prior Treatment, n (%)
Tafamidis	53 (31%)	40 (45%)	13 (16%)	0 (0%)	1 (10%)	4 (44%)	0 (0%)
Diflunisal	49 (28%)	14 (16%)	35 (42%)	11 (50%)	7 (70%)	2 (22%)	4 (50%)
None	73 (42%)	37 (42%)	36 (43%)	11 (50%)	2 (20%)	3 (33%)	4 (50%)
Disease stage^c, n (%)
Stage 1	116 (67%)	59 (66%)	57 (69%)	17 (77%)	5 (50%)	7 (78%)	5 (63%)
Stage 2	56 (33%)	30 (34%)	26 (31%)	5 (23%)	5 (50%)	2 (22%)	3 (38%)
Disease onset^d, n (%)
Early onset	56 (33%)	40 (45%)	16 (19%)	3 (14%)	2 (20%)	0 (0%)	0 (0%)
Duration of symptoms^e, yrs
Mean (SD)	5.3 (4.4)	5.3 (3.9)	5.4 (4.9)	5.4 (4.4)	6.0 (7.5)	4.6 (2.5)	5.2 (2.1)
Presence of CM^f, n (%)	108 (63%)	43 (48%)	65 (78%)	20 (91%)	4 (40%)	9 (100%)	3 (38%)
NYHA^g, n (%)
I	111 (65%)	67 (75%)	44 (53%)	10 (45%)	9 (90%)	3 (33%)	5 (63%)
II	61 (35%)	22 (25%)	39 (47%)	12 (55%)	1 (10%)	6 (67%)	3 (38%)
NT-proBNP, pg/mL
Mean (SD)	910 (1916)	829 (2332)	997 (1343)	1563 (1689)	192 (125)	641 (509)	234 (174)
Min–Max	11–19,084	11–19,084	31–7036	83–7036	37–432	207–1615	31–495
mNIS +7
Mean (SD)	78 (38)	81 (39)	74 (36)	63 (32)	83 (37)	77 (28)	97 (34)
Min–Max	11–175	11–175	14–169	14–160	35–131	45–115	67–165
NSC^h, n (%)
W-P-S-A	120 (70%)	61 (69%)	59 (71%)	15 (68%)	5 (50%)	6 (67%)	7 (88%)
W-S-P	18 (10%)	10 (11%)	8 (10%)	1 (5%)	3 (30%)	0 (0%)	1 (13%)
W-P-A	11 (6%)	2 (2%)	9 (11%)	4 (18%)	0 (0%)	3 (33%)	0 (0%)
W-S-A	5 (3%)	5 (6%)	0 (0%)	0 (0%)	0 (0%)	0 (0%)	0 (0%)
S-P-A	3 (2%)	3 (3%)	0 (0%)	0 (0%)	0 (0%)	0 (0%)	0 (0%)
Others	15 (9%)	8 (9%)	7 (8%)	2 (9%)	2 (20%)	0 (0%)	0 (0%)
PND Score, n (%)
I	55 (32%)	19 (21%)	36 (43%)	12 (55%)	3 (30%)	2 (22%)	2 (25%)
II	61 (35%)	40 (45%)	21 (25%)	5 (23%)	2 (20%)	5 (56%)	3 (38%)
III	45 (26%)	23 (26%)	22 (27%)	4 (18%)	4 (40%)	2 (22%)	1 (13%)
IV	11 (6%)	7 (8%)	4 (5%)	1 (5%)	1 (10%)	0 (0%)	2 (25%)

^a US: Ala97Ser, Asp38Ala, Glu54Ser, Glu89Gln, Gly67Arg, Ile107Val, Ile84Ser, Leu58His, Lys35Thr, Lys79Asn, Phe33Leu, Phe64Leu, Pro24Ser, Ser50Arg, Ser77Tyr, Thr49Ala, Thr59Lys, Thr60Ala, Tyr114Cys, Val30Met, Val122Ile; Europe: Ala109Ser, Glu61Lys, Glu89Gln, Glu89Lys, Gly47Ala, Ile107Phe, Phe64Leu, Ser77Phe, Ser77Tyr, Thr49Ala, Thr60Ala, Val30Met; SA: Ser77Tyr, Thr60Ala, Val30Met.

^b Modified BMI (mBMI) adjusts for serum albumin

^c Stage I does not require assistance with ambulation, Stage II requires assistance with ambulation

^d Disease symptoms before age 50 (calculated by age minus years with symptoms).

^e Duration of symptoms calculated as time between symptom onset and ICF date.

^f Presence of cardiomyopathy was defined by a diagnosis of TTR cardiomyopathy at study entry and/or by the following criteria: interventricular wall thickness of ≥13 mm on transthoracic ECHO at baseline as ascertained by a central reader, no known history of persistent hypertension ≥150 mmHg within 12 months prior to screening.

^g Study excluded NYHA III and higher

^h Neuropathy Symptom and Change (NSC) domain categories: Muscle Weakness (W), Sensory Loss (S), Positive Neuropathy Sensory Symptoms (P), Autonomic (A). Other includes combinations of 2 domains (P-A, W-A, W-P, S-P) or single domains (A).

Figure 1. Relationship of NT-proBNP to LV Septal Wall Thickness.

Figure 2. Quality of Life Corresponds to ATTRm Disease Severity (A) mNIS +7 composite score increases with worsening Norfolk QoL-DN score. The dotted horizontal line refers to the average Norfolk QoL-DN score in healthy volunteers (n = 12) [27]. (B) PND stage advances with worsening SF-36 PCS. The dotted horizontal line refers to the average SF-36 PCS score in the general US population [28]. (C) Norfolk Total Score increases with worsening SF-36 PCS.

Vinik EJ, Vinik AI, Paulson JF, et al. Norfolk QOL-DN: validation of a patient reported outcome measure in transthyretin familial amyloid polyneuropathy. J Peripher Nerv Syst. 2014;19:104–114.

 PubMed Web of Science ®Google Scholar

Ware JE, Jr., Gandek B. Overview of the SF-36 health survey and the international quality of life assessment (IQOLA) project. J Clin Epidemiol. 1998;51:903–912.

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