Comparison Of King’s Clinical Staging In Multinational Amyotrophic Lateral Sclerosis Cohorts

Figures & data

Figure 1 Participant flow diagram for the PatientsLikeMe database.

Table 1 Baseline characteristics King’s College Hospital (KCH), LiCALS and MitoTarget, PatientsLikeMe and PRO-ACT databases with values expressed as Mean (95% Confidence Interval) or Number (% of total).

Baseline characteristics	KCH database	LiCALS database	MitoTarget database	PatientsLikeMe database	PRO-ACT database
Primary country/ region of origin	UK	UK	Europe	US	US
Patient numbers	1459	214	511	3230	4,841
Mean age of onset in years	56.9 (56.3–57.6)	58.0 (56.6–59.5)	55.6 (54.6–56.6)	50.2 (49.8–50.7)	55.4 (55.0–55.7)
Sex
Male	893 (61.2%)	148 (69.2%)	331 (64.8%)	1730 (53.6%, 59.8%)	3028 (62.5%)
Female	562 (38.5%)	66 (30.8%)	180 (35.2%)	1165 (36.0%, 40.2%)	1813 (37.5%)
Unknown	4 (0.3%)	0 (0%)	0 (0%)	335 (10.4%)	0 (0%)
Site of onset
Limb	1066 (73.1%)	168 (78.5%)	411 (80.4%)	1827 (56.5%, 75.1%)	2254 (46.6%, 77.8%)
Bulbar	371 (25.4%)	46 (21.5%)	100 (19.6%)	552 (17.1%, 22.7%)	623 (12.9%, 21.5%)
Respiratory	22 (1.5%)	0 (0%)	0 (0%)	54 (1.7%, 2.2%)	0 (0%)
Limb and Bulbar	0 (0%)	0 (0%)	0 (0%)	0 (0%)	20 (0.4%, 0.7%)
Unknown	0 (0%)	0 (0%)	0 (0%)	797 (24.7%)	1944 (40.1%)
Mean duration from symptom onset to diagnosis in months (95% CI)	18.0 (16.8–19.2)	10.9 (10.0–11.7)	9.7 (9.1–10.3)	17.5 (16.7–18.4)	11.6 (11.3–11.9)
Mean follow up time post disease onset in months (95% CI)	Unknown	34.1 (32.8–35.4)	32.3 (31.4–33.2)	59.1 (57.2–60.9)	31.4 (30.8–40.0)
Number of deceased patients in cohort (% of total)	1067 (73.1%)	101 (47.1%)	159 (31.1%)	437 (13.5%)	1262 (26.1%)

For PatientsLikeMe and PRO-ACT Sex and Site of onset data, % of total excluding unknown cases are also presented after % of total.

Figure 2 Box plot of standardized times to each stage in all 3,026 deceased patients from the five databases (KCH, PatientsLikeMe, LiCALS, MitoTarget and PRO-ACT) using every milestone reached.

Figure 3 Box plot of standardized times to each stage in the 1,959 deceased patients from PatientsLikeMe, LiCALS, MitoTarget and PRO-ACT databases using every milestone reached.

Table 2 Standardized times to every milestone reached and milestone timings for King’s College Hospital (KCH), PatientsLikeMe, LiCALS, MitoTarget and PRO-ACT databases.

Staging milestone	N	Median milestone timing in months (IQR)	Median standardized time to staging milestone (IQR)
King’s College Hospital database
Stage 2	958	10.0 (4.0–19.0)	0.32 (0.14–0.53)
Stage 3	610	16.0 (9.0–29.0)	0.60 (0.37–0.79)
Stage 4A	232	21.4 (15.6–32.0)	0.77 (0.65–0.89)
Stage 4B	163	24.3 (16.0–40.3)	0.80 (0.65–0.92)
Stage 4	341	20.0 (12.2–32.4)	0.77 (0.64–0.89)
LiCALS database
Stage 2	53	18.4 (12.8–22.6)	0.61 (0.48–0.73)
Stage 3	68	18.5 (12.6–25.2)	0.66 (0.55–0.78)
Stage 4A	36	21.0 (17.2–25.1)	0.77 (0.66–0.87)
Stage 4B	37	27.8 (18.2–34.8)	0.89 (0.78–0.96)
Stage 4	60	19.8 (14.5–26.0)	0.82 (0.69–0.89
MitoTarget database
Stage 2	82	16.0 (11.6–22.0)	0.61 (0.50–0.71)
Stage 3	107	16.3 (10.5–23.7)	0.66 (0.54–0.76)
Stage 4A	50	20.3 (15.3–26.1)	0.78 (0.66–0.91)
Stage 4B	56	22.3 (16.5–30.4)	0.89 (0.81–0.94)
Stage 4	81	19.4 (13.5–28.9)	0.84 (0.69–0.93)
PatientsLikeMe database
Stage 2	139	17.0 (9.3–28.3)	0.41(0.29–0.57)
Stage 3	190	20.1 (12.5–35.9)	0.56 (0.39–0.74)
Stage 4A	56	29.4 (18.7–38.4)	0.76 (0.60–0.87)
Stage 4B	261	28.6 (18.7–45.0)	0.74 (0.56–0.87)
Stage 4	296	26.3 (15.2–41.6)	0.74 0.58–0.87)
PRO-ACT database
Stage 2	640	15.8 (10.7–25.3)	0.64 (0.51–0.78)
Stage 3	954	19.0 (13.0–28.0)	0.70 (0.58–0.82)
Stage 4A	336	23.0 17.9–31.7)	0.84 (0.74–0.92)
Stage 4B	175	22.1 (16.0–31.2)	0.88 (0.77–0.94)
Stage 4	444	21.5 (14.5–29.1)	0.86 (0.75–0.93)
Analysis of all five databases (KCH, PatientsLikeMe, LiCALS, MitoTarget and PRO-ACT)
Stage 2	1872	13.1 (7.0–23.0)	0.50 (0.28–0.68)
Stage 3	1929	18.1 (11.8–28.2)	0.66 (0.51–0.81)
Stage 4A	710	22.3 (17.1–31.5)	0.81 (0.69–0.91)
Stage 4B	692	24.6 (17.1–37.1)	0.82 (0.67–0.92)
Stage 4	1222	22.1 (13.7–32.6)	0.80 (0.67–0.91)
Analysis of PatientsLikeMe, LiCALS, MitoTarget and PRO-ACT databases
Stage 2	914	16.2 (10.6–25.2)	0.61 (0.47–0.75)
Stage 3	1319	18.9 (12.7–28.0)	0.68 (0.56–0.81)
Stage 4A	478	22.7 (17.6–31.5)	0.82 (0.71–0.91)
Stage 4B	529	24.6 (17.4–36.6)	0.82 (0.69–0.92)
Stage 4	881	22.4 (14.5–32.6)	0.82 (0.69–0.92)

IQR: interquartile range.

Table 3 Standardized times in PatientsLikeMe, LiCALS, MitoTarget and PRO-ACT databases in limb onset versus bulbar onset patients.

	Limb Onset		Bulbar Onset
	N	Median standardized time (IQR)	N	Median standardized time (IQR)
Stage 2	587	0.60 (0.46–0.75)	198	0.58 (0.47–0.70)
Stage 3	780	0.68 (0.55–0.81)	238	0.64 (0.50–0.76)
Stage 4A	158	0.86 (0.75–0.94)	180	0.78 (0.64–0.89)
Stage 4B	352	0.82 (0.67–0.91)	113	0.81 (0.63–0.92)
Stage 4	453	0.83 (0.69–0.92)	245	0.77 (0.64–0.89)

IQR: interquartile range.