Effect of age on Outcomes After Allogeneic Disc Tissue Supplementation in Patients with Chronic Discogenic low Back Pain in the VAST Trial

Figures & data

Figure 1. Subgroup analysis for age, sex and levels treated on response measured by visual analog scale and Oswestry Disability Index at 12 months.

ODI: Oswestry Disability Index; VAS: Visual analog scale.

Reproduced with permission, Pain Physician, ASIPP Publishing [19].

Table 1. Baseline demographic and disease characteristics according to age.

	Patients aged <42 years			Patients aged ≥42 years
	Active allograft n = 68	Saline n = 19	Conservative care n = 17	Active allograft n = 72	Saline n = 20	Conservative care n = 22
Age (years): median (min, max)	36.0 (19.0, 41.0)	35.0 (20.0, 41.0)	32.0 (19.0, 41.0)	48.0 (42.0, 65.0)	49.0 (42.0, 73.0)	50.0 (43.0, 60.0)
Male, n (%)	42 (61.8)	12 (63.2)	10 (58.8)	37 (51.4)	12 (60.0)	11 (50.0)
Race, n (%) ^†   Native American   Asian   Black or African American   Native Hawaiian/Pacific Islander   White or Caucasian   Other   Not reported	4 (5.9) 0 4 (5.9) 0 59 (86.8) 1 (1.5) 1 (1.5)	1 (5.3) 0 1 (5.3) 0 16 (84.2) 0 1 (5.3)	2 (11.8) 0 2 (11.8) 0 12 (70.6) 0 1 (5.9)	4 (5.6) 0 8 (11.1) 1 (1.4) 58 (80.6) 0 2 (2.8)	0 1 (5.0) 1 (5.0) 0 16 (80.0) 1 (5.0) 1 (5.0)	0 1 (4.5) 2 (9.1) 0 17 (77.3) 1 (4.5) 1 (4.5)
Ethnicity, n (%)   Hispanic   Non-Hispanic   Not reported	3 (4.4) 61 (89.7) 4 (5.9)	1 (5.3) 16 (84.2) 2 (10.5)	1 (5.9) 15 (88.2) 1 (5.9)	2 (2.8) 52 (72.2) 18 (25.0)	2 (10.0) 14 (70.0) 4 (20.0)	2 (9.1) 15 (68.2) 5 (22.7)
Body mass index, kg/m^2   Mean (SD)   Median (range)	27.06 (4.19)^‡ 27.3 (18.0–38.0)	26.95 (4.88) 26.6 (17.8–34.6)	26.09 (5.30) 26.7 (17.7–34.8)	28.50 (4.98) 28.8 (20.0–50.2)	29.92 (3.07) 30.1 (22.2–35.4)	26.32 (5.06) 25.9 (17.0–35.4)
Smoking history, n (%)   Never   Past smoker   Current smoker   Not reported	39 (57.4) 19 (27.9) 10 (14.7) 0	8 (42.1) 6 (31.6) 4 (21.1) 1 (5.3)	15 (88.2) 1 (5.9) 1 (5.9) 0	51 (70.8) 16 (22.2) 4 (5.6) 1 (1.4)	10 (50.0) 8 (40.0) 2 (10.0) 0	11 (50.0) 7 (31.8) 4 (18.2) 0
History of endocrine or metabolic disorders, n (%)   Yes   No   Not reported	2 (2.9) 64 (94.1) 2 (2.9)	2 (10.5) 16 (84.2) 1 (5.3)	0 17 (100) 0	7 (9.7) 61 (84.7) 4 (5.6)	3 (15.0) 17 (85.0) 0	3 (13.6) 19 (86.4) 0
Levels of treatment, n (%)   One level   Two levels   Not reported	39 (57.4) 28 (41.2) 1 (1.5)	13 (68.4) 6 (31.6) 0	11 (64.7) 4 (23.5) 2 (11.8)	37 (51.4) 35 (48.6) 0	7 (35.0) 13 (65.0) 0	11 (50.0) 9 (40.9) 2 (9.1)

Data are based on intent-to-treat population.

† Patients could report more than one race, so numbers may be greater than the total.

‡ n = 67.

SD: Standard deviation.

Table 2. Mean change in visual analog scale score and Oswestry Disability Index at 12 months according to age.

	Active allograft n = 140	Saline n = 39	Crossover n = 39	Overall p-value^†	Allograft vs saline p-value	Allograft vs crossover p-value	Saline vs crossover p-value
Patient age <42 years Change in ODI from baseline   n   Mean (SD)   Median (min, max) Change in VAS average back pain from baseline   n   Mean (SD)   Median (min, max)	55 -29.69 (18.53) -29.0 (-80.0, 17.0) 56 -34.46 (26.87) -40.0 (-93.0, 23.0)	17 -17.35 (22.31) -9.0 (-64.0, 9.0) 16 -26.63 (31.44) -21.5 (-82.0, 18.0)	7 -45.00 (11.09) -42.0 (-62.0, -34.0) 7 -39.43 (22.28) -30.0 (-79.0, -20.0)	0.004 0.533	0.042 0.567	0.062 0.974	0.025 0.596
Patient age ≥42 years Change in ODI from baseline   n   Mean (SD)   Median (min, max) Change in VAS average back pain from baseline   n   Mean (SD)   Median (min, max)	64 -25.44 (18.83) -27.5 (-58.0, 43.00) 64 -33.64 (28.73) -35.0 (-89.0, 36.00)	13 -32.62 (17.09) -42.0 (-51.0, -2.0) 14 -34.93 (30.99) -45.0 (-77.0, 15.0)	17 -32.94 (23.93) -40.0 (-67.0, 2.0) 16 -49.88 (23.05) -47.5 (-82.0, -10.0)	0.244 0.146	0.351 0.976	0.439 0.110	0.899 0.526

Data are derived from a subpopulation analysis using the modified intent-to-treat population.

† p-value is derived from the Kruskal–Wallis Test. Pairwise group comparisons were derived using the Dwass–Steel–Critchlow–Fligner Method. Conservative care 12-month crossover visit is used. Month 3 value is used as baseline.

ODI: Oswestry Disability Index; SD: Standard deviation; VAS: Visual analog scale.

Figure 2. (A) Oswestry Disability Index responder and (B) visual analog scale responder analyses at 12 months in patients aged <42 years.

Data derived from a subpopulation analysis using the modified intent-to-treat population. p-values are derived from the Fisher exact test. Conservative care 12-month crossover visit is used. Month 3 value is used as baseline.

Note: active allograft, n = 55; placebo, n = 17; crossover, n = 7.

ODI: Oswestry Disability Index; VAS: Visual analog scale.

Table 3. Responder analyses at 12 months in patients aged <42 years by number of levels treated.

	Active allograft	Saline	Crossover	Overall p-value^†	Allograft vs saline p-value^†	Allograft vs crossover p-value^†	Saline vs crossover p-value^†
One level of treatment   ODI     n     ≥10-point reduction, n (%)     ≥15-point reduction, n (%)     ≥20-point reduction, n (%)   VAS average back pain     n     ≥50% reduction, n (%)     ≥20-point reduction, n (%)	32 28 (87.5) 24 (75.0) 19 (59.4) 32 20 (62.5) 22 (68.8)	11 4 (36.4) 3 (27.3) 3 (27.3) 10 4 (40.0) 5 (50.0)	5 5 (100.0) 5 (100.0) 5 (100.0) 6 3 (50.0) 6 (100.0)	0.002 0.005 0.021 0.466 0.115	0.002 0.010 0.088 0.281 0.451	>0.999 0.564 0.140 0.663 0.168	0.034 0.026 0.026 >0.999 0.093
Two levels of treatment   ODI     n     ≥10-point reduction, n (%)     ≥15-point reduction, n (%)     ≥20-point reduction, n (%)   VAS average back pain     n     ≥50% reduction, n (%)     ≥20-point reduction, n (%)	23 20 (87.0) 20 (87.0) 19 (82.6) 24 15 (62.5) 17 (70.8)	6 4 (66.7) 3 (50.0) 3 (50.0) 6 3 (50.0) 3 (50.0)	2 2 (100.0) 2 (100.0) 2 (100.0) 1 1 (100.0) 1 (100.0)	0.489 0.100 0.153 0.792 0.574	0.269 0.083 0.131 0.660 0.372	>0.999 >0.999 >0.999 >0.999 >0.999	>0.999 0.464 0.464 >0.999 >0.999

Data are derived from a subpopulation analysis using the modified intent-to-treat population.

† p value is derived from the Fisher exact test. Conservative care 12-month crossover visit is used. Month 3 value is used as baseline.

ODI: Oswestry Disability Index; VAS: Visual analog scale.

Figure 3. Interaction plot showing change from baseline in Oswestry Disability Index.

Data derived from a subpopulation analysis using the modified intent-to-treat population. Conservative care 12-month crossover visit is used with Month 3 value as baseline. The interaction plot illustrates the differences in change from baseline between patients receiving allograft and those who received saline. The plot shows that younger patients (<42 years) showed a benefit that was not observed in older patients (≥42 years) (p = 0.0071; R² = 0.099). Note: modified intent-to-treat population: active allograft, n = 119; placebo, n = 30; crossover, n = 24.

ODI: Oswestry Disability Index.

Table 4. Adverse events by age.

	No. of patients with events, n/n (%)
	Active allograft	Saline	Crossover	Overall p-value^†
Adverse events    Age <42 years   Age ≥42 years	21/68 (30.9) 21/73 (28.8)	2/19 (10.5) 3/19 (15.8)	3/17 (17.6) 2/22 (9.1)	0.155 0.136
Serious adverse events   Age <42 years   Age ≥42 years	1/68 (1.5) 4/73 (5.5)	0/19 (0.0) 0/19 (0.0)	0/17 (0.0) 1/22 (4.5)	NA 0.823

Data are derived from the safety population. Patients were analyzed according to the treatment received at baseline, regardless of initial randomization.

† p-value is derived from the Fisher exact test.

NA: Not applicable.

Beall DP , DavisTT , DePalmaMet al. Viable disc tissue allograft supplementation; one- and two-level treatment of degenerated intervertebral discs in patients with chronic discogenic low back pain: one year results of the VAST randomized controlled trial. Pain Physician24(6), 465–477 (2021).

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Data sharing statement

The authors certify that this manuscript reports the secondary analysis of clinical trial data that have been shared with them, and that the use of this shared data is in accordance with the terms (if any) agreed upon their receipt. The source of this data is: NCT03709901. The datasets generated and/or analysed during the current study are available from the corresponding author on reasonable request.