|
Subgroup
|
Response rate
|
Relapse rate
|
|
Studies/patients, n/N
|
Response rate [95% CI]
|
p value
|
p value for interaction
|
Studies/patients, n/N
|
Relapse rate [95% CI]
|
p value
|
p value for interaction
|
|
Route of GM-CSF
|
|
Subcutaneous
|
5/50
|
0.71 [0.46–0.96]
|
< 0.001
|
0.023
|
5/50
|
0.24 [−0.08–0.55]
|
0.14
|
0.262
|
|
Inhaled
|
5/65
|
0.89 [0.71–1.06]
|
< 0.001
|
5/65
|
0.19 [0.00–0.37]
|
0.047
|
|
Age, years
|
|
< 45
|
5/40
|
0.83 [0.61–1.04]
|
< 0.001
|
0.18
|
5/40
|
0.33 [0.01–0.64]
|
0.04
|
0.006
|
|
≥ 45
|
5/75
|
0.79 [0.57–1.01]
|
< 0.001
|
5/75
|
0.10 [−0.03–0.23]
|
0.13
|
|
Gender, men %
|
|
< 70
|
6/77
|
0.81 [0.62–1.01]
|
< 0.001
|
0.543
|
6/77
|
0.32 [0.05–0.60]
|
0.02
|
0.349
|
|
≥ 70
|
4/38
|
0.80 [0.51–1.09]
|
< 0.001
|
4/38
|
0.09 [−0.08–0.26]
|
0.293
|
|
Smoker, %
|
|
< 60
|
4/84
|
0.63 [0.40–0.86]
|
< 0.001
|
0.002
|
4/84
|
0.37 [0.01–0.72]
|
0.041
|
0.84
|
|
≥ 60
|
4/24
|
0.93 [0.80–1.07]
|
< 0.001
|
4/24
|
0.19 [−0.06–0.43]
|
0.136
|
|
Combined therapy with WLL, %
|
|
< 80
|
6/76
|
0.77 [0.59–0.96]
|
< 0.001
|
0.962
|
6/76
|
0.27 [0.00–0.53]
|
0.047
|
0.965
|
|
≥ 80
|
4/39
|
0.86 [0.57–1.15]
|
< 0.001
|
4/39
|
0.16 [−0.03–0.35]
|
0.098
|
|
Anti GM-CSF antibody titer
|
|
< 40μg/ml
|
3/50
|
0.86[0.58–1.14]
|
< 0.001
|
0.051
|
3/50
|
0.06[−0.06–0.19]
|
0.313
|
0.045
|
|
≥ 40μg/ml
|
3/18
|
0.95[0.80–1.10]
|
< 0.001
|
3/18
|
0.27[−0.02–0.56]
|
0.066
|
|
Initial dose of GM-CSF
|
|
≤ 250μg/d
|
7/96
|
0.74[0.55–0.93]
|
< 0.001
|
0.005
|
7/96
|
0.25[0.04–0.47]
|
0.022
|
0.751
|
|
> 250μg/d
|
3/19
|
0.95[0.80–1.10]
|
< 0.001
|
3/19
|
0.16[−0.15–0.46]
|
0.312
|
|
Subgroup
|
PaO2, mmHg
|
P[A-a]O2, mmHg
|
|
Studies/patients, n/N
|
WMD [95% CI]
|
p value
|
p value for interaction
|
Studies/patients, n/N
|
WMD [95% CI]
|
p value
|
p value for interaction
|
|
Route of GM-CSF
|
|
Subcutaneous
|
3/38
|
8.28 [6.3–10.26]
|
< 0.001
|
< 0.001
|
3/38
|
9.15 [7.53–10.78]
|
< 0.001
|
< 0.001
|
|
Inhaled
|
2/17
|
21.02 [15.41–26.62]
|
< 0.001
|
4/62
|
19.63 [5.82–33.45]
|
0.005
|
|
Age, years
|
|
< 45
|
3/29
|
12.11 [3.65–20.57]
|
0.005
|
0.614
|
4/35
|
14.14 [6.85–21.44]
|
< 0.001
|
0.725
|
|
≥ 45
|
2/26
|
15.88 [1.96–29.80]
|
0.025
|
4/68
|
24.56 [15.41–33.72]
|
< 0.001
|
|
Gender, men %
|
|
< 70
|
2/25
|
11.32 [1.19–21.46]
|
0.029
|
0.712
|
4/70
|
11.36 [7.27–15.45]
|
< 0.001
|
0.186
|
|
≥ 70
|
3/30
|
16.00 [4.31–27.69]
|
0.007
|
3/30
|
18.23 [−0.14–36.59]
|
0.052
|
|
Smoker, %
|
|
< 60
|
1/13
|
6.77 [3.87–9.67]
|
< 0.001
|
< 0.001
|
3/58
|
8.53 [6.87–10.18]
|
< 0.001
|
< 0.001
|
|
≥ 60
|
4/42
|
16.27[7.16–25.37]
|
< 0.001
|
4/42
|
18.40 [5.10–31.69]
|
0.007
|
|
Combined therapy with WLL, %
|
|
< 80
|
3/29
|
12.11 [3.65–20.57]
|
0.005
|
0.614
|
4/68
|
10.64 [6.87–14.4]
|
< 0.001
|
0.006
|
|
≥ 80
|
2/26
|
15.88 [1.96–29.80]
|
0.025
|
4/35
|
33.59 [14.54–52.64]
|
0.001
|
|
Anti GM-CSF antibody titer
|
|
< 40μg/ml
|
1/5
|
23.16(18.36–27.96)
|
< 0.001
|
-*
|
3/50
|
20.11(1.48–38.74)
|
0.034
|
0.516
|
|
≥ 40μg/ml
|
1/12
|
17.20(9.37–25.03)
|
< 0.001
|
2/15
|
48.88(−12.16–109.92)
|
0.117
|
|
Initial dose of GM-CSF
|
|
≤ 250μg/d
|
4/43
|
13.02(6.36–19.67)
|
< 0.001
|
0.715
|
6/88
|
14.53(8.85–20.20)
|
< 0.001
|
0.466
|
|
> 250μg/d
|
1/12
|
17.20(9.37–25.03)
|
< 0.001
|
2/15
|
48.88(− 12.16–109.92)
|
0.117
|
- GM-CSF granulocyte macrophage colony stimulating factor, aPAP autoimmune pulmonary alveolar proteinosis, PaO2 alveolar oxygen partial pressure, P[A-a]O2 alveolar-arterial oxygen gradient, WMD Weighted Mean Difference; * only one study included in each subgroup, p value for interaction not available
