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|
Health outcome of interest
|
After advanced stage date (n=12,659)
|
After anti-cancer therapy date (n=7,723)
|
|---|
|
Events
|
Person-years
|
IRa
|
95% CI
|
Events
|
Person-years
|
IR
|
95% CI
|
|---|
|
Serious infectionb
|
6662
|
25868
|
25.78
|
25.17
|
26.41
|
5,862
|
15938
|
41.42
|
40.36
|
42.49
|
|
Rash
|
|
Any rash
|
686
|
22684
|
3.02
|
2.8
|
3.26
|
431
|
14095
|
3.06
|
2.78
|
3.36
|
|
Severe cutaneous rash safety events
|
87
|
25534
|
0.34
|
0.27
|
0.42
|
62
|
15752
|
0.39
|
0.3
|
0.5
|
|
Colitis
|
725
|
23251
|
3.12
|
2.9
|
3.35
|
464
|
14567
|
3.19
|
2.91
|
3.49
|
|
Pneumonitis
|
|
Interstitial lung disease
|
119
|
25622
|
0.46
|
0.39
|
0.55
|
62
|
15812
|
0.39
|
0.3
|
0.5
|
|
Hypersensitivity pneumonitis
|
≤10
|
n/a
|
0.03
|
0.02
|
0.06
|
≤10
|
n/a
|
0.03
|
0.01
|
0.06
|
|
Pneumonitis or acute interstitial pneumonitis
|
137
|
25653
|
0.53
|
0.45
|
0.63
|
83
|
15824
|
0.52
|
0.42
|
0.65
|
|
Hepatitis
|
|
Hepatic failure
|
764
|
23057
|
3.31
|
3.08
|
3.55
|
510
|
14112
|
3.61
|
3.31
|
3.94
|
|
Autoimmune hepatitis
|
≤10
|
n/a
|
0.02
|
0.01
|
0.05
|
≤10
|
n/a
|
0.03
|
0.01
|
0.07
|
|
Hepatitis (not specified as viral)
|
66
|
25559
|
0.26
|
0.2
|
0.33
|
23
|
15798
|
0.15
|
0.09
|
0.21
|
|
Liver disorder
|
1439
|
21567
|
6.67
|
6.33
|
7.02
|
960
|
13128
|
7.31
|
6.86
|
7.79
|
|
Transaminases increased
|
272
|
25086
|
1.08
|
0.96
|
1.22
|
169
|
15483
|
1.09
|
0.94
|
1.27
|
|
Nephritis
|
1966
|
21201
|
9.27
|
8.87
|
9.69
|
1,309
|
13361
|
9.80
|
9.28
|
10.34
|
|
Renal failure
|
2057
|
21425
|
9.60
|
9.19
|
10.02
|
1,379
|
13524
|
10.20
|
9.67
|
10.75
|
|
Endocrinopathies
|
|
Adrenal insufficiency
|
87
|
25608
|
0.34
|
0.27
|
0.42
|
44
|
15839
|
0.28
|
0.2
|
0.37
|
|
Acute and chronic thyroiditis
|
88
|
25310
|
0.35
|
0.28
|
0.43
|
45
|
15665
|
0.29
|
0.21
|
0.38
|
|
Diabetes mellitus, type 1
|
124
|
24894
|
0.50
|
0.42
|
0.59
|
65
|
15482
|
0.42
|
0.33
|
0.53
|
|
Diabetic ketoacidosis
|
40
|
25745
|
0.16
|
0.11
|
0.21
|
20
|
15891
|
0.13
|
0.08
|
0.19
|
|
Hypogonadism
|
≤10
|
n/a
|
0.02
|
0.01
|
0.05
|
≤10
|
n/a
|
0.01
|
0
|
0.03
|
|
Hypophysitis or hypopituitarism
|
90
|
25653
|
0.35
|
0.28
|
0.43
|
49
|
15826
|
0.31
|
0.23
|
0.41
|
|
Hypothyroidism
|
636
|
18796
|
3.38
|
3.13
|
3.65
|
325
|
12002
|
2.71
|
2.43
|
3.01
|
|
Thyroid hyperfunction disorders
|
121
|
25084
|
0.48
|
0.4
|
0.57
|
59
|
15554
|
0.38
|
0.29
|
0.49
|
|
Other safety events
|
|
Abdominal pain
|
1825
|
5206
|
35.06
|
33.48
|
36.69
|
859
|
3098
|
27.73
|
25.92
|
29.63
|
|
Anemia
|
2925
|
11827
|
24.73
|
23.85
|
25.64
|
1,978
|
7576
|
26.11
|
24.98
|
27.28
|
|
Anorexia
|
649
|
24889
|
2.61
|
2.41
|
2.81
|
469
|
15316
|
3.06
|
2.79
|
3.35
|
|
Autoimmune disorder
|
182
|
25347
|
0.72
|
0.62
|
0.83
|
135
|
15657
|
0.86
|
0.73
|
1.02
|
|
Backache
|
1632
|
20754
|
7.86
|
7.49
|
8.25
|
963
|
13124
|
7.34
|
6.89
|
7.81
|
|
Constipation
|
2086
|
18379
|
11.35
|
10.87
|
11.85
|
1,404
|
11460
|
12.25
|
11.62
|
12.91
|
|
Cough
|
1421
|
19219
|
7.39
|
7.02
|
7.79
|
848
|
12341
|
6.87
|
6.42
|
7.35
|
|
Diarrhea
|
1502
|
20365
|
7.38
|
7.01
|
7.76
|
1,028
|
12630
|
8.14
|
7.65
|
8.65
|
|
Disorders of bilirubin excretion
|
66
|
25798
|
0.26
|
0.2
|
0.32
|
52
|
15904
|
0.33
|
0.25
|
0.43
|
|
Disorders of phosphorus metabolism
|
294
|
25265
|
1.16
|
1.04
|
1.3
|
177
|
15637
|
1.13
|
0.97
|
1.31
|
|
Dizziness and giddiness
|
977
|
21121
|
4.63
|
4.34
|
4.92
|
604
|
13504
|
4.47
|
4.13
|
4.84
|
|
Edema
|
1773
|
20466
|
8.66
|
8.27
|
9.07
|
1,107
|
12978
|
8.53
|
8.04
|
9.04
|
|
Encephalitis
|
18
|
25811
|
0.07
|
0.04
|
0.11
|
13
|
15904
|
0.08
|
0.05
|
0.14
|
|
Fever
|
1848
|
20676
|
8.94
|
8.54
|
9.35
|
1,313
|
12860
|
10.21
|
9.67
|
10.77
|
|
Guillain-Barre Syndrome
|
≤10
|
n/a
|
0.02
|
0.01
|
0.05
|
≤10
|
n/a
|
0.03
|
0.01
|
0.06
|
|
Hypertension
|
1243
|
10422
|
11.93
|
11.28
|
12.6
|
775
|
6820
|
11.36
|
10.58
|
12.18
|
|
Hypopotassemia
|
1808
|
20815
|
8.69
|
8.29
|
9.09
|
1,211
|
12983
|
9.33
|
8.81
|
9.86
|
|
Hyposmolality and/or hyponatremia
|
1475
|
23036
|
6.40
|
6.08
|
6.74
|
965
|
14302
|
6.75
|
6.33
|
7.18
|
|
Hypoxemia
|
1034
|
23624
|
4.38
|
4.12
|
4.65
|
590
|
14805
|
3.99
|
3.67
|
4.32
|
|
Iritis
|
36
|
25653
|
0.14
|
0.1
|
0.19
|
13
|
15839
|
0.08
|
0.05
|
0.14
|
|
Leukocytosis
|
1280
|
23275
|
5.50
|
5.2
|
5.81
|
792
|
14379
|
5.51
|
5.13
|
5.9
|
|
Localized superficial swelling, mass, or lump
|
385
|
25036
|
1.54
|
1.39
|
1.7
|
240
|
15436
|
1.55
|
1.37
|
1.76
|
|
Lymphocytopenia
|
17
|
25841
|
0.07
|
0.04
|
0.1
|
12
|
15926
|
0.08
|
0.04
|
0.13
|
|
Malaise and fatigue
|
2945
|
14296
|
20.60
|
19.87
|
21.35
|
2,089
|
9143
|
22.85
|
21.88
|
23.84
|
|
Myasthenia gravis
|
≤10
|
n/a
|
0.03
|
0.01
|
0.05
|
≤10
|
n/a
|
0.02
|
0.01
|
0.05
|
|
Myocarditis
|
≤10
|
n/a
|
0.01
|
0
|
0.02
|
≤10
|
n/a
|
0.01
|
0
|
0.04
|
|
Myositis
|
352
|
22731
|
1.55
|
1.39
|
1.72
|
192
|
14275
|
1.34
|
1.16
|
1.55
|
|
Nausea and vomiting
|
3436
|
13816
|
24.87
|
24.05
|
25.71
|
2,615
|
8033
|
32.55
|
31.32
|
33.82
|
|
Pain in joint
|
1584
|
14017
|
11.30
|
10.75
|
11.87
|
930
|
9254
|
10.05
|
9.42
|
10.71
|
|
Pain in limb
|
1741
|
16749
|
10.39
|
9.91
|
10.89
|
1,048
|
10874
|
9.64
|
9.07
|
10.24
|
|
Pancreatitis (acute or autoimmune)
|
146
|
25386
|
0.58
|
0.49
|
0.67
|
82
|
15678
|
0.52
|
0.42
|
0.65
|
|
Psoriasis
|
59
|
25370
|
0.23
|
0.18
|
0.3
|
30
|
15634
|
0.19
|
0.13
|
0.27
|
|
Respiratory abnormalities
|
≤10
|
n/a
|
0.01
|
0
|
0.02
|
≤10
|
n/a
|
0.01
|
0
|
0.03
|
|
Rheumatoid Arthritis
|
130
|
24912
|
0.52
|
0.44
|
0.62
|
70
|
15387
|
0.45
|
0.36
|
0.57
|
|
Sarcoidosis
|
32
|
25689
|
0.12
|
0.09
|
0.17
|
≤10
|
n/a
|
0.06
|
0.03
|
0.1
|
|
Systemic inflammatory response syndrome
|
116
|
25634
|
0.45
|
0.38
|
0.54
|
82
|
15789
|
0.52
|
0.42
|
0.64
|
|
Thrombocytopenia
|
1389
|
23210
|
5.98
|
5.68
|
6.31
|
1,181
|
13985
|
8.44
|
7.97
|
8.94
|
|
Uveitis
|
≤10
|
n/a
|
0.00
|
0
|
0.02
|
0
|
15938
|
0.00
|
0
|
0.02
|
|
Vitiligo
|
≤10
|
n/a
|
0.03
|
0.01
|
0.05
|
≤10
|
n/a
|
0.04
|
0.02
|
0.08
|
|
Overall Mortality
|
3051
|
18414
|
16.57
|
15.99
|
17.16
|
1903
|
8731
|
21.80
|
20.83
|
22.79
|
- Abbreviations: CI Confidence interval, IR Incidence rate
- aEstimates of IR are shown per 100 person-years. Incidence is calculated as the number of new events divided by the sum of person-time at risk, defined as the time between the start of follow-up and the date of the event. In each row, individuals who had a diagnosis of the applicable event prior to the start of follow-up (i.e., prevalent cases) were not included.
- bBecause serious infections were defined based on the need for acute care, all events occurred in hospital or emergency room settings.