Why carry out this study?
|
There is a lack of real-world data on the clinical effectiveness and safety of thyrotropin alfa (recombinant human thyroid-stimulating hormone) in Japanese patients |
This study was conducted to investigate the clinical effectiveness and safety of thyrotropin alfa, either as a diagnostic or therapeutic agent, in a real-world population of Japanese patients (n > 9000) between May 2012 and October 2018 |
What was learned from this study?
|
Thyrotropin alfa was generally well tolerated, with adverse drug reactions being reported in 9.4% and 5.8% of patients who received it for diagnostic and therapeutic (ablation) purposes, respectively |
Over 80% of patients who received thyrotropin alfa for ablation were considered to have a successful treatment outcome 6–12 months post-procedure |
In real-world use in Japan, thyrotropin alfa appears to have clinical effects comparable to those achieved in randomised controlled trials in the Japanese population |
Introduction
Methods
Study Design and Patients
Data Collection
Outcomes and Measures
Statistical Analysis
Results
Patient disposition and characteristics
Total (n = 9268) | Supporting diagnostic ( n = 3444) | Adjunctive treatment for ablation (n = 5822) | Other (n = 2) | |
---|---|---|---|---|
Female sex, n (%) | 6447 (69.6) | 2472 (71.8) | 3974 (68.3) | 1 (50.0) |
Age, years | ||||
Mean (SD) | 56.0 (15.0) | 57.0 (14.6) | 55.5 (15.2) | 58.5 (24.8) |
< 15 | 12 (0.1) | 3.0 (0.1) | 9 (0.2) | – |
≥ 15 – < 65 | 6021 (65.0) | 2192 (63.6) | 3828 (65.8) | 1 (50.0) |
≥ 65 | 3235 (34.9) | 1249 (36.3) | 1985 (34.1) | 1 (50.0) |
Unknown/unstated | – | – | – | – |
Body weight, kg | ||||
n | 8792 | 3235 | 5556 | 1 |
Mean (SD) | 60.2 (13.1) | 59.7 (12.6) | 60.4 (13.3) | 61.3 (–) |
Body mass index, kg/m2 | ||||
n | 8720 | 3197 | 5522 | 1 |
Mean (SD) | 23.4 (4.1) | 23.4 (4.0) | 23.5 (4.2) | 27.6 (–) |
Inpatient/outpatient at registration | ||||
Outpatient | 6535 (70.5) | 2908 (84.4) | 3626 (62.3) | 1 (50.0) |
Inpatient | 2713 (29.3) | 532 (15.4) | 2180 (37.4) | 1 (50.0) |
Unknown/unstated | 20 (0.2) | 4 (0.1) | 16 (0.3) | – |
Comorbiditiesa | ||||
No | 4518 (48.7) | 1882 (54.6) | 2636 (45.3) | – |
Yes | 4741 (51.2) | 1562 (45.4) | 3177 (54.6) | 2 (100.0) |
Unknown/unstated | 9 (0.1) | – | 9 (0.2) | – |
Dose of radioactive iodine (mCi) as supporting diagnostic | ||||
n | 2266 | 2266 | – | – |
Median (min, max) | 8.4 (0.3, 131.0) | 8.4 (0.3, 131.0) | – | – |
Dose of radioactive iodine (mCi) as adjunctive treatment for ablation | ||||
n | 5776 | – | 5776 | – |
Median (min, max) | 30 (3, 300) | – | 30 (3, 300) | – |
Dose of thyrotropin alfa | ||||
n | 9268 | 3444 | 5822 | 2 |
Median (min, max) | 2 (1, 2) | 2 (1, 2) | 2 (1, 2) | 2 (2, 2) |
Total (n = 9268) | Supporting diagnostic (n = 3444) | Adjunctive treatment for ablation (n = 5822) | Other (n = 2) | |
---|---|---|---|---|
Histologic classification of differentiated thyroid cancer | ||||
Papillary carcinoma | 8504 (91.8) | 3145 (91.3) | 5357 (92.0) | 2 (100.0) |
Follicular carcinoma | 694 (7.5) | 277 (8.0) | 417 (7.2) | 0 (0) |
Other | 164 (1.8) | 65 (1.9) | 99 (1.7) | 0 (0) |
Unknown/unstated | 4 (0.0) | 0 (0) | 4 (0.1) | 0 (0) |
Duration of illness, years | ||||
< 5 | 3071 (33.1) | 991 (28.8) | 2080 (35.7) | 0 (0) |
≥ 5 – < 10 | 418 (4.5) | 210 (6.1) | 207 (3.6) | 1 (50.0) |
≥ 10 | 410 (4.4) | 237 (6.9) | 173 (3.0) | 0 (0) |
Unknown | 5369 (57.9) | 2006 (58.2) | 3362 (57.7) | 1 (50.0) |
Number of previous surgeries | ||||
1 | 7838 (84.6) | 2878 (83.6) | 4960 (85.2) | 0 (0) |
2 | 1327 (14.3) | 513 (14.9) | 814 (14.0) | 0 (0) |
3 | 71 (0.8) | 38 (1.1) | 33 (0.6) | 0 (0) |
≥ 4 | 26 (0.3) | 14 (0.4) | 11 (0.2) | 1 (50.0) |
Unknown/unstated | 6 (0.1) | 1 (0.0) | 4 (0.1) | 1 (50.0) |
Previous thyroid surgery | ||||
Total thyroidectomy | 9020 (97.3) | 3267 (94.9) | 5752 (98.8) | 1 (50.0) |
Near-total thyroidectomy | 184 (2.0) | 131 (3.8) | 53 (0.9) | 0 (0) |
Subtotal thyroidectomy | 17 (0.2) | 13 (0.4) | 4 (0.1) | 0 (0) |
Partial thyroidectomy | 2 (0.0) | 2 (0.1) | 0 (0) | 0 (0) |
Hemithyroidectomy | 36 (0.4) | 28 (0.8) | 8 (0.1) | 0 (0) |
Unknown/unstated | 9 (0.1) | 3 (0.1) | 5 (0.1) | 1 (50.0) |
Previous ablations, times | ||||
None | 5454 (58.8) | 684 (19.9) | 4769 (81.9) | 1 (50.0) |
Any | 3783 (40.8) | 2741 (79.6) | 1041 (17.9) | 1 (50.0) |
1 | 3231 (34.9) | 2402 (69.7) | 828 (14.2) | 1 (50.0) |
2 | 369 (4.0) | 212 (6.2) | 157 (2.7) | 0 (0) |
3 | 94 (1.0) | 63 (1.8) | 31 (0.5) | 0 (0) |
≥ 4 | 89 (1.0) | 64 (1.9) | 25 (0.4) | 0 (0) |
Unknown/unstated | 31 (0.3) | 19 (0.6) | 12 (0.2) | 0 (0) |
Total radioiodine dose, mCi | ||||
< 10 | 37 (0.4) | 36 (1.0) | 1 (0.0) | 0 (0) |
≥ 10 – < 30 | 112 (1.2) | 101 (2.9) | 11 (0.2) | 0 (0) |
≥ 30 – < 50 | 2046 (22.1) | 1462 (42.5) | 584 (10.0) | 0 (0) |
≥ 50 – < 100 | 680 (7.3) | 532 (15.4) | 148 (2.5) | 0 (0) |
≥ 100 | 908 (9.8) | 610 (17.7) | 297 (5.1) | 1 (50.0) |
Time from onset to date of total thyroidectomy, years | ||||
< 5 | 3287 (35.5) | 1132 (32.9) | 2154 (37.0) | 1 (50.0) |
≥ 5 – < 10 | 205 (2.2) | 76 (2.2) | 129 (2.2) | 0 (0) |
≥ 10 | 176 (1.9) | 79 (2.3) | 97 (1.7) | 0 (0) |
Unknown | 5352 (57.7) | 1980 (57.5) | 3372 (57.9) | 0 (0) |
Safety
Preferred term | Total (n = 9268) | Supporting diagnostic (n = 3444) | Adjunctive treatment for ablation (n = 5822) |
---|---|---|---|
Vomiting | 4 | – | 4 |
Nausea | 2 | – | 2 |
Loss of consciousness | 1 | 1 | – |
Back pain | 1 | 1 | – |
Atrial fibrillation | 1 | – | 1 |
Pleural effusion | 1 | – | 1 |
Acute myocardial infarction | 1 | 1 | – |
Dizziness | 1 | – | 1 |
Laryngeal oedema | 1 | – | 1 |
Cancer pain | 1 | 1 | – |
Nephrotic syndrome | 1 | – | 1 |
Hyponatraemia | 1 | – | 1 |
Effectiveness
Sign/symptom | Number of patients evaluated | Number of patients affected, n (%) | |
---|---|---|---|
Before first dose | After second dose | ||
Reduced sweating | 6902 | 17 (0.25) | 18 (0.26) |
Dry skin | 6904 | 81 (1.17) | 72 (1.04) |
Coldness | 6905 | 93 (1.35) | 87 (1.26) |
Weight gain | 6904 | 60 (0.87) | 49 (0.71) |
Constipation | 6908 | 109 (1.58) | 104 (1.51) |
Hoarseness | 6898 | 254 (3.68) | 236 (3.42) |
Dysesthesia | 6906 | 33 (0.48) | 47 (0.68) |
Hearing loss | 6907 | 47 (0.68) | 43 (0.62) |
Slow movement | 6905 | 20 (0.29) | 25 (0.36) |
Rough skin | 6906 | 39 (0.56) | 40 (0.58) |
Skin coldness | 6906 | 32 (0.46) | 34 (0.49) |
Oedema of the eyelids | 6905 | 19 (0.28) | 20 (0.29) |
Slow Achilles tendon reflex | 6877 | 32 (0.47) | 15 (0.22) |
Decreased pulse rate | 6905 | 3 (0.04) | 6 (0.09) |
Oedema | 6903 | 64 (0.93) | 48 (0.70) |
Leg cramps | 6875 | 158 (2.30) | 119 (1.73) |