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Contact in Context 2023Thyrotropin alfa is a heterodimeric glycoprotein containing human thyroid stimulating hormone (TSH). It is used as an adjunctive diagnostic tool for serum thyroglobulin...
Thyrotropin alfa is a heterodimeric glycoprotein containing human thyroid stimulating hormone (TSH). It is used as an adjunctive diagnostic tool for serum thyroglobulin (Tg) testing with or without radioiodine imaging in the follow-up of patients with well-differentiated thyroid cancer who have previously undergone thyroidectomy. Inter-lot variability in the Fourier transform near-infrared spectra of 30 samples obtained from four separate lots of Thyrogen was detected in the Drug Quality Study (DQS). The vials fell into two distinct groups (r = 0.90, r= 0.98, =0.02). In addition, one vial of the 30 (3%) appeared 4.7 multidimensional SDs from all of the other vials, suggesting that it also represents a different material.
PubMed: 37396298
DOI: 10.6084/m9.figshare.23524530 -
Advances in Therapy Sep 2021Real-world evidence of the safety and effectiveness of recombinant human thyroid-stimulating hormone (rhTSH; thyrotropin alfa) in Japanese patients is lacking.
INTRODUCTION
Real-world evidence of the safety and effectiveness of recombinant human thyroid-stimulating hormone (rhTSH; thyrotropin alfa) in Japanese patients is lacking.
METHODS
This was a post-marketing surveillance study that included all Japanese patients who received thyrotropin alfa, either as a supporting diagnostic from January 2009 to December 2016, or as adjunctive treatment for ablation from May 2012 to October 2018. Information was collected on patient demographics, thyroid cancer characteristics, adverse drug reactions (ADRs), scintigraphy, serum thyroglobulin (Tg) testing, and hypothyroidism symptoms.
RESULTS
A total of 9268 patients were included in the safety analysis and 9031 in the effectiveness analysis. In the safety analysis set, 3444 patients received thyrotropin alfa as a diagnostic and 5822 received it as treatment. ADRs occurred in 7.1% (n = 660) of patients, including 9.4% (n = 324) of patients who received thyrotropin alfa as a diagnostic and 5.8% (n = 336) of patients who received it as treatment. Nausea was the most common ADR (4.0% of overall safety population). Among patients who received thyrotropin alfa as a diagnostic (n = 1835), the Tg test was positive in 53.6% after the second dose. The scintigram was rated as "readable" in 3023 of the 3054 patients included in this analysis (99.0%). Of the 765 patients who were included in the assessment of response to ablation at 6 months to 1 year after the procedure, 621 (81.2%) were considered to have had "treatment success". There were no significant differences in the proportions of patients who had hypothyroidism symptoms before the first and after the second dose of thyrotropin alfa.
CONCLUSION
In this large post-marketing surveillance study, thyrotropin alfa was well tolerated and showed effectiveness that was comparable to that observed in randomised, controlled trials.
Topics: Humans; Iodine Radioisotopes; Japan; Product Surveillance, Postmarketing; Recombinant Proteins; Thyroglobulin; Thyroid Neoplasms; Thyrotropin; Thyrotropin Alfa
PubMed: 34386895
DOI: 10.1007/s12325-021-01866-9 -
Thyroid : Official Journal of the... Oct 2021Thyrotropin alfa (rhTSH) is not currently approved by the Food and Drug Administration or European Medicines Agency for the preparation of radioactive iodine therapy...
Thyrotropin alfa (rhTSH) is not currently approved by the Food and Drug Administration or European Medicines Agency for the preparation of radioactive iodine therapy (RAIT) in patients with distant metastatic papillary thyroid cancer (PTC). There are only a few studies comparing rhTSH with levothyroxine withdrawal (LTW) in this context. Our main aim was to compare the two methods of RAIT preparation in terms of avidity and structural/biochemical response in distant metastatic PTC. We also intended to evaluate whether the two methods of RAIT preparation represented independent prognostic factors for progression-free survival (PFS) and disease-specific survival (DSS) in this subset of patients. We performed a retrospective analysis of all patients with PTC treated with RAIT for distant metastatic disease between 2006 and 2018. We included 95 PTC patients-27 (28.4%) had LTW and 68 (71.6%) had rhTSH for RAIT. The two groups presented similar clinicopathological characteristics, except for median age at PTC diagnosis, which was higher in the rhTSH group ( = 0.001), but the median age at first RAIT for distant metastatic disease was not different between the two methods of preparation, 63 years old (interquartile range [IQR] 23) in the LTW group versus 70 (IQR 26.75), = 0.06. Avidity was similar between the two groups ( = 0.973). Median estimate PFS ( = 0.076) and DSS ( = 0.084) were also similar between LTW and rhTSH. Regarding RAIT-related side effects, only 1 (3.7%) patient and 5 (7.4%) patients in the LTW and rhTSH groups, respectively, reported sialadenitis ( = 0.670). There were no differences between the two methods of RAIT preparation regarding avidity and clinical response. rhTSH may be used as an alternative method of preparation for RAIT in patients with known distant lesions, as it presents similar clinical outcomes to LTW and a good safety profile.
Topics: Aged; Disease-Free Survival; Female; Humans; Iodine Radioisotopes; Male; Middle Aged; Neoplasm Metastasis; Radiopharmaceuticals; Radiotherapy; Retrospective Studies; Thyroid Cancer, Papillary; Thyroid Neoplasms; Thyrotropin Alfa; Thyroxine; Treatment Outcome
PubMed: 34155923
DOI: 10.1089/thy.2021.0013 -
Clinical Cancer Research : An Official... Jul 2023To evaluate the efficacy and safety of dabrafenib-trametinib-131I for the treatment of radioactive iodine refractory metastatic differentiated thyroid cancer (DTC) with...
PURPOSE
To evaluate the efficacy and safety of dabrafenib-trametinib-131I for the treatment of radioactive iodine refractory metastatic differentiated thyroid cancer (DTC) with a BRAF p.V600E mutation.
PATIENTS AND METHODS
A prospective phase II trial including patients with RECIST progression within 18 months and no lesion > 3 cm. Following a baseline recombinant human (rh)TSH-stimulated diagnostic whole-body scan (dc1-WBS), dabrafenib and trametinib were given for 42 days. A second rhTSH-stimulated dc WBS (dc2-WBS) was done at day 28 and 131I (5.5 GBq-150 mCi after rhTSH) was administered at day 35. Primary endpoint was the 6-month RECIST objective response rate. In case of partial response (PR) at 6 or 12 months, a second treatment course could be given. Among 24 enrolled patients, 21 were evaluable at 6 months.
RESULTS
Abnormal 131I uptake was present on 5%, 65%, and 95% of the dc1-WBS, dc2-WBS, and post-therapy scans, respectively. At 6 months, PR was achieved in 38%, stable disease in 52%, and progressive disease (PD) in 10%. Ten patients received a second treatment course: one complete response and 6 PRs were observed at 6 months. The median progression-free survival (PFS) was not reached. The 12- and 24-month PFS were 82% and 68%, respectively. One death due to PD occurred at 24 months. Adverse events (AE) occurred in 96% of the patients, with 10 grade 3-4 AEs in 7 patients.
CONCLUSIONS
Dabrafenib-trametinib is effective in BRAF p.V600E-mutated DTC patients for restoring 131I uptake with PR observed 6 months after 131I administration in 38% of the patients.
Topics: Humans; Thyroid Neoplasms; Iodine Radioisotopes; Proto-Oncogene Proteins B-raf; Thyrotropin Alfa; Prospective Studies; Pyridones; Pyrimidinones; Oximes; Adenocarcinoma; Antineoplastic Combined Chemotherapy Protocols; Mutation
PubMed: 37074727
DOI: 10.1158/1078-0432.CCR-23-0046 -
The New England Journal of Medicine May 2012It is not known whether low-dose radioiodine (1.1 GBq [30 mCi]) is as effective as high-dose radioiodine (3.7 GBq [100 mCi]) for treating patients with differentiated... (Comparative Study)
Comparative Study Randomized Controlled Trial
BACKGROUND
It is not known whether low-dose radioiodine (1.1 GBq [30 mCi]) is as effective as high-dose radioiodine (3.7 GBq [100 mCi]) for treating patients with differentiated thyroid cancer or whether the effects of radioiodine (especially at a low dose) are influenced by using either recombinant human thyrotropin (thyrotropin alfa) or thyroid hormone withdrawal.
METHODS
At 29 centers in the United Kingdom, we conducted a randomized noninferiority trial comparing low-dose and high-dose radioiodine, each in combination with either thyrotropin alfa or thyroid hormone withdrawal before ablation. Patients (age range, 16 to 80 years) had tumor stage T1 to T3, with possible spread to nearby lymph nodes but without metastasis. End points were the rate of success of ablation at 6 to 9 months, adverse events, quality of life, and length of hospital stay.
RESULTS
A total of 438 patients underwent randomization; data could be analyzed for 421. Ablation success rates were 85.0% in the group receiving low-dose radioiodine versus 88.9% in the group receiving the high dose and 87.1% in the thyrotropin alfa group versus 86.7% in the group undergoing thyroid hormone withdrawal. All 95% confidence intervals for the differences were within ±10 percentage points, indicating noninferiority. Similar results were found for low-dose radioiodine plus thyrotropin alfa (84.3%) versus high-dose radioiodine plus thyroid hormone withdrawal (87.6%) or high-dose radioiodine plus thyrotropin alfa (90.2%). More patients in the high-dose group than in the low-dose group were hospitalized for at least 3 days (36.3% vs. 13.0%, P<0.001). The proportions of patients with adverse events were 21% in the low-dose group versus 33% in the high-dose group (P=0.007) and 23% in the thyrotropin alfa group versus 30% in the group undergoing thyroid hormone withdrawal (P=0.11).
CONCLUSIONS
Low-dose radioiodine plus thyrotropin alfa was as effective as high-dose radioiodine, with a lower rate of adverse events. (Funded by Cancer Research UK; ClinicalTrials.gov number, NCT00415233.).
Topics: Ablation Techniques; Adolescent; Adult; Aged; Aged, 80 and over; Combined Modality Therapy; Female; Follow-Up Studies; Humans; Hypothyroidism; Iodine Radioisotopes; Length of Stay; Male; Middle Aged; Quality of Life; Radiotherapy Dosage; Thyroid Hormones; Thyroid Neoplasms; Thyroidectomy; Thyrotropin Alfa; Treatment Outcome; Young Adult
PubMed: 22551128
DOI: 10.1056/NEJMoa1109589 -
Recombinant human thyrotropin (rhTSH)-aided radioiodine treatment for non-toxic multinodular goitre.The Cochrane Database of Systematic... Dec 2021Multinodular goitre is common in women. Treatments for non-toxic multinodular goitre include surgery, levothyroxine suppressive therapy, and radioiodine. Radioiodine... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Multinodular goitre is common in women. Treatments for non-toxic multinodular goitre include surgery, levothyroxine suppressive therapy, and radioiodine. Radioiodine therapy is the only non-surgical alternative for non-toxic multinodular goitre. However, a high amount of radioiodine is needed to enable the thyroid nodules to adequately take up the radioiodine, because the multinodular goitre takes up a low amount of iodine. Recombinant human thyrotropin (rhTSH) has been used to increase radioiodine uptake and reduce thyroid volume of the multinodular goitre. Whether the improved reduction of the goitre resulting from rhTSH-stimulated radioiodine therapy is beneficial to the person remains controversial.
OBJECTIVES
To assess the effects of recombinant human thyrotropin-aided radioiodine treatment for non-toxic multinodular goitre.
SEARCH METHODS
We searched the CENTRAL, MEDLINE, Scopus as well as ICTRP Search Portal and ClinicalTrials.gov. The date of the last search of all databases was 18 December 2020.
SELECTION CRITERIA
We included randomised controlled clinical trials (RCTs) comparing the effects of rhTSH-aided radioiodine treatment compared with radioiodine alone for non-toxic multinodular goitre, with at least 12 months of follow-up.
DATA COLLECTION AND ANALYSIS
Two review authors independently screened titles and abstracts for relevance. Screening for inclusion, data extraction, and risk of bias assessment were carried out by one review author and checked by a second. Our main outcomes were health-related quality of life (QoL), hypothyroidism, adverse events, thyroid volume, all-cause mortality, and costs. We used a random-effects model to perform meta-analyses, and calculated risk ratios (RRs) for dichotomous outcomes, and mean differences (MDs) for continuous outcomes, using 95% confidence intervals (CIs) for effect estimates. We evaluated the certainty of the evidence using the GRADE approach.
MAIN RESULTS
We included six RCTs. A total of 197 participants were allocated to rhTSh-aided radioiodine therapy, and 124 participants were allocated to radioiodine. A single dose of radioiodine was administered 24 hours after the intramuscular injection of a single dose of rhTSH. The duration of follow-up ranged between 12 and 36 months. Low-certainty evidence from one study, with 85 participants, showed uncertain effects for QoL for either intervention. RhTSH-aided radioiodine increased hypothyroidism compared with radioiodine alone (64/197 participants (32.5%) in the rhTSH-aided radioiodine group versus 15/124 participants (12.1%) in the radioiodine alone group; RR 2.53, 95% CI 1.52 to 4.20; 6 studies, 321 participants; moderate-certainty evidence in favour of radioiodine alone). A total of 118/197 participants (59.9%) in the rhTSH-aided radioiodine group compared with 60/124 participants (48.4%) in the radioiodine alone group experienced adverse events (random-effects RR 1.24, 95% CI 0.94 to 1.63; 6 studies, 321 participants; fixed-effect RR 1.23, 95% CI 1.02 to 1.49 in favour of radioiodine only; low-certainty evidence). RhTSH-aided radioiodine reduced thyroid volume with a MD of 11.9% (95% CI 4.4 to 19.4; 6 studies, 268 participants; moderate-certainty evidence). One study with 28 participants reported one death in the radioiodine alone group (very-low certainty evidence). No study reported on costs.
AUTHORS' CONCLUSIONS
RhTSH-aided radioiodine treatment for non-toxic multinodular goitre, compared to radioiodine alone, probably increased the risk of hypothyroidism but probably led to a greater reduction in thyroid volume. Data on QoL and costs were sparse or missing.
Topics: Female; Goiter; Humans; Iodine Radioisotopes; Quality of Life; Randomized Controlled Trials as Topic; Thyrotropin; Thyrotropin Alfa
PubMed: 34961921
DOI: 10.1002/14651858.CD010622.pub2 -
Endocrine Practice : Official Journal... 2013To describe the evolving role of recombinant human thyrotropin in the diagnostic evaluation of patients treated for differentiated thyroid carcinoma. (Review)
Review
OBJECTIVE
To describe the evolving role of recombinant human thyrotropin in the diagnostic evaluation of patients treated for differentiated thyroid carcinoma.
METHODS
A systematic review was performed of published English language articles appearing in PubMed using terms "recombinant thyrotropin" and "thyroid cancer". The author selected articles for inclusion based upon potential for clinical impact of the reported findings.
RESULTS
The addition of recombinant human thyrotropin to diagnostic testing replaced the requirement for thyroid hormone withdrawal and symptomatic hypothyroidism that had been necessary to generate sufficient endogenous thyrotropin for radioiodine scanning and thyroglobulin testing. The high negative predictive value of stimulated thyroglobulin testing removed the need for serial radioiodine scanning for many patients, but repeated stimulated testing rarely appeared to add significantly. The development of highly sensitive second generation thyroglobulin assays may replace the need for stimulated testing in a subset of patients.
CONCLUSION
Recombinant human thyrotropin-stimulated testing continues to be a valuable component of follow-up testing in the first year after initial treatment of differentiated thyroid cancer.
Topics: Humans; Iodine Radioisotopes; Radionuclide Imaging; Thyroid Neoplasms; Thyrotropin Alfa
PubMed: 23435044
DOI: 10.4158/EP12315.RA -
Journal of Endocrinological... 2012Recombinant human TSH (rhTSH) (thyrotropin alfa, Genzyme Co.) has been developed to improve the management of patients with differentiated thyroid cancer, who need... (Review)
Review
Recombinant human TSH (rhTSH) (thyrotropin alfa, Genzyme Co.) has been developed to improve the management of patients with differentiated thyroid cancer, who need radioiodine (131I) for treatment or follow-up diagnosis. Data available from published series involving approximately 500 patients prove that rhTSH is safe and that mostly unspecific non-severe side effects may occur (e.g. nausea, vomiting, headache or fatigue and dizziness). Tumor swelling which has been occasionally observed after rhTSH injection is a phenomenon well known from the past attributed to endogenous TSH stimulation after thyroid hormone withdrawal (THW) and can be prevented or alleviated by concomitant administration of glucocorticoids. The absorbed dose to the tumor after preparation of 131I therapy with rhTSH as compared to THW is not statistically different. The radiation dose to the blood and the remainder, however, is significantly lower if rhTSH is used instead of THW which is a strong argument in favor of rhTSH. Most importantly, the quality of life (QOL) after rhTSH is preserved as compared to THW where symptoms of hypothyroidism significantly impair QOL. Last but not least, more convenient scheduling of patients and shorter duration of time to be spent in the radioprotective ward are further arguments in favor of rhTSH.
Topics: Cell Differentiation; Evaluation Studies as Topic; Humans; Quality of Life; Thyroid Neoplasms; Thyrotropin Alfa
PubMed: 23014071
DOI: No ID Found -
Radiotherapy and Oncology : Journal of... Jan 2014We conducted a meta-analysis of randomized controlled trials (RCTs) to compare the effects of recombinant human thyrotropin (rhTSH) and thyroid hormone withdrawal (THW)... (Meta-Analysis)
Meta-Analysis Review
Recombinant human thyrotropin-aided versus thyroid hormone withdrawal-aided radioiodine treatment for differentiated thyroid cancer after total thyroidectomy: a meta-analysis.
BACKGROUND AND PURPOSE
We conducted a meta-analysis of randomized controlled trials (RCTs) to compare the effects of recombinant human thyrotropin (rhTSH) and thyroid hormone withdrawal (THW) on thyrotropin stimulation prior to remnant ablation of differentiated thyroid cancer (DTC).
MATERIAL AND METHODS
A comprehensive search was conducted for articles discussing rhTSH and THW prior to December 2012. After applying the inclusion criteria, all the available data were summarized to analyze the efficacy of rhTSH and THW for stimulating TSH.
RESULTS
Seven RCTs that involved a total of 1535 patients, were included in the analysis. The ablation rates of the rhTSH group and the THW group were not significantly different (RR=0.97, 95% CI: 0.94-1.01, p=0.1). Patients in the rhTSH group had a better quality of life (QoL) than those in the THW group on the day of ablation (RR=3.92, 95% CI: 3.44-5.40, p<0.00001). However, there was no difference in the QoL 3 months after ablation (RR=-0.9, 95% CI: -2.20-0.39, p=0.17). Additionally, there were no significant differences in serum thyroglobulin (Tg) levels measured just before radioiodine remnant ablation (preablation thyroglobulin levels) (RR=-0.14, 95% CI: -0.73-0.45, p=0.65), or in days of hospital isolation (RR=-10.51, 95% CI: -32.79-11.73, p=0.35) CONCLUSIONS: Our findings indicate that the administration of rhTSH had resulted in an ablation rate similar to that of THW for DTC patients, but rhTSH provided a better QoL at the time of ablation.
Topics: Humans; Iodine Radioisotopes; Quality of Life; Randomized Controlled Trials as Topic; Thyroid Neoplasms; Thyroidectomy; Thyrotropin Alfa
PubMed: 24485353
DOI: 10.1016/j.radonc.2013.12.018