Levothyroxine Treatment Adequacy and Formulation Changes in Patients with Hypothyroidism: A Retrospective Study of Real-World Data from the United States.

Background: The prevalence of hypothyroidism (HT) has increased over time. To assess the effectiveness of treatment, we (1) studied thyrotropin (TSH) levels among patients receiving levothyroxine (LT4) and (2) determined the percentages of patients switching among LT4 formulations. Methods: Data on patients with HT receiving LT4 from the Optum™ Clinical and Claims Database were analyzed from March 2013 through February 2020. Eligible adult patients had ≥1 medical claim with an HT diagnosis and all patients were observed for ≥12 months. Patients included in Objective 1 were indexed on a randomly selected TSH result and had ≥2 results for TSH 1-15 months apart. Patients included in Objective 2 were indexed on a randomly selected LT4 pharmacy claim and had ≥2 LT4 claims ≥1 month apart and ≥1 claim during follow-up. Outcomes were the proportion of patients with low, normal, or high (<0.45, 0.45-4.5, or >4.5 mIU/L, respectively) TSH levels and the proportion of patients switching LT4 formulations, respectively. Data were stratified by age group, sex, and insurance type. All data reported were analyzed using descriptive statistics. Results: Of patients who were in the indexed TSH group, 81.1% [confidence intervals: 80.4-81.8; n/N = 9130/11,259] achieved normal TSH values. When stratified by age group, sex, and insurance type, ≥70% of patients in each of these subgroups exhibited normal mean TSH values at follow-up. For Objective 2 (N = 25,076), 24.9% (N = 6238) of the LT4-indexed group had ≥1 formulation switch in 12 months, of which 67.3% only switched once, and 41.4% (N = 10,370) had ≥1 formulation switch in up to 24 months. A significantly higher proportion of Medicare vs. commercially insured patients had switched formulations (26.2% vs. 23.1%, p < 0.001). Conclusions: Most LT4-treated patients maintain normal TSH levels, which is an improvement vs. previous reports. Continued physician engagement and patient education are advised to further reduce the number of patients who maintain off-target TSH levels. Contrary to clinical recommendations, about 25% of patients receiving LT4 switched formulations within 1 year, with >40% switching within 2 years; among patients who switched, most only switched once.

Novel recombinant human thyroid-stimulating hormone in aiding postoperative assessment of patients with differentiated thyroid cancer-phase I/II study.

PURPOSE: Thyroid hormone withdrawal (THW) inevitably induced hypothyroidism in patients with differentiated thyroid cancer (DTC), and we aimed to evaluate the safety and efficacy of a novel recombinant human thyroid-stimulating hormone (rhTSH, ZGrhTSH) as an alternative of THW in China. METHODS: Totally, 64 DTC patients were enrolled with 24 in the dose-escalation cohort equally grouped into 0.9 mg × 1 day, 0.9 mg × 2 day, 1.8 mg × 1 day, and 1.8 mg × 2 day dosage, and 40 further enrolled into 0.9 mg × 2 day dose-expansion cohort. All patients underwent both ZGrhTSH phase and levothyroxine (L-T4) withdrawal phase for self-comparison in terms of TSH levels, the radioactive iodine (RAI) uptake, stimulated thyroglobulin level, and the quality of life (QoL). RESULTS: In ZGrhTSH phase, no major serious adverse events were observed, and mild symptoms of headache were observed in 6.3%, lethargy in 4.7%, and asthenia in 3.1% of the patients, and mostly resolved spontaneously within 2 days. Concordant RAI uptake was noticed in 89.1% (57/64) of the patients between ZGrhTSH and L-T4 withdrawal phases. The concordant thyroglobulin level with a cut-off of 1 µg/L was noticed in 84.7% (50/59) of the patients without the interference of anti-thyroglobulin antibody. The QoL was far better during ZGrhTSH phase than L-T4 withdrawal phase, with lower Billewicz (- 51.30 ± 4.70 vs. - 39.10 ± 16.61, P < 0.001) and POMS (91.70 ± 16.70 vs. 100.40 ± 22.11, P = 0.011) scores which indicate the lower the better. Serum TSH level rose from basal 0.11 ± 0.12 mU/L to a peak of 122.11 ± 42.44 mU/L 24 h after the last dose of ZGrhTSH. In L-T4 withdrawal phase, a median of 23 days after L-T4 withdrawal was needed, with the mean TSH level of 82.20 ± 31.37 mU/L. The half-life for ZGrhTSH clearance was about 20 h. CONCLUSION: The ZGrhTSH held the promise to be a safe and effective modality in facilitating RAI uptake and serum thyroglobulin stimulation, with better QoL of patients with DTC compared with L-T4 withdrawal.

Comparative Effectiveness of Persistent Use of a Name-Brand Levothyroxine (Synthroid®) vs. Persistent Use of Generic Levothyroxine on TSH Goal Achievement: A Retrospective Study Among Patients with Hypothyroidism in a Managed Care Setting.

INTRODUCTION: Levothyroxine monotherapy (Synthroid® or multiple generic levothyroxine [GL] formulations) is standard treatment for hypothyroidism. Our objective was to compare effectiveness (as measured by achievement of thyroid-stimulating hormone [TSH] levels) and economic outcomes of Synthroid vs. any one of multiple GLs in patients with hypothyroidism. METHODS: Data for this retrospective cohort study were obtained from the HealthCore Integrated Research Database®. All study patients had ≥ 2 claims between 1 January 2006 and 31 December 2017 with ICD-9/10-CM diagnosis codes for hypothyroidism; were persistent users of Synthroid vs. any GL; and had ≥ 1 TSH laboratory result during 12-month follow-up. Patients were divided into one of two cohorts based on index medication and were 1:1 matched using propensity scores. The primary outcome was the proportion of patients with last TSH laboratory result during follow-up within the reference range (0.3-4.12 mIU/L). Secondary outcomes included all-cause and hypothyroidism-related healthcare resource utilization (HCRU) and costs. RESULTS: After propensity score matching, the Synthroid and GL cohorts each contained 18,382 patients. At follow-up, significantly more patients receiving Synthroid were in the TSH reference range vs. GL (78.5% vs. 77.2%, respectively, p = 0.002). HCRU and costs were broadly similar between the cohorts in terms of all-cause inpatient hospitalizations, emergency department visits, outpatient services, and pharmacy fills. Irrespective of index medication, patients with TSH within the reference range had significantly lower hypothyroidism-related medical and total costs compared to those outside the range. CONCLUSIONS: This real-world data study showed Synthroid was associated with better TSH target achievement vs. GL in a US managed care population. Achieving TSH goals may provide substantial economic value by reducing hypothyroidism-related HCRU and costs.

Eficacia y seguridad de tirotropina recombinante para el tratamiento de pacientes adultos posoperados de cáncer de tiroides diferenciado que requieren terapia radioablativa y no tienen contraindicación de suspensión del reemplazo hormonal con hormona tiroidea exógena / Efficacy and safety of recombinant thyrotropin for the treatment of postoperative adult patients with differentiated thyroid cancer who require radioablative therapy and have no contraindication to suspend hormone replacement with exogenous thyroid hormone

INTRODUCCIÓN: El presente dictamen expone la evaluación de la eficacia y seguridad de tirotropina recombinante (rhTSH) en pacientes adultos posoperados de cáncer de tiroides diferenciado (CTD), sin contraindicación de suspensión del reemplazo hormonal con hormona tiroidea exógena (THW) y que requieren terapia radioablativa (RAI). El cáncer de tiroides es la neoplasia endocrina más frecuente. Entre 2012 y 2016, la incidencia de cáncer de tiroides en Estados Unidos fue de 15.8/100 000 habitantes. En oposición a la alta incidencia, la mortalidad en el mismo periodo de tiempo se estimó en 0.5/100 000 hombres y mujeres. El año 2017, se diagnosticaron 637 nuevos casos de cáncer de tiroides en el Instituto Nacional de Enfermedades Neoplásicas de Perú. Estudios poblacionales sugieren que entre el 70 % y 90 % de los casos corresponderían al sobrediagnóstico1 de lesiones asintomáticas detectadas durante exámenes de rutina. El tratamiento de los pacientes con cáncer de tiroides diferenciado (CTD) se basa en tres actividades: la resección quirúrgica del tumor, la terapia radioablativa con yodo (RAI) y la terapia de reemplazo hormonal con hormona tiroidea exógena. Para realizar la RAI, el tejido tiroideo remanente debe absorber el yodo radioactivo (I 131). La absorción y retención del I131 se consigue aumentando el nivel de hormona estimulante de la tiroides (TSH, por sus siglas en inglés). La terapia de reemplazo hormonal suprime la TSH; por lo tanto, la forma más sencilla de estimular la producción de TSH es suspender la terapia de reemplazo hormonal. Sin embargo, la suspensión de la terapia de reemplazo hormonal (THW, por sus siglas en inglés) también induce hipotiroidismo clínico secundario debido a la falta de hormona tiroidea. Actualmente, en EsSalud, los pacientes con CTD que requieren RAI del tejido tiroideo remanente son preparados mediante THW, excepto para los pacientes que tienen contraindicación de THW. De acuerdo con lo señalado en el Dictamen Preliminar de Evaluación de Tecnología Sanitaria N° 053-SDEPFYOTS-DETS- IETSI-2019 del IETSI, la tirotropina recombinante humana (rhTSH, por sus siglas en inglés) puede utilizarse en pacientes con contraindicación de THW, así el paciente puede acceder a la RAI sin el riesgo que conlleva la THW. La TSH recombinante humana (rhTSH, por sus siglas en inglés) es una forma recombinante de la TSH humana desarrollada para elevar los niveles de TSH antes del escaneo con I131 de la realización de la prueba de tiroglobulina y antes del procedimiento de RAI. El uso de rhTSH estimula la captación de yodo por la tiroides, de este modo la radiación del I131 usado en la RAI elimina las células neoplásicas que no fueron extraídas durante la cirugía. Adicionalmente, con rhTSH no hay necesidad de la THW, por lo tanto, se evita el hipotiroidismo secundario a THW. METODOLOGÍA: Se llevó a cabo una búsqueda sistemática de la literatura con respecto a la eficacia y seguridad de rhTSH en el tratamiento de pacientes adultos posoperados de CTD, que requieren RAI y no tienen contraindicación de THW. Se realizó tanto una búsqueda sistemática como una búsqueda manual en las páginas web de grupos dedicados a la investigación y educación en salud que elaboran guías de práctica clínica (GPC) y evaluaciones de tecnologías sanitarias (ETS). RESULTADOS: En la presente sinopsis se describe la evidencia disponible según el tipo de publicación, siguiendo lo indicado en los criterios de elegibilidad. CONCLUSIONES: El presente dictamen preliminar tuvo como objetivo evaluar la evidencia disponible la eficacia y seguridad de rhTSH en términos de: sobrevida global, calidad de vida e incidencia de eventos adversos, en comparación con placebo, para el tratamiento de pacientes adultos posoperados de CTD sin contraindicación de THW, y que requieren RAI. Tras la búsqueda sistemática de literatura, se incluyeron tres GPC (Pacini et al. 2012; Haugen et al. 2016; Pacini et al. 2016), dos ETS (Deminco, Alemán, y Pérez-Galán 2011; CCATES 2016) y una RS con MA (Xu et al. 2015) como evidencia para responder la pregunta PICO de interés del presente dictamen preliminar. Con respecto a lo expuesto previamente, el equipo técnico del IETSI valoró los siguientes aspectos: i) El CTD es una enfermedad infrecuente y de buen pronóstico, y, ii) La evidencia disponible sugiere que rhTSH y THW tienen resultados similares en eficacia y calidad de vida en pacientes con CTD que son preparados para la RAI. Por todo lo expuesto, el IETSI no aprueba el uso de rhTSH como parte del tratamiento de pacientes adultos posoperados de cáncer de tiroides diferenciado que requieren terapia radioablativa y no tienen contraindicación de suspensión del reemplazo hormonal con hormona tiroidea exógena.

Eficacia y seguridad de tirotropina recombinante para el tratamiento de pacientes adultos posoperados de cáncer de tiroides diferenciado que requieren terapia radioablativa y tienen contraindicación de suspensión del reemplazo hormonal con hormona tiroidea exógena / Efficacy and safety of recombinant thyrotropin for the treatment of postoperative adult patients with differentiated thyroid cancer who require radioablative therapy and have contraindication for suspension of exogenous thyroid hormone replacement

INTRODUCCIÓN: El presente dictamen expone la evaluación de la eficacia y seguridad de tirotropina recombinante en pacientes adultos posoperados de cáncer de tiroides diferenciado con contraindicación de suspensión del reemplazo hormonal con hormona tiroidea exógena y que requieren terapia radioablativa. El cáncer de tiroides es una neoplasia infrecuente (incidencia mundial alrededor de 15.0/100 000 varones y 22.0/100 000 mujeres); aunque se estima que entre el 70 % y 90 % de estos casos corresponde a un sobrediagnóstico. Se estima que la sobrevida a los 5 años es del 98.1 %, aproximadamente. En Perú, en el año 2017, se diagnosticaron 637 nuevos casos de cáncer de tiroides en el Instituto Nacional de Enfermedades Neoplásicas. El cáncer de tiroides que se forma a partir de las células epiteliales foliculares se denomina cáncer de tiroides diferenciado (CTD). TECNOLOGÍA SANITARIA DE INTERÉS: Tirotropina Recombinante Humana: La TSH es un estimulante específico de la tiroides, esencial para la función tiroidea, promoviendo la captación de yodo, la síntesis de tiroglobulina, y el crecimiento celular. Los CTD mantienen algunas características de la glándula tiroidea normal; entre ellas, la captación de yodo y la síntesis de tiroglobulina estimulada por la TSH. METODOLOGÍA: Se llevó a cabo una búsqueda sistemática de la literatura con respecto a la eficacia y seguridad de rhTSH en el tratamiento de pacientes adultos posoperados de CTD con contraindicación de THW y que requieren RAI. Se realizó tanto una búsqueda sistemática como una búsqueda manual en las páginas web de grupos dedicados a la investigación y educación en salud que elaboran guías de práctica clínica (GPC) y evaluaciones de tecnologías sanitarias (ETS). RESULTADOS: No se encontró evidencia que responda directamente al objetivo del presente dictamen preliminar La presente evaluación de tecnología sanitaria muestra la evidencia indirecta encontrada luego de una búsqueda sistemática, con respecto. a la eficacia y seguridad de rhTSH en términos de: sobrevida global, calidad de vida e incidencia de eventos adversos, en comparación con THW, para el tratamiento de pacientes adultos posoperados de CTD que requieren RAI. Al respecto, se identificaron tres guías de práctica clínica (GPC) elaboradas por la European Society for Medical Oncology (ESMO) en 2012, la American Thyroid Association (ATA) en 2015 y la Italian Society of Endocrinology (ISE) en 2016; dos evaluaciones de tecnologías sanitarias (ETS) elaboradas por El Ministerio de Salud Pública de Uruguay en 2011 y el Centro de colaboración del SUS: evaluación de tecnología & excelencia en salud (CCATES) en 2016; y, una revisión sistemática (RS) publicada en 2015. CONCLUSIONES: El equipo técnico del IETSI valoró los siguientes aspectos: i) El CTD es una enfermedad infrecuente y de buen pronóstico, pero que requiere de un tratamiento eficaz para mantener una adecuada calidad de vida, ii) Desde el punto de vista clínico, la evidencia disponible sugiere que rhTSH y THW presentan similar eficacia y seguridad como preparación para la RAI, en pacientes con CTD, iii) Dado que la población de interés del presente dictamen son pacientes con contraindicación de THW, es necesario ofrecer una alternativa que les permita recibir un tratamiento adecuado iv) La evidencia indirecta utilizada, sugiere que en pacientes con contraindicación de THW, el uso de rhTSH ofrecería resultados similares a los que se obtendrían con THW si no existiese dicha contraindicación. El Instituto de Evaluación de Tecnologías en Salud e Investigación ­ IETSI, aprueba el uso de rhTSH como parte del tratamiento de pacientes adultos posoperados de CTD que requieren RAI y tienen contraindicación de THW, según lo establecido en el Anexo N° 01. La vigencia del presente dictamen preliminar es de un año a partir de la fecha de publicación. Así, la continuación de dicha aprobación estará sujeta a la evaluación de los resultados obtenidos y de nueva evidencia que pueda surgir en el tiempo.

Levothyroxine Formulations: Pharmacological and Clinical Implications of Generic Substitution.

Oral levothyroxine (LT4) is the standard therapy for patients with hypothyroidism. Oral LT4 is available in several formulations, including tablets, soft gel capsules and oral solution. Multiple brand-name and generic LT4 tablets are available. In the US, the Food and Drug Administration (FDA) has developed a protocol for establishing bioequivalence of LT4 formulations based on serum thyroxine (T4) levels after a single oral dose administered to healthy volunteers. This protocol has been criticized by professional endocrinology associations for using healthy individuals and ignoring serum thyroid-stimulating hormone (TSH) levels. In addition, the protocol did not initially correct for baseline T4 levels, although this was changed in a later version. There are concerns that the FDA's protocol could allow products with clinically significant differences in bioavailability to be declared therapeutically equivalent and interchangeable. Once a generic LT4 has been shown to be bioequivalent to a brand-name LT4, it may be substituted for that brand-name LT4 with no need for dose adjustment or follow-up therapeutic monitoring. Often, the substitution is made by the pharmacy without the physician's knowledge. Even small differences between LT4 formulations can cause significant changes in TSH levels. This may be a particular concern in vulnerable populations, including elderly, pregnant, and pediatric patients. Problems that can be encountered when switching between formulations or when original products are reformulated are discussed in this review. These problems include altered efficacy and adverse events, some of which can be caused by excipients. Patients should be maintained on the same LT4 preparation if possible. If the LT4 preparation is changed, TSH levels should be evaluated and, if necessary, the dose of LT4 adjusted.Funding: Merck.Plain Language Summary: Plain language summary available for this article.

Cost-effectiveness of using recombinant human thyroid-stimulating hormone before radioiodine ablation for thyroid cancer treatment in Spanish hospitals. / Coste-efectividad de la utilización de la tirotropina recombinante humana previa a la ablación con radioyodo en el tratamiento del cáncer de tiroides en hospitales españoles.

OBJECTIVES: In thyroid cancer treatment, the thyroid-stimulating hormone (TSH) must be elevated before radioiodine ablation, either by exogenous (with recombinant human thyrotropin [rhTSH]) or endogenous stimulation by thyroid hormone withdrawal (THW). The use of rhTSH avoids hypothyroidism and favours the subsequent elimination of radioiodine, but involves the cost of the product. For this reason, a cost-effectiveness analysis was performed, taking into account all costs involved and the benefits associated with the use of this therapy. MATERIAL AND METHODS: Using a Markov modelling with two analysis arms (rhTSH and THW), stratified into high (100mCi/3700 MBq) and low (30mCi/1110 MBq) radioiodine doses, and using 17 weekly cycles, the incremental cost per quality-adjusted life-year (QALY) related to the use of rhTSH was determined. The clinical inputs included in the model were based on published studies and in a treatment survey conducted in Spain. RESULTS: Radioablation preparation with rhTSH is superior to THW, showing additional benefits (0.048 AVAC), as well as cost savings (-€614.16), with an incremental cost-effectiveness rate (ICER) of -€12,795/QALY. The univariate and multivariate sensitivity analyses showed the result to be robust. CONCLUSIONS: The use of rhTSH previous to radioablation in Spain has cost savings, as well as a series of health benefits for the patient, making it highly cost-effective.

Quality of Life and Cost-Effectiveness Assessment of Radioiodine Ablation Strategies in Patients With Thyroid Cancer: Results From the Randomized Phase III ESTIMABL Trial.

PURPOSE: In the ESTIMABL phase III trial, the thyroid ablation rate was equivalent for the two thyroid-stimulating hormone (TSH) stimulation methods (thyroid hormone withdrawal [THW] and recombinant human TSH [rhTSH]) and the two iodine-131 ((131)I) activities (1.1 or 3.7 GBq). The objectives of this article were to present health-related quality-of-life (HRQoL) results and a cost-effectiveness evaluation performed alongside this trial. PATIENTS AND METHODS: HRQoL and utility were longitudinally assessed, from random assignment to the follow-up visit at 8 ± 2 months for the 752 patients with thyroid cancer, using the Short Form-36 and the EuroQoL-5D questionnaires, respectively. A cost-effectiveness analysis was performed from the societal perspective in the French context. Resource use (hospitalization for (131)I administration, rhTSH, sick leaves, and transportation) was collected prospectively. We used the net monetary benefit approach and computed cost-effectiveness acceptability curves for both TSH stimulation methods and (131)I activities. Sensitivity analyses of the costs of rhTSH were performed. RESULTS: At (131)I administration, THW caused a clinically significant deterioration of HRQoL, whereas HRQoL remained stable with rhTSH. This deterioration was transient with no difference 3 months later. rhTSH was more effective than THW in terms of quality-adjusted life-years (QALYs; +0.013 QALY/patient) but more expensive (+€474/patient). The probability that rhTSH would be cost effective at a €50,000/QALY threshold was 47% in France. The use of 1.1 GBq of (131)I instead of 3.7 GBq reduced per-patient costs by €955 (US$1,018) but with slightly decreased efficacy (-0.007 QALY/patient). CONCLUSION: rhTSH avoids the transient THW-induced deterioration of HRQoL but is unlikely to be cost effective at its current price.

The widened use of exogenous stimulation with recombinant human TSH to treat metastatic thyroid carcinoma in Italy.

Recently, in Italy, the reimbursement for the use of rhTSH in preparing patients for radiometabolic treatment of iodine-avid metastases from differentiated thyroid cancer has been made possible. Intramuscular administration of rhTSH increases the radioiodine uptake and thyroglobulin production by thyroid cells. In addition to the previous indications on the use of rhTSH (mainly: serum thyreoglobulin assay with or without 131I scintigraphy and ablation with 131I of remnants in low risk patients), the reimbursement is now allowed for the treatment with radioiodine of iodine-avid loco-regional and distant metastases, in subjects with inability to reach adequate TSH levels and/or severe clinical conditions which could be potentially worsened by other concurrent diseases (history of stroke or transient ischemic attack, severe cardiac disease, renal failure or major psychiatric disorders). The Italian Medicines Agency (AIFA) approved this use (and added this hormone in the special list of drugs regulated by the D.Lgs 648/96) on the basis of a series of scientific evidences, proposed by a "team of experts". In the present paper we illustrate the scientific background of the use of rhTSH (clinical usefulness, economic considerations, aspects related to a better quality of life) that allowed the modification of the reimbursement and how it was made possible in the Italian legislative context.

Recombinant human TSH versus hypothyroidism. Cost-minimization-analysis in the follow-up care of differentiated thyroid carcinoma.

UNLABELLED: The primary aim of this study was to compare pharmacoeconomic effects of hypothyroidism secondary to hormone withdrawal (THW) and recombinant human TSH (rhTSH) for follow-up WBS in patients with differentiated thyroid cancer (DTC). The second aim was to determine patients' preference for one procedure or the other. PATIENTS, METHODS: This retrospective survey included 327 patients with DTC who underwent at least one in-hospital WBS with rhTSH between 1999 and 2006. They had also undergone THW for WBS. Patients received a two-page questionnaire via mail addressing five symptoms and ten items regarding managing their daily life which was answered by 61.6%. The responder group did not differ from the entire group. The medical and societal cost of both procedures for diagnostic WBS was calculated including direct and all ascertainable indirect cost for the reference year 2005. A sensitivity analysis included the German DRG system of 2007 and 2010. RESULTS: After THW, 94% of patients reported hypothyroid symptoms. Using rhTSH, symptoms occurred significantly less. As a result, 97% of patients favored rhTSH over THW. Mean absence from salaried work was 12.3 days after THW compared to 4 days with rhTSH. Family members of salaried employees missed 3 and 0.7 workdays after THW and rhTSH, respectively. Almost twice as often, medical attention was sought after THW (36%) compared to rhTSH (19 %). Undergoing THW, 48% of patients still used their car while hypothyroid. Our cost calculation revealed a slight benefit of about 89.00 Euro in favour of rhTSH stimulation. CONCLUSION: Hypothyroidism after THW causes significant morbidity and safety risks. The clinical and societal benefits associated with rhTSH are roughly gained at equivalent overall cost to that of THW.

To stimulate or withdraw? A cost-utility analysis of recombinant human thyrotropin versus thyroxine withdrawal for radioiodine ablation in patients with low-risk differentiated thyroid cancer in the United States.

CONTEXT: Use of recombinant human TSH (rhTSH) prior to radioactive iodine remnant ablation for patients with differentiated thyroid cancer avoids the hypothyroid state and improves quality of life. European studies have shown that use of rhTSH vs. thyroid hormone withdrawal is a cost-effective method for preparing patients for ablation. OBJECTIVE: The objective of the study was to determine the cost-utility of rhTSH prior to ablation in the United States. DESIGN/SETTING/SUBJECTS: A Markov decision model was developed for a hypothetical group of adult patients with low-risk differentiated thyroid cancer who were prepared for ablation by either rhTSH or thyroid hormone withdrawal. Patients entered the model after initial thyroidectomy; follow-up was in accordance with current American Thyroid Association guidelines. Input data were obtained from the literature, Medicare reimbursement schedule, and U.S. Bureau of Labor Statistics. Sensitivity analyses were performed for all clinically relevant inputs. MAIN OUTCOME MEASURES: Cost-utility, measured in U.S. dollars per quality-adjusted life-year ($/QALY), was measured. RESULTS: Use of rhTSH yielded an incremental cost-utility of $52,554/QALY (95% confidence interval $52,058-53,050/QALY) (incremental societal cost of $1,365/patient; incremental benefit of 0.026 QALY/patient). The majority of cost and benefit occurs during the preablation, ablation, and postablation period; differences in cost are due to cost of rhTSH and differences in productivity loss (days off work). The model was most sensitive to changes in time off work, cost of rhTSH, and differences in utilities of health states. CONCLUSIONS: In the United States, the cost-effectiveness of rhTSH for ablation in patients with low-risk differentiated thyroid cancer is highly dependent on potential variations in cost of rhTSH, rates of remnant ablation, time off work, and quality of life.

Cost-effectiveness of using recombinant human thyroid-stimulating hormone before radioiodine ablation for thyroid cancer: the Canadian perspective.

OBJECTIVES: Radioiodine ablation for the treatment of thyroid cancer is traditionally performed after preparing patients by inducing hypothyroidism. Exogenous stimulation of thyroid-stimulating hormone (TSH) using recombinant human TSH (rhTSH) avoids hypothyroidism and hastens the clearance of radioiodine from the patient. These advantages are achieved without jeopardizing the success rate of remnant ablation. An economic analysis was performed to place the increased acquisition cost of rhTSH in the context of the health benefits achieved and the earlier discharge from radioprotection. METHODS: Markov modeling, using 17 individual weekly cycles, was used to assess the incremental cost per quality-adjusted life-year (QALY) associated with exogenous stimulation. Clinical inputs were largely sourced from a multicenter, randomized, controlled trial comparing remnant ablation success after either rhTSH or hypothyroid preparation. The model applied Canadian unit costs, taking a societal perspective. Additional costs associated with rhTSH were considered in the context of the clinical benefits and cost offsets. These included avoidance of hypothyroidism, increased work productivity, earlier administration of ablation after surgery, and earlier discharge from the radio-protective ward because of faster radioiodine clearance following rhTSH preparation. The model duration avoided the need for discounting. RESULTS: The additional benefits of rhTSH (0.0576 QALY) are obtained with an incremental cost of CDN$87, generating an incremental cost per QALY of CDN$1520. Deterministic one-way and two-way sensitivity analyses demonstrated the result to be robust. CONCLUSIONS: The use of rhTSH before radioiodine ablation represents a reasonable allocation of costs, with the benefits to patients, hospitals, and society as a whole, obtained at modest cost.

Length and cost of hospital stay of radioiodine ablation in thyroid cancer patients: comparison between preparation with thyroid hormone withdrawal and thyrogen.

PURPOSE: Treatment of thyroid cancer consists of thyroidectomy and radioiodine ablation following thyroid-stimulating hormone (TSH) stimulation. Similar ablation rates were obtained with either thyroid hormone withdrawal (THW) or rhTSH. But with rhTSH, the elimination of radioiodine is more rapid, thus reducing its whole-body retention and potentially resulting in a shorter hospital stay. The aim of this study was to assess the financial impact of a reduced length of hospital stay with the use of rhTSH. METHODS: This was a case-control study of thyroid cancer patients treated postoperatively with 3,700 MBq (100 mCi) radioiodine; 35 patients who received rhTSH were matched with 64 patients submitted to THW according to covariates influencing radioiodine retention. The length of hospitalization (LOH) was estimated for each method according to the threshold of radioiodine retention below which the patient can be discharged from the hospital. The economic analysis was conducted from a hospital perspective. Simulations were performed. RESULTS: For a threshold of 400 MBq, the LOH was 2.4 days and 3.5 days with rhTSH and THW, respectively, and the cost for an ablation stay was, respectively, 2,146 and 1,807 . In the French context, 57% of the acquisition cost of rhTSH was compensated by the reduction of the length of hospitalization. CONCLUSION: By increasing the iodine excretion, rhTSH allows a shorter hospitalization length, which partially compensates its acquisition cost.

Cardiovascular assessment of hyperthyroid patients with multinodular goiter before and after radioiodine treatment preceded by stimulation with recombinant human TSH.

Treatment of large multinodular goiter (MNG) with radioiodine preceded by recombinant human thyrotropin (0.1 mg rhTSH) has been shown to be a safe alternative for patients with comorbidities that preclude surgery. However, the increase in serum thyroid hormones that follows both treatments may be harmful for some patients, particularly those with underlying cardiovascular disease. In this study, we evaluated cardiac parameters (clinical, ECG, 24-h Holter, Doppler echocardiogram, treadmill stress test) in 27 of 42 patients (ages 42-80 years) with large MNGs who were treated with rhTSH before receiving 30 mCi radioiodine therapy. At baseline, 18 patients had subclinical and six patients had overt iodine-induced hyperthyroidism. All patients had a transient surge in serum levels of free T4 and total T3 into the hyperthyroid range after therapy. However, repeated cardiac evaluation did not show significant changes as compared with baseline evaluation. In conclusion, rhTSH stimulated RAI treatment of MNG did not affect structural and functional parameters of the heart, despite transient high-serum levels of thyroid hormones.

Cost-effectiveness of using recombinant human TSH prior to radioiodine ablation for thyroid cancer, compared with treating patients in a hypothyroid state: the German perspective.

OBJECTIVE: This investigation evaluated the cost-effectiveness of radioiodine remnant ablation following preparation with recombinant human TSH (rhTSH), compared with the standard preparation, whereby patients are rendered hypothyroid. DESIGN: The economic evaluation relates to patients with well differentiated thyroid cancer who have undergone thyroidectomy, but have no metastases. The evaluation takes a societal perspective, considering costs and benefits to all parties. The benefits were expressed in units of quality-adjusted life years (QALY), so differences in life expectancy were captured with consideration of quality of life. METHODS: A lifetime Markov model with Monte Carlo simulation of 100,000 patients was used to assess cost per QALY gained. The clinical inputs were sourced from a multi-centre, randomised controlled trial comparing remnant ablation success after rhTSH-preparation with hypothyroid preparation. The model applied German unit costs, however, the structure is generalisable to other jurisdictions. The additional cost of rhTSH procurement and administration is considered relative to the clinical benefits and cost offsets. These included avoidance of hypothyroidism, increased work productivity, earlier discharge from radioprotection and a theoretical reduction in the risk of secondary malignancy. The latter two benefits relate to faster radioiodine clearance after rhTSH preparation. RESULTS: The additional benefits of rhTSH (0.0495 QALY) are obtained with an incremental societal cost of 47 euro, equating to an incremental cost per QALYof 958 euro. Sensitivity analyses had only a modest impact upon cost-effectiveness, with all one-way sensitivity results remaining under 15,000 euro/QALY. CONCLUSIONS: The use of rhTSH prior to radioiodine ablation represents good value-for-money with the benefits to patient and society obtained at modest net cost.

Thyroid hormone withdrawal in patients with differentiated thyroid carcinoma: a one hundred thirty-patient pilot survey on consequences of hypothyroidism and a pharmacoeconomic comparison to recombinant thyrotropin administration.

The study objective was to elucidate clinical, quality-of-life, and pharmacoeconomic effects of hypothyroidism secondary to thyroid hormone withdrawal (withdrawal) in athyroid patients with differentiated thyroid cancer (DTC). We also intended to compare societal costs of withdrawal and recombinant human thyroid-stimulating hormone administration (rhTSH) in this population. We mailed a 13-item pilot survey to patients with DTC who had undergone withdrawal before diagnostic whole-body scan (dxWBS). Using survey results and actual and estimated cost data, we retrospectively constructed a societal cost model comparing withdrawal versus rhTSH and performed a sensitivity analysis by increasing the conservatism of 8 assumptions about withdrawal costs. One hundred thirty (55%) of 236 patients answered the questionnaire. Among respondents, 92% had symptomatic and 85% multisymptomatic hypothyroidism. Almost half sought medical attention for hypothyroid complaints. Approximately one third drove motor vehicles while hypothyroid. Median absence from salaried work was 11 days per withdrawal. In the pharmacoeconomic model, societal costs per dxWBS were approximately 326 euro (25%) greater for withdrawal than for rhTSH. In the sensitivity analysis, societal costs of rhTSH exceeded those of withdrawal by approximately 307 euro (30%). In conclusion, hypothyroidism secondary to withdrawal causes important morbidity, safety risks, and productivity impairment. rhTSH avoids these drawbacks at roughly equivalent societal cost to that of withdrawal.