Block-and-replace regimen versus titration of antithyroid drugs: a recent meta-analysis
, 12
Abstract
Introduction: Drug therapy for Graves’ disease (GD) is the first-line treatment in Europe. The use of a specific regimen for the administration of anti-thyroid drugs (ATDs) is still controversial. The objective was to compare block-and-replace therapy (BRT) with a titration (T) regimen in terms of incidence of overt hypothyroidism and development of Graves’ orbitopathy (GO) over 18 months of treatment.
Material and methods: Two databases (PubMed, Cochrane Library) and reference lists were searched. Prospective and retrospective observational cohort studies were included. Data collection and analysis were performed independently by 2 authors.
Results: Two studies with 716 GD patients (40.36% treated with BRT, 59.64% with T regimen) were included. No statistically significant differences were observed between the ATDs regimens used in terms of incidence of overt hypothyroidism during 18 months of treatment [Mantel-Haenszel (M-H) odds ratio (OR): 1.54, 95% confidence interval (CI): 0.75–3.16, p-value = 0.24]. GD patients who followed BRT were less likely to achieve control of thyroid function than patients on T regimen (M-H OR: 0.55, 95% CI: 0.34–0.88, p = 0.01). One study reported fewer thyroid function tests (TFT) during BRT than during the T regimen. The other study included patients without GO at baseline and reported a lower incidence of GO during BRT than in the T regimen (9.1% versus 17.8%), with no statistical difference
between the 2 regimens (M-H OR: 0.47, 95% CI: 0.19–1.14, p = 0.10).
Conclusion: BRT may be more useful than the T regimen for patients with complicated GD or for those who required fewer TFTs.
Keywords: thyroidGravesblock-replacetitration
References
- Bartalena L, Chiovato L, Vitti P. Management of hyperthyroidism due to Graves' disease: frequently asked questions and answers (if any). J Endocrinol Invest. 2016; 39(10): 1105–1114.
- Menconi F, Marcocci C, Marinò M. Diagnosis and classification of Graves' disease. Autoimmun Rev. 2014; 13(4-5): 398–402.
- Bartalena L, Baldeschi L, Boboridis K, et al. European Group on Graves' Orbitopathy (EUGOGO). The 2016 European Thyroid Association/European Group on Graves' Orbitopathy Guidelines for the Management of Graves' Orbitopathy. Eur Thyroid J. 2016; 5(1): 9–26.
- Subekti I, Pramono LA, Azizi F, et al. Management of hyperthyroidism during pregnancy in Asia. Endocr J. 2014; 61(8): 751–758.
- Girgis CM, Champion BL, Wall JR. Current concepts in graves' disease. Ther Adv Endocrinol Metab. 2011; 2(3): 135–144.
- Ross DS, Burch HB, Cooper DS, et al. 2016 American Thyroid Association Guidelines for Diagnosis and Management of Hyperthyroidism and Other Causes of Thyrotoxicosis. Thyroid. 2016; 26(10): 1343–1421.
- Drui D, Du Pasquier Fediaevski L, Vignal Clermont C, et al. Graves' orbitopathy: Diagnosis and treatment. Ann Endocrinol (Paris). 2018; 79(6): 656–664.
- Wiersinga WM. Graves' Disease: Can It Be Cured? Endocrinol Metab (Seoul). 2019; 34(1): 29–38.
- Struja T, Fehlberg H, Kutz A, et al. Can we predict relapse in Graves' disease? Results from a systematic review and meta-analysis. Eur J Endocrinol. 2017; 176(1): 87–97.
- Abraham P, Avenell A, McGeoch SC, et al. Antithyroid drug regimen for treating Graves' hyperthyroidism. Cochrane Database Syst Rev. 2003; 153(4): CD003420–498.
- Kahaly GJ, Bartalena L, Hegedüs L, et al. 2018 European Thyroid Association Guideline for the Management of Graves' Hyperthyroidism. Eur Thyroid J. 2018; 7(4): 167–186.
- Abraham P, Avenell A, McGeoch SC, et al. Antithyroid drug regimen for treating Graves' hyperthyroidism. Cochrane Database Syst Rev. 2003; 2010(4): CD003420.
- Hashizume K, Ichikawa K, Sakurai A, et al. Administration of thyroxine in treated Graves' disease. Effects on the level of antibodies to thyroid-stimulating hormone receptors and on the risk of recurrence of hyperthyroidism. N Engl J Med. 1991; 324(14): 947–953.
- Morgan RL, Thayer KA, Bero L, et al. GRADE: Assessing the quality of evidence in environmental and occupational health. Environ Int. 2016; 92-93: 611–616.
- Vaidya B, Wright A, Shuttleworth J, et al. Block & replace regime versus titration regime of antithyroid drugs for the treatment of Graves' disease: a retrospective observational study. Clin Endocrinol (Oxf). 2014; 81(4): 610–613.
- Žarković M, Wiersinga W, Perros P, et al. EUGOGO (European Group on Graves’ Orbitopathy). Antithyroid drugs in Graves' hyperthyroidism: differences between "block and replace" and "titration" regimes in frequency of euthyroidism and Graves' orbitopathy during treatment. J Endocrinol Invest. 2021; 44(2): 371–378.
- Bonnema SJ, Grupe P, Boel-Jørgensen H, et al. A randomized trial evaluating a block-replacement regimen during radioiodine therapy. Eur J Clin Invest. 2011; 41(7): 693–702.
- Elbers L, Mourits M, Wiersinga W. Outcome of very long-term treatment with antithyroid drugs in Graves' hyperthyroidism associated with Graves' orbitopathy. Thyroid. 2011; 21(3): 279–283.
- Grebe SK, Feek CM, Ford HC, et al. A randomized trial of short-term treatment of Graves' disease with high-dose carbimazole plus thyroxine versus low-dose carbimazole. Clin Endocrinol (Oxf). 1998; 48(5): 585–592.
- Kung AW, Yau CC, Cheng A. The incidence of ophthalmopathy after radioiodine therapy for Graves' disease: prognostic factors and the role of methimazole. J Clin Endocrinol Metab. 1994; 79(2): 542–546.
- Kung AW, Yau CC, Cheng AC. The action of methimazole and L-thyroxine in radioiodine therapy: a prospective study on the incidence of hypothyroidism. Thyroid. 1995; 5(1): 7–12.
- Lantz M, Calissendorff J, Träisk F, et al. Adjuvant Treatment of Graves' Disease with Diclofenac: Safety, Effects on Ophthalmopathy and Antibody Concentrations. Eur Thyroid J. 2016; 5(1): 50–56.
- Laurberg P, Berman DC, Andersen S, et al. Sustained control of Graves' hyperthyroidism during long-term low-dose antithyroid drug therapy of patients with severe Graves' orbitopathy. Thyroid. 2011; 21(9): 951–956.
- McIver B, Rae P, Beckett G, et al. Lack of effect of thyroxine in patients with Graves' hyperthyroidism who are treated with an antithyroid drug. N Engl J Med. 1996; 334(4): 220–224.
- Rittmaster RS, Zwicker H, Abbott EC, et al. Effect of methimazole with or without exogenous L-thyroxine on serum concentrations of thyrotropin (TSH) receptor antibodies in patients with Graves' disease. J Clin Endocrinol Metab. 1996; 81(9): 3283–3288.
- Stefanic M, Karner I. Thyroid peroxidase autoantibodies are associated with a lesser likelihood of late reversion to hyperthyroidism after successful non-ablative treatment of Graves' disease in Croatian patients. J Endocrinol Invest. 2014; 37(1): 71–77.
- Wise PH, Marion M, Pain R. Mode of action of carbimazole in Graves' disease. Clin Endocrinol (Oxf). 1979; 10(6): 655–664.
- Wise PH, Marion M, Pain RW, et al. Single dose, "block-replace" drug therapy in hyperthyroidism. Br Med J. 1973; 4(5885): 143–145.
- Rodionova T, Frolova A. Clinical and Imunological Assesment of efficiency and safety of various schemes aplication for curing Graves' disease. Eur Thyroid J. 2014; 3(Suppl. 1): 73–226.
- McIver B, Morris JC. The pathogenesis of Graves' disease. Endocrinol Metab Clin North Am. 1998; 27(1): 73–89.
- Boelaert K, Visser WE, Taylor PN, et al. Endocrinology in the time of COVID-19: Management of hyperthyroidism and hypothyroidism. Eur J Endocrinol. 2020; 183(1): G33–G39.
- Fan W, Tandon P, Krishnamurthy M. Oscillating hypothyroidism and hyperthyroidism - a case-based review. J Community Hosp Intern Med Perspect. 2014; 4(5): 25734.
- Lewandowski KC, Rechciński T, Krzemińska-Pakuła M, et al. Acute myocardial infarction as the first presentation of thyrotoxicosis in a 31-year old woman - case report. Thyroid Res. 2010; 3(1): 1.
