Effectiveness of Somatostatin Analogs versus Placebo for Graves Ophthalmopathy: A Meta-Analysis

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1 Review Articles Chin J Evid-based Med 2013, 13(1): * Graves GO PubMed EMbase The Cochrane Library WanFang Data CNKI VIP CBM Graves RCT RevMan 5.0 Meta 5 RCT 210 Meta GO MD= %CI P=0.04 mmmd= %CI P=0.24 GO OR= %CI P=0.61 GO GO RCT Graves Meta Effectiveness of Somatostatin Analogs versus Placebo for Graves Ophthalmopathy: A Meta-Analysis SHI Shao-min, HE Ye-bing * Department of Endocrinology, Tongji Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology, Wuhan , China Abstract Objective To systematically evaluate the effectiveness of somatostatin analogs versus placebo for Graves ophthalmopathy (GO). Methods Such databases as PubMed, EMbase, The Cochrane Library, WanFang Data, CNKI, VIP and CBM were searched to collect the randomized controlled trails (RCTs) about somatostatin analogs for Graves Ophthalmopathy (GO) pulished by March 2012, while the bibliographies of the included literatue were also retrieved. According to the inclusion criteria, two reviewers screened literature, extracted data and assessed the quality of the included studies. Then meta-analysis was conducted using RevMan 5.0 software. Results A total of 5 RCTs involving 210 patients were included. The results of meta-analysis showed that somatostatin analogs could reduce the clinical activity score (CAS) of GO patients (MD=0.58, 95%CI 0.02 to1.13, P=0.04), but the effects in reducing the degree of proptosis (mm) was still unverifiable (MD=0.21, 95%CI 0.14 to 0.56, P=0.24). It did not show obvious effects for diplopia, orbital volume, intraocular pressure, visual acuity or the restriction of eye movements. The existing evidence could not confirm that somatostatin analogs were effective for GO (OR=1.32, 95%CI 0.45 to 3.9, P=0.61). Conclusion Somatostatin analogs can reduce the CAS of GO patients, but without significantly clinical significance. Moreover, the effect of reducing proptosis is sitll unverifiable. So the existing evidence cannot confirm that somatostatin analogs are effective for GO. For the quality and quantity limitation of the included studies, this conclusion needs to be proved by performing more high quality RCTs. Key words Graves ophthalmopathy; Somatostatin analogs; CAS; Proptosis; Meta-analysis Graves Graves ophthalmopathy GO DOI: / Graves shishaomin@foxmail.com * mr.heyebing@163.com Graves [1] Editorial Board of Chin J Evid-based Med

2 2013, 13(1): GO GO [2] GO GO [3] [4,5] GO GO RCT GO GO clinical active score CAS Mouritis GO CAS [6] NOSPES no sigh or symptoms only sighs soft tissue involvement proptosis extraocular muscle involment cornea involvement sight loss 1.2 PubMed EMbase The Cochrane Library WanFang Data CNKI VIP CBM 2013 Graves RCT Graves ophthalmopathy Graves obitorpathy thyroid associated ophthalmopathy thyroid eye disease endocrine ophthalmopathy endocrine eye and somatostatin ananlogue octreotide lanreotide SOM230 Graves SOM Cochrane RCT / 1.4 RevMan 5.0 Meta χ 2 P>0.10 I 2 <50% Meta P<0.10 I 2 50% Meta CAS MD 95%CI OR 95%CI RCT [5-9]

3 Review Articles Cochrane RCT [10] 5 RCT Meta CAS 4 [6-9] GO CAS P=0.37 I 2 =4% Meta CAS MD= %CI P= [6-8] GO P=0.56 I 2 =0% Meta GO MD= %CI P= [5-9] GO P=0.06 I 2 =55% Chin J Evid-based Med 2013, 13(1): Meta GO OR= %CI P= Chang [7] n=671 n=296 n=25 n=16 n=5 Meta n=5 1 n=0 n=9 n=11 1 % T/C Krassas 1995 [5] /8 100 μg ih.tid 3 Wemeau 2005 [6] /25 30 mg im Chang 2006 [7] Stan 2006 [8] /11 20 mg im. 1 4 tid 30 mg im NOSPECS NOSPECS CAS 30/30 30 mg 30 mg CAS im. 1 im mg CAS im Dickinson 2004 [9] /27 30 mg 30 mg CAS im. 4 1 im GO CAS Krassas 1995 [5] Wemeau 2005 [6] Chang 2006 [7] Stan 2006 [8] Dickinson 2004 [9] Editorial Board of Chin J Evid-based Med

4 2013, 13(1): GO Stan [8] 2 [7,8] Stan [8] GO 3 [5,6,9] [8] [11] Wemeau [6] Krassas [5] GO OR= %CI P= GO CAS Meta 3 GO Meta 4 GO Meta

5 Review Articles 3.1 GO Meta GO CAS CAS mm GO 2 [7,8] GO GO GO 3.2 GO GO IGF-1 IGF-1 [6] SstR SstR 1 5 SOM 230 [6,12,13] 3.3 [14] GO 3 5 [14] 3 Krassas [5,11,15] GO 110 Chin J Evid-based Med 2013, 13(1): CAS MD CAS CAS Wemeau [6] 2 mm 4 26 vs Stan [8] 2 mm 4 14 vs GO 3 [11,15,16] Wemeau [6] RCT 1 Bartalena L, Baldeschi L, Dickinson A, et al. Consensus statement of the European Group on Graves' orbitopathy (EUGOGO) on management of GO. European Journal of Endocrinology, 2008, 158: Bartalena L, Marcocci C, Tanda ML, et al. An update on medical management of Graves' ophthalmopathy. J Endocrinol Invest, 2005, 28: Bartalena L, Marcocci C, Pinchera A. Editorial: Somatostatin analogs for Graves' ophthalmopathy - Do they bounce off like a rubber bullet? J Clin Endocrinol Metab, 2004, 89(12): Kung AW, Michon J, Tai KS, et al. The effect of somatostatin versus corticosteroid in the treatment of Graves' ophthalmopathy. Thyroid, 1996, 6(5): Krassas GE, Dumas A, Pontikides N, et al. Somatostatin receptor scintigraphy and octreotide treatment in patients with thyroid eye disease. Clin Endocrinol, 1995, 42: Wemeau JL, Caron P, Beckers A, et al. Octreotide (long-acting release formulation) treatment in patients with Graves' orbitopathy: clinical results of a four-month, randomized, placebo-controlled, double-blind study. J Clin Endocrinol Metab, 2005, 90(2): Chang TC, Liao SL. Slow-release lanreotide in Graves' ophthalmopathy: A double-blind randomized, placebo-controlled clinical trial. J Endocrinol Invest, 2006, 29: Stan MN, Garrity JA, Bradley EA, et al. Randomized, double-blind, placebo-controlled trial of long-acting release octreotide for treatment of Graves' ophthalmopathy. J Clin Endocrinol Metab, 2006, 91(12): Dickinson AJ, Vaidya B, Miller M, et al. Double-blind, placebo-controlled trial of octreotide long-acting repeatable (LAR) in thyroidassociated ophthalmopathy. J Clin Endocrinol Metab, 2004, 89(12): Julian PT, Sally G (editors). Cochrane Handbook for Systematic Reviews of Interventions Version [updated March 2011]. Available from: 11 Krassas GE, Kaltsas T, Dumad A, et al. Lanreotide in the treatment of patients with thyroid eye disease. European journal of endocrinol Editorial Board of Chin J Evid-based Med

6 2013, 13(1): ogy, 1997, 136: Cozma I, Zhang L, Uddin J, et al. Modulation of expression of somatostatin receptor subtypes in Graves' ophthalmopathy orbits: relevance to novel analogs. Am J Physiol Endocrinol Metab, 2007, 293: E1630-E ,.., 2011, 35(5): Graves Meta., 2004, 25(4): Krassas GE, Doumas A, Kaltsas T, et al. Somatostatin receptor scintigraphy before and after treatment with somatostatin analogues in patients with thyroid eye disease. Thyroid, 1999, 9(1): Pichler R, Maschek W, Holzinger C. Therapy with somatostatin analogs in patient with orbitopathy and positive Octreoscan. Acta Med Austriaca, 2001, 28: