The clinical implications of thalidomide in inflammatory bowel diseases

References

• Benchimol EI, Guttmann A, Griffiths AM, et al. Increasing incidence of paediatric inflammatory bowel disease in Ontario, Canada: evidence from health administrative data. Gut 2009;58:1490-7
   PubMed Web of Science ®Google Scholar
• Jakobsen C, Paerregaard A, Munkholm P, et al. Pediatric inflammatory bowel disease: increasing incidence, decreasing surgery rate, and compromised nutritional status: a prospective population-based cohort study 2007–2009. Inflamm Bowel Dis 2011;17:2541-50
   PubMed Web of Science ®Google Scholar
• Molodecky NA, Soon IS, Rabi DM, et al. Increasing incidence and prevalence of the inflammatory Bowel disease with time based on systematic review. Gastroenterology 2012;142:46-54
   PubMed Web of Science ®Google Scholar
• Sawczenko A, Sandhu BK. Presenting features of inflammatory bowel disease in Great Britain and Ireland. Arch Dis Child 2003;88:995-1000
   PubMed Web of Science ®Google Scholar
• Griffiths AM. Specificities of inflammatory bowel disease in childhood. Best Pract Res Clin Gastroenterol 2004;18:509-23
   PubMed Web of Science ®Google Scholar
• Turunen P, Ashorn M, Auvinen A, et al. Long term health outcomes in pediatric inflammatory bowel disease: a population based study. Inflamm Bowel Dis 2009;15:56-62
   PubMed Web of Science ®Google Scholar
• Waters MFR, Laing ABG, Ambikapathy A, et al. Treatment of ulcerative colitis with thalidomide. BMJ 1979;1:792
   PubMed Web of Science ®Google Scholar
• Ehrenpreis ED, Kane SV, Cohen LB, et al. Thalidomide therapy for patients with refractory Crohn’s disease: an open-label trial. Gastroenterology 1999;117:1271-7
   PubMed Web of Science ®Google Scholar
• Vasiliauskas EA, Kam LY, Abreu-Martin MT, et al. An open-label pilot study of low-dose thalidomide in chronically active, steroid-dependent Crohn’s disease. Gastroenterology 1999;117:1278-87
   PubMed Web of Science ®Google Scholar
• Kane S, Stone LJ, Ehrenpreis E. Thalidomide as “salvage” therapy for patients with delayed hypersensitivity response to infliximab: a case series. J Clin Gastroenterol 2002;35:149-50
   PubMed Web of Science ®Google Scholar
• Bariol C, Meagher AP, Vickers CR, et al. Early studies on the safety and efficacy of thalidomide for symptomatic inflammatory bowel disease. J Gastroenterol Hepatol 2002;17:135-9
   PubMed Web of Science ®Google Scholar
• Bauditz J, Wedel S, Lochs H. Thalidomide reduces tumour necrosis factor alpha and interleukin 12 production in patients with chronic active Crohn’s disease. Gut 2002;50:196-200
   PubMed Web of Science ®Google Scholar
• Bauditz J, Schachschal G, Wedel S, et al. Thalidomide for treatment of severe intestinal bleeding. Gut 2004;53:609-12
   PubMed Web of Science ®Google Scholar
• Plamondon S, Ng SC, Kamm MA. Thalidomide in luminal and fistulizing Crohn’s disease resistant to standard therapies. Aliment Pharmacol Ther 2007;25:557-67
   PubMed Web of Science ®Google Scholar
• Facchini S, Candusso M, Martelossi S, et al. Efficacy of long-term treatment with thalidomide in children and young adults with Crohn disease: preliminary results. J Ped Gastroenterol Nutr 2001;32:178-81
   PubMed Web of Science ®Google Scholar
• Ahmed M, El-Hadi S, Jenkins HR. Thalidomide in Crohn disease and the risk of peripheral neuropathy. J Pediatr Gastroenterol Nutr 2003;37:522
   PubMed Web of Science ®Google Scholar
• Lazzerini M, Martelossi S, Marchetti F, et al. Efficacy and safety of thalidomide in children and young adults with intractable inflammatory bowel disease: long-term results. Aliment Pharmacol Ther 2007;25:419-27
   PubMed Web of Science ®Google Scholar
• Zheng CF, Xu JH, Huang Y, et al. Treatment of pediatric refractory Crohn’s disease with thalidomide. World J Gastroenterol 2011;17:1286-9
   PubMed Web of Science ®Google Scholar
• Felipez LM, Gokhale R, Tierney MP, et al. Thalidomide use and outcomes in pediatric patients with Crohn disease refractory to infliximab and adalimumab. J Pediatr Gastroenterol Nutr 2012;54:28-33
   PubMed Web of Science ®Google Scholar
• Lazzerini M, Marteloss i S, Magazzu G, et al. Effect of thalidomide on clinical remission in children and adolescents with refractory Crohn disease: a randomized clinical trial. JAMA 2013;310:2164-73
   PubMed Web of Science ®Google Scholar
• Ginsburg P, Hanan I, Ehrenpreis ED. Treatment of severe esophageal Crohn’s disease with thalidomide. Am J Gastroenterol 2001;96:1305-6
   PubMed Web of Science ®Google Scholar
• Barkin JA, Schonfeld WB, Deshpande AR. Successful use of thalidomide for refractory esophageal Crohn’s disease. Am J Gastroenterol 2013;108:855-6
   PubMed Web of Science ®Google Scholar
• Weinstein TA, Sciubba JJ, Levine JJ. Thalidomide for the treatment of oral aphthous ulcers in Crohn’s disease. J Pediatr Gastroenterol Nutr 1999;28:214-16
   PubMed Web of Science ®Google Scholar
• Odeka EB, Miller V.E. Thalidomide in oral Crohn’s disease refractory to conventional medical treatment. J Pediatr Gastroenterol Nutr 1997;25:250-1
   Web of Science ®Google Scholar
• Hegarty A, Hodgson T, Porter S. Thalidomide for the treatment of recalcitrant oral Crohn’s disease and orofacial granulomatosis. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2003;95:576-85
   PubMed Web of Science ®Google Scholar
• Leite MR, Santos SS, Lyra AC, et al. Thalidomide induces mucosal healing in Crohn’s disease: case report. World J Gastroenterol 2011;17:5028-31
   PubMed Web of Science ®Google Scholar
• Rajpara SM, Siddha SK, Ormerod AD, et al. Cutaneous penile and perianal Crohn’s disease treated with a combination of medical and surgical interventions. Australas J Dermatol 2008;49:21-4
   Google Scholar
• Kolivras A, De Maubeuge J, André J, et al. Thalidomide in refractory vulvar ulcerations associated with Crohn’s disease. Dermatology 2003;206:381-3
   PubMed Web of Science ®Google Scholar
• Hersfield NB. Disappearance of Crohn’s ulcers in the terminal ileum after thalidomide therapy. Can J Gastroenterol 2004;18:101-4
   PubMed Web of Science ®Google Scholar
• Fishman SJ, Feins NR, D’ Amato RJ, et al. Long-term remission of Crohn’s disease treated with thalidomide: a seminal case report. Angiogenesis 1999;3:201-4
   PubMedGoogle Scholar
• Lazzerini M, Bramuzzo M, Martelossi S, et al. Amenorrhea in women treated with thalidomide: report of two cases and literature. Inflamm Bowel Dis 2013;19:E10-11
   Web of Science ®Google Scholar
• Diamanti A, Knafelz D, Panetta F, et al. Thalidomide as rescue therapy for acute severe ulcerative colitis. Eur Rev Med Pharmacol Sci 2014;18:1690-9
   PubMed Web of Science ®Google Scholar
• Sabate JM, Villarejo J, Lemann M, et al. An open-label study of thalidomide for maintenance therapy in responders to infliximab in chronically active and fistulizing refractory Crohn’s disease. Aliment Pharmacol Ther 2002;16:1117-24
   PubMed Web of Science ®Google Scholar
• Scribano ML, Cantoro L, Marrollo M, et al. Mucosal healing with thalidomide in refractory Crohn’s disease patients intolerant of anti-TNF-α drugs: report of 3 cases and literature review. J Clin Gastroenterol 2014;48:530-3
   PubMed Web of Science ®Google Scholar
• Kumar N, Sharma U, Singh C, et al. Thalidomide: chemistry, therapeutic potential and oxidative stress induced teratogenicity. Curr Top Med Chem 2012;12:1436-55
   PubMed Web of Science ®Google Scholar
• Ruemmele FM, Veresd G, Kolho KL, et al. Consensus guidelines of ECCO/ESPGHAN on the medical management of pediatric Crohn’s disease. J Crohns Colitis 2014;8(10):1179-207
   PubMed Web of Science ®Google Scholar
• Turner D, Travis SP, Griffiths AM, et al. Consensus for managing acute severe ulcerative colitis in children: a systematic review and joint statement from ECCO, ESPGHAN, and the porto IBD working group of ESPGHAN. Am J Gastroenterol 2011;106:574-88
   PubMed Web of Science ®Google Scholar
• Akobeng AK, Stokkers PC. Thalidomide and thalidomide analogues for maintenance of remission in Crohn’s disease. Cochrane Database Syst Rev 2009;15(2):CD007351
   Google Scholar
• Bartlett J, Dredge K, Dalgleish A. The evolution of thalidomide and its IMiD® derivatives as anti-cancer agents. Nat Rev Cancer 2004;4:314-22
   PubMed Web of Science ®Google Scholar
• Hideshima T, Chauhan D, Shima Y, et al. Thalidomide and its analog overcome drug resistance of human multiple myeloma cells to conventional therapy. Blood 2000;96:2943-50
   PubMed Web of Science ®Google Scholar
• Theo SK. Properties of thalidomide and its analogues: implications for anticancer therapy. AAPS J 2005;7:E14-19
   Web of Science ®Google Scholar
• Mansfield JC, Parkes M, Hawthorne AB, et al. A randomized double blind, placebo-controlled trial of lenalidomide in the treatment of moderately severe active Crohn’s disease. Aliment Pharmacol Ther 2007;26:421-30
   PubMed Web of Science ®Google Scholar
• Franks ME, Macpherson GR, Figg WD. Thalidomide. Lancet 2004;363:1802-11
   PubMed Web of Science ®Google Scholar
• Bessmertny O, Pham T. Thalidomide use in pediatric patients. Ann Pharmacother 2002;36:521-5
   PubMed Web of Science ®Google Scholar
• Kaplan G, Thomas S, Fierer DS, et al. Thalidomide for the treatment of AIDS-associated wasting. AIDS Res Hum. Retroviruses 2000;16:1345-55
   Google Scholar
• Lebrin F, Srun S, Raymond K, et al. Thalidomide stimulates vessel maturation and reduces epistaxis in individuals with hereditary hemorrhagic telangiectasia. Nat Med 2010;16:420-8
   PubMed Web of Science ®Google Scholar
• Coelho A, Souto MI, Cardoso CR, et al. Long-term thalidomide use in refractory cutaneous lesions of lupus erythematosus: a 65 series of Brazilian patients. Lupus 2005;14:434-9
   PubMed Web of Science ®Google Scholar
• van de Donk NW, Kröger N, Hegenbart U, et al. Remarkable activity of novel agents bortezomib and thalidomide in patients not responding to donor lymphocyte infusions following nonmyeloablative allogeneic stem cell transplantation in multiple myeloma. Blood 2006;107:3415-16
   PubMed Web of Science ®Google Scholar
• Direskeneli H, Ergun T, Yavuz S, et al. Thalidomide has both anti-inflammatory and regulatory effects in Behcet’s disease. Clin Rheumatol 2008;27:373-5
   PubMed Web of Science ®Google Scholar
• Sheskin J. Further observation with thalidomide in lepra reactions. Lepr Rev 1965;36:183-7
   PubMedGoogle Scholar
• Bousvaros A, Mueller B. Thalidomide in gastrointestinal disorders. Drugs 2001;61:777-87
   PubMed Web of Science ®Google Scholar
• Yasui K, Uchida N, Akazawa Y, et al. Thalidomide for treatment of intestinal involvement of juvenile-onset Behcet disease. Inflamm Bowel Dis 2008;14:396-400
   PubMed Web of Science ®Google Scholar
• Mehta P, Kedar A, Graham-Pole J, et al. Thalidomide in children undergoing bone marrow transplantation: series at a single institution and review of the literature. Pediatrics 1999;103:806-10
   Web of Science ®Google Scholar
• Rovelli A, Arrigo C, Nesi F, et al. The role of thalidomide in the treatment of refractory chronic graft-versus-host disease following bone marrow transplantation in children. Bone Marrow Transplant 1998;21:577-81
   PubMed Web of Science ®Google Scholar
• Cole CH, Rogers PCJ, Pritchard S, et al. Thalidomide in the management of chronic graft-versus-host disease in children following bone marrow transplantation. Bone Marrow Transplant 1994;14:937-42
   PubMed Web of Science ®Google Scholar
• Heney D, Bailey CC, Lewis IJ. Thalidomide in the treatment of graft versus-host disease. Biomed Pharmacother 1990;44:199-204
   PubMed Web of Science ®Google Scholar
• Ringden O, Aschan J, Westerberg L. Thalidomide for severe acute graft versus-host disease (letter). Lancet 1988;2:568
   PubMed Web of Science ®Google Scholar
• Browne PV, Weisdorf DJ, DeFor T, et al. Response to thalidomide therapy in refractory chronic graft-versus-host disease. Bone Marrow Transplant 2000;26:865-9
   PubMed Web of Science ®Google Scholar
• Parker PM, Chao N, Nademanee A, et al. Thalidomide as salvage therapy for chronic graft-versus host disease. Blood 1995;86:3604-9
   PubMed Web of Science ®Google Scholar
• Youle M, Clarbour J, Farthing C, et al. Treatment of resistant aphthous ulcerations with thalidomide in patients positive for HIV antibody. Br Med J 1989;298:432
   PubMed Web of Science ®Google Scholar
• Soler RA, Migliorati C, van Waes H, et al. Thalidomide treatment of mucosal ulcerations in HIV infection. Arch Dis Child 1996;74:64-5
   PubMed Web of Science ®Google Scholar
• Jacobson JM, Greenspan JS, Spritzler J, et al. Thalidomide for the treatment of oral aphthous ulcers in patients with human immunodeficiency virus infection. N Engl J Med 1997;336:1487-93
   PubMed Web of Science ®Google Scholar
• Callen JP. Management of antimalarial-refractory cutaneous lupus erythematosus. Lupus 1997;6:203-8
   PubMed Web of Science ®Google Scholar
• Ordi-Ros J, Cortes F, Cucurull E, et al. Thalidomide in the treatment of cutaneous lupus refractory to conventional therapy. J Rheumatol 2000;27:1429-33
   PubMed Web of Science ®Google Scholar
• Atra E, Sato EI. Treatment of the cutaneous lesions of systemic lupus erythematosus with thalidomide. Clin Exp Rheumatol 1993;11:487-93
   PubMed Web of Science ®Google Scholar
• Duong DJ, Spigel T, Moxley RT, et al. American experience with low dose thalidomide therapy for severe cutaneous lupus erythematosus. Arch Dermatol 1999;135:1079-87
   PubMed Web of Science ®Google Scholar
• Walchner M, Meurer M, Plewig G, et al. Clinical and immunologic parameters during thalidomide treatment of lupus erythematosus. Int J Dermatol 2000;39:383-8
   PubMed Web of Science ®Google Scholar
• Knop J, Bonsmann G, Happle R, et al. Thalidomide in the treatment of sixty cases of chronic discoid lupus erythematosus. Br J Dermatol 1983;108:461-6
   PubMed Web of Science ®Google Scholar
• Weinstein AR, Meagler AP. Thalidomide in Crohn’s disease. Lancet 1997;350:1445-6
   Web of Science ®Google Scholar
• Hamuryudan V, Mat C, Saip S, et al. Thalidomide in the treatment of the muco-cutaneous lesions of the Behçet’s syndrome. Ann Intern Med 1998;128:443-50
   PubMed Web of Science ®Google Scholar
• Jorizzo JL, Schmalstieg FC, Solomon AR. Jr, et al. Thalidomide effects in Behçet’s syndrome and pustular vasculitis. Arch Intern Med 1986;146:878-81
   PubMed Web of Science ®Google Scholar
• Chao NJ, Parker PM, Niland JC, et al. Paradoxical effect of thalidomide prophylaxis on chronic graft-vs-host disease. Biol Blood Marrow Transplant 1996;2:86-92
   PubMedGoogle Scholar
• Zeldis JB, Williams BA, Thomas SD, et al. S.T.E.P.S.: a comprehensive program for controlling and monitoring access to thalidomide. Clin Ther 1999;21:319-30
   PubMed Web of Science ®Google Scholar
• Uhl K, Cox E, Rogan R, et al. Thalidomide use in the US: experience with pregnancy testing in the S.T.E.P.S. programme. Drug Saf 2006;29:321-9
   PubMed Web of Science ®Google Scholar
• Tavares JL, Wangoo A, Dilworth P, et al. Thalidomide reduces tumour necrosis factor-alpha production by human alveolar macrophages. Respir Med 1997;91:31-9
   PubMed Web of Science ®Google Scholar
• Peterson PK, Hu S, Sheng WS, et al. Thalidomide inhibits tumor necrosis factor-alpha production by lipopolysaccharide- and lipoarabinomannan-stimulated human microglial cells. J Infect Dis 1995;172:1137-40
   PubMed Web of Science ®Google Scholar
• Keifer JA, Guttridge DC, Ashburner BP, et al. Inhibition of NF-kappa B activity by thalidomide through suppression of IkappaB kinase activity. J Biol Chem 2001;276:22382-7
   PubMed Web of Science ®Google Scholar
• Rowland TL, McHugh SM, Deighton J, et al. Differential regulation by thalidomide and dexamethasone of cytokine expression in human peripheral blood mononuclear cells. Immunopharmacology 1998;40:11-20
   PubMed Web of Science ®Google Scholar
• Laffitte E, Revuz J. Thalidomide: an old drug with new clinical applications. Expert Opin Drug Saf 2004;3:47-56
   PubMedGoogle Scholar
• Ginsburg PM, Dassopoulos T, Ehrenpreis ED. Thalidomide treatment for refractory Crohn’s disease: a review of the history, pharmacological mechanisms and clinical literature. Ann Med 2001;33:516-25
   PubMed Web of Science ®Google Scholar
• D’Amato RJ, LOughnan MS, Flynn E, et al. Thalidomide is an inhibitor of angiogenesis. Proc Natl Acad Sci USA 1999;91:4082-5
   Google Scholar
• Koutroubakis IE, Trsiolakidou G, Karmiris K, et al. Role of angiogenesis in inflammatory bowel disease. Inflamm Bowel Dis 2006;12:515-23
   PubMed Web of Science ®Google Scholar
• Junquera F, Saperas E, de Torres I, et al. Increased expression of angiogenic factors in human colonic angiodysplasia. Am J Gastroenterol 1999;94:1070-6
   PubMed Web of Science ®Google Scholar
• Griga T, May B, Pfisterer O, et al. Immunohistochemical localization of vascular endothelial growth factor in colonic mucosa of patients with inflammatory bowel disease. Hepatogastroenterology 2002;49:116-23
   PubMedGoogle Scholar
• Griga T, Tromm A, Spranger J, et al. Increased serum levels of vascular endothelial growth factor in patients with inflammatory bowel disease. Scand J Gastroenterol 1998;33:504-8
   PubMed Web of Science ®Google Scholar
• Bousvaros A, Leichtner A, Zurakowski D, et al. Elevated serum vascular endothelial growth factor in children and young adults with Crohn’s disease. Dig Dis Sci 1999;44:424-30
   PubMed Web of Science ®Google Scholar
• Rafiee P, Stein DJ, Nelson VM, et al. Thalidomide inhibits inflammatory and angiogenic activation of human intestinal microvascular endothelial cells (HIMEC). Am J Physiol Gastrointest Liver Physiol 2010;298:G167-762
   Web of Science ®Google Scholar
• Kenyon BM, Browne F, D’Amato RJ. Effects of thalidomide and related metabolites in a mouse corneal model of neovascularization. Exp Eye Res 1997;64:971-8
   PubMed Web of Science ®Google Scholar
• Sampaio EP, Sarno EN, Galilly R, et al. Thalidomide selectively inhibits tumor necrosis factor alpha production by stimulated human monocytes. J Exp Med 1991;173:699-703
   PubMed Web of Science ®Google Scholar
• Moreira AL, Sampaio Moreira AL, Sampaio EP, et al. Thalidomide exerts ITS inhibitory action on tumor necrosis factor alpha by enhancing MRNA degradation. J Exp Med 1993;177:1675-80
   PubMed Web of Science ®Google Scholar
• Dredge K, Marriott JB, Dalgleish AG. Immunological effects of thalidomide and its chemical and functional analogs. Crit Rev Immunol 2002;22:425-37
   PubMed Web of Science ®Google Scholar
• Haslett PA, Corral LG, Albert M, et al. Thalidomide co-stimulates primary human T lymphocytes, preferentially inducing proliferation, cytokine production, and cytotoxic responses in the CD8+ subset. J Exp Med 1998;187:1885-92
   PubMed Web of Science ®Google Scholar
• Krieg S, Ulrich E. Novel immune modulators used in hematology: impact on NK cells. Front Immun 2013;3:388
   PubMed Web of Science ®Google Scholar
• Geitz H, Nandt S, Zwingenberger K. Thalidomide selectively modulates the density of cell surface molecules involved in the adhesion cascade. Immunopharmacology 1996;31:213-21
   PubMed Web of Science ®Google Scholar
• McHugh SM, Rifkin IR, Deighton J, et al. The immunosuppressive drug thalidomide induces T helper cell type 2 (TH2) and concomitantly inhibits TH1 cytokine production in mitogen- and antigen-stimulated human peripheral blood mononuclear cell cultures. Clin Exp Immunol 1995;99:160-7
   PubMed Web of Science ®Google Scholar
• Dredge K, Marriott J, Macdonald C, et al. Novel thalidomide analogues display anti-angiogenetic activity independently of immunomodulatory effects. Br J Cancer 2002;87:1166-72
   PubMed Web of Science ®Google Scholar
• Owens DK, Lohr KN, Atkins D, et al. AHRQ Series Paper 5: grading the strength of a body of evidence when comparing medical interventions–Agency for Healthcare Research and Quality and the Effective Health-Care Program. J Clin Epidemiol 2010;63(5):513-23
   PubMed Web of Science ®Google Scholar
• El Moutawakil B, Rafai MA, Gam I, et al. Crohn’s disease presenting with recurrent acute polyradiculo-neuropathy. Rev Neurol 2007;163:244-6
   PubMedGoogle Scholar
• Pineda Marfa M. Neurological involvement in rheumatic disorders and vasculitis in childhood. Rev Neurol 2002;35:290-6
   PubMed Web of Science ®Google Scholar
• Cavalletti G, Beronio A, Reni L, et al. Thalidomide sensory neurotoxicity: a clinical and neurophysiologic study. Neurology 2004;62:2291-3
   PubMed Web of Science ®Google Scholar
• Giannini F, Volpi N, Rossi S, et al. Thalidomide-induced neuropathy: a ganglionopathy? Neurology 2003;60:877-8
   PubMed Web of Science ®Google Scholar
• Fullerton P, O’Sullivan D. Thalidomide neuropathy: a clinical, electrophysiological, and histological follow-up study. J Neurol Neurosurg Psychiatry 1968;31:543-51
   PubMed Web of Science ®Google Scholar
• Xu Y, Sladky J, Brown M. Dose-dependent expression of neuronopathy after experimental pyridoxine intoxication. Neurology 1989;9:1077-83
   Google Scholar
• Chaudhry V, Cornblath DR, Corse A, et al. Thalidomide-induced neuropathy. Neurology 2002;59:1872-5
   PubMed Web of Science ®Google Scholar
• Tseng S, Pak G, Washenik K, et al. Rediscovering thalidomide: a review of its mechanism of action, side effects, and potential uses. J Am Acad Dermatol 1996;35:969-79
   PubMed Web of Science ®Google Scholar
• Bastuji-Garin S, Ochonisky S, Bouche P, et al. Incidence and risk factors for thalidomide neuropathy: a prospective study of 135 dermatologic patients. J Invest Dermatol 2002;119:1020-6
   PubMed Web of Science ®Google Scholar
• Priolo T, Lamba LD, Giribaldi G, et al. Childhood thalidomide neuropathy: a clinical and neurophysiologic study. Pediatr Neurol 2008;38:196-9
   PubMed Web of Science ®Google Scholar
• European Medicines Agency Evaluation of Medicines for Human Use 7 Westferry Circus, Canary Wharf, London E14 4HB, UK Tel. (44-20) 74 18 84 00 Fax (44-20) 74 18 84 16 E-mail.: [email protected]. Available from: www.emea.europa.eu; © European Medicines Agency, 2008. Reproduction is authorised provided the source is acknowledged. Doc. Ref: EMEA/176582/2008
   Google Scholar
• Initial REMS Approval 8/2010 Most Recent Modification 9/2014 THALOMID ® (thalidomide) NDA # 020785.
   Google Scholar