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CASE REPORT |
1 Department of Gastroenterology, Hepatology and Endocrinology, 2 Institute of Pathology and 3 Institute for Clinical Pharmacology, Charité-Universitätsmedizin Berlin, 10117 Berlin, Germany, 4 Pfizer Pharma GmbH, Karlsruhe, Germany, 5 Department of Neurosurgery, University Hosiptal, Erlangen, Germany, 6 Division of Endocrinology, Department of Medicine, University of Duisberg-Essen, Germany and 7 Oldenburg, Germany
(Correspondence should be addressed to C J Strasburger, Division of Clinical Endocrinology, Department of Medicine, Charité-Universitätsmedizin Berlin, Schumannstr. 20/21, 10117 Berlin, Germany; Email: Christian.Strasburger{at}charite.de)
Abstract
Objective: The new GH receptor antagonist pegvisomant is the most effective medical therapy to normalize IGF-I levels in patients with acromegaly. Based on currently available data pegvisomant is well tolerated; however, treatment-induced elevation of transaminases has been reported and led to the necessity for drug discontinuation in some patients in the pivotal studies. The aim of this study was to evaluate and characterize the prevalence of elevated transaminases and to describe in detail the findings in a single case who required drug discontinuation because of elevation of transaminases which emerged during treatment and who underwent liver biopsy.
Design and methods: Retrospective safety analyses were carried out on 142 patients with acromegaly receiving pegvisomant treatment in Germany between March 2003 and the end of 2004. Of these patients, 123 were documented in a post-marketing surveillance study, one case of elevated transaminases was reported spontaneously and the other patients were treated in a clinical study.
Results: Mean treatment duration with pegvisomant in the ongoing observational study at the end of 2004 was 28.3 ± 19.9 (S.D.) weeks. Twelve out of the 142 patients had elevated transaminases above three times the upper limit of normal, likely caused by biliary obstruction in five of the patients. All patients but one affected by elevated transaminases had been previously treated with somatostatin analogues. In six out of 142 (4%) of patients, pegvisomant was permanently withdrawn because of elevated transaminases. The same number of patients showed a transient increase of transaminases with either spontaneous remission without dose modification (n = 4) or no re-increase of transaminases after temporary discontinuation and re-exposure (n = 2). The liver biopsy of one patient who was permanently withdrawn showed a chronic mild hepatitis with a mixed portal inflammation including eosinophilic granulocytes.
Conclusions: Liver function tests should be regularly followed on pegvisomant treatment. Biliary complications, which may arise from restitution of normal gall bladder motility after cessation of somatostatin analogue treatment, need to be differentiated from pegvisomant-induced abnormalities. The histological pattern of the liver biopsy performed in one of the patients showed a mild chronic active hepatitis. The lack of dose dependency and rather low frequency of elevated transaminases in those cases where a biliary disorder was excluded render this reaction an idiosyncratic drug toxicity.
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  S. J. C. M. M. Neggers, M. O. van Aken, J. A. M. J. L. Janssen, R. A. Feelders, W. W. de Herder, and A.-J. van der Lely Long-Term Efficacy and Safety of Combined Treatment of Somatostatin Analogs and Pegvisomant in Acromegaly J. Clin. Endocrinol. Metab., December 1, 2007; 92(12): 4598 - 4601. [Abstract] [Full Text] [PDF]
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 I Schreiber, M Buchfelder, M Droste, K Forssmann, K Mann, B Saller, and C J Strasburger Treatment of acromegaly with the GH receptor antagonist pegvisomant in clinical practice: Safety and efficacy evaluation from the German Pegvisomant Observational Study Eur. J. Endocrinol., January 1, 2007; 156(1): 75 - 82. [Abstract] [Full Text] [PDF]
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 S. Melmed Acromegaly N. Engl. J. Med., December 14, 2006; 355(24): 2558 - 2573. [Full Text] [PDF]
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J Feenstra, M O van Aken, W W de Herder, R A Feelders, and A J van der Lely Drug-induced hepatitis in an acromegalic patient during combined treatment with pegvisomant and octreotide long-acting repeatable attributed to the use of pegvisomant. Eur. J. Endocrinol., June 1, 2006; 154(6): 805 - 806. [Abstract] [Full Text] [PDF]
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