CASE REPORT Antitumor necrosis factor-induced neutropenia: a case report with double positive rechallenges E. Montané & M. Sallés & A. Barriocanal & E. Riera & J. Costa & X. Tena Received: 30 June 2006 / Revised: 14 July 2006 / Accepted: 14 July 2006 / Published online: 10 October 2006 # Clinical Rheumatology 2006 Abstract A 50-year-old man with ankylosing spondylitis who developed neutropenia after treatment of etanercept, with two positive rechallenges, and after the first infliximab infusion, is described. Although leukopenia and neutrope- nia related to etanercept and infliximab have been described as rare adverse events from clinical trials data, their mechanism of action are unknown. This patient developed recurrent mild neutropenia after exposition of two different antitumor necrosis factors; therefore, it seems to be an adverse reaction related to the therapeutic group. Doctors should be aware of this potentially severe adverse effect in patients treated with antitumor necrosis factor. Keywords Antitumor necrosis factor . Etanercept . Infliximab . Neutropenia . Positive rechallenge Tumor necrosis factor (TNF)-a is a proinflammatory cytokine synthesized in response to infectious or inflam- matory stimuli. Infliximab, etanercept, and adalimumab are TNF-a antagonists [1]. TNF inhibitors are generally well tolerated; the most commonly adverse effects reported are injection site reactions and infections [2]. Serious hemato- logical reactions have been reported in patients treated with anti-TNF therapy [3, 4]. Leukopenia due to etanercept is a potentially severe side effect reported from patients includ- ed in clinical trials [5], and from postmarketing cohort studies, with an estimated incidence of 1.5/1,000 patient– years [6]. There were safety warnings from the European Medicines Evaluation Agency and the US Food and Drug Administration (FDA) on etanercept regarding aplastic anemia and pancytopenia and on the increased risk of neutropenia when etanercept is associated with anakinra. Recently, in February 2005, FDA advised again of serious hematological events related to etanercept (http://www.fda. gov/foi/warning_letters/g5207d.pdf; accessed 27 June 2006). We report on a case of etanercept-induced recurrent neutropenia and also related to the first infliximab infusion. This case was reported to the Catalan Pharmacovigilance Centre. Case report A 50-year-old man with a more than 30-year history of severe ankylosing spondylitis was being treated with sulphasalazine, which was discontinued because of fixed drug eruption, and nonsteroidal antiinflammatory drugs with poor clinical results. Etanercept was started at doses of 25 mg every 3 days subcutaneously. During the first month, he also was taking butazolidine but was stopped because the patient improved clinically and biologically. Three weeks after starting the etanercept therapy, asymptomatic mild leukopenia (3,200/mm 3 ) and neutropenia (1,260/mm 3 ) were noted, and the drug was Clin Rheumatol (2007) 26:1527–1529 DOI 10.1007/s10067-006-0415-y E. Montané (*) : A. Barriocanal : J. Costa Department of Clinical Pharmacology, Hospital Universitari Germans Trias i Pujol, Carretera de Canyet s/n, 08916 Badalona (Barcelona), Spain e-mail: emontane.germanstrias@gencat.net E. Montané : J. Costa Department of Pharmacology, Therapeutics and Toxicology, Universitat Autònoma de Barcelona, Bellaterra, Spain M. Sallés : E. Riera : X. Tena Department of Rheumatology, Hospital Universitari Germans Trias i Pujol, Carretera de Canyet s/n, 08916 Badalona, Spain X. Tena Department of Medicine, Universitat Autònoma de Barcelona, Bellaterra, Spain