OVERVIEW

PRODUCT INFORMATION

CHEMICAL FORMULA AND STRUCTURE

ANNOTATED BIBLIOGRAPHY

References updated: 11 April 2016

• Zimmerman HJ. Drugs used to treat rheumatic and musculospastic disease. In, Zimmerman HJ. Hepatotoxicity: the adverse effects of drugs and other chemicals on the liver. 2nd ed. Philadelphia: Lippincott, 1999, pp. 517-54.

  (Expert review of hepatotoxicity published in 1999, well before the availability of most monoclonal antibody therapies).
• Reuben A. Hepatotoxicity of immunosuppressive drugs. In, Kaplowitz N, DeLeve LD, eds. Drug-induced liver disease. 3rd ed. Amsterdam: Elsevier, 2011, pp. 569-91.

  (Review of hepatotoxicity of immunosuppressive agents; "the biological immuno-suppressants are largely free from hepatotoxicity, with the exception of the TNF alpha antagonists"; mepolizumab is not specifically mentioned).
• Barnes PJ. Pulmonary pharmacology. In, Brunton LL, Chabner BA, Knollman BC, eds. Goodman & Gilman's the pharmacological basis of therapeutics. 12th ed. New York: McGraw-Hill, 2011, pp. 1031-65.

  (Textbook of pharmacology and therapeutics).
• Rothenberg ME, Klion AD, Roufosse FE, Kahn JE, Weller PF, Simon HU, Schwartz LB, et al.; Mepolizumab HES Study Group. Treatment of patients with the hypereosinophilic syndrome with mepolizumab. N Engl J Med 2008; 358: 1215-28. [PubMed: 18344568]

  (Among 84 patients with hypereosinophilic syndromes treated with mepolizumab or placebo intravenously every 4 weeks for 32 weeks, reduction in daily corticosteroid dose was more frequent with treatment and side effects were similar; while there were “no clinically relevant trends” in laboratory tests, one mepolizumab treated subject developed “hepatitis” but no details given).
• Haldar P, Brightling CE, Hargadon B, Gupta S, Monteiro W, Sousa A, Marshall RP, et al. Mepolizumab and exacerbations of refractory eosinophilic asthma. N Engl J Med 2009; 360: 973-84. [PMC free article: PMC3992367] [PubMed: 19264686]

  (Among 61 patients with refractory eosinophilic asthma treated with iv mepolizumab or placebo every 4 weeks for one year, severe exacerbations of asthma were less with mepolizumab [2.0 vs 3.4 per subject] and side effects besides hospitalization for asthma were uncommon; no mention of ALT elevations or hepatotoxicity).
• Straumann A, Conus S, Grzonka P, Kita H, Kephart G, Bussmann C, Beglinger C, et al. Anti-interleukin-5 antibody treatment (mepolizumab) in active eosinophilic oesophagitis: a randomised, placebo-controlled, double-blind trial. Gut 2010; 59: 21-30. [PubMed: 19828470]

  (Among 11 adults with eosinophilic esophagitis who were treated with iv mepolizumab or placebo twice at one week intervals, eosinophils decreased in esophageal biopsies on mepolizumab, and there were no serious adverse events).
• Pavord ID, Korn S, Howarth P, Bleecker ER, Buhl R, Keene ON, Ortega H, et al. Mepolizumab for severe eosinophilic asthma (DREAM): a multicentre, double-blind, placebo-controlled trial. Lancet 2012; 380 (9842): 651-9. [PubMed: 22901886]

  (Among 621 patients with severe eosinophilic asthma treated with iv mepolizumab [75, 250 or 750 mg] or placebo every 4 weeks for 1 year, exacerbations of asthma were less with mepolizumab [1.2 vs 2.4 per year] and adverse events were similar; no mention of ALT elevations or hepatotoxicity).
• Roufosse FE, Kahn JE, Gleich GJ, Schwartz LB, Singh AD, Rosenwasser LJ, Denburg JA, et al. Long-term safety of mepolizumab for the treatment of hypereosinophilic syndromes. J Allergy Clin Immunol 2013; 131: 461-7. [PMC free article: PMC3558744] [PubMed: 23040887]

  (Among 78 patients with hypereosinophilic syndromes treated with mepolizumab for up to 6 years, median prednisone dose fell to zero and there were no hepatic related adverse events or mention of ALT elevations).
• Drugs for asthma and COPD. Treat Guidel Med Lett 2013; 11 (132): 75-86. [PubMed: 23896773]

  (Concise summary of guidelines for therapy of asthma mentions that omalizumab [monoclonal antibody to IgE] is approved for use in severe, persistent asthma; no mention of ALT elevations or hepatotoxicity).
• Bel EH, Wenzel SE, Thompson PJ, Prazma CM, Keene ON, Yancey SW, Ortega HG, et al.; SIRIUS Investigators. Oral glucocorticoid-sparing effect of mepolizumab in eosinophilic asthma. N Engl J Med 2014; 371: 1189-97. [PubMed: 25199060]

  (Among 135 patients with severe asthma treated with iv mepolizumab or placebo every 4 weeks for 20 weeks, the average daily corticosteroid dose was less and exacerbations of asthma fewer among mepolizumab treated subjects and side effect rates were similar; no mention of ALT elevations or hepatotoxicity).
• Haldar P, Brightling CE, Singapuri A, Hargadon B, Gupta S, Monteiro W, Bradding P, et al. Outcomes after cessation of mepolizumab therapy in severe eosinophilic asthma: a 12-month follow-up analysis. J Allergy Clin Immunol 2014; 133: 921-3. [PubMed: 24418480]

  (Among 27 patients with eosinophilic asthma who were withdrawn from mepolizumab therapy after one year, exacerbations of asthma were similar to rates of non-treated subjects).
• Ortega HG, Liu MC, Pavord ID, Brusselle GG, FitzGerald JM, Chetta A, Humbert M, et al.; MENSA Investigators. Mepolizumab treatment in patients with severe eosinophilic asthma. N Engl J Med 2014; 371: 1198-207. [PubMed: 25199059]

  (Among 576 patients with severe eosinophilic asthma treated with mepolizumab [75 mg iv or 100 mg sc] or placebo every 4 weeks for 32 weeks, rates of exacerbation were less with mepolizumab [0.83 to 0.93 yearly] vs placebo [1.7 yearly] and side effects were similar; no mention of ALT elevations or hepatotoxicity).
• Mepolizumab (Nucala) for severe eosinophilic asthma. Med Lett Drugs Ther 2016; 58 (1486): 11-2. [PubMed: 26761344]

  (Concise summary of the mechanism of action, clinical efficacy, safety and costs of mepolizumab shortly after its approval in the US for eosinophilic asthma, mentions side effects of headache, back pain, fatigue and infusion site reactions, but does not mention ALT elevations or hepatotoxicity).