Eculizumab Is Safe and Effective as a Long-term Treatment for Protein-losing Enteropathy Due to CD55 Deficiency. Issue 3 (March 2019)

• Record Type: Journal Article
• Authors: Kurolap, Alina; Eshach Adiv, Orly; Hershkovitz, Tova; Tabib, Adi; Karbian, Netanel; Paperna, Tamar; Mory, Adi; Vachyan, Arcadi; Slijper, Nadav; Steinberg, Ran; Zohar, Yaniv; Mevorach, Dror; Baris Feldman, Hagit
• Is Part Of: Journal of pediatric gastroenterology and nutrition. Volume 68:Issue 3(2019)
• Publication Date: 2019-03
• Subjects: anti-C5 -- decay accelerating factor -- intestinal lymphangiectasia; Children -- Nutrition -- Periodicals; Pediatric gastroenterology -- Periodicals; Infants -- Nutrition -- Periodicals; Nutrition disorders in children -- Periodicals; Child Nutrition -- Periodicals; Digestive System -- growth & development -- Periodicals; Gastrointestinal Diseases -- Periodicals; Infant Nutrition -- Periodicals; Nutrition Disorders -- Periodicals; Child; 618.923
• DOI: 10.1097/MPG.0000000000002198
• Languages: English
• ISSNs: 0277-2116

Abstract

ABSTRACT: Objectives: Loss of the complement inhibitor CD55 leads to a syndrome of early-onset protein-losing enteropathy (PLE), associated with intestinal lymphangiectasia and susceptibility to large-vein thrombosis. The in vitro and short-term treatment benefits of eculizumab (C5-inhibitor) therapy for CD55-deficiency have been previously demonstrated. Here we present the 18-months treatment outcomes for 3 CD55-deficiency patients with sustained therapeutic response. Methods: Three CD55-deficiency patients received off-label eculizumab treatment. Clinical and laboratory treatment outcomes included frequency and consistency of bowl movements, weight, patient/parent reports of overall well-being, and serum albumin and total protein levels. Membrane attack complex deposition on leukocytes was tested by flow cytometry, before and during eculizumab treatment. Results: Marked clinical improvement was noted in all 3 patients with resolution of PLE manifestations, that is, diarrhea, edema, malabsorption, overall well-being, growth, and quality of life. In correlation with the clinical observations, we observed progress in all laboratory outcome parameters, including increase in albumin and total protein levels, and up to 80% reduction in membrane attack complex deposition on leukocytes ( P < 0.001). The progress persisted over 18 months of treatment without any severe adverse events. Conclusions: CD55-deficiency patients present with early-onset diarrhea, edema, severe hypoalbuminemia, abdominal pain, and malnutrition. Targeted therapy with the terminal complement inhibitor eculizumab has positive clinical and laboratory outcomes in PLE related to CD55 loss-of-function mutations, previously a life-threatening condition. Our results demonstrate the potential of genetic diagnosis to guide tailored treatment, and underscore the significant role of the complement system in the intestine. Abstract : Supplemental Digital Content is available in the text