Granulocyte/ Monocyte Absorption for Infliximab Refractory Crohnʼs Disease

Abstract

Purpose: Peripheral immune-disorder has been focused to play an important role in ignition and development of Crohn's disease (CD) and anti-cytokine therapy with biologics has been recognized as the main therapeutic strategy for refractory CD patients. In Japan, infliximab (IFX), a chimeric monoclonal IgG1 antibody against tumor necrosis factor (TNF)-α, has been an only one available among the biologics. IFX has been associated with a significant improvement of patients' quality of life. However, it has been recognized that many patients who revealed resistance to IFX or initially respond well to IFX worsen during repeated administration. Hence, we have hypothesized that the granulocyte/ monocytes absorption (GMA), an extracorporeal hemoabsorption therapy removing patient's peripheral granulocytes and monocytes semiselectively, could be effective for such IFX refractory CD patients. In Japan, the weekly GMA therapy has been approved by national health-insurance policy since Feb. 2009. In this study, we aimed to evaluate the clinical efficiency of GMA for IFX refractory CD patients who have treated with or without IFX since then. Methods: Subjects were 12 CD patients. Their mean clinical disease activity index (CDAI) and CD duration were 222.68 points and 10.8 years, respectively. Their type of CD were 4 colonic type and 8 ileocolonic type. Three had past episode(s) of intestinal resection. Three had been stopped IFX, because of infusion-reaction and/or ineffectiveness, and 6 did not accept to be given IFX. We have applied 5-10 times of the weekly GMA sessions for them instead of IFX for remission induction. Also, 3 were repeated 3-4 times of weekly GMA prior to their IFX infusion every 8 weeks because of loose of its response. Results: The remission induction therapy with 5-10 GMA has been demonstrated significant decrease of CDAI without IFX (P=0.05). And, IFX and GMA combination therapy has indicated to maintain the patients in stable clinical remission without experiencing shorten and increase IFX administration. Conclusion: IFX appears to induce and maintain remission of CD, but it may lose its efficacy after repeated administration. GMA is safe and by selectively depleting elevated/activated leukocytes may be a useful adjunct for IFX efficacy.