Effect and Safety of Granulocyte-Monocyte Adsorption Apheresis for Patients with Ulcerative Colitis Positive for Cytomegalovirus in Comparison with Immunosuppressants

Abstract

Background: Cytomegalovirus (CMV) infection exacerbates ulcerative colitis (UC) refractory to immunosuppressive therapies (IMT). However, the underlying UC remained active in some UC patients, despite the fact that CMV-DNA in colonic mucosa became negative after antiviral therapy. Therefore, new therapeutic strategies for UC patients concomitant with CMV infection in mucosa are required. Aims: The aim of this study was to evaluate the effect and safety of granulocyte-monocyte adsorption apheresis (GMA) in UC patients positive for CMV infection after antiviral therapy. Methods: From October 2003 to December 2008, 64 patients with UC refractory to IMT, including steroids and immunomodulators, were enrolled in this retrospective, observational, multicenter study, which was reviewed and approved by the Institutional Review Board of Kyoto University. CMV infection was investigated by 3 methods (histologic examination, CMV antigenemia, and polymerase chain reaction). We investigated the clinical outcomes of GMA and IMT after 2 weeks of treatment with ganciclovir. Results: Thirty-one (48.4%) of 64 patients with UC refractory to IMT were positive for CMV. Of the 31 patients, 4 (12.9%) underwent colectomy. Twenty-seven patients (87.1%) underwent antiviral therapy. Of those 27 patients, 7 achieved remission following antiviral therapy alone. Of the remaining 20 patients who did not achieve remission despite the disappearance of CMV-DNA, 11 and 9 patients were treated with additional GMA (GMA group) and IMT (IMT group), respectively. Of 11 patients (GMA group), 9 achieved remission and 2 underwent colectomy. Out of the remaining 9 patients (IMT group), 4 achieved remission and 5 underwent colectomy. CMV-DNA was not detected in 11 patients after GMA, but it was detected again in all 5 patients of the IMT group who underwent colectomy. The total colectomy rate in UC patients positive for CMV was 35.5% (11/31). In addition, colectomy-free survival in the CMV relapse (+) group was estimated to be 12.9% at 65 months, while that in the CMV relapse (–) group was estimated to be 100% at 60 months. Conclusion: The colectomy ratio tends to be high in refractory UC patients with recurrent CMV reactivation or infection. Therefore, GMA might be a safe and effective treatment for UC patients positive for CMV because it does not induce CMV reactivation.

Effect of intensive granulocyte and monocyte adsorptive apheresis in patients with ulcerative colitis positive for cytomegalovirus

“…In fact, Yoshino et al reported that GMAA did not induce colonic CMV reactivation in UC patients with a history of CMV infection. 22 In the present study, the clinical remission rate and mucosal healing following intensive GMAA did not differ significantly between UC patients positive for CMV and UC patients negative for CMV. A similar tendency was observed for the mucosal healing ratio.…”

“…[19][20][21] Furthermore, it was recently reported that GMAA could be safe for UC patients with a history of CMV infection due to the avoidance of colonic CMV reactivation compared with UC patients treated with immunosuppressive drugs. 22 Theoretically, GMAA removes granulocytes and monocytes/macrophages, where CMV infection is latent and reactivates. GMAA does not affect colonic CMV reactivation.…”

Letter: not the end of the role of anti‐viral therapy in ulcerative colitis with cytomegalovirus reactivation

“…Also, current clinical and experimental data demonstrate that insufficient control of inflammation could result in the exacerbation of UC disease activity with the induction of HCMV reactivation. 2,3 In fact, our previous report demonstrated that 26% of UC patients positive for HCMV-DNA in colonic tissue achieved clinical remission with anti-viral treatment, and the remainder required anti-inflammatory treatments without affecting HCMV reactivation, even after elimination of HCMV in colonic tissue. 2 It must be kept in mind that optimal control of colonic inflammation should be done in cases of UC patients positive for HCMV who are refractory to conventional immunosuppressive therapies.…”

“…2,3 In fact, our previous report demonstrated that 26% of UC patients positive for HCMV-DNA in colonic tissue achieved clinical remission with anti-viral treatment, and the remainder required anti-inflammatory treatments without affecting HCMV reactivation, even after elimination of HCMV in colonic tissue. 2 It must be kept in mind that optimal control of colonic inflammation should be done in cases of UC patients positive for HCMV who are refractory to conventional immunosuppressive therapies. Therefore, we consider that to only focus the therapeutic effect of anti-viral treatment on active UC patients with HCMV reactivation is not favourable.…”

Granulocyte-Monocyte Apheresis – Not the End of the Road Yet!

“…In the study by Yoshino et al [4] presented in this journal, 64 patients with ulcerative colitis refractory to immunosuppressive therapies (such as steroids and immunomodulators) were retrospectively enrolled and the clinical outcomes of GMA and immunosuppressive therapy after 2 weeks of ganciclovir treatment were investigated. The total colectomy rate in ulcerative colitis patients positive for CMV was 36%.…”