Journal of IiME Volume 7 Issue 1 Syndrome. A Double-Blind and Placebo-Controlled Study". Dr Øystein Fluge Bergen University Hospital, Norway (May 2013) the criteria defined in the randomized study. The main endpoint defining response was change in Fatigue score during the observation period, although improvements in fatigue were generally followed also by decrease in other ME-symptoms. Follow-up is a minimum of 28 mths in all patients. Two patients had serious allergic reactions and had to stop Rtx treatment (one responding patient given alternative B-cell depleting agent with new response). Two had repeated airway infections and were given antibiotics and eventually gamma globulin. Seven had transient ME-symptom increase shortly after Rtx infusion. Two had late onset neutropenia of short duration. Dr Øystein Fluge received medical degree in 1988 at the University of Bergen, and is a specialist in oncology since 2004. He has worked as a Research Fellow with support from the Norwegian Cancer Society and is now chief physician at the Cancer Department, Haukeland University Hospital. Doctoral work emanates from the Surgical Institute and Depart. of Molecular Biology, University of Bergen. Abstract: Intervention and maintenance treatment with the B-lymphocyte depleting monoclonal anti-CD20 antibody Rituximab in ME patients. A Phase II study. Fluge Ø, Mella O. Dept. of Oncology and Medical Physics, Haukeland University Hospital and University of Bergen, Norway. We have previously published a case series and a small double blind, placebo-controlled study using immune manipulation with the B-lymphocyte depleting, monoclonal anti-CD20 antibody Rituximab (Rtx). These studies showed that Rtx yielded clinically meaningful responses, with symptom alleviation, although usually transiently, in the majority of patients. Patients in the double-blinded study having received placebo were according to protocol offered inclusion into an open-label Phase II with Rtx treatment. This study pursued the concept of repeated Rtx infusions to see if responses were more durable than in the randomized study, and to estimate side effects of the drug including adverse effects of prolonged B-cell depletion. 28 patients (including 2 pilot patients) were treated with Rtx 500 mg/m2 day 1 and 15 (as in the randomized study) and with maintenance Rtx infusions at 3, 6, 10 and 15 mths. Patients in slow responses were offered additional infusions up to 24 mths. Study endpoints were predefined according to Invest in ME (Charity Nr. 1114035) 20 of the 28 patients had moderate or major response to treatment. 7 of the 9 placebo patients from the randomized study (without response) responded in the present study. Median selfestimated level of functioning, compared to completely healthy condition, was changed from 10% at baseline to 78% at 18-24 mths after inclusion in responders, and from 15 to 18% in nonresponders. Response durations were evidently longer than in the randomized study. However, later than 24 mths into the study, 9 of 20 responding patients have had ME-symptom recurrences. We conclude that the present Phase II study supports previous data on good clinical responses to immune manipulation with Rtx in ME-patients and that maintenance treatment seems to prolong responses. Based on the studies, we have sought financial support for a Norwegian multicenter, double-blinded and placebo-controlled study of Rtx given at day 1 and 15, and at 3, 6, 9 and 12 mths, with 24 mths observation time. This study will also include prospective analyses of bio bank material and physical tests to verify the subjective measures that are the prime endpoints. Parallel to the clinical studies, we have performed multiple analyses to get a better understanding of the mechanisms that trigger and maintain the symptoms in ME. Although preliminary, this has given us a candidate system we presently are investigating as a possible effector system in the body that may explain the symptoms and responses to interventions in ME-patients. What could be a possible link between such a system and the immune manipulation that Rtx induces? Dr. Fluge will cover this aspect of our studies in his presentation at the meeting. Supported by the Kavli Foundation and the Western Norway Health Authority. www.investinme.org Page 31 of 36
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