%0 Generic %A Rekeland, Ingrid G. %A Fosså, Alexander %A Lande, Asgeir %A Ktoridou-Valen, Irini %A Sørland, Kari %A Holsen, Mari %A Tronstad, Karl J. %A Risa, Kristin %A Alme, Kine %A Viken, Marte K. %A Lie, Benedicte A. %A Dahl, Olav %A Mella, Olav %A Fluge, Øystein %D 2020 %T Table_2_Intravenous Cyclophosphamide in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. An Open-Label Phase II Study.docx %U https://frontiersin.figshare.com/articles/dataset/Table_2_Intravenous_Cyclophosphamide_in_Myalgic_Encephalomyelitis_Chronic_Fatigue_Syndrome_An_Open-Label_Phase_II_Study_docx/12211184 %R 10.3389/fmed.2020.00162.s004 %2 https://frontiersin.figshare.com/ndownloader/files/22458164 %K myalgic encephalomyelitis %K chronic fatigue syndrome %K ME %K CFS %K cyclophosphamide %K clinical trial %K medical treatment %K HLA %X

Introduction: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a disease with high symptom burden, of unknown etiology, with no established treatment. We observed patients with long-standing ME/CFS who got cancer, and who reported improvement of ME/CFS symptoms after chemotherapy including cyclophosphamide, forming the basis for this prospective trial.

Materials and methods: This open-label phase II trial included 40 patients with ME/CFS diagnosed by Canadian criteria. Treatment consisted of six intravenous infusions of cyclophosphamide, 600–700 mg/m2, given at four-week intervals with follow-up for 18 months, extended to 4 years. Response was defined by self-reported improvements in symptoms by Fatigue score, supported by Short Form 36 (SF-36) scores, physical activity measures and other instruments. Repeated measures of outcome variables were assessed by General linear models. Responses were correlated with specific Human Leukocyte Antigen (HLA) alleles.

Results: The overall response rate by Fatigue score was 55.0% (22 of 40 patients). Fatigue score and other outcome variables showed significant improvements compared to baseline. The SF-36 Physical Function score increased from mean 33.0 at baseline to 51.5 at 18 months (all patients), and from mean 35.0 to 69.5 among responders. Mean steps per 24 h increased from mean 3,199 at baseline to 4,347 at 18 months (all patients), and from 3,622 to 5,589 among responders. At extended follow-up to 4 years 68% (15 of 22 responders) were still in remission. Patients positive for HLA-DQB1*03:03 and/or HLA-C*07:04 (n = 12) had significantly higher response rate compared to patients negative for these alleles (n = 28), 83 vs. 43%, respectively. Nausea and constipation were common grade 1–2 adverse events. There were one suspected unexpected serious adverse reaction (aggravated POTS) and 11 serious adverse events in eight patients.

Conclusion: Intravenous cyclophosphamide treatment was feasible for ME/CFS patients and associated with an acceptable toxicity profile. More than half of the patients responded and with prolonged follow-up, a considerable proportion of patients reported ongoing remission. Without a placebo group, clinical response data must be interpreted with caution. We nevertheless believe a future randomized trial is warranted.

Clinical Trial Registration:www.ClinicalTrials.gov, identifier: NCT02444091.

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