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B-Lymphocyte Depletion in Myalgic Encephalopathy/ Chronic Fatigue Syndrome. An Open-Label Phase II Study with Rituximab Maintenance Treatment.

Fluge Ø, Risa K, Lunde S, Alme K, Rekeland IG, Sapkota D, Kristoffersen EK, Sørland K, Bruland O, Dahl O, Mella O - PLoS ONE (2015)

Bottom Line: We previously reported a pilot case series followed by a small, randomized, placebo-controlled phase II study, suggesting that B-cell depletion using the monoclonal anti-CD20 antibody rituximab can yield clinical benefit in ME/CFS.Clinically significant responses were seen in 18 out of 28 patients (64%) receiving rituximab maintenance treatment.The observed patterns of delayed responses and relapse after B-cell depletion and regeneration, a three times higher disease prevalence in women than in men, and a previously demonstrated increase in B-cell lymphoma risk for elderly ME/CFS patients, suggest that ME/CFS may be a variant of an autoimmune disease.

View Article: PubMed Central - PubMed

Affiliation: Department of Oncology and Medical Physics, Haukeland University Hospital, Bergen, Norway.

ABSTRACT

Background: Myalgic Encephalopathy/Chronic Fatigue Syndrome (ME/CFS) is a disease of unknown etiology. We previously reported a pilot case series followed by a small, randomized, placebo-controlled phase II study, suggesting that B-cell depletion using the monoclonal anti-CD20 antibody rituximab can yield clinical benefit in ME/CFS.

Methods: In this single-center, open-label, one-armed phase II study (NCT01156909), 29 patients were included for treatment with rituximab (500 mg/m2) two infusions two weeks apart, followed by maintenance rituximab infusions after 3, 6, 10 and 15 months, and with follow-up for 36 months.

Findings: Major or moderate responses, predefined as lasting improvements in self-reported Fatigue score, were detected in 18 out of 29 patients (intention to treat). Clinically significant responses were seen in 18 out of 28 patients (64%) receiving rituximab maintenance treatment. For these 18 patients, the mean response durations within the 156 weeks study period were 105 weeks in 14 major responders, and 69 weeks in four moderate responders. At end of follow-up (36 months), 11 out of 18 responding patients were still in ongoing clinical remission. For major responders, the mean lag time from first rituximab infusion until start of clinical response was 23 weeks (range 8-66). Among the nine patients from the placebo group in the previous randomized study with no significant improvement during 12 months follow-up after saline infusions, six achieved a clinical response before 12 months after rituximab maintenance infusions in the present study. Two patients had an allergic reaction to rituximab and two had an episode of uncomplicated late-onset neutropenia. Eight patients experienced one or more transient symptom flares after rituximab infusions. There was no unexpected toxicity.

Conclusion: In a subgroup of ME/CFS patients, prolonged B-cell depletion with rituximab maintenance infusions was associated with sustained clinical responses. The observed patterns of delayed responses and relapse after B-cell depletion and regeneration, a three times higher disease prevalence in women than in men, and a previously demonstrated increase in B-cell lymphoma risk for elderly ME/CFS patients, suggest that ME/CFS may be a variant of an autoimmune disease.

Trial registration: ClinicalTrials.gov NCT01156909.

No MeSH data available.


Related in: MedlinePlus

Consort 2010 Flow Diagram for the KTS-2-2010 study.Consort Flow Diagram for the KTS-2-2010 study, with enrollment, allocation to induction and maintenance rituximab treatment, and follow-up showing number of patients who withdrew from study before 36 months.
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pone.0129898.g001: Consort 2010 Flow Diagram for the KTS-2-2010 study.Consort Flow Diagram for the KTS-2-2010 study, with enrollment, allocation to induction and maintenance rituximab treatment, and follow-up showing number of patients who withdrew from study before 36 months.

Mentions: The Consort flow diagram for the KTS-2-2010 study is shown in Fig 1. Between September 2010 and February 2011, 27 patients were included. In addition, two pilot patients started maintenance rituximab treatment from July 2009. End of follow-up was in February 2014. The patients were partly recruited through referrals from the Dept. of Neurology, Haukeland University Hospital, and partly through primary care physicians.


B-Lymphocyte Depletion in Myalgic Encephalopathy/ Chronic Fatigue Syndrome. An Open-Label Phase II Study with Rituximab Maintenance Treatment.

Fluge Ø, Risa K, Lunde S, Alme K, Rekeland IG, Sapkota D, Kristoffersen EK, Sørland K, Bruland O, Dahl O, Mella O - PLoS ONE (2015)

Consort 2010 Flow Diagram for the KTS-2-2010 study.Consort Flow Diagram for the KTS-2-2010 study, with enrollment, allocation to induction and maintenance rituximab treatment, and follow-up showing number of patients who withdrew from study before 36 months.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4488509&req=5

pone.0129898.g001: Consort 2010 Flow Diagram for the KTS-2-2010 study.Consort Flow Diagram for the KTS-2-2010 study, with enrollment, allocation to induction and maintenance rituximab treatment, and follow-up showing number of patients who withdrew from study before 36 months.
Mentions: The Consort flow diagram for the KTS-2-2010 study is shown in Fig 1. Between September 2010 and February 2011, 27 patients were included. In addition, two pilot patients started maintenance rituximab treatment from July 2009. End of follow-up was in February 2014. The patients were partly recruited through referrals from the Dept. of Neurology, Haukeland University Hospital, and partly through primary care physicians.

Bottom Line: We previously reported a pilot case series followed by a small, randomized, placebo-controlled phase II study, suggesting that B-cell depletion using the monoclonal anti-CD20 antibody rituximab can yield clinical benefit in ME/CFS.Clinically significant responses were seen in 18 out of 28 patients (64%) receiving rituximab maintenance treatment.The observed patterns of delayed responses and relapse after B-cell depletion and regeneration, a three times higher disease prevalence in women than in men, and a previously demonstrated increase in B-cell lymphoma risk for elderly ME/CFS patients, suggest that ME/CFS may be a variant of an autoimmune disease.

View Article: PubMed Central - PubMed

Affiliation: Department of Oncology and Medical Physics, Haukeland University Hospital, Bergen, Norway.

ABSTRACT

Background: Myalgic Encephalopathy/Chronic Fatigue Syndrome (ME/CFS) is a disease of unknown etiology. We previously reported a pilot case series followed by a small, randomized, placebo-controlled phase II study, suggesting that B-cell depletion using the monoclonal anti-CD20 antibody rituximab can yield clinical benefit in ME/CFS.

Methods: In this single-center, open-label, one-armed phase II study (NCT01156909), 29 patients were included for treatment with rituximab (500 mg/m2) two infusions two weeks apart, followed by maintenance rituximab infusions after 3, 6, 10 and 15 months, and with follow-up for 36 months.

Findings: Major or moderate responses, predefined as lasting improvements in self-reported Fatigue score, were detected in 18 out of 29 patients (intention to treat). Clinically significant responses were seen in 18 out of 28 patients (64%) receiving rituximab maintenance treatment. For these 18 patients, the mean response durations within the 156 weeks study period were 105 weeks in 14 major responders, and 69 weeks in four moderate responders. At end of follow-up (36 months), 11 out of 18 responding patients were still in ongoing clinical remission. For major responders, the mean lag time from first rituximab infusion until start of clinical response was 23 weeks (range 8-66). Among the nine patients from the placebo group in the previous randomized study with no significant improvement during 12 months follow-up after saline infusions, six achieved a clinical response before 12 months after rituximab maintenance infusions in the present study. Two patients had an allergic reaction to rituximab and two had an episode of uncomplicated late-onset neutropenia. Eight patients experienced one or more transient symptom flares after rituximab infusions. There was no unexpected toxicity.

Conclusion: In a subgroup of ME/CFS patients, prolonged B-cell depletion with rituximab maintenance infusions was associated with sustained clinical responses. The observed patterns of delayed responses and relapse after B-cell depletion and regeneration, a three times higher disease prevalence in women than in men, and a previously demonstrated increase in B-cell lymphoma risk for elderly ME/CFS patients, suggest that ME/CFS may be a variant of an autoimmune disease.

Trial registration: ClinicalTrials.gov NCT01156909.

No MeSH data available.


Related in: MedlinePlus