Further evidence of Rituximab’s effectiveness in treating ME/CFS | PlosOne publish results of Phase 2 trial | 1 July 2015

From PLoSOne, 1 July 2015.

The results of a phase 2 clinical trial into the treatment with the anti-lymphoma drug Rituximab of a group of 29 patients with ME/CFS are announced today in the US open access science journal, PloSOne. They have been welcomed by the ME Association as evidence of possibly “the first major advance” in the drug treatment of the illness.

The trial is being carried out by the Norwegian group that first announced it was investigating the use of Rituximab in ME/CFS in 2011. Eighteen of the 29 patients– 64% – experienced major or moderate responses, and some have now been symptom-free for five years. Rituximab wipes out most of the B cells that make antibodies, yet patients don’t experience remissions of their symptoms until months later.

STATEMENT BY DR CHARLES SHEPHERD, MEDICAL ADVISER, ME ASSOCIATION

The Norwegian clinical trials (which are being followed closely by people with ME/CFS) indicate that Rituximab could be the first major advance in the drug treatment of ME/CFS.

The findings are also support a key role for immune system dysfunction in the causation of ME/CFS and explain why (immunomodulatory) treatments that remove B cells from circulation could then be used in some cases.

The downside is that Rituximab is a very expensive drug with a potential to cause serious side-effects.

So, while a much larger phase 3 clinical trial is now taking place in Norway, we also need to set up up other multi-centre clinical trials to confirm the efficacy and safety of Rituximab in ME/CFS, and to obtain a clearer (clinical and immunological) profile of which patients respond to Rituximab and which do not.

Otherwise, there will be a significant delay before what could be a very effective form of treatment becomes available here in the UK.

Dr Charles Shepherd
Hon Medical Adviser, ME Association

NB:

1 Researchers at University College London are currently carrying out further research on B cell dysfunction in ME/CFS in preparation for a UK clinical trial of Rituximab.

2. Dr Øystein Fluge will be speaking at the CFS/ME Research Collaborative Conference in Newcastle on Wednesday, 14 October 2015.

www.meassociation.org.uk/2015/03/early-bird-bookings-open-for-the-two-day-research-collaborative-conference-newcastle-13-14-october-2015/

3 The Norwegian group are also looking at the use of another immunomodulatory drug, cyclophosphamide:

www.meassociation.org.uk/2015/02/second-anti-cancer-drug-now-being-investigated-in-norway-for-treatment-of-mecfs-10-february-2015/

ABSTRACT FROM PLoSONE, 1 JULY 2015 (FULL TEXT AVAILABLE)

B-lymphocyte depletion in Myalgic Encephalopathy/ Chronic Fatigue Syndrome. An open-label phase II study with rituximab maintenance treatment

Øystein Fluge(1*), Kristin Risa(1), Sigrid Lunde(1), Kine Alme(1), Ingrid Gurvin Rekeland(1), Dipak Sapkota(2,1), Einar Kleboe Kristoffersen(3,4), Kari Sørland(1), Ove Bruland(5,1), Olav Dahl(4,1), Olav Mella(1,4*)
1) Department of Oncology and Medical Physics, Haukeland University Hospital, Bergen, Norway
2) Department of Clinical Medicine, University of Bergen, Haukeland University Hospital, Bergen, Norway
3) Department of Immunology and Transfusion Medicine, Haukeland University Hospital, Bergen, Norway
4) Department of Clinical Science, University of Bergen, Haukeland University Hospital, Bergen, Norway
5) Department of Medical Genetics and Molecular Medicine, Haukeland University Hospital, Bergen, Norway
* Correspondence: E-mail: oystein.fluge@helse-bergen.no (ØF); olav.mella@helse-bergen.no (OM)

Trial registration: ClinicalTrials.gov; NCT01156909

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.

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