ResearchSpeak & OffLabel: off-label rituximab to treat MS and autoimmunity

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ResearchSpeak & OffLabel: off-label rituximab to treat MS and autoimmunity

Permission to post by Gavin Giovannoni. Comments are his own.

My comment is that appears from Giovarnnoni comments here and elsewhere that it will be difficult to get NHS approval for Rituximab for off label use in treating autoimmune diseases. @Jonathan Edwards would know more about NHS involvement in off label use of rituximab if the UK rituximab trial is successful in treating ME/CFS patients.

Should we be using more off-label rituximab to treat MS? #ResearchSpeak #OffLabel #MSResearch #MSBlog

"As you are aware I have been promoting the use of off-label rituximab as a therapy in MS for potentially three different indications. I now want to add a fourth indication, i.e. concomitant autoimmune disease.

(1) Rituximab as a safe and more effective alternative to fingolimod post-natalizumab in pwMS who are JCV seropositive. The idea is to prevent rebound activity post-natalizumab and to leave the T-cell arm of the immune system intact to limit the consequences of carry-over PML. This off-label indication is supported by real-life data from the Swedish experience.

(2) As an off-label alternative to high-cost drugs in resource poor environments where access to innovative high-cost drugs is problematic. This is based on phase 2 data of rituximab in RRMS and supported by recent data of other anti-CD20 agents in MS.

(3) As a potential strategy to prevent secondary autoimmunity post-alemtuzumab; the PAPA study. The idea here is to give a small dose of rituximab after each course of alemtuzumab to prevent rebound in the B cell numbers. Unfortunately we have not been able to convince anyone yet to fund this study, but we have not given up on the idea just yet of doing this study.

(4) A fourth indication is a treatment of MS in patients with concomitant autoimmune disease. The paper below describes the successful use of rituximab in two pwMS who also had idiopathic thrombocytopenic purpura (ITP); the aim is for rituximab to treat both the MS and the ITP.

I have a similar anecdote and have used rituximab in a patient with both active MS and sacroiliitis. Her rheumatologist was keen to treat her with an anti-TNF-alfa drug, which I was strongly against as there is very good data that shows that inhibiting TNF-alpha makes MS worse.

A compromise we reached was to treat her with rituximab. She is now 4-years into her rituximab treatment and her MS is NEDA and her sacroiliitis is much improved. This is one case where I have been successful in getting NHS England to agree to funding of rituximab. The reason for this is that she is a unique, or at least a very rare, case and is therefore suitable for an IFR (individual funding request).

The use of off-label drugs to treat MS in resource-rich environments remains a hot potato. Despite been given the green-light to do so by our politicians the problem remains one of cost and the wide adoption of the practice by the peer group. At a systems level there are also legal hurdles to overcome. I suspect we have reached an impasse on this issue and are unlikely to be given permission by the NHS to use rituximab widely to treat MS."


OBJECTIVES:
The aim of the study was to describe the effectiveness and safety data of rituximab in a group of patients with relapsing-remitting multiple sclerosis (MS) treated with rituximab due to failure of previous treatments or concomitant autoimmune diseases.

METHODS:
This is an observational study. Rituximab was considered in case of failure of the second-line therapy, failure of the first-line therapy and a contraindication to second-line therapies, or concomitant autoimmune disease. Relapses, the Expanded Disability Status Scale, the EQ VAS, and magnetic resonance imaging activity were assessed.

RESULTS:
This study included 12 patients with relapsing-remitting MS. The mean (range) age of the patients was 35 (19-54) years. Ten patients were treated with rituximab because of treatment failure, and 2 patients were treated with rituximab because of the development of idiopathic thrombocytopenic purpura (ITP).

The mean (range) follow-up duration after beginning rituximab was 40 (18-72) months. Rituximab was well tolerated, because no patient experienced serious adverse reactions or discontinued treatment.

During treatment with rituximab, no patient suffered a clinical relapse, and magnetic resonance imaging activity was not detected. The Expanded Disability Status Scale scores improved in 11 of 12 patients and remained stable in 1 patient. The EuroQol visual analogue scale scores improved in 8 of 9 patients in whom the EuroQol visual analogue scale was assessed.

CONCLUSIONS:
Treatment with rituximab seems to be safe and effective for some patients with relapsing-remitting MS who have failed to respond to first- and second-line therapies and may also be a useful option for patients with concomitant autoimmune disorders.

Gavin Giovannoni

 

[Jonathan Edwards]

I think the situations for MS and ME are a bit differen. There are several biologic options for treating MS and I think the problem there is that things are a mess. ME may be easier because there are no other options. Off label usage on the NHS with expensive drugs has certainly become harder and harder and with the NHS more or less strangled by the present government, such that we spend about a third per head than Norway does, and are in negotiation for having India provide all our doctors for us, things are looking bleak, But at least in the past were there was a will there was often a way.

My impression is that rituximab should have been licensed for MS long ago and the reason it is not is simply a business decision on the part of Genentech, partly related to patents and partly related to bad press from adverse events and partly related to uncertain market share. The neurologists have only themselves to blame, since I suggested they got on and did what I did for RA in 2002. No takers.

(I am a bit puzzled about the anecdote about a patient with sacroiliitis, since sacroiliitis is part of anylosing spondylitis, which is not an autoimmune disease, has nothing to do with B cells and does not respond to riuximab (as one would expect). )

 

[SB_1108]

(I am a bit puzzled about the anecdote about a patient with sacroiliitis, since sacroiliitis is part of anylosing spondylitis, which is not an autoimmune disease, has nothing to do with B cells and does not respond to riuximab (as one would expect). )

I developed sacroiliitis and/or sacroiliac joint dysfunction about four years into ME/CFS and I have two ideas about this...
1) Sitting (even for short periods) is difficult on the SI joints. If the patient's MS went into remission, the patient would probably be more active/sitting less often thus the sacroiliitis pain was reduced.
2) Not all sacroiliitis is associated with ankylosing spondylitis as sacroiliitis has also been found in autoimmune diseases like Lupus.

 

[Jonathan Edwards]

I developed sacroiliitis and/or sacroiliac joint dysfunction about four years into ME/CFS and I have two ideas about this...
1) Sitting (even for short periods) is difficult on the SI joints. If the patient's MS went into remission, the patient would probably be more active/sitting less often thus the sacroiliitis pain was reduced.
2) Not all sacroiliitis is associated with ankylosing spondylitis as sacroiliitis has also been found in autoimmune diseases like Lupus.

Thanks SB_1108,
I think we can be pretty sure that sacroiliitis has nothing to do with lupus or autoimmunity. There is no statistical association. Clearly by chance a few people may have both. Inflammatory sacroiliitis is based on an enthesopathy that is linked to HLA-B27 and certain cytokine receptor polymorphisms. It is not always associated with generalised spinal change, but it is not linked to lupus. Mechanical sacroiliac pain is something different that anyone can get. It may hurt to sit but I doubt it is caused by prolonged sitting. Sacroiliac joint dysfunction is a term used by osteopaths that seems to be largely based on taking x-rays slightly sideways and claiming that the joint is out of position. I am not quite sure what it could mean since the sacroiliac joint does not really 'function' - it is just two bones tied tightly by string for embryological reasons. Sheep do not have these joints and do not seem to suffer as a result!. Humans can get sacroiliac pain after pregnancy because the ligament loosening can lead to changes. Ligament loosening is probably important for childbirth in mice but not in humans so sheep may be better off!