Rituximab has a good history for a drug (the European patent for Roche
expires next year and GenTech in the U.S. loses their patent in 2015)
for patients who have latent and or active microbial infections the
side effects can be severe including death.
Also, the one person in the placebo arm of the trial who showed marked
long term improvement may have had an affective disorder only
according to the study authors as that person did not meet the
Canadian Consensus Criteria although they met the international 1994
Fukuda criteria which does not require post exertional malaise or
cognitive problems. This highlights the problems inherent with being
unable or unwilling to separate those who have a disease from those
who do not.
Chronic Fatigue Syndrome -- A Treatable Autoimmune Disease
Matthew Edlund, M.D./ Huffington Post
Posted: 10/26/11 11:22 AM ET
Chronic fatigue syndrome wrecks people's lives. It does so
physicially, socially and economically. Appearing "normal" yet not
being able to think or work causes enormous hardship compounded by
many doctors who think the illness does not really exist -- a position
health and disability insurance companies are more than happy to
endorse. And those who firmly believe it exists are often stumped by
how to treat it -- beyond stretching, physical activity and
Now a new study out of Bergen, Norway adds much to the data that
chronic fatigue is an autommune disease. If not entirely definitive,
it points in the direction that many CFS sufferers and clinicians have
argued for decades -- that the illness is a disorder of the immune
system, is preceded in most cases by some kind of infection and
continues to provoke multiple debilities for a long time.
The Haukelund Study:
Many ideas for clinical treatment occur from observing the clinically
unexpected. In this case, the Haukelund Hospital researchers were
struck by a patient with lymphoma and CFS whose fatigue also improved
with treatment. They decided to treat 30 people with CFS, mainly young
(average age 37.3 for those treated and 31.5 years for placebo) and
female (80 percent) with rituximab, a potent anti-inflammatory
monoclonal antibody that markedly depletes B cells. None of the
patients allowed into the study were suffering from endogenous
depression, which afflicts a large number of CFS sufferers. None of
them showed evidence of the XMRV virus, which previously had been
reported as more common in some CFS sufferers, though critics felt
such studies were methodologically flawed.
Some major findings were:
1. About two-thirds of the study group saw their fatigue (self-rated)
as considerably improved compared to only 13 percent of the placebo
group. Cognitive and other functions also improved, though not
necessarily as much.
2. Effects were delayed. Some patients only showed improvement 6-7
months after treatment with the drug, and none quickly.
3. Some people showed marked long term improvement, but only a few
(more or less complete in 2/15 on rituximab and 1/15 on placebo at
A. This is a small study. The number of people treated was not large,
the placebo group had the disease longer, and as the authors are very
aware, this study needs replication and expansion with ongoing
B. The study group may not be reflective of the majority of CFS
patients, many of whom are older, have other intercurrent autoimmune
problems (about one-fifth of the study group also did) and who often
suffer from depression and sleep disorders.
C. Though the authors believe this study shows rituximab is moderating
a long term immunological effect through B cells and autoantibodies,
nobody has a clear sense of why it works.
D. Rituximab is expensive and has lots of side effects, including
infusion reactions, renal failure, immunological disorders and
Despite the problems, there is much cheering in the Bergen study.
First, something seems to work. Most clinical trials of CFS patients,
like with acyclovir, show only subsets of patients who experience real
Second, this study goes a fair way to knocking off the strong belief
in the medical community that CFS is "only in people's heads." Many
with CFS are told that they are depressed -- they know that, but also
know very well something else is going on that causes that depression.
Third, if something works, further treatment along the lines of
oncology/rheumatologic trials may now get funded. Ritixumab and other
monoclonal antibodies may be tried, alone or in combination.
The biggest change may occur with public acceptance and awareness.
It's one thing to live with a chronic disease that controls much of
your life; it's another to live with an illness many do not believe
I think the Bergen study will provoke many more arguments about CFS,
particularly what its main manifestations really are and what to do
about it. Many sufferers will want immediate treatment with rituximab
or other monoclonal antibodies, which may be clinically premature.
Immunity is fiendishly complicated, and the effects of monoclonal
antibodies on immunity profound. But the argument that CFS is not
related to the immune system may now be less stridently asserted. That
would be real progress.