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Hypogammaglobulinaemia after rituximab treatment—incidence and outcomes

Discussion in 'Rituximab: News and Research' started by Firestormm, Jun 14, 2014.

  1. Firestormm

    Firestormm Senior Member

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    Cornwall England
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  2. daisybell

    daisybell Senior Member

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    How do they know that this is a result of the Rituximab treatment rather than the primary medical condition given that this will have been something affecting the immune system?
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  3. N.A.Wright

    N.A.Wright Guest

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    Hypogammaglobulinaemia is a rare condition, highest prevalence estimates are around 1:20,000 - http://ccjm.org/content/73/2/133.full.pdf . If one considers Rituximab to be used only in cases of RA - where the the highest prevalence rates are put at 1.5% then one can see that only a small percentage of RA patients could be expected to have pretreatment hypogammaglobulinaemia, this is borne out by research http://www.abstracts2view.com/eular/view.php?nu=EULAR11L_FRI0324 .

    In dealing with serious illness, there's rarely such a thing as a free lunch (pharmacetical industry promos excepted) and treatments such as Rituximab should be expected to have downsides, a least for some patients. At this stage we really need be looking at what Rituximab tells us about ME, not whether Rituximab is a cureall for ME. In cases where Rituximab treatment is not a major alleviation of symptoms, an inheritance of hypogammaglobulinaemia could be a pretty grim prospect.
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  4. daisybell

    daisybell Senior Member

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    Thanks for that link @N.A.Wright
    Looking at the abstract for the article Firestormm posted, I see this was patients referred to Immunology. I don't know if the authors have any way of knowing what percentage of people with RA treated with Rituximab this represents...

    Given that the incidence of such immunological problems in people with RA is around 5%, it would be interesting to know by how much Rituximab actually increases the incidence, if it does do so. Presumably if this was a serious risk, the approval of the drug would have been withdrawn?
  5. N.A.Wright

    N.A.Wright Guest

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    Re: the Oxford Journals article - what I read they are saying is that hypogammaglobulinaemia is an emerging problem - and from that I would assume it would be unlikely that there's data on the scale of the problem because no one has been looking for it as a long term issue. It would not have been a question that regulators addressed because it wasn't envisioned as problematic, in any case the consequences of hypogammaglobulinaemia are probably managable in otherwise reasonably healthy people, so it's a side effect to be dealt with rather than a fatal flaw in the treatment.

    But ME/CFS isn't RA; of course the incidence of Rituximab promoted hypogammaglobulinaemia may turn out to be low in both RA and ME/CFS but the spectrum of aetiologies covered by the ME/CFS label is likely to mean that the ME/CFS population is far more diverse than the RA population. That could in turn mean that a much smaller proportion of ME/CFS patients could benefit from Rituximab while the consequences of long term hypogammaglobulinaemia in ME/CFS could be less easily managed, in some cases it could be devastating. Rituximab promoted hypogammaglobulinaemia isn't a reason not to explore Rituximab's potential benefits but we should not be blind to potential risks and at the very least be prepared for how to deal with them.
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  6. Jonathan Edwards

    Jonathan Edwards Senior Member

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    This is actually a rather oddly written article, especially as I know some of the co-authors. Hypogammaglobulinaemia after rituximab is not 'an emerging problem' really. We have been looking at it in RA for 16 years and know how big a problem it is and have a reasonably good idea how to minimise the risk. Falling gammaglobulin levels were reported by our group even before the major trial in RA. In lymphoma I think the problem has been known about since about 1994. I think the problem is that this article is written from the viewpoint of an immunology service receiving referrals rather than primarily from people giving rituximab on a regular basis. There is no harm in raising awareness of the problem but it is not new.

    The great majority of patients treated with rituximab fro RA do not get panhypogammaglobulinaemia. Some get low levels that need monitoring and may require switch to other treatments. A very few get sudden drops in levels even with the first treatment - I think the figure is 1 out of the first 200 patients I am aware of treating. One or two more developed low enough levels to need replacement after repeated treatments which were given in full knowledge that levels were dropping. There is no doubt that it is a real problem that has to be taken seriously, if infrequent. What I think is misleading is to suggest that it is only just now becoming apparent and might be underappreciated.
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