Case report of Adalimumab in POTS

GasDoc

New Member
Put the kettle on, make yourself a cuppa, grab some biscuits, etc, this, my first, is going to be a long post.

The context:
Since retiring from medicine I started hearing that many of my former colleagues and their families were not recovering from Covid-19 infection, many having persistent or fluctuating symptoms ranging from mild to severe for months or without end in some cases. We now know that they are suffering with was has been termed LongCovid. As I have time on my hands I started digging and educating myself about this condition. I've got to admit I'm not an expert in dysautonomia, but have learnt quickly.

LongCovid, is likely to be a heterogeneous condition, lots of different conditions all lumped under the same title. This is something that is done a lot in medicine when we don't know what is going on. Some are due to lung disease, some due to cardiac disease, some due to clotting issues, etc. One thing that struck me was that however that a lot of the patients had symptoms that could be explained by an autoimmune basis. Persistent "odd" multiorgan involvement and symptoms scream out autoimmune to me if chronic. If acute, they suggest a drug reaction or acute infection. A lot of my colleagues seemed to be suffering from POTS and/or ME/CFS, not exactly surprising given the high incidence of autonomic antibodies in these conditions in a subset of patients.

As a consequence of the above I started educating myself about these "invisible" conditions which can often be devastating in their impact.

This leads me onto the reason for this, my first post, - interesting publications and research news that lead to better treatments and hopefully cures POTS and ME/CFS.

I'm going to start with a case report for POTS. Before I start however, a disclaimer, so I don't get peoples hope up. Case reports are the lowest level of evidence for a treatment or intervention. They can point you towards treatments that work, but they don't offer the best level of evidence for effect. This is the double blind controlled clinical trial, the "gold standard". You also won't persuade many doctors, if any, to start you on a novel treatment on the basis of one case.
However, case reports are invaluable for highlighting areas of interest. It was serendipity that male patients on a drug trial for an anti-hypertensive weren't handing back their samples at the end of the study lead to the finding that it was for the reason that Viagra helps with erections. The rest is history.

Immunomodulation is a fertile area for treatment options for autoimmune conditions. Whether the manipulation of T cells, B cells, immune modulators or autoantibodies. The case report is about POTS and adalimumab.

The case report:
In this case report a 29 yr old woman was treated with adalimumab for seronegative ankylosing spondylitis. Incidentally she also had POTS, almost certainly associated with Ehlers-Danlos syndrome and mast cell activation syndrome. Within a week she reported that her many of her POTS symptoms had improved, though I can't really see this reflected in the Likert scale questionnaire (completed retrospectively). At 4 month follow up she reported, “It is just like I just don’t have POTS anymore”. Some weaknesses in the case report are that she didn't have autoantibodies measured pre or post treatment and no objective measurements, such as tilt testing were carried out. However, what can't be disputed is her statement of “It is just like I just don’t have POTS anymore”. At the end of the day that is a powerful statement and points to a potential treatment of the underlying condition. Obviously it may be coincidence, but seems unlikely given the association and mechanism of action of the medication.

So what is adalimumab? It is a human IgG1 monoclonal antibody against tumor necrosis factor (TNF)-alpha and is administered subcutaneously. It's mechanism of action in this case was proposed to be modulation of adrenergic autoantibodies, though I would suggest it could exert an effect on any of the G protein linked vascular autoantibodies and others, that are raised in many patients with POTS. What can't be disputed is that adalimumab is not a vasoactive drug, unlike most treatments currently used.
It is a pity that a panel of autoantibodies, such as the CellTrend POTS autoantibody screen was not performed pre and post treatment, but you can't have everything. Hopefully if a similar POTS patient requires adalimumab in the future these will be performed prospectively. Maybe it is a treatment that could be the focus of a pilot study?

This is another piece in the puzzle that some POTS patients have an autoimmune basis for their condition, in my view immunomodulation treatments should be where the bulk of the research money is directed.

Sorry about the length of the post just to get to a single case report. When I find something I find of interest in future I'll post a short review and my take on it. I'm going to limit these posts mainly to treatments that point to the holy grail of a cure as this is something that is achievable in my view or at the very least, treatments that improve activities of daily living.
 

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