Tolerability & Efficacy of s.c. IgG Self-Treatment in ME/CFS Patients with IgG/IgG Subclass Deficiency: A Proof-of-Concept Study, 2021, Scheibenbogen

Abstract

Background: Chronic fatigue syndrome (ME/CFS) is a complex disease frequently triggered by infections. IgG substitution may have therapeutic effect both by ameliorating susceptibility to infections and due to immunomodulatory effects.

Methods: We conducted a proof of concept open trial with s.c. IgG in 17 ME/CFS patients suffering from recurrent infections and mild IgG or IgG subclass deficiency to assess tolerability and efficacy. Patients received s.c. IgG therapy of 0.8 g/kg/month for 12 months with an initial 2 months dose escalation phase of 0.2 g and 0.4 g/kg/month.

Results: Primary outcome was improvement of fatigue assessed by Chalder Fatigue Scale (CFQ; decrease ≥ 6 points) and of physical functioning assessed by SF-36 (increase ≥ 25 points) at month 12. Of 12 patients receiving treatment per protocol 5 had a clinical response at month 12. Two additional patients had an improvement according to this definition at months 6 and 9. In four patients treatment was ceased due to adverse events and in one patient due to disease worsening. We identified LDH and soluble IL-2 receptor as potential biomarker for response.

Conclusion: Our data indicate that self-administered s.c. IgG treatment is feasible and led to clinical improvement in a subset of ME/CFS patients.
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Open access, https://www.mdpi.com/2077-0383/10/11/2420/htm

 

This seems to be the main result:

Figure 2. (a) The Chalder Fatigue Scale (CFQ) and the (b) SF-36 physical functioning of all patients receiving 12 months of treatment before (pre) during (months 3-12) and 3 months after the treatment (month 15) is shown.

The results do not look that impressive. Strange that the graph for the Chalder goes to 40 while the maximum score is normally 33.

 

But it was significant.....

 

Unblinded trial so not impressive. The Chalder scale abnormality is probably just how the software displays the data in the graph.

 

Not really. You cannot meaningfully compare a pretreatment with follow-up in an uncontrolled trial and treat a difference as 'statistically significant'. Statistical significance is based on a null hypothesis that populations are the same and a finding that they cannot be. But it is absurd to consider pre-treatment and follow up populations as the same in this sort of context. It may have a mathematical meaning but it has no real life meaning.

Competent scientists simply don't do analyses like that. They would focus on the size of the difference and its potential biological relevance. If the difference is as unimpressive as this it looks pretty much like a non-starter. It would be surprising to get less difference than this just from non-specific effects.

 

OK—but do you think IG therapy holds any promise for improving MECFS?

 

IgG therapy for ME seems a muddle.

I cannot see any point in giving it to people with slightly low IgG levels or subclass levels - which are common enough findings and unlikely to have anything to do with immunodeficiency'.

IgG has been given for autoimmune disease in the past but mostly that has been given up because it hardly works if at all. The exception is immune thrombocytopenia where the mechanism probably has to do with short term complex formation - which is not likely to be relevant to ME.

I cannot get any enthusiasm on either score. IVIg is a traditional last resort that doesn't work in medicine. Probably time it was scrapped except for genuine immunodeficiency.

 

Why are these researchers using the CFQ and no objective measures, even a pedometer would be more useful?