GVHD in US, page-29

I've long viewed MSB's aGvHD product as a steroid replacement in acute medicine, only far superior, a multi organ rescuer. . 

I think MSB's cells have superior action because they support the body to heal in the natural way; if the body heals naturally you get that thorough inside out healing. This process has been observed and documented in gut and skin by respected clinicians who have published in prestigious journals. Currently, though, it's a very long process and difficult to achieve. 

The microbiome has emerged as crucial in GvHD. More diverse gut flora is linked to improved survival. Doctors are well onto this in clinical practice but there's evidence that even for the most potent probiotic to take hold you need to first heal the gut well. Steroids are known to be ineffective in inducing mucosal healing (Atreya et al, 2017)

There's recent evidence that even a short course of steroids can do harm.

Could steroids' Reign be coming to an End?

We know steroids are the most dangerous drug to take long term but even a short course can do damage and raise the risk of sepsis (Waljeee et al. BMJ. 2017). GvHD patients have a very high risk of infection, including sepsis. I've often wondered if steroids turn acute cases into chronic ones. The question we need to ask in dermatology is: If steroids didn't exist, would severe eczema even exist?  

Dr Marvin Rapaport is one of the leading experts on Red Skin Syndrome. He's published in prestigious journals and given lectures on how to diagnose RSS. The patient can look like a chemical burns victim. Dr Rapaport says these patients do not have eczema but are suffering from addiction to topical steroids. RSS is said to be rare but I believe it's rarely reported; there are 7000 members on the forum and Dr Rapaport is getting an 'avalanche' of enquires. RSS is said to result from 'overuse' and 'misuse' of steroids but ITSAN organisation reports cases resulting from just short term use, including a baby after just 10 applications. The cure is the cessation of steroids. When the battle with RSS is over there's often (but not always) a complete cure of the original atopic eczema. 

This is relevant to MSB because chronic GvHD is on the rise in pediatrics (Arai et al.2015)  The biggest predictor of cGvHD is prior acute. I never thought of steroids in medicine as being addictive in that they give a 'high' but some patients do talk about that feeling (A wry observation about the opioid crisis was recently made on one GvHD forum).  I wonder if some people are more susceptible than others and can become dependent very quickly. 

There's a drug approved for cGvHD based on a p2 single arm study, but it doesn't seem to be steroid-sparing,  According to Hill et al only 5/42 patients on the trial were able to discontinue steroids during the course of the study. 

Microbiome in GvHD and Other 

Fecal microbiota Transplant has now been accepted into mainstream for conditions other than c.diff. It has also been done in SR-Gvhd. It's not just the idea of using a healthy donor to cure an unhealthy one; it puts the microbiome and the gut at the centre of disease.

A clinical trial in ulcerative colitis showed promising results. (Paramsothy et al. Lancet, 2017). What I took from reading the study was that even for what is considered the ultimate probiotic, better results are achieved with less inflammation. As Borody said years ago, bacteria won't adhere well to inflammation. You can change the microbiome quickly but it's difficult to make it stick. 

Prof Tim Spector a rheumatologist at Kings College London was quoted in an interview originally with 6minutes.com.au. He says we should expect to see clinical trials planned in FMT for RA soon: "There's a good chance that what works in colitis is also going to work in rheumatoid arthritis." The efficacy of dietary therapy in children with severe JIA (Berntson et al, 2015) imo gives weight to what Spector says. Berntson says the gastrointestinal canal should be studied in these patients. 

Methotrexate is the anchor drug for RA. Many drugs, including the new biologics, are paired with it. Its GI side effects are well documented, even in a low dose (Salliot & Van der Heidge, 2009). I'd say there's a probability that even a person who has suffered from severe bowel disease and later develops inflammatory arthritis will be offered MTX. That's pretty much all they have that's steroid-sparing. 

There's a concern about doing FMT in patients who are immune suppressed. I previously mentioned exclusive enteral nutrition (EEN) as a good adjunct therapy. This is said to favourably alter the microbiome. It can't be kept up for long as the child has to temporarily give up eating. It can kick in with the power of high dose steroids but its effects often wear off quickly once stopped. 

Regensburg University Hospital, Germany says EEN is a good a substitute for systemic steroids.  The following quote is from their workshop on GI-GvHD, 2015:

" Since pediatric Crohn’s disease andGI-GvHD have many features in common including various treatment options,several years ago we started exclusive enteral feeding in GI-GvHD using thesame enteral formulas as employed in pediatric Crohn’s disease."

Lafferty et al 2017 reported on a study in paediatric CD comparing remission rates between steroids and EEN. Results were 86% for EEN v 54% for steroids. Best results obtained when EEN was used as initial therapy (P= 0.004) and in children over 10 (p= 0.04) EEN showed, as have other studies, superior mucosal healing to steroids. 

Maybe it's worth considering what is done and what is not done with children in the early stages to get the best results. There's evidence that the fire with fire approach may not be the best therapy in these patients.  There's a good case for giving MSB's cells first line without compromising safety but the issue isn't efficacy or safety; it's the expense of the product. 

I often wonder how this myth of the incurable chronic disease took hold, particularly in children.  I think it has a lot to do with the widespread use of steroids and methotrexate and imo the writing's on the wall for both of them.

 

  

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