Hey folks just checking in. I haven't commented very much since joining last year but I have been "listening" and I certainly appreciate everyone's input.
What's new with me is that I started URSO at the first of this year. My Alk. Phos level dropped from 400 to about 200 (based on two tests - I get them quarterly). I know that URSO has not been proven to change any outcomes or delay liver failure, so I'm not sure what to think about the improvement in the numbers. Anyone have some perspective on this?
Also, does anyone have suggestions on how to find a clinical trial? I did some looking around a few months ago, but it seemed really difficult to find something in the right time and location.
About ALP drop: I think you concluded it appropriately. That was exactly what I would have said too.
There are some additional Urso trials or combination trials so maybe they show done effectiveness.
Until some new treatments are approved by FDA (such as nor udca), I think oral vancomycin is the most promising treatment to use.
A big focus recently has been ALP and its influence on outcome. We've had two retrospective trials bundling the data from multiple prior Urso trials. One trial compared the rate of end points for PSC patients with normal ALP compared to the rate of end points to non-normalizers. The other trial did the same thing but expanded the normalizer group to those less than 1.5 times the normal upper limit of ALP. Both trials found that those in the normalizer group experienced far fewer end points compared to the non-normalizer group at all time intervals.
The retrospective trials didn't focus on Urso, but a number of doctors subsequently provided additional analysis by further dividing the normalizer and non-normalizer groups into those that used and did not use Urso. Of those not using Urso, roughly 30% were spontaneous normalizers (they didn't do anything to normalize). Of those in the Urso group, roughly 40% were normalizers, suggesting that roughly 10% of the PSC population achieves ALP normalization due to Urso. Regarding outcomes, the Urso normalizers fared just as well if not slightly better out to 10 years compared to the non-Urso normalizers. This includes the high-dose Lindor subjects - the high-dose normalizers did very well but this was offset by the high rate of end points of the Urso non-normalizers.
The takeaway is that we can improve our outcome considerably by getting ALP down to near-normal levels. A small subset of the PSC population can achieve this normalization of ALP through the use of Urso.
My opinion: if Urso dropped your ALP from say 600-400 and if it wasn't helping with any symptoms, it probably isn't worth taking. We don't have any evidence to suggest that a high ALP reduced to a still high ALP has any influence on outcome. In your case, Urso may have played a role in getting your ALP down to 200 which is very near the lower rate of end points 1.5 upper limit mark used in one of the studies. I'd say this is a good place to be.
Kayakdave,, regardless of what decreased the alp, I am glad yours got cut in half. That is a wonderful step in the right direction.
Thanks all for the helpful replies. It is hard to know what to do at this point. My MRIs over several years show increased scarring and some tube narrowing, but I haven't had any symptoms yet (at least ones I'm sure are from PSC). The bilirubin levels have never been elevated. Should I be more proactive and try oral Vanc (thanks Ted for that input)? It seems like it might be a good match to take URSO with Vanc since they act in different ways, with one helping to ease the impact to the biliary tubes (presumably) and the other acting in the digestive tract to hopefully cut off the inflammation mechanism. Of course I will raise this with my liver doc/transplant specialist, but chances are he will have to research all of this.
I think if I were you, I would explore oral vancomycin, or local clinical trial.
If you live near Atlanta, at least OCA phase 2 trial is available. FDA gave it already special breakthrough designation for another liver disease (I think it is in final phases for PBC and Nash).
For oral vancomycin, you need to find doctor who is familiar with it or willing to learn (eg talk to specialists at Stanford U, or somebody like dr Shah in New Orleans).