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Primary Sclerosing Cholangitis (PSC) - Online Support Group

Caution with Entyvio!


#1

Hello,
I wanted to share my experience over the last year. In June of 2017 I was started on Entyvio (Vedolizumab) for remission of Ulcerative Colitis. In February 2018 following routine blood work I was found to have extremely elevated LFTs and after liver biopsy was diagnosed with PSC. MRI showed mild to moderate fibrosis of my bile ducts. Devastated I started to try and understand as much as I could about PSC and did a lot of research. In my reading I found that in the initial clinical trial for Entyvio and in subsequent case reports there have been patients with cholestatic liver injury on the medication.
I immediately stopped the medication and also made some dietary changes. As of this month my LFTs are only mildly abnormal and my most recent MRI showed a normal liver! Both my hepatologist and gastroenterologist did not know of the cases of liver injury with Entyvio as it is a rare side effect. My improvement could be the Entyvio or something else however I felt it was important to share. Consult with your doctor about possibilities if you are on Entyvio.

From the Entyvio (Vedolizumab) website

  • Liver problems can happen in people who receive ENTYVIO. Tell your healthcare provider right away if you have any of the following symptoms: tiredness, loss of appetite, pain on the right side of your abdomen, dark urine, or yellowing of the skin and eyes (jaundice).

#2

SeaBehr,
Thanks for your post. I am glad you are doing much better and your LFT’s have normalized. I would encourage you to followup in 6 months with your hepatologist with labs. You need to be absolutely sure that it’s not PSC and that all is still good, which hopefully will be the case. I wish you the very best in the coming year.

Mark


#3

Same story with me. Started entyvio last year in October. Enzymes starting going up in November and drastically climbing and itching set in. It’s possible I had psc before , but I am definitely suspicious about the entyvio waking it up.


#4

Hi All,
This is very interesting. My daughter was started on Entyvio 2months before her PSC showed up. We were told that they were actually investigated it to treat PSC and that Entyvio couldn’t cause it. I still wonder about it because she developed Vasculitis in her left eye after starting Remicade and the doctors said that could have been a reaction to Remicade so she should not take biologics but that Entyvio was different because it targets the abdominal area. It’s all very frustrating!


#5

That’s exactly the reason why there is so-called phase IV clinical trials. Some side effects won’t be exposed in phase III trials until the new drug is on market, particularly for those patients with specific diseases. For PSCers, you just need to watch very closely when on any new drugs.
BTW, I’m kind of confused by your MRI results. MRI won’t be able to show the fibrosis of bile ducts. That’s not even the correct term. Good communication with your doctors is critical. Obviously you did a good job with that. Sometimes, you may need a second opinion.


#6

PSC-Mom while there has been no clinical trials to prove that Entyvio can cause PSC there have been a small number of patients who were in the clinical trials who had increased liver enzymes that resembled a “cholestatic picture” i.e. (Higher alkaline phosphatase, and elevated AST and ALT but as much as the alkaline phosphatase.) As is common, the authors of the studies don’t include much else in terms of specifics of what happens to those individuals who had the enzyme elevations in terms of follow up imaging, biopsies etc.)

In prelicensure controlled trials, rates of serum ALT elevations during vedolizumab were not reported, although instances of serum enzyme elevations were described. ALT elevations above 5 times the upper limit of normal (ULN) were said to occur in < 2% of vedolizumab and in a similar proportion of placebo recipients, and only rare patients had to stop therapy because of serum enzyme elevations. In the prelicensure trials, 3 patients were reported to have a severe adverse reaction of hepatitis, but the specific details were not given and there have been no case reports of clinically apparent, acute liver injury with symptoms or jaundice attributed to vedolizumab, but experience with its use has been limited. - https://livertox.nlm.nih.gov/Vedolizumab.htm

It looks like the the livertox page on Entyvio hasn’t been updated since 2015. Since then there have been case reports of cholestatic liver injury with Entyvio.

A total of 23 hepatobiliary events were observed among vedolizumab-treated patients, most of which were hepatic steatosis and transaminase increases. Five hepatic events were considered serious and vedolizumab was interrupted. Appropriate treatment resulted in resolution or near resolution of the liver abnormalities. https://www.wjgnet.com/1■■■■/full/v24/i23/2457.htm.

I’m not sure where you’re located at or when the last time you talked with your hepatologist was but the U.S. trial of vedolizumab and psc was stopped in March of 2017 before having anyone enrolled. I’m not sure if there’s any other trials in other countries or why this one was stopped.

DHC Yes, MRI can show fibrosis and PSC on imaging, you may know it as MRCP but it’s the same test just different names. Also, unfortunately yes, PSC is a fibrotic disease. The definition of PSC from the American Association for the Study of Liver Disease " Primary sclerosing cholangitis (PSC) is a chronic, cholestatic liver disease characterized by inflammation and fibrosis of both intrahepatic and extrahepatic bile ducts, leading to the formation of multifocal bile duct strictures."

I don’t want anyone to immediately revolt against Entyvio, that is not my intention with this post. I was just hoping to make sure other people with PSC knew of the possible side effects that have been shown in a small number of patients on Entyvio so that they could discuss with their hepatologist in case they had a situation similar to mine i.e. normal LFTs, no liver damage, then months after starting Entyvio damage shows up.

If you are on Entyvio and suspect anything talk with your hepatologist and gastroenterologist for a treatment plan that you are comfortable with. You can always suggest a trial of stopping the Entyvio, it’s not the only biological or treatment choice out there for UC. It will take close to 3 months to completely leave your system, so a trial of stopping for 6 months is what I think would be acceptable to determine if enzymes improve.


#7

The portion you cited also states that subjects with abnormal liver function is in a similar proportion of placebo recipients. So you never know its drug or the subjects, unless there is a specifically designed trial. As to that cholestatic picture, connecting it to PSC might be overstretched at this moment.
MRI can’t see fibrosis of bile ducts, as stated in your original post. It just can’t see that much detail. Technology does have its limit.


#8

Yes placebo patients can also get PSC in clinical trials. I’m not looking at just that study, I only listed that one because you don’t need to buy the article as with other medical journal sites. There are a small number of patients in multiple studies with a trend towards higher incidence of elevated liver enzymes in the Entyvio groups along with other case reports. I am more than happy to send you those if you would like.

I’m sorry but you’re mistaken. Yes MRI can see fibrosis and the U.S. guidelines state that you should be getting MRIs on an annual basis to track the fibrosis. If you still don’t believe me do an internet search, you’ll get the answer on any number of links on the first page.


#9

SeaBehr,
I must agree with DHZ on this point as well. MRCP can see “strictures” and “beading” of the bile ducts, but fibrosis of the liver is detected/measured by either a fibro scan or liver biopsy. I’ve never heard of fibrosis of the bile ducts. I’m always open to learning something new, but this one I’m not aware of.

Mark
PSC 2011 / Liver Transplant 2015


#10

There is no confirmed patient get PSC in clinical trials. Yes, there is abnormal liver function test result. But NO, there is no PSC diagnosis.
MRI can’t see fibrosis of bile ducts, period.


#11

Maybe try reading my references before replying with your opinion DHZ. I could be wrong but then so would the American College of Gastroenterology (i.e. the society that governs all gastroenterologists and hepatologists in America and certifies them as experts in gastroenterology/hepatology). Below is verbatim from their guidelines on PSC and the link to check for yourselves.

Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver and biliary tract disease that has a highly variable natural history (1). The pathogenesis of the disorder remains elusive, although the complications of the disease are a direct result of fibrosis!!! and strictures involving intra and extrahepatic bile ducts (1). -https://gi.org/guideline/primary-sclerosing-cholangitis/

Those “strictures” in the MRCP report IS the fibrotic tissue.

Also on the issue of PSC in clinical trials like I said there is nothing in the articles I shared to confirm PSC. Even then if Entyvio was causing sclerosing cholangitis it would be considered secondary sclerosing cholangitis. I could still have PSC only time will tell, but as I’ve said my imaging and enzymes have improved off of it which leads to improved outcomes. Like my experience though there are case reports of liver and bile duct damage on Entyvio with improvement after stopping Entyvio. While it has not yet reached what in research is called “statistical significance” there is a trend to higher incidence of liver damage on Entyvio and why livertox.org (a favorite reference on drug interactions for most hepatologists) and the Entyvio website both mention it.

If you have better references or credentials (M.D.) than mine please share. I’m open to an intelligent debate about statistics and research. Have a happy new year!


#12

Mark, to piggyback on SeaBehr’s explanation, PSC is an inflammatory condition of the bile ducts that results in scarring, aka fibrosis, of the bile ducts. This results in a cascade of issues with the following typical progression: bile duct fibrosis -> liver tissue fibrosis -> liver tissue cirrhosis. PSC bile duct inflammation tends to be patchy leading to its signature beading. In the context of PSC, the strings or strictures seen on imaging are a visualization of bile duct fibrosis.


#13

JTB,
Thanks for that clear description. Of course you realize I’m very familiar with PSC having almost died from it😊. I do though appreciate the tying of fibrosis explanation to the ducts as well. I always thought of the fibrosis and cirrhosis as only in the liver with strictures being in the ducts. Of course the ducts in miniature are in the liver as well. I’m sure some of this is being technical and all. Bottom line though is cirrhosis and eventual transplant when liver gets to the end of the line.

Mark


#14

You simply do not describe bile duct with the term of fibrosis. Bile ducts, just like your blood vessels, are made of mainly connective tissues (fibers), and endothelium, smooth muscles etc. Fibrosis is used to describe liver tissues. You may argue that you want to stick to use that on bile ducts. That’s fine and that’s your freedom. But that’s just not what we usually use. MRI can see scaring or beads or dilation by looking at the lumen of bile ducts. But it can’t see fibrosis there. That will need microscopy.


#15

I get it DHZ, but let’s not get all bent out of shape over this. We need to focus in this forum on helping one another to get through this disease providing good sound advice without getting all hung up in technical terms that may be difficult for some to fully comprehend. . We all should be approaching this from a layman’s perspective. Our descriptions at times may be a little off but we must gently correct each other knowing we are not medical professionals nor do we want any here taking over the conversation to make the patients look bad. Let’s move on from this topic and focus on patient care instead. We may not always say it exact but those of us who have been here a while pretty much know what the patient is trying to say or ask. I know we can all do better in this area.

Mark


#16

I’m gonna leave this topic with this last post.
I jumped into this thread because of way too much misinformation. It’s just unlikely that you can develop PSC within a few months. Based on what we know about this disease, it’s just unlikely. It’s true that certain things could be the cause of PSC, since we still know so little about it. We just can not be certain right now.
This disease is unpredictable as we all know. Any change of your condition could be the natural course of this disease or due to certain triggering factors we simply couldn’t find out.
We have to be patient with this disease. It’s only a small portion of our lives. We learn to live with it. Most importantly, we have to live beyond it.


#17

Totally agree. Seems we started to write at the same time:slightly_smiling_face:


#18

Mark, I know you are an old hand at this, but thought it important to clarify for any readers. Scarring begins at the bile ducts and eventually leads to damage in surrounding liver tissue. This is a fairly unique way towards liver failure and this puts PSC patients at a disadvantage in our current system as we often reach “end points” long before cirrhosis and a high MELD score.

DHZ, perhaps portal fibrosis, versus bile duct fibrosis, has more precision. It is my understanding that in PSC this is typically periductal fibrosis where fibrotic tissue surrounds and eventually obliterates the bile duct. The effects of this can be seen on imaging.

I think this is a useful topic. Vedolizumab is prescribed for IBD and IBD patients have higher odds of ending up with PSC. It is helpful to know that Vedolizumab can potentially emulate aspects of PSC and that there is a potential risk of false positive diagnoses.