Thalidomide and Crohn's (An Update): 3 Patients in Remission Long Term Study

I wrote this blog post about thalidomide a while ago and it seems as if now thalidomide may possibly be a treatment for Crohn's. This recent study in the July 2014 edition of Journal of Clinical Gastroenterology (if you want something to read before bed) found 3 patients who took thalidomide. All patients achieved a complete clinical remission and showed endoscopic evidence of healing. The dosage amount that patients took was between 50 and 150 mg/d. Treatment ranged from 4-8 years (which is very long for a clinical trial). 2 patients had perianal fistuals and the other patient had upper gastrointestinal Crohn's lesions and an inflammatory ileocolonic stricture. There were some side effects such as drowsiness, peripheral neuropathy. Peripheral neuropathy was reported in half of the patients (however is reversible once the medication is stopped). The rule seems to be once patients have a cumulative dosage of 50 grams of thalidomide then neuropathy occurs. Patients also have to be careful in not trying to conceive during the treatment or 6 months after ending the drug.

In the same issue of Journal of Clinical Gastroenterology is a letter from someone discussing the possible future for thalidomide. In one study with 12 male patients who had low doses of thalidomide (50-100 mg) daily 70% of patients had a response with 20% getting to remission in 3 months. In another study however when the dosage was increased to 300 mg each night 75% of patients responded within 1 month and 40% were in remission by 3 months. In a multicenter, double blind, placebo controlled (these types of studies are considered the gold standard when doing clinical trials) in 56 children showed that 46% of children achieved remission compared to a 12% placebo. The patients who were given the placebo were given thalidomide 52% of these patients achieved remission.

Thalidomide which was thought of as one of the worse drugs ever created caused some serious birth defects for women that took the drug. These days thalidomide is making a come back and is used to treat a wide range of diseases such as multiple myeloma, cancers, HIV, rheumatoid arthritis. Now it looks like Crohn's may have a role for Crohn's patients especially for patients that are having a flare up for a short period of time. Also patients who are older with Crohn's would benefit since they are not likely to conceive. I hope more studies can be done to show how this drug could help many people.  

Weekend Links: Smoking, Fecal Transplants for IBD, Remicade Generic, Crohnology, and Lasers for IBD

Smoking and Crohn's 
     This article studied people who smoke and use to smoke and found that patients who smoked required more treatment that non-smokers. Smokers were more likely to have strictures, receive steroids, immunosuppressants, or on anti-TNF drugs (this tells me the smokers had more moderate to severe cases of Crohn's). Last year I did a post showing that showed that smokers were more likely to require surgery than non smokers (80% increase actually). Also in that post I mentioned that at 10 years the need for repeat surgery was only 41% for nonsmokers and 70% for smokers. The policy recommendation would be to obviously stop smoking.

Fecal Transplants Treating Bowel Diseases
Early data from a study out of Canada shows that fecal transplant may help people with inflammatory bowel disease (IBD). Canada actually has the highest rate of Crohn's disease in the world. The study plans to look at 120 people (as I write this 60 patients have been treated so far). Patients are using enemas in this trial. Dr. Paul Moayyedi said that some patients have done extremely well so far and one patient was in remission for 6 months. Patient Anna Fernande has been in remission since last fall (she has ulcerative colitis). Personally I believe fecal transplants will help the people with ulcerative colitis more than Crohn's. Perhaps researchers can study why this is the case.

Remicade Going Generic?
It looks like Remicade might be going generic in Europe at least. Drug companies are given a patent to market and sell a particular drug for a decade. However, after this time period a drug then become a generic and usually the cost is substantially less. The generic and the real drug made are on the molecular level however in practice and be a little different. However, with biologics this is trickier to do since you aren't replicating a pill. Inflectra would be what is known as a biosimilar to Remicade. What is interesting is in a trial of people with rheumatoid arthritis patients actually did better under Inflectra (the biosimilar) than Remicade the more expensive drug! Inflectra also showed that is had similar side effects as Remicade. Estimates show that biosimilars could save patients $23 billion by the year 2020. However, one issue is this would only be approved in Europe and not the United States. Perhaps we should have some reciprocal approval program to where if a drug is approved in one country it can be approved in other countries.

Crohnology: Crohn's Patients Helping Other Crohn's Patients
This is a pretty good article on a website Crohnology (which I am a member of) were people with Crohn's and ulcerative colitis discuss what they prescriptions they are on and how they deal with Crohn's. The website is powerful in terms of you can track your health everyday and get a text message that asks how you are doing. Crohnology was founded in 2011 and already has over 4,200 people. Patients helping others is wonderful and there may be important knowledge in Crohnology that researchers could use to better understand this horrible disease.

Laser Peers Through Intestinal Walls
A new laser could be used to help determine if a patients needs a colonoscopy or biopsy. The technology can give doctors a more focused approach to where the biopsy needs to take place instead of guessing.

Weekend Links: ChemoCentryx Drug Crohn Failure, Chronic Bowel Disease Increases in UAE, Vedolizumab Remission

ChemoCentryx SHIELD-1 for Verniron Fails
     The drug company ChemoCentryx that their drug verciron (chemokine receptor CCR9) really didn't help patients with Crohn's disease. The clinical endpoint is was whether or not patients has a decrease of at least 100 points in their CDAI score after 4 months. 608 patients were enrolled in the study (which is not only timely but very costly). Vercirnon was suppose to launch in 2016. Vercirnon was an oral drug and had lower costs associated with it since it wasn't a biologic which are much more expensive according to this article.

Bowel Disease Increasing In UAE
     It appears that doctors in the UAE are seeing a rise in the amount of inflammatory bowel disease. Dr. Nathwani has said he has seen a 10%-15% increase since 2007. Dr. Nathwani sees about 3 or 4 new patients every week with IBD every week. Dr. Kataa says that white people who are young are a higher risk of getting it. Perhaps one theory which I might believe to be true is the clean hypothesis which basically states that autoimmune diseases are on the rise because we might be in fact too clean which explains why developed countries have seen an increase in autoimmune diseases while undeveloped countries with more parasites have fewer cases of autoimmune disease. The pigworm drug trials will shed more light onto this.

Vedolizumab Helps Remission for Ulcerative Colitis
According to this study from the New England Journal of Medicine. The medicine actually had better results for patients with ulceartive colitis than Crohn's disease. In patients with ulcerative colitis 42% were in clinical remission after one year according to this article. The remission rate for Crohn's patients was only 15%. This is a very low remission rate for Crohn's. What would be interesting to see if the 15% of Crohn's patients had anything in common.

Mid-Week Links Part II: Probotics Don't Help Crohn's, Fecal Transplant Cures 97% of C Diff, Pill Camera Approved For Crohn's

Probiotics Doesn't Help Flares For Crohn's
     This study showed that taking probiotics doesn't help Crohn's patients. 47% of the people who took probiotics had relapsed while 53% of the patients in the placebo group relapsed. Really there was no statistical difference between the two groups.

 Fecal Transplant at Mayo: 97% Effective in C Difficile
    This study out of the Arizona Mayo Clinic (they have branches all over the United States) showed that 97% of patients who received a fecal transplant got rid of their c difficile. A majority of patients noticed an improvement in 3 days. The study was only done on 31 patients however this is another data point showing fecal transplants are effective! Hopefully, we can see in the future if fecal transplants can help things like ulcerative colitis, Crohn's, Parkinson's disease, multiple sclerosis, autism, obesity, and maybe even depression.

Pill Camera Approved For Crohn's
     The FDA cleared the PillCamera SB 3 for Crohn's disease and anemia. I believe the SB stands for small bowel. What is interesting is that 75% of Crohn's patients have lesions in their small bowel. What is even more interesting is that after 3 months of using the camera 62% of patients changed treatment and 40% of patients changed medication. Basically you just take the pill camera with a glass of water and it takes pictures of your small bowel and sends them to your doctor (you wear a small belt and recorder). More than 2 million people have already taken the PillCamera which is interesting. The risks are pretty minor. The risk of retention is less than 3% for Crohn's patients.

Mid-Week Links: Heat and Crohn's Flares, $1.5 Million Crohn's Research, MicroBiome in Crohn's, and Implantable Device For Crohn's

Heat Waves and Crohn's Flares 
     This article from the August issue of The American Journal of Gastroenterology shows that a heat wave increased IBD flares by about 5%. This is interesting because I live in both a hot and humid state. What would be interesting is it there was a worldwide study looking at patients from various countries all over the world and looking to see if warmer temperatures in general caused flares. I know someone who is dating a guy who has Crohn's for a long period of time and his metric is every 4th of July he knows he will feel bad. Maybe there is some truth to this study.

Kenneth Rainin Foundation Awards $1.5 million For IBD Research
    The Kenneth Rainin Foundation which is a non-profit created by Kenneth Ranin who was an entrepreneur founded an instrument company and created a foundation to support the arts, sciences, and health research. The foundation actually established an IBD center at UCSF. Ranin has a daughter (Jennifer) that was diagnosed with ulcerative colitis (she also has a Ph.D). The $1.5 million will be used to invest in research that can help understand causes and cures for inflammatory bowel disease (IBD).

Distinct Microbiome in Crohn's Intestinal Mucosa
      Researchers examined Crohn's patients who were undergoing surgery for either Crohn's or for reasons other than inflammatory bowel disease. What is interesting is that patients with diseased Crohn's tissues had more than several hundreds times the amount of bacteria compared to patients with normal tissue. What this really would say is that there are different subtypes of Crohn's disease. Hopefully this research will result in more targeted therapies in the future.

Implantable Biologic For Crohn's Disease?
     A California company called SetPoint Medical has developed a very small device that can be implanted and somehow mediate the immune system to reduce inflammation for people with both rheumatoid arthritis and Crohn's disease. Below is a picture

   

Weekend Links: Methotrexate Safe In Long Run, Mouse Model, Fecal Transplants, and Crohn Cancer Risk

Methotrexate Safe In Long Run 
A study shows that methotrexate is safe for Crohn's patients in the long run (and also beneficial). 63% of patients saw benefits after 1 year, which decreased to 47% at 2 years, and at 5 years only 20% of patients saw benefits.

New Mouse Model To Study Crohn's disease 

Researchers at McMaster University in Canada are using mice that have e-coli in them to study how inflammation affects the mice.

Crohn's Cancer Risk

In a study done in Norway the mortality and cause of death was looked at in Crohn's patients. The study looked over a 20 year period after patients were initially diagnosed with Crohn's. The study found no significant difference between Crohn's patients and regular people (about 14% of Crohn's patients died as opposed to 13% of the control group). 

FDA Backing Off Fecal Transplants

In a wise move by the FDA it said this past week it would no longer need agency approval before performing fecal transplants. I am glad to see the FDA did something wise for once. I estimated over regulating fecal transplants would have let thousands of people die and left even tens of thousands or more people in pain.

Marijuana 45% Remission in Crohn's Disease and 90% Clinical Response Rate: Why is Marijuana Illegal?

A recent study came out showing that cannabis (marijuana) may help relieve symptoms in people with Crohn’s disease. A complete remission was achieved in 45% of patients while a clinical response was seen in 90% of patients. These numbers would put marijuana on par with Humira or other biologics, however without the possible side effects and for a small fraction of the cost. 

This isn’t the first time there has been this same finding. In 2011 this study was done that 70% of patients using cannabis had a positive effect and possibly may reduce the need for surgery. Nearly 87% of the patients were male. I am curious to know if cannabis would have a different effect in women as opposed to men. Patients with Crohn’s disease often need surgery. However, after they have surgery the risk of having surgery decreases (depending on how severe their Crohn’s is). What is interesting is both of these studies were done in Israel. One problem is that in the United States cannabis is illegal under federal law even though certain states have legalize it. Federal law is superior to state law and at any time people could get thrown in jail for using cannabis.

What is interesting is that 48% of Crohn’s patients have used cannabis during their lifetime according to this study which is only a little higher than the 42% of people in the United States that have used it during their life time.  

Marijuana may not only reduce symptoms in Crohn’s but also multiple sclerosis, chronic pain, rheumatoid arthritis, and other awful disease. The website NORML has a great review of the scientific literature here (and they say potheads are not organized).

The United States should let people with medical issues be able to consume cannabis. Some people claim that smoking cannabis will increase lung cancer. However in one of the largest studies ever done (they looked at people over a 25 year period and couldn’t find any significant increase in risk of lung cancer). Interesting that cannabis may cut the growth of lung cancer. 

What is interesting is that according to a Pew Research poll about 52% of people find that marijuana should be made legal. In 1980, only 24% of people believe it should be legalized which increased to 32% by 2002. Over time I believe this will increase. For people suffering from a chronic illness such as Crohn’s disease, multiple sclerosis, and other awful disease marijuana may help manage these symptoms.  I would be okay with the government legalizing marijuana for medical use which would be much safer than individuals having to go to drug dealers (in states where it is not legal). I personally would not use marijuana until it was okay to do so under federal law. However, if things got really bad I would be open to the possibility. We have to remember that more people die from smoking, drinking, and even eating. Virtually no one dies from using cannabis. What is even worse is that since marijuana is illegal in the United States scientist and researchers can’t study it (why research is done in Israel). The federal government needs to stop harming people and let people use cannabis for medical reasons.  For the people that don’t want people using cannabis I would ask them one question. Have you ever lived with or known someone with a chronic disease?

Olmstead County, Minnesota 1970-2004 Crohn’s Study

I saw this recent saw this article in the Journal of Gastroenterology (my night time reading) that studied a group of people from Olmsted County, Minnesota. The study is ongoing and looked at people from 1970-2004 (updated from 2001). The study concluded that the cumulative probably of having major abdominal surgery were 38% at 5 years, 48% at 10 years, and 58% at 20 years.  The major factors that were significantly associated with major surgery were being male, smoking, early steroid use, and penetrating disease behavior. What seems to be positive though is that if you look at this chart that shows the cumulative risk of having surgery after being diagnosed in different decades.  In recent times it seems that the people who were diagnosed in the early 2000’s who are a little below 10 years from diagnosis have the lowest risk out of all the decades of having to have surgery at around 35% (which is down from 60% which is was in the late 1970s). Also remember Humira was not introduced for Crohn’s until February of 2007 which may bring down the requirement for surgery even more. My gastro doctor had told me one time that with Humira he was seeing fewer and fewer patients in the hospital and fewer requiring surgery which fits the data. What was also interesting is that people claim Crohn’s has a genetic component to it (however even my gastro doctor said none of his patients had family members who have it and neither do I) and the data in this graph supports that as close to 86% of patients have no family history of inflammatory bowel disease.

This data makes me feel a little bit better. With the cost of genome analysis going down it might be interesting to see if certain genes affect who has to get surgery or multiple surgeries. Although the odds are by definition I will need surgery I think I will be able to handle this and hope it is years away when the technology will improve and perhaps down without a scratch with NOTES as I mentioned in this post. I will be honest the thing I am scared of most of having an ostomy bag.  I know other Crohn’s and ulcerative colitis patients worry about it and I would even be okay with a temporary one if I had to but a permanent one would scare me just a little bit.  

Crohn’s and Depression

I saw this recent story of a young man named Michael Isreal who was only 20 years old who suffered from Crohn’s and also suffered from prescription drug abuse. He committed suicide in May 2011. He was an architecture major at University of Buffalo. He suffered Crohn’s since he was 12 years old.

Once Michael turned 18 his prescriptions started to change. He took pill after pill and they never fixed his Crohn’s. Michael was taking 21 pills per day. Among these drugs were hydrocodone which can become addicted I am curious if he ever took Humira or Remicade which has actually helped people. He told his father about his addiction and enrolled in a detox program (however the detox program was out of beds). Right after this is when Michael Isreal took his life at only 20 years old.

In light of Michael’s death the family is pushing for the Internet System for Tracking Over Prescribing Act (I-STOP)  which would set up databases to give doctors information on prescription drugs that patients take. This would just create an underground market for drugs like hydrocodone and other pain medications which would make the problem worse. If anything we should be allowing more people to use these type of drugs in order to treat the addiction people have. If people really want to take their own life they will. If you make it harder to use prescription drugs people will commit suicide in other ways.

I did some research on any links between Crohn’s and depression or other mental illnesses. In this study found that Crohn’s patients had a greater chance of having psychiatric disorder and more had depression then the controls. Personally when I was younger I use to see a psychotherapist who helped me through some self esteem issues however that was when I was a young adolescent. The only other time I really filled down was right after I got Crohn’s. At first I had no idea what I had and when I was in the hospital felt good and then when I came out came to the realization of what I had and got down knowing I had a life long illnesses. A few of the first nights I cried and was kind of blue. Over time I came to realize I have to live life to the fullest and not let Crohn’s get in the way. After Humira I felt like I never had Crohn’s.

In this study it was found that lifetime prevalence for Crohn’s patients is 29% which is higher than ulcerative colitis (21%) or cystic fibrosis. It should be pointed out that this study was done in 1989 which was before Humira, Remicade, and other biologics were introduced. In an odd way if you get Crohn’s now is the time to get it given all the technological advances that have been made.  This doesn't even include the future things that will be discovered or created

I wonder if any genes are related to Crohn’s and depression. This would be an interesting study for researchers to undertake. Also who knows what advances they might make in treating depression. I have a feeling studying the genome, understanding of inflammatory bowel diseases, and understanding the immune system better will give patients a better shot of turning their frown upside down.