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Dr. Whitington

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Dear Group,

I know that Dr. Gene Whitington is one of the doctors involved with research for PSC. I believe he diagnosed the disease in the 's son which led to the establishment of the foundation.

I recently had a phone call from an old friend that is a pharmaceutical rep for Remicade. He knows of our son's PSC and told me Dr. Whitington is a strong believer in the postive results of remicade and PSC. I missed this year's PSC conference because we were moving from NY to TX, but hope to make it to ville.

Can anyone give me the bottom line on the research findings of this drug for PSC?

I am not a frequent poster, but keep up daily with the group. A friend asked me why I torture myself reading the post everyday. I told her I think deep down I'm going to open up a message one day and there will be a huge breakthrough in getting closer to a cure. I'm a very impatient person, especially when it comes to my children and their well being.

Thanks,

Terry ( 's mom, diagnosed 3/2000 age 25 ).See what's free at AOL.com.

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We see Dr. Whittington out of Chldrens Memorial in Chicago and I believe Gene and are brothers. My son, Tyler is 9 and has Ulcerative colitis and PSC. We could not get the colitis under control, so they did suggest Remicaid infusions. We were hesitant because it is known to cause a type of cancer but the cancer normally occurs with those with Chrons and PSC not UC and PSC. It can also cause TB, I believe and it is made from mouse antibodies not human. Dr. Whittington said that despite the bad possibilities, it is a great drug to treat both of Tylers diseases and he and Dr. Brown (GI doctor) were insisting on it. However, miraculously after his most recent colonoscopy, the colitis is healing as a result of several drugs he is on (Prednisone, 6MP, Alo purinol and Azacol), he is also on Urso for the PSC. So, he did ot have to have the infusions after all. Both Dr, Brown and Dr. whittington are involved in a study to ascertain the correlation between PSC and UC. They have been outstanding and voluntarily call to see how Tyler is doing. I am very impressed with the explanations and time they spend with Tyler. And that is our story...

Ostos

jterry05@...

jterry05@...

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06/27/2007 12:20 PM

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Dr. Whitington

Dear Group,

I know that Dr. Gene Whitington is one of the doctors involved with research for PSC. I believe he diagnosed the disease in the 's son which led to the establishment of the foundation.

I recently had a phone call from an old friend that is a pharmaceutical rep for Remicade. He knows of our son's PSC and told me Dr. Whitington is a strong believer in the postive results of remicade and PSC. I missed this year's PSC conference because we were moving from NY to TX, but hope to make it to ville.

Can anyone give me the bottom line on the research findings of this drug for PSC?

I am not a frequent poster, but keep up daily with the group. A friend asked me why I torture myself reading the post everyday. I told her I think deep down I'm going to open up a message one day and there will be a huge breakthrough in getting closer to a cure. I'm a very impatient person, especially when it comes to my children and their well being.

Thanks,

Terry ( 's mom, diagnosed 3/2000 age 25 ).

See what's free at AOL.com.

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Hi ;

According to this recent paper, the efficacy of infliximab (remicade)

in PSC is " unknown " :

___________________

Curr Treat Options Gastroenterol. 2007 Jun;10(3):178-84.

Efficacy of infliximab for extraintestinal manifestations of

inflammatory bowel disease.

Siemanowski B, Regueiro M

Regueiro, MD Division of Gastroenterology, Hepatology, and

Nutrition, University of Pittsburgh Medical Center, 200 Lothrop

Street, PUH-C Wing Mezzanine Level, Pittsburgh, PA 15213, USA.

mdr7@....

Crohn's disease (CD) and ulcerative colitis (UC), collectively

referred to as inflammatory bowel disease (IBD), are associated with

extraintestinal manifestations (EIMs) in approximately 40% of

patients. Infliximab, a chimeric monoclonal antibody to tumor

necrosis factor-alpha, is effective for induction and maintenance of

remission of CD and UC. The role of infliximab for EIMs related to

IBD has been less studied, but it is likely as effective. The EIMs

may run a course that parallels IBD activity or may present

separately. The EIMs that parallel intestinal inflammation (eg,

peripheral arthritis, pyoderma gangrenosum, erythema nodosum, and

episcleritis) generally respond to infliximab. Therefore, treating

patients with IBD who have one of these EIMs will more often than not

improve the EIM. The EIMs that run a separate course from IBD are

more difficult to treat. Ankylosing spondylitis (AS), uveitis, and

primary sclerosing cholangitis (PSC) have variable responses to IBD

medications. Infliximab is efficacious for uveitis and is approved by

the US Food and Drug Administration for treatment of AS. The efficacy

of infliximab for PSC is unknown. The dosing schedule of infliximab

for IBD patients with EIMs should be induction doses with 5 mg/kg at

0, 2, and 6 weeks followed by every 8 weeks. Whether long-term

infliximab therapy is necessary to maintain remission of EIMs, as in

the case of IBD, has not been established. PMID: 17547856.

________________

There was a report that another tumor necrosis factor-alpha

inhibitor, etanercept (enbrel), was ineffective in PSC in a small

pilot trial:

________________

Dig Dis Sci. 2004 Jan;49(1):1-4.

A pilot study of etanercept in the treatment of primary sclerosing

cholangitis.

Epstein MP, Kaplan MM.

Division of Gastroenterology, Tufts New England Medical Center,

Boston, Massachusetts 02111, USA.

There is no effective medical treatment for primary sclerosing

cholangitis (PSC), a chronic cholestatic liver disease that usually

progresses to cirrhosis and liver failure. The aim of this study was

to determine the safety and efficacy of etanercept, an inhibitor of

tumor necrosis factor, in the treatment of PSC. Ten patients with

clinically active PSC were studied. All had elevated serum alkaline

phosphatase levels, cholangiograms that were diagnostic of PSC, and

liver histology consistent with PSC. Five patients had elevated serum

bilirubin levels, five had pruritus, eight had failed to respond to

ursodiol and/or methotrexate, and six had rapidly recurring dominant

bile duct strictures. Patients were to receive etanercept, 25 mg

subcutaneously twice weekly, for 6 months if there were no side

effects and for 1 year if there was evidence of efficacy after 6

months. Biochemical tests of liver function did not improve in any

patient. Mean serum bilirubin levels increased significantly, from

2.0 to 3.6 mg/dl (P = 0.026). Two of the five patients with pruritus

had resolution of pruritus during treatment with etanercept,

recurrence when etanercept was stopped, and resolution when it was

restarted, although there was little change in liver enzymes or

bilirubin levels. There was no decrease in the rate of stricture

formation and there were no side effects. Etanercept, at the dosage

used, was well tolerated but not effective in the treatment of PSC.

It may be helpful in treating pruritus due to cholestasis. PMID:

14992426.

________________

But it is now known that etanercept is NOT very effective in IBD:

________________

Curr Treat Options Gastroenterol. 2007 Jun;10(3):195-207.

Current and Future Anti-TNF Therapy for Inflammatory Bowel Disease.

Osterman MT, Lichtenstein GR

R. Lichtenstein, MD Hospital of the University of Pennsylvania,

University of Pennsylvania School of Medicine, Division of

Gastroenterology, 3rd Floor Ravdin Building, 3400 Spruce Street,

Philadelphia, PA 19104-4283, USA. grl@....

Anti-tumor necrosis factor-alpha (anti-TNF) therapy has become a very

important modality in the treatment of patients with inflammatory

bowel disease. A number of anti-TNF medications have been

investigated for this purpose, many via randomized controlled trials.

Infliximab, the most studied of these agents, has shown impressive

efficacy in the treatment of luminal and fistulizing Crohn's disease,

as well as ulcerative colitis. Adalimumab and certolizumab have shown

similar efficacy in Crohn's disease but have not yet been studied in

ulcerative colitis. Less impressive results were seen in randomized

controlled trials involving CDP-571, etanercept, or onercept for

patients with Crohn's disease. Thalidomide and CNI-1493 have been

evaluated only preliminarily in small, open-label pilot studies in

patients with Crohn's disease. The future of anti-TNF therapy in

inflammatory bowel disease is very bright, as exciting new

developments continue to be made at a rapid pace. PMID: 17547858.

________________

So, would etanercept be expected to be useful for PSC? There

definitely needs to be a controlled clinical trial of infliximab

(remicade) in PSC. I heard from Gene Whittington last July that such

a trial was planned as part of the STOPSC initiative:

https://web.emmes.com/study/psc/index.html

Best regards,

Dave

> Can anyone give me the bottom line on the research findings of this

drug for PSC?

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I work at the University of Florida in Gainesville and my son who was

diagnosed with PSC and UC in June 2005 and later informed that there

may be an overlap with AIH sees a doctor at Shands. Another doctor

who is in the school of medicine and was formally from Mayo in MN was

recruiting people for a study (which was a joint study with folks from

Mayo) using infliximab (remicade) about a year ago. I had a chat with

her and got the forms which required that to get on the study, he had

to stop taking one of his current medications (ursadiol or asacol,

can't remember which). I discussed with my son's doctor and he told

me that since my son is doing well on his current medication, he

wouldn't change it and so I listened to his advice and we never got on

the study. I don't know if that is a wrong decision but it is

difficult to make decisions on these issues sometimes.

Rita (Florida)

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