Qing Dai, A Chinese #Herb & #Acupuncture Clear Ulcerative #Colitis - Good Read

This is good news for people looking for an alternative therapy option for hard to treat cases of ulcerative colitis (UC).  Read the case about the man with UC under the Clinical Highlight section of this article.  It's hopeful in my opinion.  

My $0.02 - It's nice to see herbal forms of medicine being tested clinically and seeing the results published in known journals.  I'd like to see a larger study though.  The 1st thing a skeptic would point out about this research is the size of the study.  It's way too small, but not small enough to say that the results don't show significance.  There just needs to be larger clinical studies being conducted to make an impact.  The more participants that have a beneficial result, the more noteworthy the findings will be.  Size matters in this case, especially since TCM and naturopathic medicine are not recognized as effective in the medical community........ still.  You would think that by now alternative approaches of treating diseases would be accepted more than they are.  Unfortunately the pharmaceutical presence is all we can see and hear because the industry's ability to market their drugs.  

When we are faced with a choice in respects to treatment (alternative approach vs. conventional), we have to take into consideration the two types of areas of medicine and the facts surrounding them.  This part is simple.  Large markets get more exposure.  More exposure leads to something being talked about more, used more, and becoming the popular choice that is opted for the masses. Who has never heard of Cymbalta, Humira, Lunesta?  If you have a tv, you've heard of at least one of these drugs.  Are the drugs that we hear about on a constant basis a better choice than the little guy that doesn't have the multimillion dollar advertising budget? You make that decision.   Research and figure it out.

Chinese Herb & Acupuncture Clear Ulcerative Colitis - New Research [814] | Acupuncture Continuing Education News | Acupuncture News:

New research finds a very powerful Traditional Chinese Medicine (TCM) herb effective in resolving ulcerative colitis. The patients examined in the study published in the World Journal of Gastroenterology suffered from intractable ulcerative colitis and were unresponsive to conventional drug therapy. After use of the herbal medicine, 6 of the 7 patients in the study were able to completely discontinue the use of anti-inflammatory medications. This included the use of aminosalicylates, corticosteroids and azathioprine. Endoscopy and symptomatic responses showed everything from significant clinical improvements to a complete resolution of the condition.

Herbal Powder
The patients orally self-administered 1 gram of Qing Dai (Indigo Naturalis) powder, 2 times per day for 4 months. The results of the herbal program demonstrated significant clinical and objective improvements such that 6 of the 7 patients completely discontinued the use of prednisolone, a corticosteroid used to control ulcerative colitis. The researchers examined Qing Dai to learn more about its effective mechanisms of action. Using electron spin resonance, they discovered that Qing Dai has potent hydroxl radical scavenging activity. This discovery prompted the researchers to recommend further investigation into the mechanisms of Qing Dai’s anti-inflammatory effects.

This research coincides with other recent research demonstrating that acupuncture and herbal medicine are effective in the clearing of chronic ulcerative colitis. Published in the Clinical Journal of Chinese Medicine, the study showed that a combination of herbal enemas consisting of Ku Shen and Bai Tou Weng combined with an acupuncture treatment regime was significantly more effective than taking antibiotics for resolving ulcerative colitis.

The Qing Dai study examined the oral administration of Qing Dai in its powdered form. Qing Dai has received a great deal of attention in modern research. One recent research study found that I3M, synthesized from the indirubin found in Qing Dai, downregulates cancerous tissues when applied topically to oral cancer. This shows great potential for the treatment of oral cancer. Historically, TCM documents Qing Dai as an important herb in the treatment of ulcers in the mouth and tongue. TCM also documents the use of Qing Dai as a topical paste for the treatment of acne and topical ointment for the treatment psoriasis. HealthCMi recently published instructions on how to prepare the anti-acne topical paste in its blog section. Visit the Healthcare Medicine Institute's blog to learn more.

The I3M study cited the TCM formula Dang Gui Long Hui Wan as an historically important herbal compound for the treatment of chronic myelocytic leukemia. Many sources include Qing Dai as one of the ingredients in this formula that contains Dang Gui, Long Dan Cao, Zhi Zi, Huang Lian, Huang Bai, Huang Qin, Lu Hui, Da Huang, Qing Dai, Mu Xiang, She Xiang and Sheng Jiang. The researchers suggest that the indigo dye found in Qing Dai is partially responsible for the herbal formula’s efficaciousness given the modern research demonstrating that indirubin powerfully inhibits several types of human cancer cells. The Qing Dai researchers noted that modern studies demonstrate that indirubin has anti-inflammatory effects by suppressing interferon-alpha, interleukin-6 and nuclear factor. They added that Qing Dai has been shown to exert anti-inflammatory “effects on human neutrophils based on its ability to suppress superoxide generation.”

Clinical Highlight
The Qing Dai study highlighted specific clinical results of its participants. One patient vignette was of a man suffering from ulcerative colitis with hematochezia, the passage of fresh blood through the anus. This patient had taken antibiotics and prednisolone to control the hematochezia. However, he was unable to reduce the dosage of prednisolone without the return of hematochezia. Over time, the patient needed to increase the drug dosages to maintain clinical results and he showed no clinical improvements in his baseline condition. After 3 years, he began the Qing Dai treatments and after one month the hematochezia resolved completely. Objective testing also showed a marked decrease in serum C-reactive protein levels. The patient was able to discontinue the use of all drugs. Endoscopy revealed that his ulcers completely disappeared. A follow-up confirmed that the therapeutic effect of Qing Dai therapy lasted for more than 2 years.

The researchers note that other related research finds important clinical results from the use of Qing Dai. Yuan, et al, discovered that Qing Dai enemas are clinically effective for the treatment of chronic hemorrhagic radiation proctitis. Given the recent research combining acupuncture with herbal medicine demonstrating that enemas of Ku Shen combined with Bai Tou Weng are effective for the treatment of ulcerative colitis, it may be consistent that adding Qing Dai to the enema will enhance its therapeutic effects.

Distinct from Qing Dai used as a one herb formula for the treatment of chronic ulcerative colitis is its use within herbal formulas within the scope of Traditional Chinese Medicine (TCM). Differential diagnostics within the TCM system recognise Qing Dai’s appropriate application for this biomedically defined disorder in cases of Heat in the Blood, Damp Heat and Heat and Toxins. However, some clinical presentations of chronic ulcerative colitis may be due to cases of cold and deficiency. In these instances, herbal medicines with very different biological functions may exert more effective clinical actions for the treatment of chronic ulcerative colitis.

How serious is this research? Below is an image of three colon wall sections that are inflamed due to chronic ulcerative colitis. The image speaks to the importance of integrating TCM herbal medicine into the healthcare system.

Colon wall inflamed from ulcerative colitis

References:
Suzuki, Hideo, Tsuyoshi Kaneko, Yuji Mizokami, Toshiaki Narasaka, Shinji Endo, Hirofumi Matsui, Akinori Yanaka, Aki Hirayama, and Ichinosuke Hyodo. "Therapeutic efficacy of the Qing Dai in patients with intractable ulcerative colitis." World journal of gastroenterology: WJG 19, no. 17 (2013): 2718.

Clinical observation on treating chronic ulcerative colitis with retention enema by Baitouweng Kushen decoction and acupuncture, Clinical Journal of Chinese Medicine, 1674-7860, 2013.

Lo W-Y, Chang N-W (2013) An Indirubin Derivative, Indirubin-3′-Monoxime Suppresses Oral Cancer Tumorigenesis through the Downregulation of Survivin. PLoS ONE 8(8): e70198. doi:10.1371/journal.pone.0070198.Editor: A. R. M. Ruhul Amin, Winship Cancer Institute of Emory University, United States of America.

Yuan G, Ke Q, Su X, Yang J, Xu X. Qing Dai, A traditional Chinese medicine for the treatment of chronic hemorrhagic radiation proctitis. Zhong De Linchuang Zhongliuxue Zazhi. 2009;8:114–116.

Lin YK, Leu YL, Huang TH, Wu YH, Chung PJ, Su Pang JH, Hwang TL. Anti-inflammatory effects of the extract of indigo naturalis in human neutrophils. J Ethnopharmacol. 2009;125:51–58.

REDHILL BIOPHARM - News -> RHB-104 - Possible Breakthrough Treatment for Crohn's Disease

I get so excited when I read about this possible treatment, RHB-104, for Crohn's!  I've been watching this drug for over a year now.  This is a  treatment that if approved by the FDA, I will be jumping on it as soon as it becomes available.  No doubt!  This is the kind of treatment we need.  Everything else just treats symptoms.
So, why is this so exciting?  If you read current research about what causes Crohn's disease, you will see that researchers are leaning away from considering Crohn's disease an autoimmune condition.  They have found that there is an underlying cause for the immune response to activate.  Crohn's is said to be caused by a combo of 3 factors - Immune system abnormalities, environmental influences and bacteria.  I just wiki'd Crohn's disease and this is what is said about what is believed to be the cause - "Crohn's disease is caused by interactions between environmental, immunological and bacterial factors in genetically susceptible individuals.[4][5][6] This results in a chronic inflammatory disorder, in which the body's immune system attacks the gastrointestinal tract possibly directed at microbial antigens.[5][7] While Crohn's is an immune related disease, it does not appear to be an autoimmune disease (in that the immune system is not being triggered by the body itself)."
What this means is that people that have Crohn's disease do not have the immune system capabilities to destroy a form of bacteria that have been introduced into the body at some point in time.  As research has indicated, a large number of people with Crohn's disease happen to have the MAP bacteria in their body somewhere.  The exact location of the bacteria is not known at this time.  Who cares where it is, as long as a treatment is available that will destroy it is my opinion.
See why this makes me super hopeful?  If Crohn's is caused by this MAP bacteria & if this new combination antibiotic eradicates the MAP bacteria from people with Crohn's disease, this could be the answer to the Crohn's disease epidemic!  Can someone say CURE :)
Wouldn't that be glorious?  

Clinical trial for a new antibiotic therapy for Crohn’s treatment started:

Crohn’s disease is an inflammatory bowel disease which may affect gastrointestinal tract from mouth to anus, and has a wide variety of symptoms. Mycobacterium avium subspecies paratuberculosis (MAP) is believed to be associated with Cronh’s disease. Professor Dr. Saleh Naser, UFC College of Medicine, believes that MAP is the cause of the disease. He said, "Crohn's disease affects more than 750,000 Americans, yet traditional treatments only address the symptoms of inflammation and not the cause." He further added, "I have seen case studies where patients' lives have been restored following treatment, which removes MAP. I have high hopes that this clinical trial may lead to finding a cure." Dr. Saleh Naser will soon conduct clinical trials on a new antibiotic therapy acquired by RedHill Biopharma for curing the disease. 240 participants will be recruited for this double blind clinical trial.

http://health-beauty-2468.blogspot.com/2013/09/clinical-trial-for-new-antibiotic.html



RedHill Biopharma to initiate phase III trial of RHB 104 in Crohn's disease patients

UCF College of Medicine professor Dr. Saleh Naser soon will participate in a clinical trial to test whether a new antibiotic therapy acquired by RedHill Biopharma can be used to treat Crohn's disease patients.

The FDA-approved phase III trial is expected to commence within weeks by RedHill Biopharma, which licensed Naser's DNA technology for detecting Mycobacterium aviumsubspecies paratuberculosis, known as MAP. It is believed to be associated with Crohn's disease. RedHill Biopharma developed the anti-MAP antibiotic regimen known as RHB 104. Crohn's disease is a chronic inflammatory disease of the gastrointestinal tract characterized by cramping and diarrhea.

Naser developed and patented a way to detect MAP from milk, blood and tissue clinical samples. The bacterium is known to cause inflammation in the intestines of cows. It is also linked to Crohn's disease, although its role has been debated for more than a century. Naser believes MAP is an underlying cause of the disease.

"Crohn's disease affects more than 750,000 Americans, yet traditional treatments only address the symptoms of inflammation and not the cause," Naser said. "I have seen case studies where patients' lives have been restored following treatment, which removes MAP. I have high hopes that this clinical trial may lead to finding a cure."

RedHill will be enrolling 240 subjects from the United States, Canada and Israel in this double blind clinical trial in which blood and intestinal biopsy specimens from Crohn's patients will be tested for MAP before, during and following the one-year treatment with the antibiotic RHB 104.

"Since we acquired the license to Dr. Saleh Naser's MAP detection technique in 2011, we have had an excellent collaboration with UCF," said RedHill's CEO Dror Ben-Asher. "The UCF team of researchers- is at the forefront of global academic research on MAP and its detection."

Naser is looking forward to the trial and hopes this will end the academic debate regarding MAP and Crohn's disease.

"I am ecstatic to be part of a team, which will help determine whether or not MAP is associated with Crohn's disease; certainly a final answer to a one hundred-year old controversy," Naser said.

Source: University of Central Florida

http://www.news-medical.net/news/20130918/RedHill-Biopharma-to-initiate-phase-III-trial-of-RHB-104-in-Crohns-disease-patients.aspx

RedHill Readying Phase III Trials In Crohn's

With a PDUFA target date of Feb. 3, 2014 for its migraine drug, RHB-103, and NDA filing planned for the first quarter of 2014 for the anti-emetic drug, RHB-102, RedHill Biopharma (RDHL) is now focusing its efforts on its flagship programs: RHB-104 for Crohn's disease and RHB-105 for Helicobacter pylori (H. pylori).

RedHill is preparing to begin a potential groundbreaking Phase III study in the current quarter in North America and Israel (the MAP U.S. Study) of Crohn's disease, using a novel patent-protected formulation that combines three antibiotic ingredients in a single capsule, and is planning and preparing a parallel Phase III study in Europe (the MAP Europe Study).

"Following the discovery of the link between H. pylori bacterium and peptic ulcers, there is a growing body of evidence supporting the proposition that Crohn's disease and other so-called autoimmune diseases, such as multiple sclerosis, are linked to infections," chief business officer Guy Goldberg says in an interview with BioTuesdays.com, referring to emerging scientific evidence that the microbiome, or the trillions of intestinal microbes, plays a major role in health and disease.

"There's a paradigm shift of viewing the body not as a single organism but as a collection of organisms, with the microbiome as the habitat within the body," he adds.

In 2005, researchers in Australia won the Nobel Prize for identifying H. pylori bacterium and the role it plays in causing peptic ulcers. Stress and lifestyle were long believed to be the primary cause of intestinal ulcers. Fellow Australian, Prof. Thomas Borody, who is now a member of RedHill's advisory board, developed the first antibiotic treatment for ulcers.

RedHill's two lead drug candidates - RHB-104, for Crohn's disease and multiple sclerosis (MS), and RHB-105, forH. pylori - were built on the success of Prof. Borody's approaches to gastrointestinal tract diseases and infections.

"RHB-104 is the biggest program in our pipeline," Mr. Goldberg says. "To the best of our knowledge, we are the only company with a Phase III combination antibiotic approach for treating Crohn's disease, even though there is a lot of academic research connecting Crohn's to a bacterial infection."

RedHill is currently advancing six clinical programs; two of which are expected to be reviewed by the FDA during 2014, and three that are entering pivotal clinical studies.

In a research report last month, Bioassociate Innovative Consulting reiterated its "buy" rating and price target of $14.91 per RedHill American Depositary Share, "given the multiple milestones approaching and the company being on-track with the clinical programs' timelines."

Crohn's is a severe inflammatory disease in the GI tract. Existing drugs, such as Remicade, treat the inflammatory symptoms of the disease by suppressing the immune system. However, they are widely considered to have a poor safety profile and limited long-term efficacy. "There clearly is a strong unmet medical need for a better alternative for Crohn's patients," Mr. Goldberg contends. The global market to treat Crohn's exceeded $3.5-billion in 2012.

(Click to enlarge)

Phase II Study Pictures in Crohn's Patients (Borody et al (2002), Digest Liver Dis 34:29-38)

He explains that RHB-104 is a novel and proprietary combination of three approved antibiotic ingredients - clarithromycin, clofazimine and rifabutin - targeting Mycobacterium Avium Paratuberculosis (MAP). Crohn's patients are believed to have seven times greater likelihood of being MAP-positive than non-Crohn's patients.

The MAP U.S. Study will enroll 240 moderately-to-severely active Crohn's patients at 50 sites in North America and Israel. The primary endpoint is the state of remission at week 26. The study will also examine safety, the maintenance of remission through week 52, efficacy outcome measures in relation to the presence of MAP infection and other secondary endpoints.

If the study is successful, RedHill may submit a new drug application to the FDA in 2015. RHB-104 previously received orphan drug status from the FDA for pediatric use. Mr. Goldberg says discussions are underway with European regulators to begin a second Phase III study with RBH-104 in Europe - the MAP Europe Study.

RedHill also is developing RHB-104 to treat patients with relapsing remitting MS. In June, the company commenced a Phase IIa proof-of-concept trial in Israel. "This is the first time that this type of antibiotic therapy will be tested on MS patients in a Phase II clinical trial," Mr. Goldberg contends.

RedHill's second lead program is RHB-105 in development to treat H. pylori bacteria, which plays an important role in gastritis, peptic ulcers and gastric cancer. Mr. Goldberg points out that H. pylori is increasingly developing resistance to treatment with clarithromycin and metronidazole, and that standard therapy fails in up to 30% to 40% of patients who continue to remain H. pylori-positive.

A Phase IIa study in 2005 by Prof. Borody in Australia demonstrated over 90% eradication of the bacteria in 130 patients who had previously failed standard therapy with clarithromycin. Approximately three millionH. pylori-infected patients are treated annually in the U.S. market, resulting in a potential market estimated at $1-billion to $1.5-billion.

Mr. Goldberg explains that RHB-105 is a novel all-in-one combination of two antibiotics - rifabutin and amoxicillin - and a proton pump inhibitor, omeprazole. RedHill plans to begin a Phase II/3 clinical trial with RHB-105 during the quarter, he says, adding that a successful study could lead to an NDA filing in 2014.

http://seekingalpha.com/article/1645962-redhill-readying-phase-iii-trials-in-crohns?source=yahoo

Post-Diverticulitis Irritable Bowel Syndrome - New form of IBS Found by UCLA Researchers

This is interesting...  UCLA researchers have found that a form of IBS may be developed after a period where a person is diagnosed with diverticulitis.  The new condition is called post-diverticulitis irritable bowel syndrome (PDV-IBS).  The research also found that an increase in mood disorders was highly likely for people that suffer from IBS.  Read the article for the details.

UCLA researchers describe new form of irritable bowel syndrome / UCLA Newsroom:

UCLA researchers have described a new form of irritable bowel syndrome that occurs after an acute bout of diverticulitis, a finding that may help lead to better management of symptoms and relief for patients.

The discovery of this new condition, called post-diverticulitis irritable bowel syndrome (PDV–IBS), validates the irritable bowel symptoms that many patients report long after suffering a bout of diverticulitis but that many physicians have waved off as being part of the original condition, said Dr. Brennan Spiegel, an associate professor of medicine at the David Geffen School of Medicine at UCLA and senior author of the research.

"We've known for a long time that after some people develop diverticulitis, they're a different person. They experience recurrent abdominal pains, cramping and diarrhea that they didn't have before," Spiegel said. "The prevailing wisdom has been that once diverticulitis is treated, it's gone. But we've shown that IBS symptoms occur after the diverticulitis, and they may result from an inflammatory process, like a bomb going off in the body and leaving residual damage."

The research was published Sept. 5 in the peer-reviewed journal Clinical Gastroenterology and Hepatology.

As they age, most people develop diverticulosis, or pouches in the lining of the colon. More than 50 percent of people over 60 have the condition, but the pouches usually don't cause any problems. Occasionally, the pouches become inflamed, leading to diverticulitis, which causes pain and infection in the abdomen. Doctors usually treat it with antibiotics, or in more severe cases with surgery.

"A major surprise in our study was that diverticulitis patients not only developed IBS at a higher rate than the controls, but they also developed mood disorders like depression and anxiety at a higher rate," Spiegel said. "Because IBS and mood disorders often go hand in hand, this suggests that acute diverticulitis might even set off a process leading to long-standing changes in the brain–gut axis."

The discovery of PDV–IBS could mean better attention to patients complaining of symptoms after diverticulitis, symptoms that up until now may have been dismissed by physicians. 

"Patients often report ongoing IBS symptoms after the diverticulitis has long passed, and this study supports their beliefs and introduces a new diagnosis," Spiegel said. "If doctors recognize this, they may take the symptoms more seriously and manage them actively, just as they can manage IBS actively with various new drugs on the market and currently in development."

More than 1,000 patient records from the West Los Angeles Veteran's Affairs Medical Center were examined for the two-year study, including those of patients who had suffered acute diverticulitis and those of another group of patients who had not. The groups were matched for age and sex and had similar co-morbidities — other existing health problems. The groups were followed for many years as UCLA researchers tracked the differences in IBS diagnoses and mood disorders.

"This study expands our understanding a little bit about what might cause IBS," Spiegel said. "It's such a common condition, and there may be different flavors. We've now added a new flavor to the menu — a new risk factor for developing IBS. By learning more, we might be able to expand the therapies we can use on these patients."

The study was funded by Shire Pharmaceuticals.

"Our findings support the evolving paradigm of diverticular disease as a chronic illness — not merely an acute condition marked by abrupt complications. Far from a self-limited episode, acute diverticulitis may become a chronic disorder in some patients," the study states. "Diverticulitis is correlated with not only chronic IBS symptoms, but also long-term emotional distress beyond the event itself. Awareness of this possible risk is important because persistent, untreated gastrointestinal symptoms and comorbid depression may worsen outcome and increase the economic burden of an already prevalent disease."

Vedolizumab, A New Treatment for Ulcerative Colitis & Crohn's Disease Looks Promising - Info & Clinical Trial Included

Vedolizumab, a potentially new treatment for UC and Crohn's disease is being fast tracked for review by the FDA.  The BLA (biologics license application) will give priority review to the ulcerative colitis application and standard review to the Crohn's disease application.
The part of the clinical trial that is most important to me is the said adverse effects that were found in the patients who participated in the study.  Based on the concluding trial results, the adverse effects of the drug is said to be the same as the placebo.  That's great news.  I'm going to continue to watch this drug for new updates and news pertaining to safety. So far, this new treatment by Takeda Pharmaceuticals looks promising.
I have also included the clinical trial abstract below.  

Gastroenterology & Endoscopy News - New IBD Drug, Vedolizumab, Receives Priority Review Status for Ulcerative Colitis: 

On Sept. 4, Takeda Pharmaceutical Company Ltd., announced that it received priority review status from the FDA for its drug vedolizumab, an investigational antibody for the treatment of adults with moderately to severely active Crohn’s disease (CD) and ulcerative colitis (UC). Takeda submitted a biologics license application (BLA) to the FDA in June for the treatment of CD and UC; the UC application will receive priority review, and the application for CD will be reviewed under the standard timeline.

The FDA grants priority review status for drugs that are designed to treat a serious condition, and that if approved, would provide a significant improvement in safety or effectiveness. Priority review designation allows for an eight-month review period compared with the standard 12-month review.

“The need to seek new treatment options is well recognized,” said William J. Sandborn, MD, chief, Division of Gastroenterology, and professor of medicine, University of California, San Diego School of Medicine, in a press statement. “Vedolizumab has demonstrated the potential to be another possible treatment option for people with moderately to severely active CD and UC.”

Vedolizumab is a humanized monoclonal antibody that specifically antagonizes α4β7 integrin and inhibits it from binding to its target receptor, mucosal addressin cell adhesion molecule-1 (MAdCAM-1). MAdCAM-1 is preferentially expressed on blood vessels and lymph nodes of the gastrointestinal tract. It interacts with α4β7 integrin, which is expressed on a subset of circulating white blood cells, to mediate the inflammatory process in patients with CD and UC.

Takeda’s BLA submission is supported by four Phase III clinical studies—GEMINI I, II and III, and GEMINI LTS (Long-Term Safety)—which comprise the GEMINI Studies^TM, a clinical program designed to investigate the efficacy and safety of vedolizumab in clinical response and remission in patients with moderate to severe CD and UC. Patients enrolled in the studies failed at least one conventional therapy for inflammatory bowel disease, including corticosteroids, immunomodulators and/or a tumor necrosis factor–alpha antagonist. The results of the Phase III studies of vedolizumab in patients with CD and UC were published recently in the New England Journal of Medicine (Sandborn WJ et al. N Engl J Med2013;369:711-721 and Feagan BG et al. N Engl J Med 2013;369:699-710, respectively).

According to Takeda, vedolizumab has been studied in 2,700 patients in nearly 40 countries, making it the largest Phase III clinical trial program to date to simultaneously evaluate CD and UC. GEMINI LTS is an ongoing, open-label, long-term safety study of vedolizumab and is designed to collect data on the occurrence of important clinical safety events resulting from the administration of vedolizumab.

—Based on a press release from Takeda Pharmaceutical Company Ltd.

Clinical Trial - PUBMED.gov

 N Engl J Med. 2013 Aug 22;369(8):699-710. doi: 10.1056/NEJMoa1215734.

Vedolizumab as induction and maintenance therapy for ulcerative colitis.

Feagan BG, Rutgeerts P, Sands BE, Hanauer S, Colombel JF, Sandborn WJ, Van Assche G, Axler J, Kim HJ, Danese S, Fox I, Milch C, Sankoh S, Wyant T, Xu J, Parikh A; GEMINI 1 Study Group.

Collaborators (225)

Source

Robarts Clinical Trials, Robarts Research Institute, and Department of Medicine, University of Western Ontario, London, Canada. bfeagan@robarts.ca

Abstract

BACKGROUND:

Gut-selective blockade of lymphocyte trafficking by vedolizumab may constitute effective treatment for ulcerative colitis.

METHODS:

We conducted two integrated randomized, double-blind, placebo-controlled trials of vedolizumab in patients with active disease. In the trial of induction therapy, 374 patients (cohort 1) received vedolizumab (at a dose of 300 mg) or placebo intravenously at weeks 0 and 2, and 521 patients (cohort 2) received open-label vedolizumab at weeks 0 and 2, with disease evaluation at week 6. In the trial of maintenance therapy, patients in either cohort who had a response to vedolizumab at week 6 were randomly assigned to continue receiving vedolizumab every 8 or 4 weeks or to switch to placebo for up to 52 weeks. A response was defined as a reduction in the Mayo Clinic score (range, 0 to 12, with higher scores indicating more active disease) of at least 3 points and a decrease of at least 30% from baseline, with an accompanying decrease in the rectal bleeding subscore of at least 1 point or an absolute rectal bleeding subscore of 0 or 1.

RESULTS:

Response rates at week 6 were 47.1% and 25.5% among patients in the vedolizumab group and placebo group, respectively (difference with adjustment for stratification factors, 21.7 percentage points; 95% confidence interval [CI], 11.6 to 31.7; P<0 .001="" 41.8="" 44.8="" 4="" 52="" 8="" and="" at="" ayo="" clinic="" clinical="" continued="" every="" in="" no="" of="" patients="" receive="" remission="" score="" subscore="" to="" vedolizumab="" week="" weeks="" were="" who="">1), as compared with 15.9% of patients who switched to placebo (adjusted difference, 26.1 percentage points for vedolizumab every 8 weeks vs. placebo [95% CI, 14.9 to 37.2; P<0 .001="" 17.9="" 29.1="" 40.4="" 4="" adverse="" and="" ci="" events="" every="" for="" frequency="" groups.="" in="" of="" p="" percentage="" placebo="" points="" similar="" the="" to="" vedolizumab="" vs.="" was="" weeks="">

CONCLUSIONS:

Vedolizumab was more effective than placebo as induction and maintenance therapy for ulcerative colitis. (Funded by Millennium Pharmaceuticals; GEMINI 1 ClinicalTrials.gov number, NCT00783718.).

Comment in

• Inhibition of leukocyte trafficking in inflammatory bowel disease. [N Engl J Med. 2013]

PMID:

 

23964932

 

[PubMed - indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov/pubmed/?term=23964932