Inflammatory Bowel Disease

Discussing the latest advances in Crohn’s disease and ulcerative colitis

August 29th, 2014 · Leave a Comment

Predicting Remission After Adalimumab Dose Optimization

By Margaret Shepard

Edward Loftus Jr., M. D., discusses a recent article published in the American Journal of Gastroenterology looking at patients on the standard dose of adalimumab, also known as Humira,  who were not doing well. The study focused on dose optimization and predicting remission in patients.

 

This French study looked at patients with either Crohn's disease or ulcerative colitis on the standard dose of adalimumab that were not doing well. In the group of roughly 100 patients, the researchers checked levels of adalimumab and antibodies to adalimumab in the patients right before delivering the next dose. Based on the profile from the tests, the researchers put the patients into three groups: patients that had therapeutic levels of adalimumab, patients that had low levels of adalimumab but no antibodies to the drug, and patients that had low levels of adalimumab and antibodies to the drug.

All the patients underwent dose optimization. If a patient wasn't doing well by receiving doses every other week, the dose was escalated to 40 mg weekly. If patients still weren't do well receiving a dose increase, they were switched to a different anti-TNF drug.

Based on the three profiles, the researchers could predict how patients were going to react. The patients who had low levels of adalimumab but no antibodies did best when the dose was doubled from every other week to weekly. The patients that had antibodies to adalimumab and already had therapeutic levels of adalimumab didn't do well with dose optimization. The patients that did the best when switching to a different anti-TNF drug were patients that had low levels of adalimumab and already had antibodies.

Based on this study, physicians can predict how patients might respond to certain therapies. This will help physicians make rational, evidence-based decisions on how to manage patients.

Read the full study online here.

For more information on IBD, visit mayoclinic.org/ibd.

Dr. Loftus is a gastroenterologist at Mayo Clinic.

Tags: adalimumab, Crohn's disease, Edward Loftus, ulcerative colitis

August 22nd, 2014 · Leave a Comment

Serrated Epithelial Changes

By Margaret Shepard

John Kisiel, M.D., discusses a recently published article in Alimentary Pharmacology & Therapeutics about serrated epithelial changes in patients with Crohn’s disease and ulcerative colitis.

 

Patients with inflammatory bowel disease are at an increased risk for colorectal cancer. The risk is increased by how long patients have had the disease, how old they are, how extensive the disease is throughout the colon, and the presence of a liver disease.

Researchers know certain polyps are precursors for colorectal cancer, and look for such polyps when performing routine surveillance colonoscopies to prevent colorectal cancer.

Recently, researchers have identified a type of tissue abnormality seen in patients with chronic colitis called serrated epithelial change or flat serrated change. The tissue is often sampled by random biopsy and has similar features as serrated polyps. The introductory findings of the new tissue among patients with chronic colitis has caused some confusion.

To address the confusion, a retrospective study was performed using patient records from 2006-2012 at Mayo Clinic. Serrated epithelial change was uncommon when looking at nearly 4,000 patients with inflammatory bowel disease (IBD) that had a colonoscopy in a three year period.

The researchers found serrated epithelial change in about 4 per 1,000 colonoscopies per patient. Also, serrated epithelial changes were more likely to occur in high risk patients for developing colorectal cancer. The researchers followed such patients' medical records forward to see how common it was for the patients to be diagnosed with colorectal cancer. They also followed forward a group of control patients. The two groups were balanced with other known risk factors for colorectal cancer such as long standing disease, disease distributed widely throughout the colon, age, sex.

The findings show the group of patients with serrated epithelial change were at an increased risk for colorectal cancer. About a third of patients developed polyps after three years of follow up. However, when the two groups were spilt, the statistical difference was abolished.

There are some important limitations for the study. The study had a small sample size and an inability to study multiple variables.

In conclusion, while the risk of developing a cancerous polyp is high for patients with or without serrated epithelial change, most of that risk was attributed to other factors.

Read the full study online here.

For more information about IBD, visit mayoclinic.org/ibd.

Dr. Kisiel is a gastroenterologist at Mayo Clinic.

Tags: Crohn's disease, John Kisiel, serrated epithelial change, ulcerative colitis

August 15th, 2014 · Leave a Comment

Stool Testing and Inflammatory Bowel Disease

By Margaret Shepard

Sunanda Kane, M.D., discusses noninvasive test options for identifying if someone has inflammatory bowel disease (IBD).

 

It's common knowledge that one of the symptoms of IBD is diarrhea. Before having a colonscopy, it's prudent to think of other noninvasive tests that may be helpful in figuring out whether a test, like a colonoscopy, is warranted. Noninvasive markers, such as blood work and stool tests, are helpful in figuring out whether someone may have IBD.

Recent studies look at certain kinds of proteins found in the stools. The proteins are reflective of active inflammation in the gut. Active inflammation can be from infection or inflammatory bowel disease. The tests will be negative and not show inflammation if the diarrhea is due to either something a patient ate or irritable bowel syndrome.

There is growing scientific evidence that noninvasive stool testing may be very helpful first stage before moving onto something more invasive, such as a colonoscopy or x-rays.

For more information on IBD, visit mayoclinic.org/ibd.

Dr. Kane is a gastroenterologist at Mayo Clinic.

Tags: IBD, noninvasive testing, stool testing, Sunanda Kane

August 8th, 2014 · Leave a Comment

Mesalamine Dose May Lower Marker of Bowel Inflammation

By Margaret Shepard

Edward Loftus Jr., M. D., discusses a recent article published in Clinical Gastroenterology and Hepatology looking at the ability of a drug to drive down calprotectin, a marker of bowel inflammation, in ulcerative colitis patients. This protein can be measured in stool, which gives physicians a proxy of how much inflammation is occurring in the bowel.

 

This multi-centered study looked at around 100 ulcerative colitis patients who were symptomatically in remission. A majority of the patients still had markers in the stool showing there was ongoing inflammation. The patients were on a medium dose of mesalamine, which is a commonly used medication in ulcerative colitis. The researchers randomized the patients to either keep receiving the same medium dose of mesalamine or receive a dose increase. The results showed that by increasing the dose of mesalamine, the stool marker went down to low levels. A lower level of calprotectin is associated with a lower risk of having an ulcerative colitis flare.

In inflammatory bowel disease (IBD), there can be a disconnect between the symptoms a patient experiences and the amount of inflammation he or she may have. One of the decisions a physician has to make is to follow the patient based on the symptoms he or she is experience or use an objective marker.

The results of this study reinforces the idea of using an objective marker to optimize a patient's therapy. Using an objective marker, like a calprotectin, will lead to better controlling the patient's symptoms.

Read the full study online here.

For more information on IBD, visit mayoclinic.org/ibd.

Dr. Loftus is a gastroenterologist specializing in the care of inflammatory bowel disease at Mayo Clinic.

Tags: bowel inflammation, Edward Loftus, mesalamine, ulcerative colitis

August 1st, 2014 · Leave a Comment

The Risk of Cancer from Certain IBD Medications

By Margaret Shepard

John Kisiel, M.D., discusses a recently published article in The Journal of the American Medical Association about the risk of cancer from certain medications used to treat inflammatory bowel disease (IBD).

 

The medications specifically looked at for this study are infliximab (Remicade), adalimumab (Humira), and certolizumab (Cimzia), which have been extremely effective for treating IBD. Studies on the cancer risk of these drugs have been an interest for clinicians and patients because the drugs all treat the immune system and could theoretically alter the ability to fight certain cancers. These drugs are also used to treat rheumatoid arthritis and other connective tissue disease. Studies of patients with those conditions have been conflicting in regard to the risk of cancer while exposed to these drugs.

In IBD literature, knowledge has been hampered by small sample sizes and short duration of follow-up. To try and address this question, Dr. Anderson and colleagues examined patients participating in the Danish nationwide cohort, which is a collect of patients in Denmark from 1992-2010 exposed to one of the anti-TNF drugs.

The researchers found more than 56,000 patients had been exposed to an anti-TNF drug during the study period and followed them forward for more than nine years. After adjusting for other risk factors, they found the risk of cancer was not specifically increased with anti-TNF drugs. This mirrors other findings commented on in an earlier blog post. The study didn't find any evidence of a dose response to anti-TNF drugs, meaning the cancer risk didn't go up with number of anti-TNF doses. Also, the researchers didn't find an increase in the specific types of cancer such as lymphoma, skin cancer, or colorectal cancer.

This study does have some limitations. The sample size was small enough that unless the cancer risk increased by a third, it might not have been detected.

In a large observation study with long-term follow-up, the cancer risk isn't significantly increased with use of infliximab (Remicade), adalimumab (Humira), and certolizamab (Cimzia). Patients should be aware that azathioprine could modestly increase the risk of cancer and they should discuss the use of this medication in combination with anti-TNF drugs with their physician. It's becoming standard practice to use this combination of drugs as the body of evidence suggests the benefit to patients with Crohn's disease and ulcerative colitis is significant and greater than the risk of cancer.

Read the full article online here.

For more information about IBD, visit mayoclinic.org/ibd.

Dr. Kisiel is a gastroenterologist specializing in the care of inflammatory bowel disease at Mayo Clinic.

Tags: cancer, Crohn's disease, IBD, JAMA, John Kisiel, ulcerative colitis

July 24th, 2014 · Leave a Comment

Anti-TNF Therapy and Remission in Pediatric Crohn’s Disease

By Margaret Shepard

Jeanne Tung, M.D., discusses a recently published article in Pediatrics about anti-TNF drug therapy and remission rates in pediatric Crohn’s disease. This study was conducting using the ImproveCareNow database.

 

The ImproveCareNow registry was started in 2006 with the idea of improving care in pediatric GI centers. Mayo Clinic joined ImproveCareNow in 2011 and there are now over 60 participating centers across the United States. When IBD patients visit the doctors office, information about their visit is entered into the central database. This includes information about the type of IBD, medications, blood work, height, weight, and Crohn's activity score. An update is sent to a doctor each month about their IBD patients, including an alert if a patient isn't doing well. This can include if a patient isn't in remission, still on steroids, or if a drug dose isn't quite correct.

For the purposes of this study, the researchers look at patients in the database who had Crohn's disease, had moderate to severe activity, started on Remicade or Humira, and had been followed for at least one year in the registry. The researchers were able to identify 603 patients. The identified patients were compared to patients receiving Azathioprine, 6-Mercaptopurine, or Methotrexate.

Using this registry, mock clinical trials were created. The researchers calculated whether patients went into remission and whether they were able to stop steroids. The calculations were based on their Crohn's disease activity. The results found that more patients taking Remicade or Humira were in remission compared to those on Azathoprine, 6-Meraptopurine, or Methotrexate. To be exact, in six months remission was achieved in 54% of patients on anti-TNF agents compared to 41%. In 12 months, remission was achieved in 67% of patients on anti-TNF medication compared to 56%. These results were similar to clinical trial results for adult and children on Remicade.

The results show anti-TNF medication is better for pediatric IBD patients than Methotrexate in inducing remission. This study indicates that using the ImproveCareNow database can be helpful in answering other medication questions.

Clinical trials are still important. In this study, the researchers didn't examine how patients were growing, didn't include blood work to verify remission, and didn't conduct a colonoscopy to verify the tissue was in remission.

For more information on ImproveCareNow, visit ImproveCareNow on Facebook and Twitter.

Read the full study online here.

For more information on IBD, visit mayoclinic.org/ibd.

Dr. Tung is a pediatric gastroenterologist at Mayo Clinic.

Tags: Crohn's disease, drug therapy, Improve Care Now, Jeanne Tung, pediatric crohn's disease, pediatrics, remission

July 17th, 2014 · Leave a Comment

Treat-to-Target Therapy in Crohn's Disease Patients

By Margaret Shepard

Do have Crohn's disease and are wondering if your treatment therapy is working? Sunanda Kane, M.D., discusses a recently published article in Clinical Gastroenterology and Hepatology about treating to target Crohn’s disease.

 

The researchers, from the University of California at San Diego, previously published a paper on treating-to-target ulcerative colitis. Treating for intestinal healing is the most effective way of getting patients in remission and feeling the best they possibly can.

What does this mean? A patient may be on a biologic, still have diarrhea, abdominal pain or unable to gain weight but feel well. It could be beneficial to look at the intestinal tissue with a scope to see if the therapy is doing the most it can for the patient. With all the biologics to treat Crohn's disease, it is possible to check blood levels and increase the dosage to target healing of the tissue. Any presence of inflammation or ulcers may contribute to continued symptoms. The goal should be treating to heal.

The expectation is that intestinal tissue can heal. While it may be uncomfortable to undergo colonoscopies, it's helpful in the short term and long term for treatment of the disease.

Read the full study online here.

For more information on IBD , visit mayoclinic.org/ibd.

Dr. Kane is a gastroenterologist at Mayo Clinic.

Tags: Crohn's disease, Sunanda Kane

July 10th, 2014 · Leave a Comment

Cancer Risk Greater in Crohn's Disease Patients Treated with Combination Drug Therapy

By Margaret Shepard

John Kisiel, M.D., discusses a recently published article in Gastroenterology about the combination therapy of adalimumab and immunomodulators and the risk for cancer in patients with Crohn’s disease.

 

Recent studies have shown greater benefit when combining anti-TNF drugs with thiopurine drugs. Doctors have known for awhile that certain thiopurine drugs raise the risk of certain types of cancer, such as nonmelanoma skin cancers and lymphomas. It's important to know that the risk for cancer is small and the combination of drugs is the best strategy to treat Crohn's disease.

Dr. Osterman and his colleagues recently conducted a study of nearly 1,600 patients that were treated with adalimumab in clinical trails that led to the approval of that drug for ulcerative colitis and Crohn's disease. They measured the risk of cancer in a follow up, about a year and a half on average for each patient, and looked to see if patients were taking another immunosuppressant during the time they were on adalimumab. The researchers compared the rate of cancer in those patients with the general population using the SEER database, which measures the incidences of cancer throughout the United States for the general population.

The researchers found that roughly 34 of the 1,600 patients developed a cancer after participating in the study. That's roughly 2%. The risk of cancer was nearly three times higher in those taking the immunosuppressant with adalimumab compared to the general population. The risk of cancer in those patients taking adalimumab alone was not increased compared to the general population. Most of the cancers were nonmelanoma skin cancers. It was also interesting that the combination therapy had a higher risk of other cancers, such as breast and colon cancer.

It's important to remember that the combination therapy still has incredible benefits over using either drug alone.

The information in this new study is important for doctors and patients in terms of counseling about skin cancer and other cancers, including monitoring and prevention. Specifically, a patient should avoid suntanning, strictly avoid tanning beds, wear high SPF sunscreen, hats and long sleeves, and schedule an annual exam with a dermatologist.

Read the full study online here.

For more information about IBD, visit mayoclinic.org/ibd.

Dr. Kisiel is a gastroenterologist at Mayo Clinic.

Tags: adalimumab, AGA, cancer, Crohn's disease, Gastroenterology, John Kisiel, nonmelanoma skin cancer

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