Long term effects of anti-TNF

A great editorial in the Annals of Internal Medicine discusses how the the two current anti-TNF treatments, infliximab and adalimumab, are not living up to their initial promise.

The article examines the latest research into the effectiveness of these antibodies, and notes that responses to infliximab lessen over time. It adds that people who have stopped responding to infliximab will then not respond as well as other people to adalimumab, and they ponder whether the infliximab has changed the underlying nature of the Crohn's disease.

I thoroughly recommend this as required reading for Crohn's patients who are considering starting on an anti-TNF regime.

Fewer Colonscopies

A Belgian study has found that PET/CT is 100% successful in diagnosing active Crohn's disease. PET, or Positron emission tomography, involves injecting the patient with a radioisotope, and watching for its decay. CT, Computed Tomography, is where multiple x-rays are taken in quick succession, and a computer combines them to form a 3D image. When referred to as PET/CT it indicates that the two procedures are done at the same time, using one integrated machine, which allows the results from each to be correlated.

Regarding the use of PET/CT for Crohn's investigation, the researcher noted:

"The big advantage of PET/CT is that it is noninvasive, simple, fast and without any side effects. There was no preparation for the patients, except that they fasted for six hours. Each study took less than 20 minutes," said Hustinx. "If the PET/CT is positive, the doctor should confirm the results using endoscopy. If the PET/CT is negative, there would be no need for the endoscopy—given the high negative predictive value of the technique," he added.

This compares very favourably with a colonoscopy, where the patient undertakes a day of strict diet, a day of fasting, and then fasting on the day of the procedure. There are also some minor risks with a colonoscopy, such as bowel perforation.

The only problem I can see with PET/CT is the exposure to radiation, which is about 3 times the annual background radiation for PET and 4 times background for CT.

Major new genetic discoveries

When the results of research are reported in three separate BBC reports you can tell it's important. Firstly, the BBC reported an overview:

A major advance in understanding the genetics behind several of the world's most common diseases has been reported.

The landmark Wellcome Trust study analysed DNA from the blood of 17,000 people to find genetic differences.

...

One of the most exciting finds was a previously unknown gene common to type 1 diabetes and Crohn's disease, a type of inflammatory bowel disorder, suggesting that they share similar biological pathways.

The team also unexpectedly found a process known as autophagy - a process of clearing bacteria from within cells - is important in the development of Crohn's disease.

The BBC then gave more details for each disease involved, including this promising quote:

Dr Miles Parkes, consultant gastroenterologist at Addenbrooke's Hospital and the University of Cambridge said: "The study has substantially advanced our understanding of what causes Crohn's disease.

"There is a lot of follow-up work required to fully understand the impact of the genetic associations that we have identified. However they have already provided some major leads regarding possible new treatment options."

Finally, the BBC did a great easy to read description of how the research came about, how it was performed, and what it means to afflicted people:

For example in Crohn's disease, the team did not expect to find that autophagy - a process of removing unwanted bacteria from within cells - was an important factor.

They now plan to study this further to find out if it is associated with specific bacteria and there are treatments available which effect autophagy that researchers can investigate for use in Crohn's disease.

You can look at the nitty gritty by going directly to Nature, where they note the interesting finding:

An emerging theme from molecular genetic studies of CD is the importance of defects in autophagy and the processing of phagocytosed bacteria. A number of other specific components within innate and adaptive immune pathways are also highlighted.

Amongst their technical details is that there seems to be some relation to

...IRGM (immunity-related guanosine triphosphatase; the human homologue of the mouse Irgm/Lrg47), the strongest signal being at rs1000113 (P = 5.1 times 10-8). IRGM encodes a GTP-binding protein which induces autophagy and is involved in elimination of intracellular bacteria, including Mycobacterium tuberculosis67. Reduced function and/or activity of this gene would be expected to lead to persistence of intracellular bacteria, consistent with existing models of CD pathogenesis57 and the recent ATG16L1 association64 (see above).

This is extremely interesting when you review my earlier blog entry about a possible Crohn's vaccine, which operated on exactly that bacteria.

All of this news leads me to think that it won't be too long before we get a treatment for the cause, rather than the symptoms, of Crohn's.