The Sydney Morning Herald reports, as predicted, that Infliximab will be available on the Pharmaceutical Benefits Scheme (PBS) from October for the treatment of Crohn's disease. Prior to this patients would have to pay the thousands of dollars themselves, or be one of the lucky few paid for by a hospital.
The Daily Telegraph reports that Humira has been approved for the treatment of Crohn's disease in Australia. However, until it is listed on the Pharmaceutical Benefits Scheme (if it ever is), its cost of $16,000 per month will be prohibitive for many people.
From the unlikely source of a new player in pharmaceuticals, Asia's largest company Hutchison, comes news of an alternative to the usual Crohn's medicines. The Independent reports that initial trials of a compound found in traditional Chinese medicine have found it to be as effective as the more common treatments in Ulcerative Colitis, and is expected to be similarly effective in Crohn's. The story is in their business section, so it's a bit sparse on details, but it's definitely an area to keep an eye on. (Image from PoYang)
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.
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.
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.
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."
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.
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.
...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.
Tests on a new form of treatment called extracorporeal photopheresis have been announced.
Results from an international multi-center Phase II clinical trial suggest that extracorporeal photopheresis (ECP) may be effective in treating patients with clinically active (OR symptomatic) Crohn's disease who cannot tolerate or are refractory to immunosuppressants and/or anti-TNF agents.
A 50% response rate after 3 months of ECP treatment was noted in the study, using standard disease activity criteria, as presented this afternoon at a scientific research session of Digestive Disease Week (DDW). The majority of patients who responded to ECP therapy had a notable improvement in their disease symptoms and signs after only six weeks of treatment.
The Australian Pharmaceutical Benefits Advisory Committee has recommended that Infliximab (Remicade) be subsidised for the treatment of Crohn's disease (it's already subsidised for other conditions):
The PBAC recommended the listing of infliximab for the treatment of patients with severe Crohn’s disease (Crohn’s Disease Activity Index ≥ 300) or patients with an ileostomy or colectomy due to Crohn’s disease on the basis of a high but acceptable cost-effectiveness ratio compared to placebo. Acceptable cost-effectiveness was demonstrated at a dose of 5 mg/kg infliximab for three doses (weeks 0, 2 and 6) and when continuation of treatment beyond three doses was determined by remission (CDAI ≤ 150) at approximately 12 weeks from the commencement of treatment.
Hot on the heels of the US and Canadian gene findings is another genome-led research article, this time from Belgium. You can read the very technical article online in full at PLoS Genetics. I present the author summary in full here, because the article itself is too complicated for me to summarise:
Individual susceptibility to many common diseases is determined by a combination of environmental and genetic factors. Identifying these genetic risk factors is one of the most important objectives of modern medical genetics, as it paves the way towards personalized medicine and drug target identification. Recent advances in SNP genotyping technology allows systematic association scanning of the entire genome for the detection of novel susceptibility loci. We herein apply this approach to Crohn disease, which afflicts an estimated 0.15% of the people in the developed world and identify a novel susceptibility locus on Chromosome 5. A unique feature of the novel 5p13.1 locus is that it coincides with a 1.25-Mb gene desert. We present evidence that genetic variants at this locus influence the expression levels of the closest gene, PTGER4, located 270 kb away, in the direction of the centromere. PTGER4 encodes the prostaglandin receptor EP4 and is a strong candidate susceptibility gene for Crohn disease as PTGER4 knock-out mice have increased susceptibility to colitis.
It has now been conclusively shown that genetics plays a role in the development of Crohn's disease, with the release of a study in Nature Genetics (full article available for purchase for US$30). Data from the Human Genome Project was used to compare the genes of people with and without the disease. The ABC mention:
Scientists previously had some indications of a genetic component to Crohn's disease. It tends to run in families and is more common in certain ethnic groups, especially people of central and eastern European Jewish descent.
Pinpointing the genes that predispose people to Crohn's disease could help lead to new ways to treat it, say the researchers.
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