INFLECTRA APPROVED AS REMICADE BIOSIMILAR
The Hospira-produced biosimilar for Remicade, known as Inflectra, has been recommended for listing on the Pharmaceutical Benefits Scheme, following a July meeting of the Pharmaceutical Benefits Advisory Committee (PBAC).
The drug has been confirmed as a suitable biosimilar after consideration of factors by PBAC including the results of three randomised clinical trials; clinical data that showed there was no difference in efficacy or safety between Inflectra and Remicade; and the Australian Department of Health’s Advisory Committee on Prescription Medicine’s support of Inflectra for treatment of ulcerative colitis and Crohn’s disease, among other conditions.
The PBAC held a consumer hearing on biosimilars earlier this year, and noted in its recommendations the public perception on them may need to be clarified.
The substitution of Remicade for Inflectra – or any other biosimilar medication – would allow for patient and prescriber choice, but would not be automatic. A prescriber – usually a patient’s doctor or specialist – may choose not to allow biosimilars to be issued. If suitable, the prescriber could allow the patient to substitute for Inflectra at the pharmacy.
With Infliximab primarily administered by an infusion at a clinic, the PBAC did not anticipate significant switching between brands.
The PBAC also recommended the Department of Health develop an implementation strategy for Infliximab, including an education campaign around biosimilars, and improving awareness among health professionals and patients of the medication choices available.
If listed, Inflectra would have the same indications applied as Remicade, with equi-effective doses set at 100 mg. The PBAC stated it would also consider including a ‘flag’ on Inflectra on the PBS, noting it as a biosimilar for Remicade.
VSL#3 ® (probiotic) is unrelated to VIVOMIXX®
VIVOMIXX® is made by Mendes SA, and is a different product to VSL#3 ®.
VSL#3 ® is created by Actial Farmaceutica Srl and has been widely used for over 20 years in the US and Europe, with recommendations from 8 gastroenterology associations including the American College of Gastroenterology and the Triennial Yale / Harvard Workshop. The product is not currently available in Australia, but Actial Farmaceutica Srl company is actively investigating the ability to do so.
Please direct all enquiries about VSL#3® to http://vsl3pharma.com/
New Tool to Improve Cancer Prevention in IBD
A new online tool that aims to radically improve cancer prevention in patients with inflammatory bowel disease (IBD) was launched on 30 June 2014 in Melbourne, Australia.
Colorectal cancer occurs more commonly in patients with inflammatory bowel disease, a source of concern for patients and their physicians.
ASSURANCE (Surveillance for Neoplasia in Inflammatory Bowel Disease), a new web-based software programme, helps doctors assess a patient’s risk of cancer developing and helps them devise a programme to keep a patient under review.
“The key aim of the program is for doctors to manage their inflammatory bowel disease patients effectively”, principal investigators Professor Michael Kamm and Dr Mark Lust said. The information will also be used to improve the way colorectal cancer surveillance is undertaken.
“Some patients with chronic inflammatory bowel disease are at above-average risk for the development of colorectal cancer,” Professor Kamm explained.
“Checking the bowel with regular colonoscopic surveillance has been used to detect early changes within the colon that lead to cancer, so that preventative treatment can be undertaken. However, surveillance programs are imperfect and adherence amongst clinicians remains poor.”
“The ASSURANCE program simplifies risk assessment, offers doctors an easy method to monitor their patients and presents a unique research opportunity to identify risk factors and best management in different global populations.”
Crohn’s & Colitis Australia CEO Francesca Manglaviti welcomed the program, noting that the increased risk of colorectal cancer in patients with IBD was a major source of anxiety for patients and their physicians.
Ms Manglaviti said:
ASSURANCE incorporates new guidelines for cancer surveillance in IBD from around the world. It is a joint project between St Vincent’s Hospital Melbourne, the University of Melbourne, and the software company EpiSoft. It has been supported by the charity Australasian Gastro Intestinal Research Foundation (AGIRF) and an unrestricted educational grant from Ferring Pharmaceuticals.
Program coordinator Amy Hamilton said:
“ASSURANCE will be offered to gastroenterologists in Australia, Singapore, Hong Kong and China. We aim to have the program in widespread use throughout the Asia-Pacific region by the end of 2014.”
“ASSURANCE will be made available to specialists in Australia without charge. Gastroenterologists will be notified about its availability, or they can pre-enrol via an email to email@example.com”
Gene profile for Crohn’s disease identified
US researchers have identified specific gene expressions and microbes associated with the inflammatory bowel disease Crohn’s disease.
The researchers compared the intestines of healthy patients to 359 children with Crohn’s disease.
In the Crohn’s patients they found altered expression of two genes known as DUOX2 and APOA1, along with a distinct microbial community.
The researchers suggested that together, this gene expression and microbial abundance could be used to predict clinical outcomes in patients with Crohn’s disease.
J Clin Invest. doi:10.1172/JCI75436.
IBD FLARES AND HEAT WAVES
A new study from Switzerland has shown that IBD flares and bouts of infectious gastroenteritis (IG) become more common during heat waves.
The retrospective, controlled observational study looked at data of 738 patients with IBD and 786 with IG who had been admitted to hospital from 2001 to 2005. The researchers then compared this data with that from non-infectious chronic intestinal inflammations, and studied climate data for 17 heat waves during the same period.
Results showed that for every additional day of heat wave, the risk for IBD flares increased by 4.6%, and the risk for IG flares by 4.7%. The control group showed no such effect.
Further, it was found that the risk for IG flares increased per day and was strongest after a seven-day lag, while the effect on IBD flares is immediate.
Dr Christine N Manser, one of the researchers, said in a press release that heat waves seem to affect flares because of the physical stress that they cause. She added: “Physical as well as mental stress has been shown to cause flares of IBD and may explain the increase in IBD hospital admissions during heat.”
The authors claim that another factor could be bacteria growth and how it affects digestion during heat waves: “During a heat wave, changes in bacterial composition of food, skin, soil, and water may occur…. Recent research suggests that temperature plays a crucial role in the expansion of enterohemorrhagic Escherichia coli and other pathogenic bacteria.
Mitigation and adaptation strategies are needed to reduce current vulnerability to climate change and to address the health risks projected to occur over the coming decades.”
Source: ‘Heat Waves, Incidence of Infectious Gastroenteritis, and Relapse Rates of IBD: A Retrospective Controlled Observational Study,’ Christine N Manser et. al, The American Journal of Gastroenterology 108 (1480-1485, September 2013)
OSTEOPOROSIS AMONG MALE IBD PATIENTS
A German study has found that male IBD patients have a higher risk of impaired bone mineral density (BMD) than female patients, especially when being treated with corticosteroids.
Osteoporosis is a frequent complication of IBD, and the study found that among 174 patients (59 male, 115 female), male patients were diagnosed more often with osteopenia or osteoporosis than females (55.9% vs 29.6%). The male patients also had a risk of bone disease comparable to postmenopausal women. In addition, duration of corticosteroid treatment and IBD were identified as risk factors for osteoporosis, and a follow-up scan demonstrated an overall deterioration of BMD in patients with normal baseline results.
The study recommends screening patients with IBD — including those with normal baseline BMD — at an early stage of disease, and monitoring BMD regularly.
Source: ‘Health Care for Osteoporosis in IBD: Unmet Needs in Care of Male Patients?’ Jens Walldorf, et. al, Journal of Crohn’s and Colitis (Vol. 7, Issue 11, pp. 901-907, 1 December 2013)
STRICTUREPLASTY IN CROHN’S DISEASE
Primary duodenal localization of Crohn’s disease (CD) is rare. Medical therapy can control symptoms, but surgery is required when progressive obstructive symptoms occur. Surgical options include bypass, resection, or strictureplasty, but it is still not clear which should be the treatment of choice. Reviewing the medical records of 1253 patients undergoing surgery for CD between January 1986 and December 2011 at the Digestive Surgery Unit of the Department of Clinical Physiopathology of the University of Florence, 10 patients (six males and four females) underwent operations for duodenal CD. Four patients had only a duodenal localization while six patients had synchronous involvement of other intestinal tracts.
Strictures were distributed in all the duodenal portions: in seven patients there were single lesions while in three patients there were multiple lesions. Eight patients were treated with strictureplasty: five with the Heineke–Mikulicz technique, two with Jaboulay, and one with a pedunculated jejunal patch. Two patients were treated with resection: one with a B2 gastro-duodenal resection, and one with a duodenal–jejunal resection and an end to side duodeno-jejunal anastomosis.
Follow-up of the patients was from two to 18years. No recurrence of duodenal CD was observed in the two patients treated with resection, while two of the eight patients treated with strictureplasty had a recurrence. In our experience, strictureplasty is indicated when less than two strictures are present in the second or third duodenal portion. In cases with multiple strictures localized in the first or the distal duodenal portion, resection is preferable.
(Abstract, ‘Symptomatic Duodenal Crohn’s disease: Is Strictureplasty the Right Choice?’ Francesco Tonelli, et. al, Journal of Crohn’s and Colitis, Vol. 7, Issue 10 pp. 791-796, 1 November 2013)
INTESTINAL CELLS AND CROHN'S DISEASE
Researchers from the University of Cambridge and Harvard University found that Crohn’s disease might be a disorder of specialised intestinal cells called Paneth cells.
Professor Arthur Kaser, lead author of the study, notes that the team’s discovery of the role that Paneth cells play in bowel inflammation “raises the possibility of entirely new novel therapeutic approaches.”
He adds: “If we are able to break down Crohn’s disease into subsets by understanding the underlying mechanisms, [we can] develop much more targeted, efficient treatments.”
The authors also identified autophagy, another mechanism in the body, as another factor that can lead to Crohn’s disease. Autophagy is the process of self-digestion by a cell through the action of enzymes originating within the same cell, and represents the breakdown and reuse of cellular components in the body. Although autophagy was previously linked to Crohn’s, as it involves several key genes associated with the disease, its role was unknown.
The process keeps the inflammatory function of the unfolded protein response in check. This response, in turn, is activated when the endoplasmic reticulum (ER) cells — a network of tubes and flattened sacs that perform a number of functions within cells — are under stress, as is common in intestines of patients with Crohn’s disease.
Professor Kaser’s study hypothesises that autophagy removes the ER membranes that are presented as inflammatory by the buildup of misfolded proteins, and that this is a result of genetic traits or the environment.
According to Professor Kaser, the findings on how genes interact with ER stress genes and the environment “is an important aspect of our understanding of complex diseases such as Crohn’s disease.”