D'Haens_edit_US.qxp 5/10/07 10:22 am Page 27
Inflammatory Bowel Disease
Developments in Biologic Therapy for Crohn’s Disease and Ulcerative Colitis
a report by
Geert D’Haens, MD, PhD
Gastrointestinal Clinical Research Center, Imelda Hospital
The widespread availability of biologic agents for the treatment of It is rather reassuring that now, after more than 10 years of infliximab use
inflammatory bowel disease (IBD) is likely to alter therapeutic strategies in worldwide, no new safety concerns have arisen. Infections remain the
these conditions significantly. Currently, most countries reimburse only the number one safety issue, in particular in patients who are concomitantly
anti-tumor necrosis factor (TNF) agent infliximab, but promising results with using corticosteroids.
5
The exception to this is the recent report of eight
other biologic agents will certainly lead to the appearance of new biologics cases of aggressive hepatosplenic T-cell lymphoma, seven of which were in
on our markets soon. patients with CD and one in a patient with UC. All patients were using
azathioprine/6-mercaptopurine (6-MP) and received between one and 21
What Is New with Infliximab? doses of infliximab. Most patients were young males. Of note, three cases
The most important finding with regard to infliximab therapy is the fact that of this lymphoma have been reported in CD patients on azathioprine (but
regular treatment with eight weekly repeated infusions is superior to not infliximab) treatment.
3
episodic administration ‘as clinically needed’ (i.e. when the patient develops
relapse of symptoms) in terms of immunogenicity, but also in terms of What About Other Anti-tumor Necrosis Factor Agents?
efficacy and mucosal healing. It has been convincingly shown that the Adalimumab (Humira™, Abbott Laboratories, Parsippany, New Jersey, US)
former strategy leads to a significant reduction of surgeries and is a fully human anti-TNF monoclonal antibody (immunoglobulin G1,
hospitalizations in IBD patients.
1
It has also been demonstrated that the IgG1), which is administered subcutaneously. The recently published
combination of infliximab with an immunosuppressive is not beneficial in Crohn’s trial of the fully Human antibody Adalimumab for Remission
reducing immunogenicity beyond a period of six months.
2
Given the recent Maintenance (CHARM) trial demonstrated that induction and maintenance
finding that all cases of hepatosplenic lymphoma during infliximab therapy with subcutaneous injections of adalimumab (Humira) was safe
treatment (the vast majority occurring in young male patients) were and effective in patients with active CD.
6
The safety profile with this
observed under combination treatment with azathioprine,
3
it should be therapy was comparable to that reported with infliximab. Approximately
recommended to withdraw the immunosuppressive to which infliximab was one-third of the patients needed to escalate their maintenance dose from
added after six months of combined treatment. 40mg every other week to 40mg every week in order to maintain their
response. Patients on immunomodulators did not have a better clinical
The situation may be different in patients in whom infliximpab is started outcome, nor a different safety profile. The Gauging Adalimumab
together with azathioprine. Here, infliximab could be considered ‘bridge effectiveness in Infliximab Non-responders (GAIN) trial demonstrated that
therapy’ for three to six months and could then be tentatively withdrawn. patients who had become intolerant to infliximab or those in whom this
Infliximab is now approved and in most European countries reimbursed for treatment had lost its effect responded to adalimumab therapy in more
both Crohn’s disease (CD) and ulcerative colitis (UC). Its efficacy is similar than 50% of cases (with remission in 21%), making this drug a potential
in both conditions, but it must be remembered that many more alternative alternative in these refractory patients.
7
treatment options are available for UC than for CD: 5-aminosalicylates,
cyclosporine, tacrolimus, and even proctocolectomy are all effective
Geert D’Haens, MD, PhD, is a Gastroenterologist and Director of
therapies for various severities of the disease.
the Gastrointestinal (GI) Clinical Research Center at Imelda
Hospital. He is also a Consultant Gastroenterologist in
A particular situation is the management of steroid-refractory patients
inflammatory bowel disease (IBD) in the Section of
Gastroenterology and Endoscopy at the University Hospital
hospitalized with a severe attack of UC. Rather than immediately considering
Gasthuisberg, and a Consultant for several pharmaceutical
a proctocolectomy, I recommend at least one medical ‘rescue’ therapy in the companies. Dr D’Haens is President of the Vlaamse Vereniging
absence of ‘alarm symptoms’ such as frank bleeding, toxic megacolon, or
voor Gastroenterologie (VVGE), a Board Member of the Belgian
IBD research club and the International Organization for
perforation. In patients who have already failed azathioprine it is unwise to
Inflammatory Bowel Disease (IOIBD), a member of the American Gastroenterological Association
start cyclosporine, since relapse is predictable once cycloporine is (AGA), and Secretary General of the European Crohn’s and Colitis Organization (ECCO). His main
discontinued. In these patients, I would recommend opting for infliximab, a
interests are in the fields of IBD, mucosal immunology, GI endoscopy, and immunosuppression.
Dr D’Haens has served as a reviewer for Gastroenterology, Digestive Disease and Sciences,
strategy that has been shown to be effective.
4
In patients who are not yet on
Digestion, Tijdschr Geneeskunde, the American Journal of Gastroenterology, Gut, The Lancet,
azathioprine, intravenous (IV) treatment with cyclosporine is often effective and IBD, and has been on the editorial board of IBD since 2003.
and can be used as ‘bridge therapy’ until the effect of azathioprine kicks in.
Of course, the same strategy could be considered using infliximab.
© TOUCH BRIEFINGS 2007
27
Page 1  |  Page 2  |  Page 3  |  Page 4  |  Page 5  |  Page 6  |  Page 7  |  Page 8  |  Page 9  |  Page 10  |  Page 11  |  Page 12  |  Page 13  |  Page 14  |  Page 15  |  Page 16  |  Page 17  |  Page 18  |  Page 19  |  Page 20  |  Page 21  |  Page 22  |  Page 23  |  Page 24  |  Page 25  |  Page 26  |  Page 27  |  Page 28  |  Page 29  |  Page 30  |  Page 31  |  Page 32  |  Page 33  |  Page 34  |  Page 35  |  Page 36  |  Page 37  |  Page 38  |  Page 39  |  Page 40  |  Page 41  |  Page 42  |  Page 43  |  Page 44  |  Page 45  |  Page 46  |  Page 47  |  Page 48  |  Page 49  |  Page 50  |  Page 51  |  Page 52  |  Page 53  |  Page 54  |  Page 55  |  Page 56  |  Page 57  |  Page 58  |  Page 59  |  Page 60  |  Page 61  |  Page 62  |  Page 63  |  Page 64  |  Page 65  |  Page 66  |  Page 67  |  Page 68  |  Page 69  |  Page 70  |  Page 71  |  Page 72  |  Page 73  |  Page 74  |  Page 75  |  Page 76  |  Page 77  |  Page 78  |  Page 79  |  Page 80  |  Page 81  |  Page 82  |  Page 83  |  Page 84  |  Page 85  |  Page 86  |  Page 87  |  Page 88  |  Page 89  |  Page 90  |  Page 91  |  Page 92  |  Page 93  |  Page 94  |  Page 95  |  Page 96  |  Page 97  |  Page 98  |  Page 99  |  Page 100