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Alimentary
tract and pancreas Alimentarni
trakt i pankreas |
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ARCH
GASTROENTEROHEPATOL 2003; 22 (No 1 - 2): 10 – 11 We
read it for you Journal:
Gut 2003; 52:377-82 Title:
Safety and efficacy of intravenous pulse cyclophosphamide in acute steroid
refractory inflammatory bowel disease Sigurnost i delotvornost intrevenskog "pulse" davanja ciklofosfamida
u akutnim, steroid rezistetnim oblicima
inflamatornih bolesti creva Authors:
A.Stallmach, BM Witting, C Moser, J Fischinger, R Duchman, M Zeitz Institution:
Department of Internal Medicine, Benjamin Franklin Medical School, Free University of Berlin, Berlin,Germany. (accepted
May 19st, 2001) |
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Abstract Background
and aims: One major problem in the management of steroid refractory
attacks of patients
with inflammatory bowel disease (IBD) is the establishment of a rapidly
acting immunosuppressive regimen.
Based on its well known efficacy in systemic vasculitis, intravenous cyclophosphamide
pulse therapy was used in refractory IBD patients to evaluate both its
efficacy and safety. Methods:
Between December 1998 and May 2001 seven patients (Crohn,s
disease, n=6; indeterminate colitis,
n=1) with severe steroid refractory IBD ( Crohn,s disease activity index
,CDAI 264-479 points)
received 4-6 cycles of monthly treatment with intrevenous cyclophosphamide
(750mg) in a prospective
uncontrolled pilot study. Results:
All patients improved after two intravenous pulses of
cyclophosphamide and six of seven patients
achieved complete remission (CDAI<150 points). One patients with Crohn,s
disease of the small
and large bowel showed an impressive clinical response but did not enter into
remission. Remission
was maintained in all patients for 18 months (median) but required a second
course of intravenous
pulse of cyclophosphamide in one patient. The drug was well tolerated except
two eisodes
of candia oesophagitis. Conclusions:
Intrevanous pulse cyclophosphamide may be safe and effective
treatment in patients with
severe IBD unrespnsive to steroid treatment and merits evaluation in a
controlled trials. EDITORís DIGEST The
nautral course of the chronic inflammatory bowel diseases
(IBD), Crohnís disease and ulcerative colitis is characterised
by acuta attacks requiring intensive medical care.
The treatment of choice during severe attacks is high dose
corticosteroids. However, 30-60% of patients develop a
steroid refractory or steroid dependent disease. Although immunosupppressive
agents such as azathioprine, 6-mercaptopurine, cyclosporin,
or anti-TNFalpha antibodies can be
effective, a substantial number of patients are refractory even
to combined use with glucocorticoids. Antibodies to
TNFalpha such as infliximab have been used in patients with
active Crohn,s disease who were resistant to standard therapy.
This drugs appears to have limitations in its efficacy as
only 33% of patients obtain a stable clinical remission and
long term strategies has not defined yet. One
unresloved problem in the treatment of severe IBD attacks
is the availability of rapidly acting and long lasting immunosuppressive
regimen. Cyclophosphamide is a potent
suppressor of immune functions, at high doses resulting
in a sustained decrease of both the number and function
of T and B cells. It is an effective therapy in ceratain autoimmune
diseases. However its efficacy varies. For
example, in severe systemic lupus erythematosus (SLE),
and various forms of systemic vasculitis such as Wegenerís
granulomatosis
or polyartheritis nodosa, its efficacy has
been proved. Intravenous cyclophosphamide appears
to be effective in controlling the lesions of pyoderma gangrenosum.
On the other hand, in rheumatoid arthitis
(except rheumatoid vasculitis) and in giant cell arteritis,
cyclophosphamide is less efefctive. Based on this above
mentioned findings, the efficacy of cyclophosphamide in
svere IBD is not predictable. Published experiences with
cyclophosphamide in severe IBD are very limited. The
remarcable clinical benefit of cyclophosphamide therapy
in this small study was striking. The onset of remission
was observed after one of two intravenous pulses of
750mg. This was accompanied with maintenance therapy
with azathioprine. To bridge the period when azathioprine starts
to work (which is ranging from 2 to 6 months)
in this study the authors contrinued intravenous cyclophosphamide
pulse therapy for additional 3-4 months (in
total 5-6 months). Using this concept the authors achieved
remission (median remission 18 months) in all 7 cases
with severe IBD characterised with poor prognosis. The
remarcable clinical benefit of cyclophosphamide therapy
in this study was obtained in the absence of relevant toxicity
or side effect. The authors used an intermittent high
dose intravenous cyclophosphamide pulse regimen as
is has been shown in severe SLE that pulse therapy had
at least comparable efficacy and less toxicity than daily
treatment with low dose cyclophosphamide. In
conclusion, in this small published study treatment with
pulse cyclophosphamide caused no major adverse events
or side effects. Most patients entered into remission after
2 cyclophosphamide pulses. Cyclophosphamide appears
to be good option to bridge the gap before the effect
of azathioprine (or 6-mercaptopurine) starts. Furthermore,
cyclophosphamide may help to reduce the need
for high doses steroids in the initial teratment phase and
therefore to minimise steroid side effects. Vojislav
N. Perišic |
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