Zusammenfassung
In den letzten Jahren wurden zahlreiche Studien zur Wirkung von Biologika bei chronisch
entzündlichen Darmerkrankungen durchgeführt. Mit Ausnahme von Infliximab und anderen
Tumornekrosefaktor-Antikörpern hat sich bisher keines der Prinzipien als hinreichend
erfolgreich erwiesen, um in die Praxis überführt zu werden. Der Integrin-Antikörper
Natalizumab zum Beispiel ist wegen Nebenwirkungsproblemen sogar vom Markt genommen
worden. Bei Betrachtung der Studien zeigt sich, dass häufig die falschen Patienten
eingeschlossen wurden, gelegentlich auch übersehen wurde, dass die Hemmung eines einzelnen
Mediators aus einem redundanten Netzwerk nicht wirklich erfolgversprechend ist. Somit
ist festzuhalten, dass Infliximab unser therapeutisches Arsenal bereichert hat, zumal
es auch bei der Colitis ulcerosa bei etlichen Patienten wirksam ist, dass aber ein
wirklicher Durchbruch in der Therapie durch die Biologika bislang nicht erfolgt ist.
Summary
During the last years numerous studies on the effects of biologics in chronic inflammatory
bowel disease have been performed. With the exception of infliximab and some other
tumor necrosis factor antibodies none of the principles has been sufficiently successful
to be included in the routine armamentarium. The integrin antibody natalizumab has
been retracted from the market due to serious side effects. When looking at the studies
it becomes obvious that often wrong patients have been included into the trials and
sometimes it has been overlooked that the inhibition of a signal mediator out of a
redundant network is not really promising. Thus, we can conclude that infliximab has
enriched our therapeutic arsenal, in particular since it also works in ulcerative
colitis in a number of patients. However, the real breakthrough in the therapy has
not yet been achieved by biologics.
Key Words
chronic inflammatory bowel diseases - biologics - Crohn's disease - ulcerative colitis
- tumor necrosis factor - hormones - cytokines
Literatur
- 1
Colombel JF, Loftus Jr EV, Tremaine WJ. et al. .
The safety profile of infliximab in patients with Crohn's disease: the Mayo Clinic
experience in 500 patients.
Gastroenterology.
2004;
126
19-31
- 2
Creed TJ, Norman MR, Probert CSJ. et al. .
Basiliximab (anti-CD25) in combination with steroids may be an effective new treatment
for steroid-resistant ulcerative colitis.
Aliment Pharmacol Ther.
2003;
18
65-75
- 3
Dieckgraefe BK, Korzenik JR.
Treatment of active Crohn's disease with recombinant human granulocyte-macrophage
colony-stimulating factor.
Lancet.
2002;
360
1478-1480
- 4
Faubion Jr WA, Loftus Jr EV, Harmsen WS. et al. .
The natural history of corticosteroid therapy for inflammatory bowel disease: a population-based
study.
Gastroenterology.
2001;
121
255-260
- 5
Feagan B, Greenberg GR, Wild G. et al. .
Treatment of ulcerative colitis with a humanized antibody to the a4b7 integrin.
N Engl J Med.
2005;
352
2499-2507
- 6
Feagan BG, Greenberg G, Wild G. et al. .
Efficacy and safety of a humanized a4b7 antibody in active Crohn's disease (CD).
Gastroenterology.
2003;
124
A25-A26
- 7
Gasché C, Schölmerich J, Brynskow J. et al. .
A simple classification of Crohn's disease: report of the Working Party for the World
Congresses of Gastroenterology, Vienna 1998.
Inflamm Bowel Dis.
2000;
6
8-15
- 8
Ghosh S, Goldin E, Gordon FH. et al. .
Natalizumab for active Crohn's disease.
N Engl J Med.
2003;
348
24-32
- 9
Hanauer S, Lukas M, MacIntosh D. et al. .
A randomized, double-blind, placebo-controlled trial of the human anti-TNF-a monoclonal
antibody adalimumab for the induction of remission in patients with moderate to severely
active Crohn's disease.
Gastroenterology.
2004;
127
332
- 10
Hanauer SB, Feagan BG, Lichtenstein GR. et al. .
Maintenance infliximab for Crohn's disease: the ACCENT I randomised trial.
Lancet.
2002;
359
1541-1549
- 11
Herrlinger K, Witthoeft T, Raedler A. et al. .
Randomized, double-blind, double-dummy, controlled trial of subcutaneous recombinant
human interleukin-11 versus prednisolone in active Crohn's disease.
Gastroenterology.
2004;
126
A466
- 12 Hommes DW, Mikhajlova TL, Stoinov S. et al. .Fontolizumab, a humanized anti-interferon-gamma
antibody, demonstrates safety and clinical activity in patients with moderate-to-severe
Crohn's disease. Gut, im Druck
- 13
Ito H, Takazoe M, Fukuda Y, Hibi T. et al. .
A pilot randomized trial of a human anti-interleukin-6 receptor monoclonal antibody
in active Crohn's disease.
Gastreoenterology.
2004;
126
989-996
- 14 Jess T, Loftus Jr EV, Harmsen WS. et al. .Survival and cause-specific mortality
in patients with inflammatory bowel disease: A long-term outcome study in Olmsted
County, Minnesota, 1940-2004. Gut, im Druck
- 15
Korzenik JR, Dieckgraefe BK, Valentine JF.
Duration of sargramostim effects in patients with moderately-to-severely active Crohn's
disease (CD): follow-up results from a randomized, double-blind, placebo-controlled
trial.
Gastroenterology.
2004;
126
A75-A76
- 16
Korzenik JR, Dieckgraefe BK.
Is Crohn's disease an immunodeficiency? A hypothesis suggesting possible early events
in the pathogenesis of Crohn's disease.
Dig Dis Sci.
2000;
45
1121-1129
- 17
Ljung T, Karlen P, Schmidt D. et al. .
Infliximab in inflammatory bowel disease: clinical outcome in a population based cohort
from Stockholm County.
Gut.
2004;
53
849-853
- 18
Loefberg R, Neurath M, Ost A, Pettersson S.
Topical NFkB p65 antisense oligonucleotides in patients with active distal colonic
IBD. A randomised, controlled pilot trial.
Gastroenterology.
2002;
122
A60
- 19
MacInthosh DG, Lukas M, Sandborn W. et al. .
A randomized, double blind, placebo-controlled trial of the clinical assessment of
adalimumab safety and efficacy studied as an induction therapy in Crohn's disease
(classic).
Gut.
2004;
53
A47
- 20
Mannon PJ, Fuss IJ, Mayer L. et al. .
Anti-interleukin-12 antibody for active Crohn's disease.
N Engl J Med.
2004;
351
2069-2079
- 21
Miner PB, Bane B, Bradley JD. et al. .
ICAM-1 antisense inhibition by enema improves pouchitis and suggests long-term mucosal
healing in patients with chronic unremitting disease.
Am J Gastroenterol.
2003;
98
S246-S247
- 22
Musch E, Andus T, Kruis W. et al. .
Interferon-beta-1a for the treatment of steroid-refractory ulcerative colitis: a randomized,
double-blind, placebo-controlled trial.
Clin Gastroenterol Hepatol.
2005;
3
581-586
- 23
Nikolaus S, Rutgeerts P, Fedorak R. et al. .
Interferon b-1a in ulcerative colitis: a placebo controlled, randomised, dose escalating
study.
Gut.
2003;
52
1286-1290
- 24
Sandborn W, Colombel JF, Enns R. et al. .
A phase III, double-blind, placebo-controlled study of the efficacy, safety and tolerability
of antegren (natalizumab) in maintaining clinical response and remission in Crohn's
disease (ENACT-2).
Gastroenterology.
2004;
127
332
- 25
Sandborn WJ, Loftus EV.
Balancing the risk and benefits of infliximab in the treatment of inflammatory bowel
disease.
Gut.
2004;
53
780-782
- 26
Sandborn WJ, Sands BE, Wolf DC. et al. .
Repifermin (keratinocyte growth factor-2) for the treatment of active ulcerative colitis:
a randomized, double-blind, placebo-controlled, dose-escalation trial.
Aliment Pharmacol Ther.
2003;
17
1355-1364
- 27
Sands BE, Blank MA, Patel K. et al. .
Long-term treatment of rectovaginal fistulas in Crohn's disease: response to infliximab
in the ACCENT II study.
Clin Gastroenterol Hepatol.
2004;
2
912-920
- 28
Sands BE, Kozarek RA, Spainhour J. et al. .
Safety and tolerability of natalizumab in patients concurrently receiving infliximab
in a phase II study of active Crohn's disease.
Gastroenterology.
2004;
126
A463
- 29
Schölmerich J, Huber G.
Biological therapy in IBD.
Dig Dis.
2003;
21
180-191
- 30 Schölmerich J. Biological therapies. In: Bernstein C (Hrsg). IBD-yearbook 2005
- 31 Schölmerich J. IBD - Pandora's box - present and future. N Y Acad Sci, im Druck
- 32
Schreiber S, Rutgeerts P, Fedorak RN. et al. .
A randomized, placebo-controlled trial of Certolizumab Pegol (CDP870) for treatment
of Crohn's disease.
Gastroenterology.
2005;
129
807-818
- 33
Sinha A, Nightingale J, West KP. et al. .
Epidermal growth factor enemas with oral mesalamine for mild-to-moderate left-sided
ulcerative colitis or proctitis.
N Engl J Med.
2003;
349
350-357
- 34
Slonim AE, Bulone L, Damore MB. et al. .
A preliminary study of growth hormone therapy for Crohn's disease.
N Engl J Med.
2000;
342
1633-1637
- 35
Tilg H, Vogelsang H, Ludwiczek O. et al. .
A randomized placebo controlled trial of pegylated interferon a in active ulcerative
colitis.
Gut.
2003;
52
1728-1733
- 36
Van Assche G, van Ranst M, Sciot R. et al. .
Progressive multifocal leukoencephalopathy after natalizumab therapy for Crohn's disease.
N Engl J Med.
2005;
353
362-368
- 37
Van Deventer SJH, Tami JA, Wedel MK. European Colitis Study Group .
A randomized, controlled, double blind, escalating dose study of alicaforsen enema
in active ulcerative colitis.
Gut.
2004;
53
1646-1651
- 38
Vaughan D, Drumm B.
Treatment of fistulas with granulocyte colony-stimulating factor in a patient with
Crohn's disease.
N Engl J Med.
1999;
340
239-240
- 39
Winther KV, Jess T, Langholz E. et al. .
Survival and cause-specific mortality in ulcerative colitis: follow-up of a population-based
cohort in Copenhagen county.
Gastroenterology.
2003;
125
1576-1582
1 A Crohn's disease Clinical study Evaluating infliximab in a New long term Treatment
regimen
Anschrift des Verfassers
Prof. Dr. Jürgen Schölmerich
Klinik und Poliklinik für Innere Medizin
Klinikum der Universität Regensburg
93042 Regensburg