Abstract

The introduction of anti-tumour necrosis factor therapies has provided highly effective treatments for Crohn's disease, making it possible to significantly improve the prognosis of patients. However, neither conventional non-biological therapies nor anti-tumour necrosis factor therapies are routinely used to optimum effect. There are several reasons for this, including a lack of specific evidence to guide common clinical questions and a lack of clearly defined treatment targets. This paper suggests some simple changes to the management of Crohn's disease that have the potential to significantly improve patient outcomes. A new treatment target, ‘deep remission’, which includes mucosal healing as well as clinical remission, may be the first step in defining the successful treatment of Crohn's disease; early clinical studies have demonstrated that this is a readily achievable target. Initiating appropriate treatment early can increase clinical remission rates, improve steroid sparing, induce mucosal healing and prevent structural bowel damage, whereby reducing the need for hospitalization and surgery. There are also clear indications that modifying treatment based on regular objective assessments of disease activity to provide tight disease control can improve patient outcomes in a similar way to that observed in rheumatoid arthritis. These simple changes to management strategy appear to allow the full potential of available treatments to be realized. Clinical studies to further define optimized treatment strategies for Crohn's disease are underway and will provide future direction.

References

1
Pariente
B
Cosnes
J
Danese
S
Sandborn
WJ
Lewin
M
Fletcher
JG
Chowers
Y
D'Haens
G
Feagan
BG
Hibi
T
Hommes
DW
Irvine
EJ
Kamm
MA
Loftus
EV
Jr
Louis
E
Michetti
P
Munkholm
P
Oresland
T
Panés
J
Peyrin-Biroulet
L
Reinisch
W
Sands
BE
Schoelmerich
J
Schreiber
S
Tilg
H
Travis
S
van Assche
G
Vecchi
M
Mary
JY
Colombel
JF
Lémann
M
Development of the Crohn's Disease Digestive Damage Score, the Lémann Score
Inflamm Bowel Dis
 
17
2011
1415
1422
2
Ghosh
S
D'Haens
G
Feagan
BG
Silverberg
MS
Szigethy
EM
What do changes in inflammatory bowel disease management mean for our patients?
J Crohn's Colitis
 
6
Suppl 2
2012
S243
S249
3
Walsh
A
Mabee
J
Trivedi
K
Inflammatory bowel disease
Prim Care
 
38
2011
415
432
4
Colombel
J-F
Rutgeerts
P
Sandborn
WJ
Camez
A
Pollack
PF
Chen
N
Yang
M
Chao
J
Mulani
PM
J Crohn's Colitis
 
4
2010
S11
(abstract OP31 at ECCO 2010).
5
Colombel
JF
Rutgeerts
P
Sandborn
WJ
Yang
M
Lomax
KG
Pollack
PF
Thakkar
R
Camez
A
Chen
N
Mulani
PM
Chaoet
J
Deep remission predicts long-term outcomes for adalimumab-treated patients with Crohn's disease: data from EXTEND
Gut
 
59
Suppl 3
2010
A80
OP371 at UEGW2010
6
Lichtenstein
GR
Hanauer
SB
Sandborn
WJ
Management of Crohn's disease in adults
Am J Gastroenterol
 
104
2009
465
483
7
van Assche
G
Dignass
A
Panes
J
Beaugerie
L
Karagiannis
J
Allez
M
Ochsenkuhn
T
Orchard
T
Rogler
G
Louis
E
Kupcinskas
L
Mantzaris
G
Travis
S
Stange
E
The second European evidence-based Consensus on the diagnosis and management of Crohn's disease: Definitions and diagnosis
J Crohns Colitis
 
4
2010
7
27
8
American Gastroenterological Association Clinical Practice Committee
American Gastroenterological Association medical position statement: perianal Crohn's disease
Gastroenterology
 
125
2003
1503
1507
9
Dignass
A
van Assche
G
Lindsay
JO
Lemann
M
Soderholm
J
Colombel
JF
Danese
S
D'Hoore
A
Gassull
M
Gomollon
F
Hommes
DW
Michetti
P
O'Morain
C
Oresland
T
Windsor
A
Stange
EF
Travis
SP
The second European evidence-based Consensus on the diagnosis and management of Crohn's disease: Current management
J Crohns Colitis
 
4
2010
28
62
10
Ferrante
M
Karmiris
K
Newnham
E
Siffledeen
J
Zelinkova
Z
van Assche
G
Lakatos
PL
Panés
J
Sturm
A
Travis
S
van der Woude
CJ
Reinisch
W
Colombel
J-F
Panaccione
R
Physician perspectives on unresolved issues in the use of conventional therapy in Crohn's disease: results from an international survey and discussion programme
J Crohns Colitis
 
6
2012
11
31
11
Summers
RW
Switz
DM
Sessions
JT
Jr
Becktel
JM
Best
WR
Kern
F
Jr
Singleton
JW
National Cooperative Crohn's Disease Study: results of drug treatment
Gastroenterol
 
77
1979
847
869
12
Modigliani
R
Mary
JY
Simon
JF
Cortot
A
Soule
JC
Gendre
JP
Rene
E
Clinical, biological, and endoscopic picture of attacks of Crohn's disease. Evolution on prednisolone. Groupe d'Etude Thérapeutique des Affections Inflammatoires Digestives
Gastroenterol
 
98
1990
811
818
13
Benchimol
EI
Seow
CH
Steinhart
AH
Griffiths
AM
Traditional corticosteroids for induction of remission in Crohn's disease
Cochrane Database Syst Rev
 
2008
CD006792.
14
Seow
CH
Benchimol
EI
Griffiths
AM
Otley
AR
Steinhart
AH
Budesonide for induction of remission in Crohn's disease
Cochrane Database Syst Rev
 
2008
CD000296.
15
Munkholm
P
Langholz
E
Davidsen
M
Binder
V
Frequency of glucocorticoid resistance and dependency in Crohn's disease
Gut
 
35
1994
360
362
16
Singleton
JW
Law
DH
Kelley
ML
Jr
Mekhjian
HS
Sturdevant
RA
National Cooperative Crohn's Disease Study: adverse reactions to study drugs
Gastroenterol
 
77
1979
870
882
17
Benchimol
EI
Seow
CH
Otley
AR
Steinhart
AH
Budesonide for maintenance of remission in Crohn's disease
Cochrane Database Syst Rev
 
2009
CD002913.
18
Brignola
C
De Simone
G
Belloli
C
Iannone
P
Belluzzi
A
Gionchetti
P
Campieri
M
Barbara
L
Steroid treatment in active Crohn's disease: a comparison between two regimens of different duration
Aliment Pharmacol Ther
 
8
1994
465
468
19
Cosnes
J
Nion-Larmurier
I
Beaugerie
L
Afchain
P
Tiret
E
Gendre
JP
Impact of the increasing use of immunosuppressants in Crohn's disease on the need for intestinal surgery
Gut
 
54
2005
237
241
20
Ramadas
AV
Gunesh
S
Thomas
GA
Williams
GT
Hawthorne
AB
Natural history of Crohn's disease in a population-based cohort from Cardiff (1986-2003): a study of changes in medical treatment and surgical resection rates
Gut
 
59
2010
1200
1206
21
Markowitz
J
Grancher
K
Kohn
N
Lesser
M
Daum
F
A multicenter trial of 6-mercaptopurine and prednisone in children with newly diagnosed Crohn's disease
Gastroenterology
 
119
2000
895
902
22
Sans
M
López-San Román
A
Esteve
M
Bermejo
F
García-Sánchez
V
Torres
Y
Early use of azathioprine has a steroid sparing effect on recently diagnosed Crohn's disease patients
Gastroenterol
 
140
Suppl 1
2011
S109
23
Mate-Jiménez
J
Hermida
C
Cantero-Perona
J
Moreno-Otero
R
6-mercaptopurine or methotrexate added to prednisone induces and maintains remission in steroid-dependent inflammatory bowel disease
Eur J Gastroenterol Hepatol
 
12
2000
1227
1233
24
Lémann
M
Mary
JY
Colombel
JF
Duclos
B
Soule
JC
Lerebours
E
Modigliani
R
Bouhnik
Y
Groupe D'Etude Thérapeutique des Affections Inflammatoires du Tube Digestif. A randomized, double-blind, controlled withdrawal trial in Crohn's disease patients in long-term remission on azathioprine
Gastroenterol
 
128
2005
1812
1818
25
Treton
X
Bouhnik
Y
Mary
JY
Colombel
JF
Duclos
B
Soule
JC
Lerebours
E
Cosnes
J
Lemann
M
Groupe D'Etude Thérapeutique Des Affections Inflammatoires Du Tube Digestif (GETAID)
Azathioprine withdrawal in patients with Crohn's disease maintained on prolonged remission: a high risk of relapse
Clin Gastroenterol Hepatol
 
7
2009
80
85
26
Nachury
M
Lemann
M
Cosnes
J
Gomet
J-M
Beaugerie
L
Allez
M
Gendre
J-P
Modigliani
R
Efficacy of a Second Course of Azathioprine in Patients with Crohn's Disease Relapsing After Azathioprine Withdrawal
Gastroenterol
 
124
2003
A-522
(Abstract T1381).
27
Bouguen
G
Peyrin-Biroulet
L
Surgery for adult Crohn's disease: what is the actual risk?
Gut
 
60
2011
117
181
28
Peyrin-Biroulet
L
Loftus
EV
Jr
Colombel
JF
Sandborn
WJ
Early Crohn disease: a proposed definition for use in disease-modification trials
Gut
 
59
2010
141
147
29
Kirwan
JR
Conceptual Issues in Scoring Radiographic Progression in RA
J Rheumatol
 
26
1999
720
725
30
Colombel
JF
Sandborn
WJ
Rutgeerts
P
Enns
R
Hanauer
SB
Panaccione
R
Schreiber
S
Byczkowski
D
Li
J
Kent
JD
Pollack
PF
Adalimumab for maintenance of clinical response and remission in patients with Crohn's disease: the CHARM trial
Gastroenterology
 
132
1
2007
52
65
31
Schreiber
S.
Reinisch
W.
Colombel
J.
Sandborn
W.J.
Hommes
D
Li
J
Kent
JD
Pollack
PF
Early Crohn's disease shows high levels of remission to therapy with adalimumab: Sub-analysis of CHARM
Gastroenterology
 
132
4 Suppl 1
2007
A147
(abstract 985).
32
D'Haens
G
Baert
F
van Assche
G
Caenepeel
P
Vergauwe
P
Tuynman
H
De Vos
M
van Deventer
S
Stitt
L
Donner
A
Vermeire
S
Van de Mierop
FJ
Coche
JC
van der Woude
J
Ochsenkuhn
T
van Bodegraven
AA
Van Hootegem
PP
Lambrecht
GL
Mana
F
Rutgeerts
P
Feagan
BG
Hommes
D
Early combined immunosuppression or conventional management in patients with newly diagnosed Crohn's disease: an open randomised trial
Lancet
 
371
2008
660
667
33
Baert
F
Moortgat
L
van Assche
G
Caenepeel
P
Vergauwe
P
De Vos
M
Stokkers
P
Hommes
D
Rutgeerts
P
Vermeire
S
D'Haens
G
Mucosal healing predicts sustained clinical remission in patients with early-stage Crohn's disease
Gastroenterology
 
138
2010
463
468
34
Colombel
J-F
Sandborn
WJ
Reinisch
W
Mantzaris
GJ
Kornbluth
A
Rachmilewitz
D
Lichtiger
S
D'Haens
G
Diamond
RH
Broussard
DL
Tang
KL
van der Woude
CJ
Rutgeerts
P
for the SONIC Study Group
Infliximab, azathioprine, or combination therapy for Crohn's disease
N Engl J Med
 
362
2010
1383
1395
35
Sandborn
WJ
Panaccione
R
Thakkar
R
Lomax
KG
Chen
N
Mulani
PM
Chao
J
Yang
M
Duration of Crohn's Disease Affects Mucosal Healing in Adalimumab-Treated Patients: Results From EXTEND
J Crohn's Colitis
 
4
2010
S36
(abstract PO69 at ECCO 2010).
36
Peyrin-Biroulet
L
Billioud
V
D'Haens
G
Panaccione
R
Feagan
B
Panés
J
Danese
S
Schreiber
S
Ogata
H
Hibi
T
Higgins
PDR
Beaugerie
L
Chowers
Y
Louis
E
Steinwurz
F
Reinisch
W
Rutgeerts
P
Colombel
J-F
Travis
S
Sandborn
WJ
Development of the Paris Definition of Early Crohn's Disease for Disease-Modification Trials: Results of an International Consensus
Am J Gastroenterol
 
2012
in press
37
Holman
RR
Paul
SK
Bethel
MA
Neil
HA
Matthews
DR
Long-term follow-up after tight control of blood pressure in type 2 diabetes
N Engl J Med
 
359
2008
1565
1576
38
Grigor
C
Capell
H
Stirling
A
McMahon
AD
Lock
P
Vallance
R
Kincaid
W
Porter
D
Effect of a treatment strategy of tight control for rheumatoid arthritis (the TICORA study): a singleblind randomised controlled trial
Lancet
 
364
2004
263
269
39
Hommes
D
Colombel
J.-F
Emery
P
Greco
M
Sandborn
WJ
Changing Crohn's disease management: Need for new goals and indices to prevent disability and improve quality of life
J Crohn's Colitis
 
6
Suppl 2
2012
S224
S234
40
Daperno
M
D'Haens
G
Van Assche
G
Baert
F
Bulois
P
Maunoury
V
Sostegni
R
Rocca
R
Pera
A
Gevers
A
Mary
JY
Colombel
JF
Rutgeerts
P
Development and validation of a new, simplified endoscopic activity score for Crohn's disease: the SES-CD
Gastrointest Endosc
 
60
2004
505
512
41
Rimola
J
Ordás
I
Rodriguez
S
García-Bosch
O
Aceituno
M
Llach
J
Ayuso
C
Ricart
E
Panés
J
Magnetic resonance imaging for evaluation of Crohn's disease: validation of parameters of severity and quantitative index of activity
Inflamm Bowel Dis
 
17
2011
1759
1768
42
Tamboli
CP
Doman
DB
Patel
A
Current and future role of biomarkers in Crohn's disease risk assessment and treatment
Clin Exp Gastroenterol
 
4
2011
127
140
43
Solem
CA
Loftus
EV
Jr
Tremaine
WJ
Harmsen
WS
Zinsmeister
AR
Sandborn
WJ
Correlation of C-reactive protein with clinical, endoscopic, histologic, and radiographic activity in inflammatory bowel disease
Inflamm Bowel Dis
 
11
2005
707
712
44
Judd
TA
Day
AS
Lemberg
DA
Turner
D
Leach
ST
Update of fecal markers of inflammation in inflammatory bowel disease
J Gastroenterol Hepatol
 
26
2011
1493
1499
45
Tibble
JA
Sigthorsson
G
Bridger
S
Fagerhol
MK
Bjarnason
I
Surrogate markers of intestinal inflammation are predictive of relapse in patients with inflammatory bowel disease
Gastroenterology
 
119
2000
15
22
46
Schmidt
C
Giese
T
Hermann
E
Zeuzem
S
Meuer
SC
Stallmach
A
Predictive value of mucosal TNF-alpha transcripts in steroid-refractory Crohn's disease patients receiving intensive immunosuppressive therapy
Inflamm Bowel Dis
 
13
2007
65
70
47
Jurgens
M
Mahachie John
JM
Cleynen
I
Schnitzler
F
Fidder
H
van Moerkercke
W
Ballet
V
Noman
M
Hoffman
I
van Assche
G
Rutgeerts
PJ
van Steen
K
Vermeire
S
Levels of C-reactive protein are associated with response to infliximab therapy in patients with Crohn's disease
Clin Gastroenterol Hepatol
 
9
2011
421
427