Area Editoriale
GR D'Haens, R Panaccione, PDR Higgins, S Vermeire, M Gassull, Y Chowers, SB Hanauer, H Herfarth, DW Hommes, M Kamm, R Löfberg, A Quary, B Sands, A Sood, G Watermayer, Bret Lashner, M Lémann, Scott Plevy, W Reinisch, S Schreiber, C Siegel, S Targan, M Watanabe, B Feagan, WJ Sandborn, JF Colombel, and S Travis. The London Position Statement of the World Congress of Gastroenterology on Biological Therapy for IBD With the European Crohn's and Colitis Organization: When to Start, When to Stop, Which Drug to Choose, and How to Predict Response? Am J Gastroenterol 2011;106: 199-212;
Conventional induction therapy for IBD
WCOG Statement 1.1
While corticosteroids for IBD provide short-term efficacy, they are associated with a significant number of adverse effects. An evolving concept is therefore, to limit long-term steroid therapy, which can be facilitated by biological therapy. [EL 1b]
How many patients with IBD need biological therapy?
WCOG Statement 1.2
Not all patients with IBD need biological therapy. [EL 5]
Identifying the need for biological therapy
WCOG Statement 1.3
Clinical characteristics can be used to select patients with CD who should receive immunosuppression and/or anti-TNF treatment at an early stage of their illness. [EL 2c]
When to avoid biological therapy
Fibrostenotic CD without inflammatory activity
WCOG Statement 1.4
Patients with fibrostenotic CD rarely benefit from biologic therapy. [EL 5]
Infections and vaccinations
WCOG Statement 1.5
Patients with infection should not receive biological therapy until the infection is under control. Any abscess needs effective drainage first. Latent infections (such as tuberculosis, hepatitis B, or immunodeficiency virus) should be excluded or treated before biological therapy starts. Patients who have received live vaccines should not receive biological therapy for 3 months. [EL 5]
WCOG Statement 1.6
Before starting biological therapy latent tuberculosis should be excluded. The vaccination status should be reviewed and updated if necessary. [EL 5]
Malignancy and other relative contraindications
WCOG Statement 1.7
Patients with a history of malignancy (excluding non-melanoma skin cancer) or lymphoproliferative disorder, severe congestive heart failure, or demyelinating neurologic disease should not be treated with anti-TNF therapy if other options exist. [EL 5]
Choice of biological therapy
WCOG Statement 1.8
Based on the available evidence on mode of administration, clinical outcomes, quality of life outcomes and economic analyses, the first-line biologic for luminal CD should be tailored to the individual patient, practice and country setting. [EL 2c]
WCOG Statement 1.9
Currently, infliximab has the longest and most extensive history of published clinical trial data and clinical experience in CD. Studies with other biologic agents (adalimumab, certolizumab pegol and natalizumab) suggest that they produce generally similar benefits in CD, although the study populations were different. [EL 5]
When to start biological therapy
Luminal CD
WCOG Statement 1.10
Biological therapy is indicated in steroid-refractory, steroid-dependent and/or immunomodulator-refractory inflammatory bowel disease and in patients intolerant to these conventional therapies. [EL 1b]
Perianal fistulizing CD
WCOG Statement 1.11
A complex fistula in CD is an indication for biological therapy in conjunction with surgical drainage. [EL 1b]
WCOG Statement 1.12
The efficacy of IFX for induction of fistula closure is better documented than for ADA or CZP [EL 2c]. The relative strength of available data suggests that IFX should be the first line biologic for fistulizing CD until more data become available. [EL 5]
Local sepsis and abscess
WCOG Statement 1.13
All septic collections need to be drained before biological therapy is started. [EL 5]
Treatment-refractory UC
WCOG Statement 1.14
Infliximab is effective for treatment-refractory, moderate or severe UC [EL 1b]. IFX can induce or maintain remission and mucosal healing [EL 2c]. It is not known whether oral immunomodulators without IFX will maintain remission. Other drugs may prove as effective, but there is insufficient published evidence. [EL 4]
Acute severe UC
WCOG Statement 1.15
For patients admitted to the hospital with severe UC colitis that is then refractory to intravenous steroids, IFX halves the need for colectomy on that admission [EL 2b]. The efficacy of IFX relative to cyclosporine remains to be determined.
Role of immunomodulators when starting biological therapy
WCOG Statement 1.16
When starting biological therapy in patients with CD naïve to thiopurines the combination of IFX and AZA is better for induction of remission and mucosal healing over 1 year [EL 1b]. The optimal maintenance strategy after this induction regimen and whether the same applies to other agents remains unknown.
Continuing biological therapy for luminal CD
WCOG Statement 1.17
Patients with moderate to severe luminal CD who have responded to an induction regimen with anti-TNF therapy should be considered for scheduled re-treatment with or without concomitant immunomodulators. This strategy is more effective than episodic therapy for maintaining response. NAT for appropriately selected patients is also effective at maintaining response. [EL 1b]
Continuing biological therapy for fistulizing CD
WCOG Statement 1.18
Patients with fistulizing CD who have responded to an induction regimen with anti-TNF therapy, should receive scheduled re-treatment with IFX or ADA, since this is effective for maintaining fistula closure or response [IFX EL 1b; ADA EL 2b]. No controlled data are available for fistula closure with NAT or CZP.
Continuing biological therapy for UC
WCOG Statement 1.19
Patients with UC refractory to conventional therapy which has responded to infliximab should best be considered for continuing therapy, since scheduled re-treatment is effective for maintaining response and reducing the risk of colectomy. [EL 1b]
Role of immunomodulators and continuing biological therapy
WCOG Statement 1.20
Combined treatment with an immunosuppressant and infliximab for patients with moderate-severe CD is more effective than monotherapy for patients naïve to both agents [IFX EL1b, ADA, CZP EL5].
Predicting response to biological therapy
Predictors of response in luminal CD
WCOG Statement 1.21
Patients with early luminal CD have a higher chance of response to anti-TNF therapy than those with longstanding disease. [EL 3]
Biological predictors
WCOG Statement 1.22
Patients with a high CRP have a higher chance of achieving and maintaining response to biological therapy than patients with a low or normal CRP. [EL 1b]
Trough drug concentrations
WCOG Statement 1.23
High trough concentrations of IFX have been associated with more durable maintenance of clinical response [EL 2b] and low trough concentrations with potential loss of response.
WCOG Statement 1.24
Despite attempts to link genetic factors to the clinical response to anti-TNF therapy, no definitive result can currently be translated into clinical practice. [EL 2c]
Therapeutic strategies
Bridging from biological therapy to immunomodulators in CD
WCOG Statement 1.25
Bridge therapy to an oral immunomodulator has been shown to be associated with a higher rate of clinical relapse than scheduled re-treatment for patients with moderate-severe luminal CD who have responded to induction biological therapy. [EL 2b]
Bridging from biological therapy to immunomodulators in UC
WCOG Statement 1.26
Hospitalized patients with UC refractory to intravenous steroids who have responded to IFX can have a prolonged response to an oral immunomodulator without scheduled re-treatment, although more data are needed. [EL 2b]
Managing loss of response to biological therapy
WCOG Statement 1.27
A diminished or suboptimal response to IFX can be managed by:
i. shortening the interval between dosing [EL 2b]
ii. increasing the dose to 10 mg/kg [EL 1b]
WCOG Statement 1.28
Patients losing response to one anti-TNF have a lower chance of responding to a second anti-TNF agent. [EL 5]
Managing intolerance to biological therapy
WCOG Statement 1.29
Patients with CD who have intolerance to one anti-TNF therapy may achieve a therapeutic response to a different anti-TNF agent. Careful consideration should be given to the reasons for intolerance. [IFX EL 1b, ADA/CZP EL 2b]
WCOG Statement 1.30
The unique risks of natalizumab, while rare, and its current approved labeling as a second-line biologic agent in some countries, will lead many practitioners to choose an anti-TNF agent as first-line and make natalizumab a second- or even third-line agent (after a second attempt at anti-TNF therapy). [EL 5]
Stopping biological therapy
WCOG Statement 1.31
In patients with UC or CD who have responded to a year of anti-TNF therapy, the benefits of continuing therapy should be weighed against the risks of discontinuation. Withdrawal of therapy is possible in patients with CD who have both complete mucosal healing and no biological evidence of inflammation [EL 2b]. The previous pattern of disease and response to different therapies are essential considerations. There are no data for UC.