D'Haens, G. et al. Early combined immunosuppression or conventional management in patients with newly diagnosed Crohn's disease: an open randomised trial. Lancet 371, 660-667

Imelda Gastrointestinal Clinical Research Centre, Bonheiden, Belgium.
The Lancet (Impact Factor: 45.22). 03/2008; 371(9613):660-7. DOI: 10.1016/S0140-6736(08)60304-9
Source: PubMed

ABSTRACT Most patients who have active Crohn's disease are treated initially with corticosteroids. Although this approach usually controls symptoms, many patients become resistant to or dependent on corticosteroids, and long exposure is associated with an increased risk of mortality. We aimed to compare the effectiveness of early use of combined immunosuppression with conventional management in patients with active Crohn's disease who had not previously received glucocorticoids, antimetabolites, or infliximab.
We did a 2-year open-label randomised trial at 18 centres in Belgium, Holland, and Germany between May, 2001, and January, 2004. We randomly assigned 133 patients to either early combined immunosuppression or conventional treatment. The 67 patients assigned to combined immunosuppression received three infusions of infliximab (5 mg/kg of bodyweight) at weeks 0, 2, and 6, with azathioprine. We gave additional treatment with infliximab and, if necessary, corticosteroids, to control disease activity. 66 patients assigned to conventional management received corticosteroids, followed, in sequence, by azathioprine and infliximab. The primary outcome measures were remission without corticosteroids and without bowel resection at weeks 26 and 52. Analysis was by modified intention to treat. This trial was registered with, number NCT00554710.
Four patients (two in each group) did not receive treatment as per protocol. At week 26, 39 (60.0%) of 65 patients in the combined immunosuppression group were in remission without corticosteroids and without surgical resection, compared with 23 (35.9%) of 64 controls, for an absolute difference of 24.1% (95% CI 7.3-40.8, p=0.0062). Corresponding rates at week 52 were 40/65 (61.5%) and 27/64 (42.2%) (absolute difference 19.3%, 95% CI 2.4-36.3, p=0.0278). 20 of the 65 patients (30.8%) in the early combined immunosuppression group had serious adverse events, compared with 19 of 64 (25.3%) controls (p=1.0).
Combined immunosuppression was more effective than conventional management for induction of remission and reduction of corticosteroid use in patients who had been recently diagnosed with Crohn's disease. Initiation of more intensive treatment early in the course of the disease could result in better outcomes.

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Available from: Sander van Deventer, Sep 11, 2014
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    • "A 2-year open-label randomized trial by D’Haens et al. [5] showed that short-term infliximab (IFX) combined with azathioprine (AZA) or 6-mercaptopurine was more effective than conventional management for the induction of remission and reduction of corticosteroid use in patients recently diagnosed with CD, and patients treated with early combined immunosuppression had consistently higher rates of remission than controls within the first year of treatment. The findings from this study suggest that early use of immunomodulators following optimal induction therapies has favorable effects on active CD. "
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    ABSTRACT: Background Early induction with biologics can reduce complications in patients with Crohn’s disease (CD) and improve their quality of life. The safety of biologics, however, is uncertain. Granulocyte and monocyte adsorptive apheresis (GMAA) is a natural biologic therapy that selectively removes granulocytes and monocytes/macrophages and has few severe adverse effects. The effects of GMAA on patients with early-diagnosed CD are unclear. We investigated the effects of GMAA combined with thiopurines on patients with early-diagnosed CD. Methods Twenty-two corticosteroid- and biologic-naïve patients with active early-diagnosed CD were treated with intensive GMAA (twice per week) combined with thiopurines administration. Active early-diagnosed CD was defined as follows: (i) within 2years after diagnosis of CD, (ii) with no history of both surgical treatment and endoscopic dilation therapy, and (iii) Crohn’s Disease Activity Index (CDAI) was higher than 200. We investigated the ratios of clinical remission defined as CDAI was less than or equal to 150 at 2, 4, 6 and 52weeks and mucosal healing defined as a Simplified Endoscopic Activity Score for Crohn’s Disease (SES-CD) as 0 at 6 and 52weeks. Adverse events were recorded at each visit. Results The ratios of clinical remission at 2, 4, and 6 weeks were 6 of 22 (27.2%), 12 of 22 (54.5%), and 17 of 22 (77.2%), respectively. At 52 weeks, 18 of 21 patients (81.8%) were in clinical remission. The ratios of mucosal healing at 6 and 52 weeks were 5 of 22 (22.7%) and 11 of 22 (50%), respectively. The difference in the mucosal healing ratio was significant between 6 and 52 weeks (p = 0.044). No serious adverse effects were observed during this study. Conclusions Combination therapy with intensive GMAA and thiopurines administration rapidly induced high remission in patients with active early-diagnosed CD without serious adverse effect. Mucosal healing was observed in 50.0% of enrolled patients. This combination therapy might be a rational option for patients with early-diagnosed CD.
    BMC Gastroenterology 07/2014; 14(1):124. DOI:10.1186/1471-230X-14-124 · 2.37 Impact Factor
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    • "The diagnosis of CD was based on published international criteria [5]. ES and AS CD were defined according with the duration of the disease, as previously described [20] [21] [22], following these criteria: Early = first attack of CD in a patient with no previous history of any gastrointestinal symptoms or surgery; Advanced = CD in a patient with at least five years history from the time of initial diagnosis and with persistent clinical activity requiring immunosuppressors, immunomodulators, steroids or surgery. ES CD patients had never received corticosteroids , antimetabolites or biological therapy and serum was collected within 3 months from the diagnoses (median 1 month). "
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    ABSTRACT: Crohn's disease (CD) represents a highly debilitating disease of difficult diagnosis and increasing incidence. Serum protein profiling of early stage Crohn's disease (ES) CD was investigated in order to improve the comprehension of the very early pathologic mechanisms and to support the difficult diagnostic procedures currently available. Inflammatory proteins and complement 3 chain C (C3c) were over-represented during ES CD, clusterin, retinol binding protein, α1-microglobulin and transthyretin were under-represented. A C3c isoform was found to be present only during ES CD. By now, lack of specific antibodies to detect isoforms made it impossible to perform alternative validation.
    EuPA Open Proteomics 06/2014; 3. DOI:10.1016/j.euprot.2014.02.010
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    • "D'Haens G et al. found that early immunomodulator and biologic therapy was more effective than conventional management for induction of remission [5]. Likewise, we showed that early immunomodulator therapy demonstrated a higher rate of remission than conventional therapy, suggesting that early intervention with immunomodulators might have much more benefit in achieving clinical remission than the conventional strategy. "
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    ABSTRACT: Background The natural course of Crohn’s disease (CD), with continuing relapses and remissions, leads to irreversible intestinal damage. Early adoption of immunomodulator therapy has been proposed in order to address this; however, it is still uncertain whether early immunomodulator therapy could affect the natural course of the disease in real practice. We evaluated the efficacy of such therapy on the prognosis of newly diagnosed patients with CD. Methods This retrospective study included 168 patients who were newly diagnosed with CD and who started treatment at Severance Hospital, Seoul, Korea between January 2006 and March 2013. The short- and long-term outcomes were compared between patients treated with early immunomodulator therapy and those treated with conventional therapy. Results A Kaplan-Meier analysis identified that administration of immunomodulators within 6 months after diagnosis of CD was superior to conventional therapy in terms of clinical remission and corticosteroid-free remission rates (P=0.043 and P=0.035). However, P=0.827). Patients with a baseline elevated CRP level were more likely to relapse (P<0.005). Drug-related adverse events were more frequent in the early immunomodulator therapy group than in the conventional therapy group P=0.029). Conclusions Early immunomodulator therapy was more effective than conventional therapy in inducing remission, but not in preventing relapse. Baseline high CRP level was a significant indicator of relapse.
    BMC Gastroenterology 05/2014; 14(1):85. DOI:10.1186/1471-230X-14-85 · 2.37 Impact Factor
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