SONIC Study Group. Infliximab, azathioprine, or combination therapy for Crohn's disease

Hôpital Claude Huriez and Centre d'Investigation Clinique, Centre Hospitalier Universitaire de Lille, Université Lille Nord de France, Lille, France.
New England Journal of Medicine (Impact Factor: 55.87). 04/2010; 362(15):1383-95. DOI: 10.1056/NEJMoa0904492
Source: PubMed

ABSTRACT The comparative efficacy and safety of infliximab and azathioprine therapy alone or in combination for Crohn's disease are unknown.
In this randomized, double-blind trial, we evaluated the efficacy of infliximab monotherapy, azathioprine monotherapy, and the two drugs combined in 508 adults with moderate-to-severe Crohn's disease who had not undergone previous immunosuppressive or biologic therapy. Patients were randomly assigned to receive an intravenous infusion of 5 mg of infliximab per kilogram of body weight at weeks 0, 2, and 6 and then every 8 weeks plus daily oral placebo capsules; 2.5 mg of oral azathioprine per kilogram daily plus a placebo infusion on the standard schedule; or combination therapy with the two drugs. Patients received study medication through week 30 and could continue in a blinded study extension through week 50.
Of the 169 patients receiving combination therapy, 96 (56.8%) were in corticosteroid-free clinical remission at week 26 (the primary end point), as compared with 75 of 169 patients (44.4%) receiving infliximab alone (P=0.02) and 51 of 170 patients (30.0%) receiving azathioprine alone (P<0.001 for the comparison with combination therapy and P=0.006 for the comparison with infliximab). Similar numerical trends were found at week 50. At week 26, mucosal healing had occurred in 47 of 107 patients (43.9%) receiving combination therapy, as compared with 28 of 93 patients (30.1%) receiving infliximab (P=0.06) and 18 of 109 patients (16.5%) receiving azathioprine (P<0.001 for the comparison with combination therapy and P=0.02 for the comparison with infliximab). Serious infections developed in 3.9% of patients in the combination-therapy group, 4.9% of those in the infliximab group, and 5.6% of those in the azathioprine group.
Patients with moderate-to-severe Crohn's disease who were treated with infliximab plus azathioprine or infliximab monotherapy were more likely to have a corticosteroid-free clinical remission than those receiving azathioprine monotherapy. ( number, NCT00094458.)

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Available from: Gerassimos Mantzaris, Sep 26, 2015
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    • "Finally, the current regulatory definitions for the approval of new drugs for UC include endoscopic healing among the secondary endpoints for trials for newer drugs [36]. The findings of the present study confirm that the Mayo score might produce sub-optimal inter-observer agreements (0.53–0.71). "
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    ABSTRACT: Background Endoscopic activity has become a therapeutic endpoint in inflammatory bowel disease. Aim of this study was to evaluate inter-observer agreement for endoscopic scores in a real-life setting. Methods 14 gastroenterologists with experience in inflammatory bowel disease care and endoscopic scoring reviewed videos of ulcerative colitis (n = 13) and postoperative (n = 10) and luminal (n = 8) Crohn's disease. The Mayo subscore for ulcerative colitis, Rutgeerts score for postoperative Crohn's disease, Crohn's disease endoscopic index of severity (CDEIS), and the simple endoscopic score-Crohn's disease (SES-CD) for luminal Crohn's disease were calculated. A subset of five endoscopic clips were assessed by 30 general gastroenterologists without specific experience in endoscopic scores. Kappa statistics and intraclass correlation coefficients were used to measure agreement. Results Mayo subscore agreement was suboptimal: kappas were 0.53 (95% confidence interval 0.47–0.56) and 0.71 (0.67–0.76) for the two groups. Rutgeerts score agreement was fair: kappas were 0.57 (0.51–0.65) and 0.67 (0.60–0.72). Agreements for CDEIS and SES-CD were good: intraclass correlation coefficients for the two groups were 0.83 (0.54–1.00) and 0.67 (0.36–0.97) for CDEIS and 0.93 (0.76–1.00) and 0.68 (0.35–0.97) for SES-CD, respectively. Conclusion The reproducibility of endoscopic scores in inflammatory bowel disease remains suboptimal, which could potentially have major effects on therapeutic choices.
    Digestive and Liver Disease 11/2014; 46(11). DOI:10.1016/j.dld.2014.07.010 · 2.96 Impact Factor
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    • "P=0.02) or AZA (30.0%; P<0.001) without an increased risk of serious infections.35 Infliximab, azathioprine, or infliximab + azathioprine for treatment of moderate to severe ulcerative colitis: The UC SUCCESS trial follows a similar design in UC patients.36 "
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    ABSTRACT: Dovepress 359 R E v i E w open access to scientific and medical research Open Access Full Text Article Abstract: Infliximab (IFX) is an effective treatment for inducing and maintaining response in Crohn's disease and ulcerative colitis patients. Some patients present lack of response or loss of response to IFX during maintenance therapy. Empirical management with combination therapy with an immunomodulator, IFX dose escalation, or switching IFX for another antitumor necrosis factor-α drug, mainly adalimumab, is common in clinical practice. Selecting the best choice with the help of serum drug concentrations and trough IFX antibody concentrations could be a very interesting approach. In addition to surgery, a broad spectrum of new drugs has been tested and could expand treatment options in the near future.
    Clinical and Experimental Gastroenterology 09/2014; 7. DOI:10.2147/CEG.S45297
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    • "On presentation this patient was treated with a combination of 6-mercaptopurine and adalimumab. There is no clear evidence to suggest that a combination of adalimumab with a thiopurine is superior to adalimumab alone in CD (as opposed to Infliximab where such benefit was clearly demonstrated [14]) and pregnancy-related data are even more limited. "
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    ABSTRACT: Background Evaluation of pregnant women with known or suspected Crohn’s disease (CD) remains a challenge. Magnetic Resonance Enterography (MRE) is a promising diagnostic tool in these patients; however, the clinical data on MRE utilization in pregnancy is scarce. The aim of the study was to describe the experience with MRE in pregnant CD patients in a tertiary referral center. Methods We retrospectively reviewed MRE studies performed in pregnant women with known or suspected CD that were performed between January 2007 and November 2012. Imaging findings, clinical management and outcome were extracted from patient’s file and electronic records. Image quality was evaluated. Results Ten studies of 9 patients were included. MRE protocol was modified to maximize maternal and fetal safety, and intravenous gadolinium was not used. In 7 patients, CD diagnosis was previously established; six were admitted with clinical symptoms consistent with CD exacerbation, and an additional patient with a recurrent groin abscess without apparent luminal symptoms. In all seven patients, imaging features consistent with active CD were detected; new penetrating complications were detected in 4 patients. Two patients underwent MRE for suspected CD which was not comforted by study results. The clinical management was significantly impacted by MRE results in all positive cases. The image quality of the fast MRE sequences obtained without gadolinium was satisfactory and allowed meaningful interpretation. Conclusion MRE with an adapted protocol for pregnancy is a reliable imaging modality to manage in pregnant women with known or suspected CD.
    BMC Gastroenterology 08/2014; 14(1):146. DOI:10.1186/1471-230X-14-146 · 2.37 Impact Factor
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