https://www.ualberta.ca/~loewen/Medicine/GIM%20Residents%20Core%20Reading/IBD,%20CROHN'S%20AND%20U.C/accent%20i%20trial.pdf

Maintenance infliximab for Crohn's disease: the ACCENT I randomised trial

Background Infliximab, a chimeric monoclonal antibody directed against tumor necrosis factor α, is an established treatment for Crohn's disease but not ulcerative colitis. Methods Two randomized, double-blind, placebo-controlled studies — the Active Ulcerative Colitis Trials 1 and 2 (ACT 1 and ACT 2, respectively) — evaluated the efficacy of infliximab for induction and maintenance therapy in adults with ulcerative colitis. In each study, 364 patients with moderate-to-severe active ulcerative colitis despite treatment with concurrent medications received placebo or infliximab (5 mg or 10 mg per kilogram of body weight) intravenously at weeks 0, 2, and 6 and then every eight weeks through week 46 (in ACT 1) or week 22 (in ACT 2). Patients were followed for 54 weeks in ACT 1 and 30 weeks in ACT 2. Results In ACT 1, 69 percent of patients who received 5 mg of infliximab and 61 percent of those who received 10 mg had a clinical response at week 8, as compared with 37 percent of those who received placebo (P<0...

/pdf/infliximab-for-induction-and-maintenance-therapy-for-4v31zm5xxu.pdf

Infliximab for induction and maintenance therapy for ulcerative colitis.

https://www.gastrojournal.org/article/S0016-5085(06)02522-4/pdf

Adalimumab for maintenance of clinical response and remission in patients with Crohn's disease: the CHARM trial.

Background Treatment with infliximab, a chimeric monoclonal IgG1 antibody against tumor necrosis factor, can result in the formation of antibodies against infliximab. We evaluated the clinical significance of these antibodies in patients with Crohn's disease. Methods In a cohort of 125 consecutive patients with Crohn's disease who were treated with infliximab infusions, we evaluated the concentrations of infliximab and of antibodies against infliximab, clinical data, side effects (including infusion reactions), and the use of concomitant medications before and 4, 8, and 12 weeks after each infusion. Results A mean of 3.9 infusions (range, 1 to 17) per patient were administered over a mean period of 10 months. Antibodies against infliximab were detected in 61 percent of patients. The presence of concentrations of 8.0 μg per milliliter or greater before an infusion predicted a shorter duration of response (35 days, as compared with 71 days among patients with concentrations of less than 8.0 μg per millilite...

Influence of immunogenicity on the long-term efficacy of infliximab in Crohn's disease.

Erroneous communication between the innate and adaptive immune systems through cytokines results in exaggerated or attenuated immune response. It is not known whether the pathologic immune response in inflammatory bowel disease has its origin in a dysbalance of pro- and anti-inflammatory cytokine release or whether it is secondary in subsequence of a defective intestinal barrier or the destructive power of aggressive microbiota in the gut lumen.

Cytokines in inflammatory bowel disease

https://www.gastrojournal.org/article/S0016-5085(99)70332-X/pdf

Efficacy and safety of retreatment with anti-tumor necrosis factor antibody (infliximab) to maintain remission in Crohn's disease.

Background and aims—New lesions of Crohn’s disease occur early after ileal or ileocolonic resection and ileocolonic anastomosis. We performed a double blind controlled trial to evaluate the safety and tolerance of recombinant human interleukin 10 (IL-10; Tenovil) in subjects operated on for Crohn’s disease. We also assessed the eVect of Tenovil in preventing endoscopic recurrence 12 weeks after surgery. Methods—Patients with Crohn’s disease who underwent curative ileal or ileocolonic resection and primary anastomosis were randomised within two weeks after surgery to receive subcutaneous Tenovil 4 µg/kg once daily (QD) (n=22) or 8 µg/kg twice weekly (TIW) (n=21), or placebo (QD or TIW) (n=22). An ileocolonoscopy was performed after 12 weeks of treatment. Results—Compliance was excellent. The most frequently observed adverse events were mild and moderate in severity and equally distributed across treatment groups. Thirty seven patients in the pooled Tenovil group and 21 patients in the pooled placebo group were evaluable by endoscopy. At 12 weeks, 11 of 21 patients (52%) in the placebo group had recurrent lesions compared with 17 of 37 patients (46%) in the Tenovil group (ns). The incidence of severe endoscopic recurrence was similar in both groups (9%). Conclusion—Tenovil treatment for 12 consecutive weeks in patients with Crohn’s disease after intestinal resection was safe and well tolerated. No evidence of prevention of endoscopic recurrence of Crohn’s disease by Tenovil was observed. (Gut 2001;49:42‐46)

https://gut.bmj.com/content/gutjnl/49/1/42.full.pdf

S.H.J. van Deventer

Papers

Efficacy and safety of retreatment with anti-tumor necrosis factor antibody (infliximab) to maintain remission in Crohn's disease.

Interleukin 10 (Tenovil) in the prevention of postoperative recurrence of Crohn's disease