Prolonged fever after Infliximab infusion

Pharmacologic management for ulcerative colitis (UC) has recently been expanded to include antitumor necrosis factor (TNF) therapy for severe disease. Infliximab, a chimeric monoclonal antibody directed again TNF α was first tested in patients with Crohn’s disease. In addition to serious infections, malignancy, drug induced lupus and other autoimmune diseases, serum sickness-like reactions, neurological disease, and infusion reactions further complicate the use of Infliximab. We report a case of prolonged fever after Infliximab infusion to treat steroid refractory UC.     

Infliximab improves inflammation and anthropometric measures in pediatric Crohn's disease

Background and Aim: Infliximab (IFX) is a monoclonal antibody licensed to treat medically refractory Crohn's disease (CD). Our aim was to elucidate the effects of IFX therapy on clinical, growth and serum parameters in children with CD in a single pediatric center in Sydney, Australia. Methods: A retrospective case series review of children treated with IFX for CD at Sydney Children's Hospital, Australia was undertaken, with a review of outcomes after starting IFX. Main outcome measures were response and remission (as measured according to improvements in Pediatric Crohn's Disease Activity Index scores and Physician Global Assessment), laboratory markers (C‐reactive protein, erythrocyte sedimentation rate, hemoglobin, white cell count, lymphocytes, neutrophils, platelets, albumin) and growth (Z scores). Results: The 16 patients included had a mean age at first infusion of 13.0 years (1.25–17.5 years). Six of 12 patients (with adequate data available) were in remission at 2 weeks following the first infusion. At 1 year, 10 of 12 patients (83%) were in remission. Mean C‐reactive protein and erythrocyte sedimentation rate had fallen significantly (P < 0.05) at 2 weeks (from 29 to 7 mg/L and 40 to 19 mm/h, respectively). Positive trends were observed for all other parameters, excluding lymphocytes and white cell count. At 1 year, mean Z score for body mass index improved significantly from ?0.9 to ?0.1 (P < 0.01). Conclusions: Disease activity subsides in most children treated with IFX for CD. IFX therapy also improves some growth parameters. The pattern of improvement requires further elucidation, as the results in the present study suggest differing dosing frequency of infusion may achieve better efficacy.     

Infliximab stopped severe gastrointestinal bleeding in Crohn's disease

To report the result of rapid ulcer healing by infliximab in Crohn's patients with severe enterocolic bleeding. During 2005 and 2010, inflammatory bowel disease database of King Chulalongkorn Memorial and Samitivej hospitals were reviewed. There were seven Crohn's disease (CD) patients (4 women and 3 men; mean age 52 ± 10.4 years; range: 11-86 years). Two of the seven patients developed severe gastrointestinal bleeding (GIB) as a flare up of CD whereas the other five patients presented with GIB as their first symptom for CD. Their mean hemoglobin level dropped from 12 ± 1.3 g/dL to 8.7 ± 1.3 g/dL in a 3-d period. Median packed red blood cells units needed for resuscitation was 4 units. Because of uncontrolled bleeding, surgical resection was considered. However, due to the poor surgical candidacy of these patients (n = 3) and /or possible development of short bowel syndrome (n = 6), surgery was not pursued. Likewise angiographic embolization was not considered in any due to the risk of large infarction. All severe GIBs successfully stopped by one or two doses of intravenous infliximab. Our data suggests that infliximab is an alternative therapy for CD with severe GIB when surgery has limitation or patient is a high risk.     

Infliximab prevents Crohn’s disease recurrence after ileal resection

Evaluation of: Regueiro M, Schraut W, Baidoo L. Infliximab prevents Crohn’s disease recurrence after ileal resection. Gastroenterology 136, 441–450 (2009).

In the evaluation of drugs for the prevention of postoperative recurrence in Crohn’s disease (CD), severe endoscopic recurrence (Rutgeerts score: i-2) is the primary outcome because of its high predictive value of clinical relapse. At 1 year, severe endoscopic recurrence rates range from 30 to 79% in untreated patients. Many drugs have been evaluated in controlled clinical trials for the prevention of postoperative recurrence of CD, such as mesalamine, azathioprine/6-mercaptopurine, metronidazole/ornidazole, probiotics, budesonide and IL-10. The results of these studies are conflicting. Amongst these drugs, mesalamine and metronidazole, alone or in combination with azathioprine, have been shown to be effective in the risk reduction of postoperative recurrence of CD, with nonhomogeneous results. A recent small trial reports the role of infliximab in the prevention of severe endoscopic recurrence; the drug was effective in obtaining an absolute risk reduction of 75.5%. Considering the cost and safety problems of biological therapy, this result should be confirmed in a large trial before infliximab can be recommended for the prevention of endoscopic recurrence in CD.     

Infliximab in pediatric inflammatory bowel disease rapidly decreases fecal calprotectin levels

AIM: To study the response to infliximab in pediatric inflammatory bowel disease (IBD), as reflected in fecal calprotectin levels. METHODS: Thirty-six pediatric patients with IBD [23 Crohn’s disease (CD), 13 ulcerative colitis (UC); median age 14 years] were treated with infliximab. Fecal calprotectin was measured at baseline, and 2 and 6 wk after therapy, and compared to blood inflammatory markers. Maintenance medication was unaltered until the third infusion but glucocorticoids were tapered off if the pat...     

Intermittent Purpura Development Associated with Leukocytoclastic Vasculitis Induced by Infliximab for Crohn's Disease

Anti-tumor necrosis factor (TNF) α agents, widely used for the treatment of Crohn''s disease (CD), can sometimes induce skin-associated adverse events, which mainly include psoriasis-like eruptions, eczema, and cutaneous infections. In contrast, purpura caused by vasculitis is rarely seen. We herein report a unique case of leukocytoclastic vasculitis induced by infliximab administered for CD in which intermittent purpura development was noted. Fluorescent immunostaining showed no immunoglobulin A deposition on the vessel walls. No purpura was initially seen after starting infliximab, but it appeared approximately 10 months later; however, administration did not have to be discontinued, and the condition was later resolved. The present findings provide important details regarding vasculitis induced by anti-tumor necrosis factor-α agent administration.     

Infliximab heals intestinal inflammatory lesions and restores growth in children with Crohn’s disease

BACKGROUND: Infliximab has recently emerged as an efficacious agent for patients with severe Crohn's disease. There are only few studies on the use of infliximab in children with Crohn's disease: most of them are retrospective and deal only with the clinical response to the drug. AIM: We aimed at assessing the efficacy of infliximab in children and adolescents with severe Crohn's disease recruited consecutively and followed up prospectively at a single centre. Clinical response, intestinal inflammation and growth pattern were evaluated. PATIENTS: Eighteen patients entered into the trial (median age: 13 years, range: 6-18). They were referred because of severe symptoms with unsatisfactory response to conventional drugs. METHODS: All patients received a baseline schedule of three intravenous infusions of infliximab (0, 2 and 6 weeks), 5 mg/kg. Paediatric Crohn's Disease Activity Index, nutritional and activity serum variables, and ileocolonoscopy (with histology) were evaluated before and 8 weeks after beginning the therapy. All patients had long-term administration of azathioprine (2 mg/kg per day). After the baseline schedule, eight patients had a retreatment infusion of infliximab (5 mg/kg) every 8 weeks. Weight and height Z scores were measured before starting the baseline infusion programme and after 6 months. RESULTS: After 8 weeks of therapy, there was a dramatic improvement in Paediatric Crohn's Disease Activity Index, in nutritional and activity blood parameters, as well as in endoscopic and histological scores; 10 patients had a clinical remission (Paediatric Crohn's Disease Activity Index < or = 10), 12 patients had an inflammatory remission (decrease in both endoscopic and histological scores for > or = 50% as compared to baseline values). In all patients corticosteroids were stopped within 4 weeks after beginning infliximab therapy. After 6 months of therapy, Paediatric Crohn's Disease Activity Index was markedly lower than the pre-treatment value; however, it was significantly lower in patients on retreatment than in those who received only three infusions of infliximab. Furthermore, a significant increase in both weight and height Z scores was observed 6 months after beginning of the baseline infusion programme. Moreover, weight and height gain was significantly higher in patients on retreatment rather than in those treated only with three baseline infusions of infliximab. Mild infusion reactions controlled by slowing infusion rate were observed in four patients. No delayed hypersensitivity-like reactions were seen. CONCLUSIONS: In children with severe Crohn's disease, infliximab is a safe and valuable treatment in inducing remission, in healing inflammatory lesions of the gut, as documented by endoscopy and histology, and in promoting growth. Retreatment infusions of infliximab may be suggested in childhood-onset Crohn's disease to maintain remission and reverse growth failure.     

Infliximab in rheumatoid arthritis

Current Rheumatology Reports -     

Comparison of Point-of-Care and Classical Immunoassays for the Monitoring Infliximab and Antibodies Against Infliximab in IBD

Digestive Diseases and Sciences - The primary objective is to assess whether the POC assays to measure infliximab residual trough level in the serum of IBD patients were non-inferior to the ELISA...     

Infliximab as disease-modifying therapy

Recent insights in the pathophysiology of Crohn's disease have revealed that tumour necrosis factor (TNF) plays a pivotal role in mucosal inflammation. Infliximab is a chimeric anti-TNF monoclonal antibody with potent anti-inflammatory effects, probably based on apoptosis of inflammatory cells. Numerous controlled trials have demonstrated efficacy in both active and fistulating Crohn's disease. Appropriate indications for using infliximab and growing experience with safety aspects have made this treatment a highly valuable tool in the management of Crohn's disease.     

Infliximab in ulcerative colitis

Infliximab is effective for treatment of moderate-to-severe UC and is recommended for patients who have had an inadequate response to medical therapy or who are intolerant of or do not desire to take the potential risk of using specific agents including immunomodulators (cyclosporine A, azathioprine, or 6-mercaptopurine), corticosteroids, and, potentially, mesalamine. Future trials are needed to assess the efficacy of infliximab with immunomodulators to see if additional benefit is achieved so that the risk-benefit ratio is positive. Based on the favorable efficacy of infliximab for UC therapy, the ground work has been established for evaluating infliximab and addressing some of the many unanswered questions and also for assessing other anti-TNF agents and streamlining the anti-TNG antibody to improve efficacy, reduce side effects, and ease administration.