Toxicity of infliximab in the course of treatment of Crohn’s disease

Abstract

Infliximab is a monoclonal antibody directed against the pro-inflammatory mediator TNF-alpha, which was approved in the US in 1998 for treatment-resistant Crohn's disease. Since that time, the indications have dramatically expanded to include rheumatoid arthritis, ankylosing spondylitis, psoriasis and most recently, active ulcerative colitis. Although the safety profile in the initial studies was quite favourable, subsequent studies have shown that a small percentage of patients reported severe side effects, including pneumonia, tuberculosis, lymphoma, drug-induced lupus and hepatotoxicity. Although these complications are rare, it is important to properly screen patients for predisposing conditions before beginning treatment. Furthermore, concurrent use of other immunosuppresive agents, such as 6-mercaptopurine, may reduce the incidence of less serious side effects, such as arthralgias, myopathies and other antibody-associated diseases. Since its approval, infliximab has revolutionised the treatment of Crohn's disease and has shown benefit in a variety of other inflammatory conditions, but significant toxicities can occur that necessitate thorough screening protocols and periodic clinical evaluation.

Use of Infliximab within 3 Months of Ileocolonic Resection is Associated with Adverse Postoperative Outcomes in Crohn’s Patients

“…Considering the function of TNF-alpha as a potent inflammatory mediator, one would expect that if this compound is blocked, there could be a potential risk for increased infection as shown in multiple studies. 23,24 Therefore, our finding of an increased incidence of sepsis and abscess after surgery is not surprising. It is also conceivable that the immunosuppressive effects of IFX may last well beyond the time when IFX is cleared from the body.…”

“…14,15 There is a paucity of data on perioperative outcomes for CD patients on IFX undergoing surgery. Two previous studies 22, 23 reported outcomes in a small heterogeneous group of patients on the medication at variable time intervals before and after surgery. Since the complexity of surgery in CD patients may be variable and may, in itself, influence outcomes, we evaluated 30-day perioperative outcomes for CD patients who received IFX at any time within 3 months prior to undergoing ileocolonic resection.…”

Early Diagnosis and Treatment of Postoperative Endoscopic Recurrence of Crohn’s Disease: Partial Benefit by Infliximab—A Pilot Study

“…Such strategy would have a number of obvious benefits compared to a standard prophylactic strategy [8][9][10]24]. Published data [5,6] do not clarify whether such strategy is truly effective [7].…”

“…By contrast, data related to the effect of infliximab therapy (rather than prophylaxis) for early endoscopic post surgical recurrence of CD are less consistent [5][6][7]. Such strategy would have clear cost and safety advantages over standard prophylaxis with the same drug [8][9][10].…”

Treatment With Anti-γ-Glutamyl Transpeptidase Antibody Attenuates Osteolysis in Collagen-Induced Arthritis Mice

“…Efficacy varies among patients, although nearly all improve to some extent. In a small percentage of patients, severe side effects, including pneumonia, tuberculosis, lymphoma, and hepatotoxicity, have been reported (31,32) . Therefore, several molecules have been studied to determine the additional therapeutic targets for arthritis.…”