Safety considerations when using anti-TNFα therapy to treat Crohn’s disease

Abstract

The safety profile of the three anti-TNFα drugs approved for clinical use in CD patients appears to be comparable among drugs. Data from clinical trials and a growing body of information from post-marketing surveillance indicate that anti-TNFα agents are generally safe, and that most of the observed side effects are mild and easily manageable. Nonetheless, serious short- and long-term adverse events may occur. Accurate selection of patients, careful pre-treatment evaluation, and regular follow-up during therapy could potentially reduce the rate of adverse events related to the use of anti-TNFα drugs.

Anti-TNF Therapy in Crohn’s Disease

“…However, multivariate analysis, demonstrated no significant increased risk of infection (OR 0.99, 95% CI 0.64–1.53) due to anti-TNF therapy after controlling for factors such as disease duration, severity and concurrent corticosteroid and immunomodulator use [117]. In a report of adalimumab safety including six clinical trials, 1.8% of patients had opportunistic infections (most commonly oral candidiasis), and 5.8% had serious infections (most commonly abscess, gastrointestinal, pulmonary and viral infection) [118,119]. Anti-TNF therapy has also been implicated in the susceptibility to tuberculous infection, due to the role of TNF in the formation of granulomas.…”

“…An analysis of the FDA’s adverse event reporting system (AERS) database from 1968–2005 found a relatively strong signal for lymphoma, both in IBD and non-IBD patients, at the disproportionality analysis [122]. The risk of T-cell non-Hodgkin lymphoma was found to be increased in combination therapy use (95% confidence interval (CI) 4.98–354.09; p < 0.0001) and thiopurines alone (95% CI 8.32–945.38; p < 0.0001) but not with anti-TNF use alone (95% CI 0.13–10.61; p = 1.00) [119,123]. There are also data suggesting an increased risk of melanoma in patients on anti-TNF treatment for IBD, with a 1.5−2× increased risk compared to those not exposed [124], however this is also impacted by an increased risk of melanoma associated with IBD independent of the use of biologic therapy [125,126].…”

“…However, most of the available data are from animal and retrospective studies, with no teratogenic effects observed [119]. Infliximab and adalimumab cross the placenta in the beginning of the second trimester, whereas certolizumab does not as it lacks the Fc fragment required for active transport to the foetus [89].…”

Skeletal Fragility in Children with Chronic Disease

“…Catch-up growth with anti-cytokine therapy in CD occurs in approximately 1/3 of children, but the magnitude of increase in height z-score following a year of therapy is only in the order of +0.2 SD [61]. Long-term use of anti-cytokine therapy may be limited by the loss of response, development of antibodies, short-term and long-term side effects including opportunistic infections and cancer risks [62]. For all these reasons and due to the limited window of opportunity to improve growth and bone accrual in some of these adolescents, early intervention may be needed.…”

Vedolizumab vs. ustekinumab as second-line therapy in Crohn’s disease in clinical practice

“…Biological treatment is an established modality in the management of patients suf fer ing from inflam matory bowel dis ease (IBD), however, only antitumor necrosis factor α (anti-TNF) antibodies were available for those patients for a long time. Despite their benefits in the management of IBD, anti-TNFs suf er from two main drawbacks: limited longterm ef cacy, and a relatively high risk of adverse events [1,2].…”