Up to 60% of Crohn disease patients taking an anti—tumor necrosis factor (TNF) monoclonal antibody medication eventually stop responding to treatment, but the optimal management of these patients has not been clearly defined.
Up to 60% of Crohn disease (CD) patients taking an anti—tumor necrosis factor (TNF) monoclonal antibody medication eventually stop responding to treatment, but the optimal management of these patients has not been clearly defined.
A recent review and meta-analysis by Christian Pagnini, MD, PhD, and colleagues, published in Gastroenterology Research and Practice concludes that there is an increasing number of treatment choices for such anti-TNF failures, including using a second anti-TNF monoclonal antibody, and biologics with alternative mechanism of action, such as the anti-integrins vedolizumab (reference biologic, Entyvio) and natalizumab (reference biologic, Tysabri), and the anti-interleukin (IL)-12/IL-23 antibody ustekinumab (reference biologic, Stelara).1 The study found that no specific agent was shown to be clearly superior to others among the only available indirect comparisons currently in the literature.
The analysis relied on 8 randomized, controlled trials (RCTs) involving 1281 CD patients who were treated with biologics and 733 CD patients who received placebo. All 8 RCTs had 2 arms, with one being placebo administration. Anti-TNF treatment failures were defined as patients who failed to respond (primary failure), those who lost their initial response (secondary failure), and those who were forced to discontinue therapy due to toxicity concerns.
Treatment with a second biologic was found to be superior to placebo for both induction of remission (odds ratio [OR] 2.2; 95% confidence interval [CI], 1.7-3) and response (OR 1.9; 95% CI, 1.5-2.5), with global rates of 24% and 42%, respectively (placebo rate: 11% and 27%; P<.0001 for both). Although no specific agent was found to be clearly superior to others, adalimumab performed relatively better with inducing disease remission, followed by vedolizumab.
Further research is needed to identify optimal management strategies for this challenging subset of patients, the study authors note. Because, for several years, anti-TNF inhibitors have been the only available option for biologic treatment (except for natalizumab, which had limited availability), the number of patients in this hard-to-treat group is rapidly increasing, and guidance about their management is an urgent need. Despite the encouraging findings, the authors note that an improved characterization and classification of CD patients is needed, with the aid of relevant molecular biomarkers or clinical features in order to appropriately identify disease phenotypes with specific responses to selected therapeutic regimens.
“The end goal should be a highly tailored therapy with improved efficacy and outcomes in all patients, minimizing unnecessary drug exposure and adverse events,” the authors conclude.
Pagnini C, Siakavellas SI, Bamias G. Systematic review with network meta-analysis: efficacy of induction therapy with a second biological agent in anti-TNF-experienced Crohn’s disease patients. Gastroenterol Res Pract. 2018; 2018:6317057. doi.org/10.1155/2018/6317057. eCollection 2018.