Abstract
Loss of response to antitumor necrosis factor (anti-TNF) therapies in inflammatory bowel disease occurs in a high proportion of patients. Our aim was to evaluate the loss of response to anti-TNF therapy, considered as the need for dose intensification (DI), DI effectiveness and the possible variables influencing its requirements. Bibliographical searches were performed. Selection: prospective and retrospective studies assessing DI in Crohn’s disease and ulcerative colitis patients treated for at least 12 weeks with an anti-TNF drug. Exclusion criteria: studies using anti-TNF as a prophylaxis for the postoperative recurrence in Crohn’s disease or those where DI was based on therapeutic drug monitoring. Data synthesis: effectiveness by intention-to-treat (random effects model). Data were stratified by medical condition (ulcerative colitis vs. Crohn’s disease), anti-TNF drug and follow-up. Results: One hundred and seventy-three studies (33,241 patients) were included. Overall rate of the DI requirement after 12 months was 28% (95% CI 24–32, I2 = 96%, 41 studies) in naïve patients and 39% (95% CI 31–47, I2 = 86%, 18 studies) in non-naïve patients. The DI requirement rate was higher both in those with prior anti-TNF exposure (p = 0.01) and with ulcerative colitis (p = 0.02). The DI requirement rate in naïve patients after 36 months was 35% (95% CI 28–43%; I2 = 98%; 18 studies). The overall short-term response and remission rates of empirical DI in naïve patients were 63% (95% CI 48–78%; I2 = 99%; 32 studies) and 48% (95% CI: 39–58%; I2 = 92%; 25 studies), respectively. The loss of response to anti-TNF agents―and, consequently, DI―occurred frequently in inflammatory bowel disease (approximately in one-fourth at one year and in one-third at 3 years). Empirical DI was a relatively effective therapeutic option.
Highlights
Biologic therapies have become the mainstay of treatment in inflammatory bowel disease (IBD)
They are effective at inducing symptom relief, disease remission and mucosal healing and reducing the need for surgery and hospitalizations among patients with moderate-to-severe IBD
A total of 157 studies assessed the need for dose intensification (DI); the response rate was evaluated in studies, and the remission rate was reported in 33 studies
Summary
Biologic therapies have become the mainstay of treatment in inflammatory bowel disease (IBD). Elevated stool and mucosal TNF concentrations in UC and CD patients have been shown to correlate with the disease activity [1]. Anti-TNF drugs operate via a multitude of mechanisms: they bind and clear soluble TNF but, cell-bound TNF, inducing cytotoxicity on immune cells, like T-cell apoptosis [2]. They are effective at inducing symptom relief, disease remission and mucosal healing and reducing the need for surgery and hospitalizations among patients with moderate-to-severe IBD
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