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.
Keywords: Crohn’s disease; anti-TNF-α; dose intensification; inflammatory bowel disease; loss of response; ulcerative colitis.