P573 Frequency and effectiveness of empirical anti-TNF dose intensification in inflammatory bowel disease: an on-going systematic review with meta-analysis

Abstract

Background Loss of response to anti-TNF therapies in inflammatory bowel disease occurs in a high proportion of patients. However, the precise incidence of dose intensification (DI) and its effectiveness remain unclear. Our aims were: (1) To evaluate the need of DI of anti-TNF therapy either by increasing the dose or decreasing doses’ interval; (2) To evaluate possible variables influencing its requirement; (3) To assess the effectiveness of empirical DI. Methods Bibliographical searches were performed until January 2019. Selection: prospective and retrospective studies assessing the loss of response to anti-TNF therapy, considered as the need of DI, in Crohn’s disease (CD) and ulcerative colitis (UC) patients treated for at least 12 weeks with an anti-TNF drug. Exclusion criteria: Studies using anti-TNF as prophylaxis for postoperative recurrence in CD or those where DI was based on therapeutic drug monitoring. Data were analyzed by means of the inverse variance method using a random effect model and stratifying by medical baseline condition (UC vs. CD), anti-TNF drug and follow-up. Effectiveness was assessed by intention-to-treat analysis. Results Up to now, 107 studies (11,377 patients) were included. The overall rate of DI requirement for naïve patients after 12 and 36 months of follow-up was 35% (95% CI=26–45%, I2=95%, 15 studies) and 48% (41–55%, I2= 77%, 9 studies); respectively. Frequencies of DI requirement stratified by subgroup analysis are presented in the table (all patients being naïve except CD patients treated with adalimumab (ADA), including naïve and no naïve). The overall short-term response and remission rates to empirical DI were 67% (95% CI: 63–72%; I2=73%; 31 studies) and 45% (95% CI: 35–55%; I2=9%; 23 studies), respectively; subgroup analyses are summarised in the table. Conclusion Loss of response to anti-TNF agents and consequent DI occurs frequently in both UC and CD, with an overall rate of DI requirement of 35% at one year and 48% at 3 years. Empirical DI is a relatively effective therapeutic option. Further data extraction and analysis is necessary to confirm these findings.