P573 Frequency and effectiveness of empirical anti-TNF dose intensification in inflammatory bowel disease: an on-going systematic review with meta-analysis
L. Guberna Blanco, O.P. Nyssen, M. Chaparro, J.P. Gisbert
Hospital Universitario de la Princesa, Gastroenterology and Hepatology, Madrid, Spain
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%,
Anti-TNF | UC/CD | Follow-up time (months) | DI requirement (%, 95% CI) | Number of studies included | |
Infliximab (IFX) | UC+CD | 12 | 37 (26–48) | 95 | 13 |
IFX | UC+CD | 36 | 48 (41–55) | 79 | 8 |
IFX | UC | 12 | 57 (48–65) | 73 | 5 |
IFX | UC | 36 | 52 (33–71) | 87 | 3 |
IFX | CD | 12 | 25 (16–44) | 89 | 8 |
IFX | CD | 36 | 46 (38–55) | 78 | 5 |
ADA | UC+CD | 12 | 31 (24–38) | 91 | 11 |
ADA | UC+CD | 36 | 43 (36–49) | 44 | 4 |
ADA | UC | 12 | 25 (18–33) | 69 | 2 |
ADA | UC | 36 | 50 (34–66) | Not applicable | 1 |
ADA | CD | 12 | 33 (24–42) | 93 | 9 |
ADA | CD | 36 | 41 (35–48) | 46 | 3 |
The overall short-term response and remission rates to empirical DI were 67% (95% CI: 63–72%;
Anti-TNF | UC/CD | Remission rate (%, 95% CI) | Number of studies included | |
IFX | UC+CD | 44 (29–59) | 89 | 10 |
IFX | UC | 51 (27–75) | 93 | 5 |
IFX | CD | 36 (27–44) | 82 | 5 |
ADA | UC+CD | 38 (22–54) | 89 | 8 |
ADA | UC | 14 (3–24) | 57 | 3 |
ADA | CD | 55(33–77) | 82 | 5 |
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.