P277 Frequency and effectiveness of empirical anti-TNF dose intensification in Inflammatory Bowel Disease: systematic review with meta-analysis
Guberna Blanco, L.(1);Nyssen, O.P.(1);Chaparro, M.(1);Gisbert, J.P.(1);
(1)Gastroenterology Unit- Hospital Universitario de La Princesa- Instituto de Investigación Sanitaria Princesa IIS-IP- Universidad Autónoma de Madrid UAM- and Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas CIBERehd, Gastroenterology Unit, Madrid, Spain
Background
Loss of response to anti-TNF (tumor necrosis factor) therapies in inflammatory bowel disease occurs in a high proportion of patients. However, the precise incidence of dose intensification (DI) and its effectiveness remains 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 in Pubmed, Embase, the Cochrane Library and CINAHL. Selection: prospective and retrospective studies assessing 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 [infliximab (IFX), adalimumab (ADA), certolizumab or golimumab]. Exclusion criteria: studies using anti-TNF as prophylaxis for postoperative recurrence in CD 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 (UC vs. CD), anti-TNF drug and follow-up. Subgroup analyses were performed to explore heterogeneity.
Results
In total, 174 studies (32,031 patients) were included. The overall rate of DI requirement after 12 months follow-up was 27% (95%CI 23-31, I2=96%, 51 studies) in naïve patients and 38% (95%CI 31-46, I2=87%, 18 studies) in non-naïve patients. The rate of DI requirement was higher in patients with prior anti-TNF exposure (c²=6.5, P=0.01) and in UC patients (c²=4.7, P=0.03). The rate of DI requirement in naïve patients after 36 months follow-up was 35% (95%CI 27-43%; I2=98%; 22 studies). The overall short-term response and remission rates to empirical DI in naïve patients were 66% (95%CI 61-71%; I2=81%; 35 studies) and 48% (95%CI 35-62%; I2=97%; 27 studies), respectively. Subgroup analyses are presented in the tables.
| Anti-TNF | UC/CD | DI requirement (%, 95%CI) after 12 months | I2 (%) | Number of included studies |
|---|---|---|---|---|
| IFX | UC+CD | 29 (23-36) | 95 | 28 |
| IFX | UC | 41 (26-55) | 97 | 9 |
| IFX | CD | 22 (15-28) | 87 | 15 |
| ADA | UC+CD | 27 (21-34) | 93 | 17 |
| ADA | UC | 29 (23-35) | 86 | 7 |
| ADA | CD | 24 (15-38) | 95 | 10 |
| Anti-TNF | UC/CD | Remission rate after DI (%, 95%CI) | Number of included studies | I2 (%) |
|---|---|---|---|---|
| IFX | UC+CD | 51 (40-61) | 16 | 86 |
| IFX | UC | 57 (35-78) | 8 | 93 |
| IFX | CD | 44 (35-54) | 7 | 47 |
| ADA | UC+CD | 44 (31-58) | 10 | 86 |
| ADA | UC | 17 (7-27) | 1 | NA |
| ADA | CD | 50 (36-64) | 8 | 79 |
Conclusion
Loss of response to anti-TNF agents ―and consequent DI― occur frequently in IBD (approximately in 1/4 at one year and in 1/3 at 3 years). DI requirement is higher in UC patients and in those with prior anti-TNF exposure. Empirical DI is a relatively effective therapeutic option.