Su1393 Primary Non Response to Infliximab in Patients With Inflammatory Bowel Disease

Abstract

Background & Aim: Patients with Crohn's disease (CD) or ulcerative colitis (UC) who fail to respond to induction therapy with infliximab (IFX) are considered as primary non responders (PNR). We aimed at investigating the prevalence, prediction and management of PNR to IFX in patients with CD or UC. Patients & Methods: Retrospective analysis of prospectively acquired data at a single-center which included PNRs to induction therapy with 5 mg/kg IFX at weeks 0, 2 and 6. PNR was defined as no improvement or worsening of clinical symptoms through week 14 after starting IFX as judged by the CDAI and physician global assessment. Using RFLP or allele-specific PCR, single nucleotide polymorphisms in the promoter region of the TNF gene (-238 G/A, -308 G/A, and -857 C/T) and the -158 V/F polymorphism of the FcγRΙΙΙa gene were determined in 79 patients. In 48 patients, the HLA class II DRB1 and DQB1 alleles were also determined using the complement-dependent lymphocytotoxicity (CDC) and where available the sequence-specificoligonucleotide (SSO) and primer (SSP) HLA typing methods. Antinuclear antibodies and perinuclear anti-neutrophil cytoplasmic antibodies at baseline were also evaluated in 104 and 87 patients, respectively. Results: Between 1/7/2007 and 31/8/2012, of 160 IFX-treated patients [107 CD, 53 with UC, 94 males, median age at diagnosis 23 years (IQR 17-32)], 26 (16.3%) were PNRs [8/107 (7.5%) NC vs 18/53 (34%) UC, p<0.001]. Differences between CD and UC in PNR rates may be due to inclusion of patients with severe UC treated with IFX rescue therapy. CD/PNRs to IFX received adalimumab (ADA, n=4), azathioprine (AZA, n=1), methotrexate (MTX, n=1) or surgical treatment (n=2); 2 of these 4 ADA-treated CD patients developed also PNR to ADA but the other two achieved sustained clinical response (n=1) or remission (n=1) after escalation of ADA dose to 40mg weekly. UC/PNRs to IFX were mainly treated surgically (n=12); one of whom received ADA after surgery for refractory pouchitis, and 6 patients received AZA. Univariate and multivariate analysis (including variables with p<0.2) did not reveal any clinical, serological, demographical or genetic factors as predictors of PNR to IFX. PNR to IFX was the only predictor of PNR to ADA [ΟR=8.889 (95% CI: 2.30234.316), p=0,032] as at the end of the study, only one more patient [with secondary loss of response (SLR) to IFX] of the total 43 who were switched to ADA (of the initial pool of the 160 patients), due to PNR (n=5), SLR (n=21), intolerance (n=9), or adverse events (n= 8) to IFX, developed also PNR to ADA. Conclusion: This study which mirrors real life experience indicates that PNR to IFX in UC is more frequent than in CD; PNR to IFX predisposes to PNR to ADA. Larger prospective studies are needed to identify any predictive factors for PNR to anti-TNF therapy and the ideal management of this phenomenon.