Predictors of Poor Outcome of Infliximab Therapy in Ulcerative Colitis

Abstract

Introduction: While the disease course of ulcerative colitis (UC) may be altered by the introduction of anti-tumor necrosis factor-alpha (TNF) therapy, a significant number of patients nonetheless still require colectomy due to primary or secondary failure to infliximab (IFX) therapy, or several adverse effects (SAE) from the agent. The aims of this study were to evaluate the predictors of poor outcome in IFX therapy in UC and SAE associated with IFX. Methods: Of 527 UC inpatients and outpatients in our tertiary care center from 2008 to 2014, 402 met inclusion criteria and included in the study. The inclusion criteria were UC patients who received any IFX administered by physicians from our IBD center or referring physicians at the time of inception. The primary outcomes were UC-related ER visits, hospitalizations or colectomy. The secondary outcomes were severe adverse effect (SAE) associated with IFX. Results: Overall, 402 patients were included, with 207 (51%) being male. The average Mayo score for UC activity before IFX start (if it was able to be calculated) was 6.6+2.2, with 181 patients (45%) having pan-colitis. One hundred thirty-six patients (33.8%) had clinical improvement with IFX within 1 year, measured as improvement in stool frequency, rectal bleeding, endoscopic, and subjective clinical improvement. Two hundred fifty-six patients (63.9%) remained on steroids and 85 (21.3%) were on immunomodulator therapy while on IFX. Thirty-eight patients (9.3%) had documented SAE, which included immediate infusion reactions, dyspnea, headache and skin rashes. One hundred sixty patients (40%) had a UC-related hospitalization within 1 year of starting IFX, while 119 patients (29.6%) underwent colectomy within 1 year, largely due to failure of medical management. On multivariable analysis, patients who had used non-steroidal anti-inflammatory drugs (NSAIDS) had significantly higher rate of failure of IFX therapy (odds ratio [OR]=13.26, confidence interval [CI]=3.94-44.63; p<0.001). Every onepoint increase in Mayo scores, and thus increased disease severity, were also found to have poor outcomes with IFX therapy, with more rates of colectomy and 1-year hospitalizations (OR=1.17, CI=1.05-1.31; p=0.004). Patients who concurrently used steroids had significantly higher rates of IFX failure (OR=3.35; CI=2.14-5.25; p<0.001). Furthermore, concomitant use of immunumodulators, in conjunction with IFX therapy was shown to be protective from adverse outcomes (OR=0.76; CI=0.47-1.24; p=0.27). Conclusion: IFX is an effective therapy for moderate to severe steroid-refractory UC. Predictors of poor outcome in IFX therapy include the concomitant use of NSAIDS, steroids, increased severity of disease, and older age. Using IFX in conjunction with currently available immunumodulator therapies will likely result in overall improved outcomes. Disclosure - Dr. Shen - serves as a consult to Johnson & Johnson, Abbvie, and Aptalis.