For the remaining authors no conflicts were declared. HSP27 inhibitor J2 Supported by: Takeda Pharmaceuticals provided funding for statistical support to analyze the data. C-reactive protein concentration was associated with increased risk for LOR to VDZ (HR 1.01 per mg/dL increase, 95% CI 1.01C1.02). Rabbit Polyclonal to TISB (phospho-Ser92) Shortening of VDZ infusion interval from 8 to every 4 or 6 weeks recaptured response in 49% and remission in 18% of patients. Conclusions LOR to a TNF antagonist before VDZ use and higher baseline C-reactive protein are important predictors of VDZ LOR. Treatment response can be recaptured in almost half of these patients with VDZ infusion interval shortening. test (2 group comparisons) or 1-way ANOVA with Bonferroni correction (3 or more group comparisons), and for the comparison of binary variables, we used Pearson chi-square or Fisher exact test. Primary and secondary outcomes were described quantitatively with Kaplan-Meier survival and time-to-event analyses. Cox proportional hazard regression analyses were performed to identify independent predictors of LOR. Baseline variables from the univariable analyses with a value of 0.20 were then fitted and a backward model selection approach was taken where the variable with the highest value of 0.05. Hazard ratios (HR) with 95% confidence interval (CI) are presented for predictors where a HR 1 indicated a predictor was associated with a reduced probability for VDZ LOR and a HR HSP27 inhibitor J2 1 indicated a predictor was associated with an increased probability for VDZ LOR. A sensitivity analysis was performed excluding patients who responded to VDZ interval escalation HSP27 inhibitor J2 after initial primary nonresponse. Study Sponsor Takeda Pharmaceuticals provided funding for statistical support to analyze the data. Takeda Pharmaceuticals and associated employees did not have access to any of the data, and all data analyses were performed at the University of California, San Diego, by consortium investigators or statisticians. RESULTS Demographics A total of 788 VDZ-treated IBD patients were identified, of whom 444 patients had a significant response to HSP27 inhibitor J2 VDZ therapy. Of the remaining 344 patients with nonresponse or insufficient response ( 25% reduction in IBD-related symptoms/severity), VDZ interval shortening was attempted in 51 of whom 15 patients (29%) achieved a significant response to VDZ therapy and were included in the current analysis. Baseline demographics for all 459 patients who achieved a significant response to VDZ are presented in Tables 1, ?,2.2. The majority of patients had failed prior TNF-antagonist therapy (n = 346, 75%), and the reason for TNF-antagonist discontinuation before starting VDZ was primary nonresponse in 114 (33%), LOR in 178 (52%), and intolerance in the remaining 54 (15%). Concomitant immunomodulators were used in approximately 40% of patients at the time of VDZ initiation. Rates of prior TNF-antagonist use were lower in UC than CD (67% vs 91%, 0.01), and UC patients were more often on concomitant steroids at the time of VDZ initiation (58% vs 48%, 0.01). TABLE 1: Baseline Clinical Characteristics Stratified by Loss of Response Status CD (n = 264)= 0.03). Rates for LOR were comparable in TNF-antagonist naive and TNF-antagonist exposed individuals (= 0.53), but patients who had LOR to a TNF-antagonist before VDZ use, were almost twice as likely to have LOR to VDZ (HR 1.94, 95% CI 1.26C2.98), whereas patients who had a primary nonresponse (PNR) to a TNF-antagonist before VDZ use, were almost 50% less likely to have LOR to VDZ (HR 0.60, 95% CI 0.36C0.97) (Table 3, Fig. 1). Among patients who had HSP27 inhibitor J2 LOR to a TNF-antagonist before VDZ use, there was no significant difference in LOR to VDZ among those who underwent an attempt at optimizing the TNF-antagonist before VDZ (dose escalation and/or interval shortening to manage) versus those who did not before starting VDZ (= 0.20), or those who were on a concomitant immunomodulator when starting VDZ (= 0.71). On multivariable analyses, the only 2 independent predictors of LOR to VDZ were disease duration (HR 0.97 per year of disease duration, 95% CI 0.95C0.99) and LOR to a TNF-antagonist before VDZ use (HR 1.93, 95% CI 1.25C2.97). TABLE 3: Univariable.