Medicine (RMH) - Research Publications

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    Examining maintenance care following infliximab salvage therapy for acute severe ulcerative colitis
    Seah, D ; Choy, MC ; Gorelik, A ; Connell, WR ; Sparrow, MP ; Van Langenberg, D ; Hebbard, G ; Moore, G ; De Cruz, P (WILEY, 2018-01)
    BACKGROUND AND AIM: Data supporting the optimal maintenance drug therapy and strategy to monitor ongoing response following successful infliximab (IFX) induction, for acute severe ulcerative colitis (ASUC), are limited. We aimed to evaluate maintenance and monitoring strategies employed in patients post-IFX induction therapy. METHODS: Patients in six Australian tertiary centers treated with IFX for steroid-refractory ASUC between April 2014 and May 2015 were identified via hospital IBD and pharmacy databases. Patients were followed up for 1 year with clinical data over 12 months recorded. Analysis was limited to patient outcomes beyond 3 months. RESULTS: Forty one patients were identified. Five of the 41 (12%) patients underwent colectomy within 3 months, and one patient was lost to follow-up. Six of 35 (17%) of the remaining patients progressed to colectomy by 12 months. Maintenance therapy: Patients maintained on thiopurine monotherapy (14/35) versus IFX/thiopurine therapy (15/35) were followed up. Two of 15 (13%) patients who received combination maintenance therapy underwent a colectomy at 12 months, compared with 1/14 (7%) patients receiving thiopurine monotherapy (P = 0.610). Monitoring during maintenance: Post-discharge, thiopurine metabolites were monitored in 15/27 (56%); fecal calprotectin in 11/32 (34%); and serum IFX levels in 4/20 (20%). Twenty of 32 (63%) patients had an endoscopic evaluation after IFX salvage with median time to first endoscopy of 109 days (interquartile range 113-230). CONCLUSION: Following IFX induction therapy for ASUC, the uptake of maintenance therapy in this cohort and strategies to monitor ongoing response were variable. These data suggest that the optimal maintenance and monitoring strategy post-IFX salvage therapy remains to be defined.
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    Predicting response after infliximab salvage in acute severe ulcerative colitis
    Choy, MC ; Seah, D ; Gorelik, A ; An, Y-K ; Chen, C-Y ; Macrae, FA ; Sparrow, MP ; Connell, WR ; Moore, GT ; Radford-Smith, G ; Van Langenberg, DR ; De Cruz, P (WILEY, 2018-07)
    BACKGROUND AND AIM: Acute severe ulcerative colitis (ASUC) is a medical emergency requiring prompt therapeutic intervention. Although infliximab has been used as salvage therapy for over 15 years, clinical predictors of treatment success are lacking. We performed a retrospective analysis to identify factors that predict colectomy and may guide dose intensification. METHODS: Fifty-four hospitalized patients received infliximab for ASUC at seven Australian centers (April 2014-May 2015). Follow-up was over 12 months. The data were primarily analyzed for predictors of colectomy. Accelerated (AI) versus standard (SI) infliximab induction strategies were also compared. RESULTS: Of 54 patients identified, the overall colectomy rate was 15.38% (8/52) at 3 months and 26.92% (14/52) at 12 months. Two patients were lost to follow-up. There was a numerically higher colectomy rate in those treated with AI compared with SI (P = 0.3); however, those treated with AI had more severe biochemical disease. A C-reactive protein (CRP)/albumin ratio cut-off of 0.37 post-commencement of infliximab and before discharge was a significant predictor of colectomy with an area under receiver operating curve of 0.73. Pretreatment CRP and albumin levels were not predictive of colectomy. A Mayo Endoscopic Score of 2 had a 94% PPV for avoidance of colectomy following infliximab salvage. CONCLUSIONS: The baseline Mayo Endoscopic Score and the CRP/albumin ratio following infliximab salvage are significant predictors of treatment response for ASUC and identify patients at high risk of colectomy. Whether this risk can be mitigated using infliximab dose intensification requires prospective evaluation before the CRP/albumin ratio can be integrated into ASUC management algorithms.