Adam Winters

Vedolizumab for Ulcerative Colitis: Treatment Outcomes from the VICTORY Consortium

OBJECTIVES: We aimed to quantify the safety and effectiveness of vedolizumab (VDZ) when used for UC, and to identify predictors of response to treatment. METHODS: Retrospective review (May 2014‐December 2016) of VICTORY Consortium data. Adults with follow‐up after starting VDZ for clinically active UC were included. Primary effectiveness outcomes were cumulative rates of clinical remission (resolution of all UC‐related symptoms) and endoscopic remission (Mayo endoscopic sub‐score 0). Key secondary effectiveness outcomes included cumulative rates of corticosteroid‐free remission and deep remission (clinical remission and endoscopic remission). Cox proportional hazard analyses were used to identify independent predictors of treatment effectiveness. Non‐response imputation (NRI) sensitivity analyses were performed for effectiveness outcomes. Key safety outcomes were rates of serious infection, serious adverse events, and colectomy. RESULTS: We included 321 UC patients (71% prior TNF&agr; antagonist exposure, median follow‐up 10 months). The 12‐month cumulative rates of clinical remission and endoscopic remission were 51% and 41%, respectively. Corresponding rates for corticosteroid‐free remission and deep remission were 37% and 30%, respectively. Using NRI, 12‐month rates were 20% (n = 64/321) for clinical remission, 17% (n=35/203) for endoscopic remission, 15% (n=30/195) for corticosteroid‐free remission, and 14% (n = 28/203) for deep remission. A majority of the patients without adequate follow‐up at 12 months who were deemed non‐responders using NRI had already achieved clinical remission (n = 70) or a significant clinical response (n=36) prior to 12 months. VDZ discontinuation prior to 12 months was observed in 91 patients, for lack of response (n =56), need for surgery (n=29), or adverse event (n=6). On multivariable analyses, prior exposure to a TNF&agr; antagonist was associated with a reduced probability of achieving clinical remission (HR 0.53, 95% CI 0.38–0.75) and endoscopic remission (HR 0.51, 95% CI 0.29–0.88). Serious adverse events and serious infections were reported in 6% and 4% of patients, respectively. Overall cumulative rates of colectomy over 12 months were 13%, with lower rates observed in patients naive to TNF&agr; antagonist therapy (2%) than those who had been exposed to TNF&agr; antagonists (19%). CONCLUSION: In this large real‐world cohort we observed that VDZ was well tolerated and effective in achieving key clinical outcomes.

Development and Validation of a Scoring System to Predict Outcomes of Vedolizumab Treatment in Patients With Crohn’s Disease

BACKGROUND & AIMSnAs more treatment options for inflammatory bowel diseases become available, it is important to identify patients most likely to respond to different therapies. We created and validated a scoring system to identify patients with Crohns disease (CD) who respond to vedolizumab.nnnMETHODSnWe collected data from the GEMINI 2 phase 3 trial of patients with active CD treated with vedolizumab for 26 weeks (nxa0= 814) and performed logistic regression analysis to identify factors associated with clinical, steroid-free, and durable remission (derivation set). We used these data to develop a clinical decision support tool, which we validated using data from 366 participants in a separate clinical practice observational cohort of patients with active CD treated with vedolizumab for 26 weeks (the VICTORY cohort). We evaluated the ability of this tool to identify patients in clinical remission or corticosteroid-free remission, or those with mucosal healing (MH), clinical remission with MH, or corticosteroid-free remission with MH after vedolizumab therapy using receiver operating characteristic area under the curve (AUC) analyses. The primary outcome was to develop and validate a list of factors associated with achieving remission by vedolizumab in patients with active CD.nnnRESULTSnIn the derivation analysis, we identified absence of previous treatment with a tumor necrosis factor antagonist (+3 points), absence of prior bowel surgery (+2 points), absence of prior fistulizing disease (+2 points), baseline level of albumin (+0.4 points per g/L), and baseline concentration of C-reactive protein (reduction of 0.5 points for values between 3.0 and 10.0 mg/L and 3.0 points for values >10.0 mg/L) as factors associated with remission. In the validation set, our model identified patients in clinical remission with an AUC of 0.67, patients in corticosteroid-free remission with an AUC of 0.66, patients with MH with an AUC of 0.72, patients in clinical remission with MH with an AUC of 0.73, and patients in corticosteroid-free clinical remission with MH with an AUC of 0.75. A cutoff value of 13 points identified patients in clinical remission after vedolizumab therapy with 92% sensitivity, patients in corticosteroid-free remission with 94% sensitivity, patients with MH with 98% sensitivity, patients with clinical remission and MH with 100% sensitivity, and patients with corticosteroid-free clinical remission with MH with 100% sensitivity.nnnCONCLUSIONSnWe developed and validated a scoring system to identify patients with CD most likely to respond to 26 weeks of vedolizumab therapy. Further studies are needed to optimize its accuracy in select populations and determine its cost-effectiveness.

Reassessing the safety concerns of utilizing blood donations from patients with hemochromatosis: Winters et al.

Hereditary hemochromatosis (HH) is a genetic disorder of iron metabolism that may lead to iron overload. Clinical penetrance is low, however those afflicted may develop cirrhosis, hepatocellular carcinoma, diabetes mellitus, and cardiomyopathy. Treatment of HH involves regular phlebotomy to reduce the systemic iron burden. In many countries—including the United States—numerous blood centers do not accept donated blood obtained from HH patients during therapeutic phlebotomy and there are inconsistent positions regarding this globally. This refusal of blood is borne out of a few concerns. First, there is a theoretical increase in the infectious risk of these blood products, particularly by siderophilic organisms such as Yersinia enterocolitica. Second, given the increased incidence of hepatitis C infection from nonvoluntary donors in the 1970s, there is a concern that blood units from HH donors may harbor additional risk given the nonvoluntary nature of their presentation. In this review, we examine the existing biological and clinical data concerning infectious risk and summarize clinical experience from centers allowing HH donors, and demonstrate that blood from HH patients is safe and should be allowed into the donor pool. We conclude that there is no convincing evidence to exclude this population from serving as blood donors. (Hepatology 2018;67:1150–1157)

Retrospective Analysis of Safety of Vedolizumab in Patients With Inflammatory Bowel Diseases

BACKGROUND & AIMSnThere are few real-world data on the safety of vedolizumab for treatment of Crohns disease (CD) or ulcerative colitis (UC). We quantified rates and identified factors significantly associated with infectious and non-infectious adverse events in clinical practice.nnnMETHODSnWe performed a retrospective review of data from a multicenter consortium database (from May 2014 through June 2017). Infectious and non-infectious adverse events were defined as those requiring antibiotics, hospitalization, vedolizumab discontinuation, or resulting in death. Rates were quantified as proportions and events per 100 patient years of exposure (PYE) or follow up (PYF). We performed multivariable logistic regression analyses to identify factors significantly associated with events and reported as odds ratios (OR) with 95% CIs.nnnRESULTSnOur analysis comprised 1087 patients (650 with CD and 437 with UC; 55% female; median age, 37 years) with 861 PYE and 955 PYF. Infections were observed in 68 patients (6.3%; 7.9 per 100 PYE, 7.1 per 100 PYF); gastrointestinal infections (nxa0= 31, 2.4 per 100 PYE, 2.2 per 100 PYF) and respiratory infections (nxa0= 14, 1.6 per 100 PYE, 1.5 per 100 PYF) were the most common. Arthralgias were the most common non-infectious adverse events (nxa0= 31, 2.9%; 3.6 per 100 PYE). Two patients developed malignancies (squamous cell skin cancer and colorectal cancer; 0.23 per 100 PYE, 0.21 per 100 PYF). Active smoker status (OR, 3.39) and number of concomitant immunosuppressive agents (corticosteroids or immunomodulators; OR, 1.72 per agent) used were independently associated with infections.nnnCONCLUSIONnIn a retrospective cohort study of patients with IBD, we found vedolizumab to be well tolerated with an overall favorable safety profile. Active smoking and concomitant use of immunosuppressive agents were independently associated with infections.