INTRODUCTION Following inadequate response, loss of response, or intolerance to a first-line biologic, patients with Crohn’s disease (CD) may switch treatment to a second-line biologic therapy. Data on the clinical outcomes of patients receiving two or more lines of biologic therapy are limited. We assessed the adverse clinical outcomes of patients with CD receiving different biologic treatment sequences. METHODS ROTARY (Real-wOrld ouTcomes Across tReatment sequences in inflammatorY bowel disease patients) part B used data from the Optum Clinical Database and included adult patients diagnosed with CD who received at least two biologics successively between January 1, 2013 and February 29, 2020. This retrospective cohort study measured adverse clinical outcomes, including the incidences of inflammatory bowel disease (IBD)-related hospitalization, IBD-related surgery, dysplasia, colorectal cancer (CRC), and infection during each line of therapy individually and for both lines of treatment overall. The start of the first line of therapy (LOT1) was defined as the date of first prescription or infusion of a biologic therapy. The start of the second line of therapy (LOT2) was defined as the first date of prescription or infusion of a second-line biologic therapy. LOT1 biologics included in the analysis were adalimumab (ADA), infliximab (IFX), ustekinumab (UST) and vedolizumab (VDZ). LOT2 biologics included were IFX and ADA. RESULTS Among all treatment sequences UST to IFX had the highest overall incidences of hospitalization, surgery, CRC, and infection. The overall incidences of hospitalization, surgery, and CRC were lowest for the VDZ to ADA treatment sequence. The overall incidences of infection and dysplasia were lowest for UST to ADA and UST to IFX, respectively; the second-lowest overall incidences for these outcomes were for VDZ to ADA (Figure 1). When comparing adverse clinical outcomes during LOT2, there were similar incidences of hospitalization, surgery, dysplasia, and infection with ADA following either VDZ or UST. In comparison, UST to IFX had higher incidences of hospitalization, surgery, and infection compared with VDZ to IFX (Table 1). DISCUSSION We identified that the VDZ to ADA biologic treatment sequence had the lowest real-world incidences of adverse clinical outcomes in patients with CD. In patients who were unsuccessfully treated with either VDZ or UST during LOT1, ADA was associated with a lower incidence of adverse clinical outcomes during LOT2 than IFX. The adverse clinical outcomes for sequences including two anti-tumor necrosis factor therapies (ADA to IFX, IFX to ADA) were similar during LOT1, LOT2, and overall. These results, although they may be influenced by selection bias, provide potential guidance to clinicians choosing sequences of biologic treatments in patients with CD.
BACKGROUND In the real-world clinical setting, patients with moderate-to-severe ulcerative colitis (UC) may undergo dose escalation when they lose response to their prescribed biologic treatment. Such dose escalation of biologic agents has an impact on healthcare utilization and costs and may have an impact on patient outcomes. Currently, limited real-world data exist that compare rates of dose escalation between anti-tumor necrosis factor (anti-TNF) biologic therapies and vedolizumab, a gut-selective integrin antagonist, in patients with UC who have not previously been treated with biologic therapies (bio-naïve patients). METHODS ODESSA (real wOrld Dose EScalation and outcomeS with biologics in IBD pAtients) was a retrospective cohort study investigating dose escalation in bio-naïve patients with UC receiving vedolizumab or anti-TNFs (adalimumab, golimumab, and infliximab) using data from the IBM MarketScan Commercial Claims and Encounters and Medicare Supplemental Databases. Adult patients with ≥1 claim for a study drug between January 1, 2017 and December 31, 2018 were selected for inclusion, with the first claim date defined as index date 1 (Figure). Patients were eligible if they had a diagnosis of UC, identified based on UC diagnosis codes, had ≥2 claims for the study drug ≥10 days apart with ≥1 claim on or before index date 1, and had received the study drug for ≥60% of days in the first 6 months after index date 1. Patients were excluded if they had received any biologic treatment before index date 1. The maintenance period began on the date of the third (adalimumab or golimumab) or fourth (infliximab or vedolizumab) pharmacy claim. Dose escalation was defined as a ≥20% increase in mean average daily dose relative to expected daily dose based on the approved prescribing information for UC. The primary endpoint was to compare the proportions of patients experiencing dose escalation of each of the study drugs in the first 6 and 12 months after initiation of maintenance dosing and in the entire maintenance period. RESULTS The final analysis cohort included 2,628 patients (vedolizumab, n=554; infliximab, n=758; adalimumab, n=1,316). As a consequence of low patient count, patients treated with golimumab were excluded. At 12 months, the proportion of patients experiencing dose escalation was lowest in the vedolizumab group (36%) and highest in the adalimumab group (44%) (Table). CONCLUSION In this retrospective, real-world cohort of bio-naïve patients with UC receiving vedolizumab or anti-TNFs, rates of dose escalation were lowest among patients receiving vedolizumab during the maintenance period. These data seem to indicate that vedolizumab maintains efficacy with less need for dose escalation; however, additional studies are required to investigate dose-escalation requirements for all biologic treatments.
Table 1. (continued) Placebo (N561) GUS 200 mg IV q4w à100 mg SC q8w (N561) GUS 600 mg IV q4w à200 mg SC q4w (N563) GUS 1200 mg IV q4w à 200 mg SC q4w (N561) UST ;6 mg/kg IV à90 mg SC q8w (N563) Wk 12 Wk 48 -0.73 (8.872), N556 -4.63 (8.869),* N558 -5.66 (10.437), N556 -3.43 (9.178),* N561 -4.85 (8.831), N558 -6.78 (7.805),** N557 -6.34 (10.188), N549 -3.86 (7.908), N563 -5.09 (6.624), N559
case reports and signal detection studies showed that enoxaparin was suspected of liver injury after arthroplasty. The objective of this study was to compare enoxaparin and rivaroxaban in their safety (liver injury and bleeding) and efficacy (DVT, PE, and mortality) by performing a meta-analysis of randomized controlled trials that focused in patients after total knee or hip arthroplasty. Methods: A comprehensive search was performed using PubMed, Embase, and Cochrane to retrieve studies that compared enoxaparin and rivaroxaban after arthroplasty. Relative risk (RR) and 95% confidence intervals using Mantel-haenszel approach were reported. Beta-Binomial model was applied to perform sensitivity analysis. The primary endpoints are liver injury and bleeding and the secondary endpoints are incidences of DVT, PE, and mortality. Results: Ten studies were included in the meta-analysis. Compared to rivaroxaban, enoxaparin had a higher risk of liver injury [RR= 1.77; 95% CI: 1.29,2.44]. Use of enoxaparin resulted in a nearly two-fold risk for DVT compared to rivaroxaban and was statistically significant. The pooled estimate for proximal DVT, distal DVT and any DVT were [RR=3.04; 95% CI: 1.34,6.88], [RR=1.72; 95% CI: 1.29,2.29], [RR=2.09; 95% CI :1.48,2.97] respectively. However, there was no statistically significant difference in the rate of symptomatic and asymptomatic DVT, PE, mortality, and bleeding between the two drugs. Conclusions: Enoxaparin was associated with a higher risk for liver injury and rivaroxaban was associated with lower rates of distal DVT, proximal DVT, and any DVT. However, no difference was observed in the risk of bleeding, PE, and mortality. Overall, enoxaparin is less effective and more risky compared to rivaroxaban for people undergoing total knee or hip arthroplasty.
two diagnostic tests resulted in fewer unnecessary revision TJA procedures per patient versus the Serum CRP test alone (TKA -0.056 two-stage revisions, 0.024 misdiagnosed one-stage revisions; THA -0.034 two-stage revisions, 0.011 misdiagnosed one-stage revisions). Conclusions: This novel Alpha Defensin detection test provides an accurate and rapid result to aid in PJI diagnosis and reduces the economic and clinical burden associated with unnecessary revision TJA procedures due to misdiagnosed PJI. This diagnostic test may offer demonstrable economic value to patients, healthcare providers and payers.
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