Baseline Steroid Use Research Articles

DOP043 Clinical outcomes and predictive factors differ in acute severe ulcerative colitis for East Asian and Western patients

Abstract Background There are limited comparisons of clinical outcomes of acute severe ulcerative colitis (ASUC) between East Asian (EA) and Western countries and many currently used scoring systems are based on Western populations. We developed a predictive model using ASUC data from EA patients and assessed its ability to predict clinical outcomes in an Australia/New Zealand (ANZ) cohort. Methods This retrospective international study was conducted across 23 referral hospitals in EA and ANZ. Patients who met Truelove and Witts criteria for ASUC between January 2015 and December 2022 were included. We compared the 1-year colectomy rates and non-response to corticosteroid therapy (NRS) between the EA and ANZ cohorts. Logistic regression analysis was employed to develop predictive models for 1-year colectomy and NRS. Each variable found as an independent predictor in the logistic regression analysis was weighted as score 1 making the scoring system range 0 to 3 or 4. Results A total of 826 patients with ASUC (411 EA and 415 ANZ) were included. The 1-year colectomy rate was significantly lower in the EA group (3.9%) compared to the ANZ group (22.7%, p<0.001), as was the NRS rate (25% vs. 58.9%, p<0.001). In the EA cohort, independent risk factors for 1-year colectomy included female sex, previous exposure to tumor necrosis factor inhibitors, and albumin levels <3 g/dL at admission. For NRS in the EA cohort, independent risk factors included age at diagnosis <37 years, baseline steroid use, albumin levels <2.5 g/dL at admission, and presence of extraintestinal manifestations. The scoring system based on this model did not predict colectomy and NRS risk effectively in the ANZ cohort (p=0.106 and p=0.012, respectively) compared to the EA cohort (p<0.0001 and p=0.001, respectively). In contrast, previously developed predictive models from Europe, including the French colectomy score and the ADMIT-ASC index for NRS, successfully predicted outcomes in the ANZ cohort (p=0.007 and p<0.0001, respectively) but were less effective in the EA cohort (p=0.106 and p=0.026, respectively). Conclusion Clinical outcomes and predictors of ASUC differ between EA and ANZ patients. Further investigation is needed to determine whether these differences arise from variations in management strategies or disease behavior between these groups. References Kim ES, Kim KO, Jang BI, et al. Comparison of 1-Year Colectomy Risk Between the US and Korean Patients with Acute Severe Ulcerative Colitis: A Propensity Score Matching Analysis. Dig Dis Sci 2022;67:2866-2875. Le Baut G, Kirchgesner J, Amiot A, et al. A Scoring System to Determine Patients’ Risk of Colectomy Within 1 Year After Hospital Admission for Acute Severe Ulcerative Colitis. Clin Gastroenterol Hepatol 2021;19:1602-1610 e1601. Adams A, Gupta V, Mohsen W, et al. Early management of acute severe UC in the biologics era: development and international validation of a prognostic clinical index to predict steroid response. Gut 2023;72:433-442.

DOP009 Effectiveness and Safety of Advanced Combination Treatment (ACT) in patients with refractory inflammatory bowel disease or concomitant immune mediated disease or extra-intestinal manifestations: A Multi-Center Canadian Study

Abstract Background Some patients with inflammatory bowel disease (IBD) do not respond to multiple advanced therapies, resulting in off-label use of two advanced therapeutic agents, known as advanced combination treatment (ACT) (1). Methods This multi-center study in 9 Canadian centers included adult IBD patients treated with either two biological therapies, a biological plus an oral small molecule, or two small molecules. The indication for ACT was characterized as: 1) refractory IBD; 2) concomitant uncontrolled IMID; 3) concomitant uncontrolled EIMs. Primary outcomes were cumulative rates of clinical and endoscopic response and remission at 12 months. Clinical activity was assessed using physician global assessments for both IBD and the concomitant IMID/EIMs. Secondary outcomes included serious adverse events and infections. Cox-proportional hazard analyses identified independent predictors of treatment effectiveness. Multivariate Imputation by Chained Equations accounted for missing data. Results We included 105 IBD patients (76 CD, 29 UC), median age 35 years (IQR 35.4-40.8). At baseline, 39% had perianal involvement, and 58% had failed at least 3 advanced therapies. Most patients (61%) had moderate to severe disease activity, and 40% had prior surgery. The cohort was categorized into three groups based on the rationale for ACT: 63.8% (67/105) received ACT for refractory IBD, 28.8% (30/105) for concomitant IMID, and 7.6% (8/105) for concomitant EIMs. The primary reason for ACT was refractory IBD (63.8%), with the add-on approach used in 97.1% combinations. The most frequent combination was anti-TNF + anti-integrin, followed by the combination of anti-IL-(12)/23 agent + anti-integrin. At 12 months, the cumulative rates of clinical and endoscopic response were 60% and 32.4%, respectively. Cumulative clinical and endoscopic remission rates were 29.5% and 28.6%, respectively (Table 1). Multivariate analysis showed perianal disease was associated with reduced chances of both clinical remission (HR = 0.33, p=0.001), and endoscopic remission (HR = 0.42, p=0.0001) (Table 2). Longer disease duration (HR = 0.96, p = 0.035), baseline moderate-severe disease (HR = 0.41, p = 0.026), and baseline steroid use (HR = 0.39, p = 0.006) were associated with a reduced likelihood of clinical remission. Serious adverse events and infections were reported in 12.4% and 7.6% of patients, respectively. Among serious infections, 5 (62.5%) required hospitalization, 3 (37.5%) were reported as important medical events, and none was life-threatening. Conclusion In this large real-world cohort, ACT was effective in achieving clinical and endoscopic outcomes in patients with refractory IBD or concomitant IMID/EIMs. ACT was well-tolerated, with a favorable safety profile.

P0866 Upadacitinib improves symptomatic, biochemical, and intestinal ultrasound parameters in active UC patients up to one year after treatment induction – one year interim results from the IBD-DACH study EUROPE

Abstract Background Upadacitinib (UPA), a reversible and selective Janus kinase-inhibitor was approved for the treatment of moderate-severe ulcerative colitis (UC) in 2022 (1). Despite substantial evidence from pivotal trials, multinational, prospective real-world (RW) data remains limited. We report symptomatic, biochemical, and intestinal ultrasound (IUS) data after one year of UPA therapy in a large, multinational RW UC cohort. Methods EUROPE is an ongoing, prospective, non-interventional, multi-country study in active UC patients who initiate UPA therapy. Primary study aim is to assess RW effectiveness and the predictive value of early (IUS) response for outcomes at week 52 (W52). Here, we show symptomatic, biochemical, and IUS results (bowel wall thickness, BWT) at baseline (BL), W8 and W52 of 111 UC patients. Safety data was available for 263 patients ((≥ 1 dose of UPA). Results Here, 111 UC patients (59.5% male, median age 37.6 (28.0 - 49.6) yrs, median disease duration 6.95 (2.36 – 12.65) yrs) with a visit at W52 were included. Of these, 50.5% (n = 56) had pancolitis and 88.3% (n = 98) were advanced therapy experienced. Of note, 39.8% (n = 39) of the latter had been exposed to ≥ 3 biologicals. Patients had signs of active inflammation at BL (median FCal: 727 (263 – 1500) µg/g, median CRP: 6.45 (1.3 – 20.5) mg/L) with BL steroid use in 46.8% of patients (n = 52). At W8 after UPA induction, the rate of patients in symptomatic remission significantly increased from 19.8% (n = 22) at BL to 69.4% (n = 77) at 8W and to 67.6% (n = 75) at W52 (both p < 0.001 vs. BL, fig.1). Fecal calprotectin and CRP decreased until W8 and remained low until W52 (table 1). BWT in the sigmoid colon decreased from median 5 (3.9-6) mm at BL to 3 (2 – 4) mm at W8 and to 2.85 (2 – 3.6) mm at W52. Of note, patients with a BWT ≤ 3mm at W8 demonstrated higher rates of symptomatic remission at W52 vs those with BWT > 3mm (62.0% vs. 38.0%). In 263 patients, 52.9% adverse events were detected (139 events, 60 patients) of which most were non-serious (SAEs: 8.4% (n = 22). One acute myocardial infarction and 8 thromboembolic events were detected (in 6 patients, one event was a pulmonary embolism. Conclusion In this one-year interim analysis of the EUROPE study, UPA treatment in UC was associated with a positive benefit/risk profile including clinical, biochemical, and IUS improvements. Patients achieving BWT normalisation at 8W were more likely to be in symptomatic remission after one year compared to those without BWT normalisation.

DOP10 Risankizumab Versus Ustekinumab for the Achievement of Endoscopic Outcomes in Patients With Moderate-to-Severe Crohn’s Disease: Results From the Phase 3b SEQUENCE Trial

Abstract Background The SEQUENCE study compared the efficacy and safety of risankizumab (RZB) and ustekinumab (UST) in patients (pts) with moderate-to-severe Crohn's disease (CD) who previously failed ≥1 anti-tumour necrosis factor (TNF)a therapies. The second primary endpoint of SEQUENCE, week (wk) 48 endoscopic remission, demonstrated superiority of RZB versus (vs) UST.1 Here, additional endoscopic and clinical/endoscopic composite outcomes are reported. Methods SEQUENCE (NCT04524611) was an open-label, multicenter, randomised, efficacy assessment-blinded study. Pts had a baseline (BL) CD Activity Index (CDAI) of 220-450, average (avg) daily stool frequency ≥4 and/or avg daily abdominal pain score ≥2, and Simple Endoscopic Score for CD (SES-CD) ≥6 (≥4 for isolated ileal disease). Pts in the primary efficacy analysis set were randomised 1:1 to receive RZB (intravenous [IV] 600mg induction at BL, wk4 and wk8, then 360mg subcutaneous [SC] maintenance doses every 8 wks [Q8w], starting at wk12) or UST (single weight-based IV induction followed by a 90mg Q8w SC maintenance treatment starting at wk8) up to wk48. Randomisation was stratified by BL steroid use and number of failed anti-TNFa therapies. A mandatory steroid taper began at wk2. Here, we assessed at wks 24 and 48 endoscopic remission (SES-CD ≤4 and at least a 2-point reduction versus BL and no subscore >1 in any individual variable, as scored by a central reader), mucosal healing (SES-CD ulcerated surface subscore of 0 in pts with SES-CD ulcerated surface subscore ≥1 at BL, as scored by a central reader), and deep remission (endoscopic remission + clinical remission [CDAI<150]); all were prespecified, non-ranked endpoints, except for wk48 endoscopic remission (second primary endpoint). Treatment differences were adjusted for the randomisation stratification factors. Missing data were handled using non-responder imputation while incorporating multiple imputation to handle missing data due to COVID-19 and/or geopolitical conflict. P values were reported as nominal, except for wk48 endoscopic remission. Results With RZB vs UST, a greater proportion of pts achieved endoscopic remission (wk24: 29.4% vs 17.4%, P= 0.001; wk48: 31.8% vs 16.2%, P<0.0001), mucosal healing (wk24: 25.1% vs 14.4%, P<0.01; wk48: 30.2% vs 12.1%, P<0.0001), and the composite endpoint of deep remission (wk24: 22.0% vs 10.2%, P< 0.001; wk48: 22.7% vs 10.9%, P<0.001) at wk24 and wk48 (Figure). The safety profiles of RZB and UST were consistent with published results.1 Conclusion Exploration of endoscopic outcomes demonstrated that pts with moderate-to-severe CD and prior anti-TNFa failure showed greater achievement of endoscopic remission, mucosal healing, and deep remission with RZB compared to UST. 1doi.org/10.1002/ueg2.12474

Patterns and Safety of Glucocorticosteroids Use Following CD19 CAR-T Cell Therapy for B-Cell Lymphoma

Introduction: CAR T-cell therapy is a well-established therapy for relapsed and/or refractory B cell non-Hodgkin's lymphomas (R/R B-NHL). However, CAR-T cell therapy may cause significant toxicities such as CRS and ICANS. Glucocorticosteroids play a pivotal role in managing these toxicities but can also suppress T cell function and may impede the persistence and effectiveness of CAR-T cells. The impact of glucocorticosteroids has resulted in conflicting conclusions in the literature. Objective: This single-center, retrospective, observational study aimed to compare the outcomes of patients with R/R B-NHL who received steroids to those who did not after CAR-T cell therapy. Methods: Patients' records were reviewed to identify any steroid administration within 30 days of CAR-T cell infusion. Patients receiving steroids within 7 days before CAR-T infusion were excluded to focus on CAR-T impact without confounding baseline steroid use. Information on the type of steroids, indication, timing and duration was collected. Steroids were expressed as dexamethasone equivalent. Steroids-associated variables were analyzed as both continuous and categorical variables, using median as the threshold. Cox regression models and Kaplan-Meier analysis was employed for PFS and OS estimation using steroids as a time-dependent covariate and a 30-day landmark analysis, with events as disease progression or death for PFS and death only for OS. Results: 292 patients with R/R B-NHL received commercial CAR-T cell therapy (48% axi-cel, 24% tisa-cel, 22% liso-cel, and 6% Brexu-cel), primarily for large B cell cell lymphoma (85%), mantle cell (11%) or follicular (4%) lymphoma. Only 49 of the 292 patients (17%) received steroids between the day of infusion (day 0) to 30 days after. The median cumulative dexamethasone-equivalent dose at 30 days was 60 mg (range: 1-1982), the median day from CAR-T cells infusion to steroids initiation was 7 days (range 0-26) and the median duration of corticosteroid use was 3 days (range, 1-27). Patients receiving steroids had a significantly higher number of lines of prior therapies (p=0.036), more stage 3-4 disease (p=0.027), and elevated pre-lymphodepletion LDH levels(p=0.004). However, there were no other significant differences, including CD19 CAR-T product type, between the groups. The rates of grade 2 or higher CRS and ICANS were documented in 42% and 18%, respectively. ICANS (47%), CRS (14%), or both (21%) were the leading indications for steroid administration. Other indications for administration of steroids were progression of disease (n=4), adrenal insufficency (n=3), graft vs host disease (n=1), and premedication with intravenous immune globulin (n=1). With a median follow-up of 20 months, median PFS and OS were 6.8 months (95% CI 6-11) and 27 months (95% CI 18-not reached), respectively. The use, duration, and cumulative dose of steroids, whether analyzed as continuous or categorial variables in univariable Cox regression models, were not associated with PFS and OS in a 30 landmark analysis ( Figure). The analysis of the adminstration of steroids as a time-dependent covariate did not show significant differences for either PFS or OS. Importantly, patients exposed to steroids were also not at increased risk for bloodstream infections (p=0.68). Conclusion: In this largest analysis to date on the impact of steroids on CAR-T outcomes, steroid exposure following CAR-T cell infusion was not associated with a greater likelihood of CAR-T cell therapy failure. Our results deviate from previous observations that associate using steroids with shorter PFS and OS (Starti et al, Blood 2021, Terao et al, JTCT 2023). The discrepancy is likely due to our study's exclusion of steroid use prior to CAR-T and statistical analysis. Overall, our findings suggest that steroid administration for CAR-T cell therapy toxicity management is safe and does not appear to have a negative impact on efficacy.

Impact of molecular and clinical variables on survival outcome with immunotherapy for glioblastoma patients: A systematic review and meta-analysis.

BackgroundGiven that only a subset of patients with glioblastoma multiforme (GBM) responds to immuno‐oncology, this study aimed to assess the impact of multiple factors on GBM immunotherapy prognosis and investigate the potential predictors.MethodsA quantitative meta‐analysis was conducted using the random‐effects model. Several potential factors were also reviewed qualitatively.ResultsA total of 39 clinical trials were included after screening 1317 papers. Patients with O6‐methylguanine‐DNA methyltransferase (MGMT) promoter methylation [hazard ratio (HR) for overall survival (OS) = 2.30, p < 0.0001; HR for progression‐free survival (PFS) = 2.10, p < 0.0001], gross total resection (HR for OS = 0.70, p = 0.02; HR for PFS = 0.56, p = 0.004), and no baseline steroid use (HR for OS = 0.52, p = 0.0002; HR for PFS = 0.61, p = 0.02) had a relatively significant favorable OS and PFS following immunotherapy. Patients with a Karnofsky Performance Status score < 80 (HR = 1.73, p = 0.0007) and undergoing two prior relapses (HR = 2.08, p = 0.003) were associated with worse OS. Age, gender, tumor programmed death‐ligand 1 expression, and history of chemotherapy were not associated with survival outcomes. Notably, immunotherapy significantly improved the OS among patients undergoing two prior recurrences (HR = 0.40, p = 0.008) but not among patients in any other subgroups, as opposed to non‐immunotherapy.ConclusionSeveral factors were associated with prognostic outcomes of GBM patients receiving immunotherapy; multiple recurrences might be a candidate predictor. More marker‐driven prospective studies are warranted.

DOP82 Achievement of steroid-free remission in patients with moderately to severely active Crohn’s Disease during treatment with risankizumab

Abstract Background The efficacy and safety of risankizumab (RZB) as induction and maintenance therapy for patients with moderately to severely active Crohn’s disease (CD) has been documented. Steroid-free clinical remission is an important additional treatment goal in CD. The efficacy of RZB by baseline steroid use during induction and steroid-free outcomes during maintenance was examined. Methods In ADVANCE (NCT03105128) and MOTIVATE (NCT03104413), patients with moderately to severely active CD received intravenous (IV) RZB induction therapy or placebo (PBO) for 12 weeks. Patients with clinical response to RZB were re-randomised in a 52-week maintenance study (FORTIFY; NCT03105102) to subcutaneous (SC) RZB or PBO (ie, withdrawal). Patients receiving steroids (maximum prednisone or equivalent ≤ 20 mg/day; budesonide ≤ 9 mg/day) at baseline of the induction studies maintained stable doses for the 12-week study duration. A mandatory steroid taper per protocol was initiated at the beginning of maintenance for patients receiving steroids during induction. Patients losing clinical response (per investigator assessment) after initiation of taper could have their steroid dose increased up to the induction baseline dose. This analysis included patients who received RZB 600 mg IV in ADVANCE or MOTIVATE and patients who received RZB 360 mg SC in FORTIFY. Endpoints reported included clinical remission (defined by CD Activity Index [CDAI] or stool frequency/abdominal pain score [SF/APS] criteria) at week 12 of induction by baseline steroid use, steroid-free clinical remission (CDAI or SF/APS), steroid-free endoscopic response, and steroid-free endoscopic remission at week 52 of maintenance. Steroid discontinuation rates over 52 weeks of maintenance were also assessed. Results Induction of clinical remission at week 12 with RZB 600 mg IV in ADVANCE or MOTIVATE was independent from baseline steroid use (Figure 1).Clinical remission rates (CDAI or SF/APS) at week 12 were similar for patients using steroids vs those who were not (33.8%–42.0% vs 34.9%–46.6%; Figure 1). Steroid use decreased over time in FORTIFY, with a greater proportion of patients receiving RZB 360 mg SC discontinuing steroids at week 52 vs withdrawal (PBO SC; Figure 2A). Rates of steroid-free clinical remission (P ≤ .012), steroid-free endoscopic response (P &amp;lt; .001), and steroid-free endoscopic remission (P &amp;lt; .001) were significantly higher with RZB 360 mg SC vs withdrawal (PBO SC) at week 52 of maintenance (Figure 2B–2C). Conclusion Efficacy of RZB induction therapy was independent of baseline steroid use. RZB maintenance promotes high rates of steroid-free clinical and endoscopic outcomes, demonstrating a benefit of RZB treatment in CD.

Genome-driven medicine for patients with recurrent glioma enrolled in early phase trials

BackgroundRecent studies showed that patients with glioma can safely participate in early phase clinical trials; however, clinical benefits in this population were limited. We aimed to evaluate the benefit of molecular profiling to guide enrolment in early phase trials for patients with recurrent glioma. MethodsRecords of patients enrolled in early phase trials of cytotoxic therapies, small molecule inhibitors or monoclonal antibodies from 2008 to 2018 were reviewed for clinico-pathological characteristics, toxicity, response, progression-free survival and overall survival (OS). The primary objective was to evaluate response rates in molecularly-oriented versus non-molecularly-oriented patients. ResultsEighty-eight patients were enrolled, of whom 45 (51.1%) patients were molecularly-oriented. Targets included IDH1/2 (n = 15), BRAF (n = 11), and FGFR1 (n = 3) mutations, FGFR2-3 fusions (n = 9), and mismatch repair deficiency (n = 7). Among patients with high-grade glioma (n = 74), the rate of stable disease ≥6 months and partial or complete response was 25.7% in molecularly-oriented versus 5.1% in non-molecularly-oriented patients (p = 0.02). Upon multivariable adjustment, baseline steroid use ≥20 mg prednisone equivalent per day was associated with shorter OS (OR 3.15 [95% CI 1.62–6.13], p = 0.0008), while molecular enrichment strategy was associated with longer OS (OR 0.40 [95% CI 0.22–0.73], p = 0.003). Nine (10.2%) patients experienced grade 3–4 toxicity and no dose limiting toxicity (DLT) occurred in both cohorts. ConclusionThe use of molecular profiling to guide enrolment in early phase trials is feasible and might provide benefits to selected patients with glioma. Further studies are warranted to confirm these results in larger randomised settings and identify the patients most likely to benefit from this approach.

Association Between Androgen Deprivation Therapy and Mortality Among Patients With Prostate Cancer and COVID-19

Androgen deprivation therapy (ADT) has been theorized to decrease the severity of SARS-CoV-2 infection in patients with prostate cancer owing to a potential decrease in the tissue-based expression of the SARS-CoV-2 coreceptor transmembrane protease, serine 2 (TMPRSS2). To examine whether ADT is associated with a decreased rate of 30-day mortality from SARS-CoV-2 infection among patients with prostate cancer. This cohort study analyzed patient data recorded in the COVID-19 and Cancer Consortium registry between March 17, 2020, and February 11, 2021. The consortium maintains a centralized multi-institution registry of patients with a current or past diagnosis of cancer who developed COVID-19. Data were collected and managed using REDCap software hosted at Vanderbilt University Medical Center in Nashville, Tennessee. Initially, 1228 patients aged 18 years or older with prostate cancer listed as their primary malignant neoplasm were included; 122 patients with a second malignant neoplasm, insufficient follow-up, or low-quality data were excluded. Propensity matching was performed using the nearest-neighbor method with a 1:3 ratio of treated units to control units, adjusted for age, body mass index, race and ethnicity, Eastern Cooperative Oncology Group performance status score, smoking status, comorbidities (cardiovascular, pulmonary, kidney disease, and diabetes), cancer status, baseline steroid use, COVID-19 treatment, and presence of metastatic disease. Androgen deprivation therapy use was defined as prior bilateral orchiectomy or pharmacologic ADT administered within the prior 3 months of presentation with COVID-19. The primary outcome was the rate of all-cause 30-day mortality after COVID-19 diagnosis for patients receiving ADT compared with patients not receiving ADT after propensity matching. After exclusions, 1106 patients with prostate cancer (before propensity score matching: median age, 73 years [IQR, 65-79 years]; 561 (51%) self-identified as non-Hispanic White) were included for analysis. Of these patients, 477 were included for propensity score matching (169 who received ADT and 308 who did not receive ADT). After propensity matching, there was no significant difference in the primary end point of the rate of all-cause 30-day mortality (OR, 0.77; 95% CI, 0.42-1.42). Findings from this cohort study suggest that ADT use was not associated with decreased mortality from SARS-CoV-2 infection. However, large ongoing clinical trials will provide further evidence on the role of ADT or other androgen-targeted therapies in reducing COVID-19 infection severity.

Trend and Predictors of Short-term Mortality of Adult Bacteremia at Emergency Departments: A 14-Year Cohort Study of 14 625 Patients.

BackgroundBacteremia is a life-threatening condition with a high mortality rate in critical care and emergency settings. The current study investigated the trend of mortality and developed predictive models of mortality for adults with bacteremia at emergency departments (EDs).MethodsWe conducted a retrospective cohort study of adults with bacteremia at the ED of China Medical University Hospital. Patient data were obtained from the Clinical Research Data Repository, and mortality information was obtained from the National Death Registry. We developed a new model to predict 7-day mortality in the derivation population and compared the model performance of the new model with Pitt Bacteremia Score (PBS) and Bloodstream Infection Mortality Risk Score (BSIMRS) in the validation population.ResultsWe identified 14625 adult patients with first-time bacteremia at the ED, of whom 8.4% died within 7 days. From 2003 to 2016, both the cumulative incidence and 7-day mortality rate of bacteremia decreased significantly. The ED bacteremia mortality (ED-BM) model included PBS parameters, age, infection source, baseline steroid use, and biochemical profiles (estimated glomerular filtration rate, platelet, blood urea nitrogen, potassium, and hemoglobin) for predicting 7-day mortality. The discrimination performance of the ED-BM model (area under curve [AUC], 0.903) was significantly better than that of PBS (AUC, 0.848) or BSIMRS (AUC, 0.885).ConclusionsAlthough the cumulative incidence and mortality of ED bacteremia decreased, its mortality burden remains critical. The proposed ED-BM model had significantly better model performance than other scoring systems in predicting short-term mortality for adult patients with bacteremia at EDs.

Safety and Clinical Outcomes of Immune Checkpoint Inhibitors in Patients With Cancer and Preexisting Autoimmune Diseases.

Immunotherapy has revolutionized treatment outcomes in numerous cancers. However, clinical trials have largely excluded patients with autoimmune diseases (ADs) due to the risk of AD flares or predilection for developing organ-specific inflammation. The objective of this study was to evaluate the safety and efficacy of immunotherapy in patients with cancer and preexisting ADs. A retrospective, single-center study of patients with cancer initiated on immune checkpoint inhibitors between 2012 and 2019 was conducted. The primary outcome was the development of immune-related adverse events (irAEs) with respect to the presence of AD at baseline. Associations were assessed using Kaplan-Meier curves, bivariate and multivariable analyses. Of the 417 patients included in this study, 63 patients (15%) had preexisting ADs. A total of 218 patients (53%) developed at least 1 irAE. There was no association between the presence of baseline AD on the development, grade, or number of irAEs; time to irAE or irAE recovery; systemic corticosteroid or additional immunosuppressant treatment for irAEs; permanent treatment discontinuation; or overall response rate. Two smaller cohorts were studied, melanoma and non-small cell lung cancer, and there was no effect of baseline AD on overall survival on either cohort. However, a greater proportion of patients with baseline ADs had full recovery from their irAE (P=0.037). Furthermore, age below 65, baseline steroid use, and single-agent immunotherapy regimens were protective in terms of the development of irAEs. Our study suggests that immune checkpoint inhibitors have similar safety and efficacy profiles in patients with preexisting ADs.

Outcomes in patients with metastatic non-small cell lung cancer (mNSCLC) with brain metastases treated with pembrolizumab-based therapy.

9599 Background: Patients (pts) with mNSCLC with active brain metastases (BM) are often excluded from clinical trials; data on efficacy and safety of immunotherapy in this population are limited. We compared outcomes of pts with mNSCLC with and without BM who received pembrolizumab-based therapy. Methods: We conducted a retrospective single-center study of pts with mNSCLC treated with pembrolizumab (P) with or without chemotherapy. Progression-free survival (PFS) and overall survival (OS) were determined by Kaplan-Meier methodology and compared using multivariable Cox regression and log rank testing. Results: We identified 587 consecutive pts with mNSCLC who began P-based therapy between 8/2013 and 12/2018: 306 (52%) female, median age 67 years (range 32-98), 437 (74%) adenocarcinoma, and 508 (87%) former/current smokers. 388 (66%) patients received P in first line therapy, and 334 (57%) received single-agent P. 131 pts (22%) had detectable BM at baseline (start of P-based therapy). Pts with BM were younger (median 65 y vs 68 y, p &lt; 0.01) and more likely to have adenocarcinoma (86% vs. 71%, p &lt; 0.01) and baseline steroid use (22% vs 1%, p &lt; 0.01). Presence of BM did not differ by race, sex, line of therapy, treatment regimen, or PD-L1 status. Of the 131 patients with detectable BM on pre-treatment brain MRI, 55 (42%) had stable BM as a result of prior local therapy, while 76 (58%) had active (new or growing) BM on pre-treatment imaging. Most patients with active BM underwent radiation therapy (RT) in either the 30 days before (n = 46) or 30 days after (n = 17) P start; of the remaining 13 treated with P-based therapy alone, intracranial responses included 2 CR, 2 PR, 3 SD, and 4 PD. As of 1/1/2020, with 15-month median follow up, there was no difference in mPFS (9.2 vs 7.3 months, p = 0.41) or mOS (18.3 vs 18.0 mo, p = 0.67) between pts with and without BM in our P-treated cohort. On multivariable analysis, female sex, ECOG 0-1, adenocarcinoma histology, and P as first line therapy were associated with improved PFS and OS. Presence of BM, baseline steroid use, and timing of local RT (before vs. after P) were not associated with inferior survival. Conclusions: In our single-center experience of pts with mNSCLC treated with P, pts with and without BM had similar PFS and OS. We observed several intracranial responses to P-based therapy alone, but most pts with active BM underwent local RT. mNSCLC pts with BM should be considered for P-based therapy; BM may be treated with RT immediately before or even after P with similar survival outcomes.

Risk stratification for the development of chronic pulmonary aspergillosis in patients with Mycobacterium avium complex lung disease.

The number of patients with pulmonary nontuberculous mycobacterial disease complicated by chronic pulmonary aspergillosis (CPA) has been increasing. Additionally, CPA is reportedly associated with mortality in patients with Mycobacterium avium complex lung disease (MAC-LD). In the present study, we aimed to identify risk factors for developing CPA and stratify the risk for CPA development in patients with MAC-LD. We retrospectively examined 361 patients newly diagnosed with MAC-LD. Risk factors for CPA development were examined using multivariate Cox proportional hazards regression analyses. A risk stratification system was established using the risk factors and receiver operating characteristic curve analyses. CPA developed in 20 (5.5%) of the 361 patients. Independent risk factors for CPA development included the presence of pulmonary emphysema, baseline steroid use, a serum albumin level <3.5g/dL, and the presence of MAC-LD cavities. A 4-point scoring system was established to stratify patients into low-risk (0-1 point) and high-risk (2-4 points) groups. The 5-year incidence rates of CPA were 2.2% and 31% in the low- and high-risk groups, respectively (P<0.001). We identified independent predictors of CPA development and established a simple risk stratification system for identifying patients with MAC-LD who were at a high risk of developing CPA.

Association of baseline steroid use with long-term rates of infection and sepsis in the REGARDS cohort

BackgroundPrior studies associate steroid use with infection risk but were limited to select populations and short follow-up periods. The association of steroid use with long-term risk of community-acquired infections is unknown. We sought to determine the association of steroid risk with long-term risks of community- acquired infections and sepsis.MethodsWe used data on 30,239 adults aged ≥ 45 years old from the Reasons for Geographic and Racial Differences in Stroke (REGARDS) cohort. The primary exposure was oral or injectable steroid use, determined from medication inventory obtained at baseline in-home visit. The primary outcome was time to first infection event during 2003–2012, determined through adjudicated review of hospital records. We determined associations between baseline steroid use and first infection hospitalization events using Cox proportional hazards models, adjusting for demographics, health behaviors, chronic medical conditions, and medication adherence. Among the first infection hospitalization events, we also determined the association between baseline steroid use and sepsis.ResultsSteroid use was reported in 2.24% (n = 677) of the study population. There were 2593 incident infection events during the 10-year follow-up period. Infection incidence rates were higher for steroid than non-steroid users (37.99 vs. 13.79 per 1000 person-years). Steroid use was independently associated with increased risk of infection (adjusted HR 2.10, 95% CI: 1.73–2.56). Among first-infection events, steroid use was associated with increased odds of sepsis (adjusted OR 2.11, 95% CI: 1.33–3.36). The associations persisted in propensity matched analyses as well as models stratified by propensity score and medication adherence.ConclusionsIn this population-based cohort study, baseline steroid use was associated with increased long-term risks of community-acquired infections and sepsis.

Examining systemic steroid Use in older inflammatory bowel disease patients using hurdle models: a cohort study.

BackgroundInterpreting clinical guideline adherence and the appropriateness of medication regimens requires consideration of individual patient and caregiver factors. Factors leading to initiation of a medication may differ from those determining continued use. We believe this is the case for systemic steroid therapy in inflammatory bowel disease (IBD), resulting in a need to apply methods that separately consider factors associated with initiation and duration of therapy. To evaluate the relationship between patient characteristics and the frequency and duration of incident steroid use we apply a 2-part hurdle model to Medicare data. We do so in older patients with tumor necrosis factor antagonist (anti-TNFs) contraindications, as they are of special interest for compliance with Medicare-adopted, quality metrics calling for anti-TNFs and nonbiologic immune therapies to reduce steroid utilization. Many older patients have contraindications to anti-TNFs. However, nonbiologics cause adverse events that are concerning in older adults, limiting their use in this population and increasing reliance on systemic steroids.MethodsWe used a national Medicare sample for 2006–2009 including patients with 12 months or greater of Parts A and B and 6 months or greater of Part D coverage, IBD confirmed with at least 2 claims for ICD-9CM 555.xx or 556.xx, anti-TNF contraindications and without contraindications to nonbiologic agents. We applied a negative binomial-logit hurdle model to examine patient characteristics associated with systemic steroid utilization.ResultsAmong the 1,216 IBD patients without baseline steroid use, 21 % used systemic steroids. Odds of receiving systemic steroids were greater in those younger, rural, and those receiving other agents. Available patient characteristics failed to predict longer steroid treatment duration.ConclusionsOur study identified differences in predictors of frequency and duration of medication use and suggests the utility of two-part models to examine drug utilization patterns. Applying such a model to Medicare data, we determined that despite medical consensus that systemic steroid use should be minimized, its use was substantial. Findings indicate anticipated difficulties in implementing recently adopted quality measures to avoid systemic steroids.

Baseline neutrophil–lymphocyte ratio (NLR) is associated with survival and response to treatment with second-line chemotherapy for advanced prostate cancer independent of baseline steroid use

The neutrophil-lymphocyte ratio (NLR), proposed as an indicator of cancer-related inflammation, has known prognostic value in prostate cancer. We examine its association with survival (OS) and response in patients treated with second-line chemotherapy. We analysed patients with metastatic castration-resistant prostate cancer (mCRPC) treated in the TROPIC trial, evaluating cabazitaxel versus mitoxantrone. Cox regression models were used to investigate the association of baseline NLR (BLNLR) with OS and the significance of a change in NLR count with treatment. Logistic regression models were used to determine the association of BLNLR counts with prostate specific antigen (PSA) and RECIST responses. The optimal NLR cut-off was established based on the concordance index of different values. Data from 755, 654 and 405 patients was available for OS, PSA and RECIST response analysis respectively. Median OS was 14.0 months [95% confidence interval (CI) 13.2-14.8]. Median NLR was 2.9 (IQR: 1.9-5.1). BLNLR was associated with survival (HR 1.5, 95% CI 1.1-2.1, P = 0.011) in multivariable analysis (MVA) independently of variables included in the Halabi nomogram, treatment arm and corticosteroid use. The optimal cut-off for a dichotomous NLR was selected at 3.0 based on its higher c-index related to survival. BLNLR ≥3.0 was associated with lower PSA response (40.1% versus 59.9%; P < 0.001) and RECIST response (7.7% versus 15.6%, P = 0.022) in MVA. Conversion from high (≥3) to low (<3) NLR was associated with improved survival (HR 0.66; 95% CI 0.51-0.85; P = 0.001) and higher PSA response rates (66.4% versus 33.6%; P = 0.000). Use of corticosteroids at baseline did not modify the association between NLR and survival. NLR is a valid prognostic biomarker in CRPC and is associated with survival, PSA and RECIST responses in patients treated with second-line chemotherapy. Changes in NLR counts with treatment may indicate benefit. NLR prognostic value is independent of prior use of corticosteroids. NCT00417079.

Patient outcome in the Belgian medical need program on bevacizumab for recurrent glioblastoma.

Bevacizumab (BEV) has demonstrated anti-tumor activity in patients with recurrent glioblastoma (rGB). Given the unmet need for active therapeutic options in rGB patients, a medical need program was initiated by the Belgian competent authorities. Between November 2010 and February 2013, a total of 313 patients with rGB initiated treatment with BEV administered at a dose of 10 mg/kg every 2 weeks. All patients had failed prior treatment with at least radiation therapy and temozolomide and the majority of patients (70 %) were treated with corticosteroids at baseline. Patients received a median of 6 BEV administrations (range 1-53). Overall, BEV was well tolerated. During BEV treatment the WHO-Performance Score (WHO-PS) improved in 59 patients (19 %) and stabilized for at least 6 weeks in an additional 139 (44 %) patients. Corticosteroid treatment could be stopped in 16 % or reduced in dose in 32 % of patients. The best objective tumor response rate using RANO criteria (investigator's assessment) was 3.5 % CR, 22 % PR, 38 % SD and 37 % PD. The median and 6-month PFS were 13 weeks (95 % CI 12.7-14) and 27.3 % (95 % CI 22.3-32.5), median and 6-month OS rates were 26 weeks (23-29) and 52 % (46.4-58.6), respectively. WHO-PS (0-1 vs. 2-3) and baseline steroid use were significantly correlated with PFS and OS. Our observations support the use of BEV as a monotherapy for patients with rGB who have no alternative treatment options. Optimal benefit from BEV treatment is likely to be obtained when treatment is initiated before the performance status deteriorates to two or less.

Steroid Use in Acute Ulcerative Colitis Predicts Need for Class Escalation or Surgical Intervention Irrespective of Oral Mesalamine Monotherapy or Dual Therapy

Purpose: First-line treatment for mild-moderate ulcerative colitis (UC) includes orally or topically administered mesalamines, with more moderatesevere patients requiring steroids, immunomodulators or biologics. There are currently no mesalamine optimization guidelines, and there are no studies investigating the effects of administering two oral mesalamines. We compared the efficacy of oral mesalamine mono-therapy and dual-therapy in the treatment of patients with active UC. Methods: We conducted a retrospective chart review of UC patients seen at our center between January 2003 and December 2009. Patients were either switched to a different mesalamine (mono-therapy), or changed to 2 mesalamines (dual-therapy). The primary endpoint was escalation of therapy to immunosuppressive agents or surgery within 6 months. Secondary endpoints included change in partial Mayo (PM) scores at 1, 3, and 6 months after the change in therapy, and factors predicting response, such as baseline steroid use. Scores were recorded in all charts at the time of the patient encounter. Mann-Whitney and Fisher's exact tests, and logistic regression analyses were performed. Results: Charts from 104 patients were reviewed. There were 67 mono- and 37 dual-therapy patients: mean ages 36.8 and 38.2, duration of disease 6.9 and 6.0 years, baseline PM score 5.0 and 4.7, use of topical therapy 87% and 86%, respectively (p=NS). Dual therapy patients were more likely to be on balsalazide (86% vs. 57%, p=0.002) or MMX mesalamine (46% vs. 27%, p=0.001). There was a decline in PM score for both mono- and dual-therapy groups of 1.3-2.5. Baseline PM score predicted need to escalate therapy OR 1.58 (CI 1.19-2.09, p<0.002), OR 1.44 (CI 1.14-1.82, p=0.002), and OR 1.44 (CI 1.15-1.81, p<0.002) at 1, 3, and 6 months respectively. After adjusting for baseline PM score, steroid use, but not 6MP or anti-TNF, is strongly associated with dose escalation, at month 1, 3 and 6 ((OR 24.3 CI4.87-121.3, p<0.0001); (OR 4.57 CI 1.45-14.47, p<0.01); (OR 5.27 CI 1.66-16.8, p<0.005)). Conclusion: Steroids at the time of switch to a different mesalamine monotherapy or dual-therapy predict an increased likelihood of class escalation to immumunomodulators or biologics or to surgical intervention. This striking association was irrespective of baseline disease activity. Despite the overall improvement in disease severity in patients receiving dual- or single-agent therapy, no regimen was proven superior, and specific mesalamines did not impact on clinical improvement. These findings underscore the negative impact of steroids on UC clinical outcomes, and suggest the need for prospective studies evaluating the role of mesalamine mono-therapy or dual-therapy prior to steroid use in mild to moderate UC. Disclosure: Dr Scherl - Consultant: Salix, Shire Dr Bosworth - Consultant: Salix.

Concurrent Oral 7 - Rheumatoid Arthritis: Clinical Aspects [OP48-OP53]: OP48. The Risk of Non-Melanoma Skin Cancer in Patients Receiving Anti-TNF Therapies for Rheumatoid Athritis: Results from the British Society for Rheumatology Biologics Register

Background: Rheumatoid arthritis (RA) is associated with an increased risk of basal cell (BCC) and squamous cell (SCC) non-melanoma skins cancers (NMSC). Anti-TNF therapy may intensify this risk, although evidence to date is conflicting. Our aim was to explore the influence of anti-TNF therapy on the incidence of NMSC in patients with RA using data from the BSRBR. Methods: 11639 patients with RA starting anti-TNF therapy and 3505 biologic-naïve subjects with active RA receiving traditional disease modifying therapy (DMARD) were compared for rates of NMSC. Patients were followed up until 12/31/2008 or death, whichever came first. Patients with a history of NMSC prior to entering the study identified by record linkage with the UK national cancer registry (NHS-IC) were excluded. Incident NMSC were identified from consultant and patient questionnaires and record linkage with the NHS-IC. Only confirmed cases were included in the analysis (histology, NHS-IC reported, or definitive cancer treatment). NMSC occurring after stopping anti-TNF was attributed to the most recent anti-TNF drug. The rates of NMSC in the anti-TNF and DMARD cohorts were compared using multivariate Cox proportional hazards models adjusted for age, gender, disease duration, disease activity, HAQ, baseline steroid use, number of prior DMARDs, smoking and year of registration. Results: 184 NMSC were verified: 155 in the anti-TNF cohort and 29 in the DMARD cohort. The ratio of BCC:SCC was similar in both cohorts: anti-TNF 88%:11%, DMARD 81%:19%. Age and male gender were associated with an increased risk of NMSC in multivariate analysis. The fully adjusted hazard ratio (aHR) of total NMSC for anti-TNF vs DMARD was 1.7 (95% CI 0.9, 3.0). The aHR was 1.6 (0.9, 3.0) for etanercept (ETA), 2.7 (1.4, 5.1) for infliximab (INF) and 1.2 (0.6, 2.3) for adalimumab (ADA). This difference in risk remained if analysis was limited to the first anti-TNF therapy only. The risk in infliximab was attenuated when analysis was limited to the first NMSC only (Table). Conclusions: In patients with no prior NMSC, the risk of total NMSCs was increased by 70% in patients with RA treated with anti-TNF therapy, although this was not significant. INF was associated with an almost three-fold increase in risk of NMSC, although this may be in part explained by more common multiple lesions. Vigilance for NMSC should be maintained in all patients with RA, especially when treated with anti-TNF therapy. Disclosure statement: BSRBR, Wyeth - Research Grant, Schering-Plough - Research Grant, Abbott - Research Grant, Biovitrum - Research Grant, Roche - Research Grant. All other authors have declared no conflicts of interest.

Joint NCCTG and NABTC prognostic factors analysis for high-grade recurrent glioma

The purpose of this study is to determine prognostic factors in patients with high-grade recurrent glioma for 3 outcome variables (overall survival, progression-free survival [PFS], and PFS rate 6 months after study registration [PFS6]). Data from 15 North Central Cancer Treatment Group (NCCTG) trials (n = 469, 1980-2004) and 12 North American Brain Tumor Consortium (NABTC) trials (n = 596, 1998-2002) were included. Eighteen prognostic variables were considered including type of treatment center (community/academic) and initial low-grade histology (yes/no). Recursive partitioning analysis (RPA), Cox proportional hazards, and logistic regression models with bootstrap resampling were used to identify prognostic variables. Longer survival was associated with last known grade (Grade) of III, younger age, ECOG performance score (PS) of 0, shorter time from initial diagnosis (DxTime), and no baseline steroid use. Factors associated with longer PFS were Grade III and shorter DxTime. For patients without temozolomide as part of the treatment regimen, the only factor associated with better PFS6 was Grade III, although DxTime was important in RPA and PS was important in logistic regression. Grade was the most important prognostic factor for all three endpoints regardless of the statistical method used. Other important variables for one or more endpoints included age, PS, and DxTime. Neither type of treatment center nor initial low-grade histology was identified as a major predictor for any endpoint.