Concurrent Use Of Corticosteroids Research Articles

P107 Real world clinical outcomes of patients with moderate-to-severe rheumatoid arthritis initiating upadacitinib in the United Kingdom: Interim analysis from a prospective observational cohort study (ENDEAVOUR)

Abstract Background/Aims Upadacitinib (UPA) 15 mg, a once-daily Janus kinase inhibitor (JAKi), is approved by NICE for treating adults with moderate-to-severe rheumatoid arthritis (RA) unresponsive to conventional Disease Modifying Antirheumatic Drugs (DMARDs). This study aims to evaluate UPA's real-world effectiveness in the UK. Methods ENDEAVOUR is a prospective observational cohort study which recruited 97 patients with moderate to severe RA whom the managing health care professional has decided to treat with UPA in line with marketing authorisation across 14 sites in the UK. Patient demographics, comorbidities, concomitant therapies and patient reported disease activity were collected at baseline, three months, and six months. Patient Reported Outcomes (PROs) were collected using an app hosted by UMotif. Primary objective was the proportion of patients achieving clinical remission (defined as DAS28<2.6) with upadacitinib at six months. The study is ongoing and therefore not all patients have completed study visits at three and six months yet however this interim analysis reports the baseline demographics of 77 patients whose data has been cleaned thus far and clinical outcomes and safety of UPA 47 adult patients at three months. Data are as observed. Results Data were available for 77 adults at baseline: 42% had moderate and 58% had severe RA based on DAS28-CRP scores. Patients' average age was 55 years, 64 (83%) were female, and most had at least one comorbidity, such as hypertension (16,21%) or asthma (12,16%). 32 (42%) had prior biologic therapy, with treatment failure the most commonly reported reason for switch (26/33, 79%). Of the 47 participants with three-month data, 18 (38%) achieved DAS28 remission. The proportion of patients with high disease activity decreased markedly from 45 (58%) at baseline to three (6%) at three months and moderate disease activity from 32 (42%) at baseline to 14 (30% at three months). Concurrent corticosteroid use declined, from 13 (17%) patients at baseline to just three (5%) by three months. The mean exposure time was six months (IQR five to seven). Nine patients (9%) stopped UPA during the study period, (5/9 due to adverse events, 4/9 due to patient or physician choice). One case of shingles occurred, with temporary treatment interruption. Reports of serious adverse events were low (4% patients of events reported) with cases of serious and opportunistic infections reported most frequently (three cases). There were no reports of MACE or venous thromboembolic events. 1 report of malignancy (extranodal marginal zone B-cell lymphoma) was considered unrelated to treatment. Conclusion This preliminary analysis of an observational study provides valuable insights into the real-world effectiveness of UPA for treatment of moderate to severe RA with similar early efficacy to that observed in clinical trials. 38% of patients achieved clinical remission by 3 months, and adverse events were infrequent. Disclosure J. Taylor: None. S. Srirangan: None. M. Bukhari: Honoraria; M.B has received honoraria for speaking and attended advisory boards with Bristol-Myers Squib, UCB celltech, Roche/Chugai, Pfizer, AbbVie, Merck, Mennarini, Sanofi-aventis, Eli-Lilly, Janssen, Amgen, Novartis and Gilead. Other; M.B. has been sponsored to attend regional, national and international meetings by UCB celltech, Roche/Chugai, Pfizer, Abbvie, Merck, Mennarini, Janssen, Bristol-Myers Squib, Novartis and Eli-lilly. S. Bilgrami: Other; S.B. has received professional and financial support from Eli Lilly, UCB & Pfizer. M.K. Nisar: Other; M.K.N undertakes clinical trials and received support (including attendance at conferences, speaker fees and honoraria) from Roche, Chugai, MSD, AbbVie, Pfizer, BMS, Novartis, Celgene, UCB and, Lilly. S. McDonald: None. N. Goodson: None. A. Allard: Other; A.A. has received payment for services, sponsorship, funding, grants or worked on clinical trials for AbbVie, Eli Lilly, Pfizer, Novartis, BMS, Roche. A. Kinder: None. M. Green: None. L. Hunt: None. S. Raizada: Honoraria; S.R. has received honoraria from AbbVie. B. Kirkham: Consultancies; B.K. has received consultant/speaker fees from AbbVie, Eli Lilly, Galapagos, Janssen, Novartis, Pfizer and UCB. Grants/research support; B.K. has received research support from Eli Lilly and Novartis. E. Thomas: Other; E.T. has been on advisory boards for Janssen and Galapagos. R. Horsfall: None. S. Bartlett: None. R. Millward: None. V. Burton: None. J. Galloway: Consultancies; J.G. has received speaker/consultancy for AbbVie, Galapagos, Janssen, Lilly, Pfizer, UCB and Vifor. Grants/research support; He has received research grants for AbbVie, Galapagos, GSK, Janssen, Lilly, Pfizer.

Predictive factors for L-asparaginase hypersensitivity in pediatric acute lymphoblastic leukemia.

L-Asparaginase is a crucial component of acute lymphoblastic leukemia (ALL) treatment. However, hypersensitivity is a common adverse event. This study aimed to identify risk factors for L-asparaginase hypersensitivity in childhood ALL. Children treated for ALL at Chiang Mai University Hospital, Thailand, between 2005 and 2020 were included. Demographic data, clinical characteristics, and factors related to L-asparaginase were retrospectively reviewed. L-Asparaginase hypersensitivity was observed in 24 of 216 children with ALL (11.1%). All patients received native L-asparaginase intramuscularly, and events occurred exclusively during the post-induction phase without concurrent corticosteroid use. Univariable analysis showed that relapsed ALL, higher accumulated doses, increased exposure days, and longer interval between drug administrations were potential risk factors. In multivariable logistic regression analysis, interruption of L-asparaginase administration for ≥ 52weeks and exposure duration of ≥ 15days were independent risk factors, with adjusted odds ratio of 16.481 (95% CI 3.248-83.617, p = 0.001) and 4.919 (95% CI 1.138-21.263, p = 0.033), respectively. Children with ALL who require re-exposure to L-asparaginase after 52-week interruption or who have received L-asparaginase for ≥ 15 exposure days are at risk of developing L-asparaginase hypersensitivity. Further management strategies in this setting should be evaluated.

Clinical factors associated with prescribing patterns of bone modifying agents in men with metastatic castration-resistant prostate cancer.

e18878 Background: Bone metastases occur in up to 90% of men with metastatic prostate cancer and cause skeletal-related events (SREs) such as fracture and spinal cord compression. Although bone modifying agents (BMAs) have been shown to decrease the risk of SREs in men with metastatic castration-resistant prostate cancer (mCRPC), BMAs are not widely used in this patient population. In this retrospective study, we report the prescribing patterns of BMAs and predictors of BMA use in a large national cohort. Methods: We used the VA corporate data warehouse to identify patients with mCRPC who were treated with first-line mCRPC therapy (abiraterone, enzalutamide, docetaxel, or ketoconazole) between 2010 and 2017. BMA prescribing frequency and patterns were analyzed. Multivariable regression analysis was used to evaluate clinical and disease-specific factors associated with BMA use which are presented as adjusted odds ratios (OR) with 95% confidence intervals (CI). Results: In the final cohort of 4,079 patients, the median age at mCRPC diagnosis was 73 years (IQR 66-81). 29% of patients in the cohort were Black. Diagnosis codes identified bone metastases at mCRPC diagnosis in 48% of the cohort (ICD-9 and 10 coding for sites of metastases are known to underestimate the actual incidence of metastases). Only 48% of patients received a BMA following initiation of treatment for mCRPC, 47% of which had already received a BMA 6 months prior to mCRPC diagnosis. For those who were new BMA starts, the median time to BMA administration from mCRPC treatment was 3.4 months (IQR 1.2-8.8). Factors associated with BMA use were having an ICD-9 or 10 diagnosis code for bone metastases at time of mCRPC treatment (OR 1.28, 95% CI 1.10-1.48), concurrent corticosteroid use (OR 1.90, 95% CI 1.53-2.38), and docetaxel use as first-line mCRPC therapy (OR 1.78, 95% CI 1.45-2.18). Factors associated with decreased BMA use were Charlson comorbidity index score of ≥ 2 (OR 0.75, 95% CI 0.62-0.90), advancing age (OR 0.86 per 10 years, 95% CI 0.79-0.94), and decreased eGFR (eGFR 30-59, OR 0.81, 95% CI 0.68-0.96; eGFR 0-29, OR 0.23, 95% CI 0.14-0.37). Having a diagnosis code for a SRE before mCRPC diagnosis (e.g., bone fracture and cord compression) did not impact BMA use, but the incidence of those events was low. Conclusions: Less than half of this VA cohort received a BMA after starting therapy for mCRPC. Key factors associated with BMA use were corticosteroid use and first-line docetaxel use, which likely represented more aggressive disease. Notably, patients who were older and had more comorbid conditions were less likely to receive a BMA despite being highest risk for frailty and SREs. Future quality improvement efforts aimed at increasing BMA use may address the needs of the geriatric mCRPC patient population.

Aspergillus Endocarditis in a prosthetic Valve following COVID-19 Infection

Endocarditis of a prosthetic valve is a known but rare occurrence. Fungal endocarditis is extremely rare. However, in the COVID-19 pandemic, there has been increasing recognition of fungal or yeast-related infections, often due to the combination of immune paresis, concurrent use of corticosteroids or underlying chronic conditions such as diabetes or neoplasms. We present a patient with fulminating, invasive aspergillosis of a prosthetic aortic valve who presented with catastrophic cardiovascular failure needing intensive care management. Early recognition and prompt therapy is the cornerstone of success in such presentations with high mortality.

E003 Why do rheumatologists request PET-CT scans and what do they show: an audit from a tertiary London Hospital

Abstract Background/Aims (18F)FDG PET-CT is an imaging tool with utility in the diagnosis of inflammation, infection and malignancy. In rheumatology settings, it is most commonly used for the diagnosis and monitoring of large vessel vasculitis (LVV), sarcoidosis, polymyalgia rheumatica (PMR), IgG-4 disease and myositis. Whilst PET-CT is highly sensitive for the detection of inflammation, concurrent corticosteroid use impairs this. Furthermore, uptake can be non-specific and incidental abnormalities are often reported. Few cohorts have investigated the real-life use of PET-CT including clinical indication, rheumatological and non-rheumatological findings and patient outcomes. Methods 98 PET-CT scans were requested by the rheumatology department at St Georges NHS Foundation Trust from January 2017 to December 2021. Data including patient demographics, pre-existing rheumatological disease, corticosteroid use and inflammatory marker levels were collected. Indication for PET-CT and PET-CT findings were reviewed. Results As summarised in Table 1, PET-CT scans were most commonly requested for the investigation of raised inflammatory markers, poor response to therapy, concerning clinical features, for the characterisation of abnormal imaging findings and for routine monitoring of disease. LVV and malignancy were the most commonly considered differential diagnoses. At the time of PET-CT scan, 59 (60%) patients were taking corticosteroids. 58 of these patients were prescribed prednisolone (dose ranging between 2mg to 80mg, mean dose 19.6mg OD, median dose 15mg OD) In our audit, 39.8% of PET-CT showed active rheumatological disease. 32.6% showed non-rheumatological abnormalities with 2% demonstrating new cancer diagnoses. The detection of incidental non-specific imaging findings commonly led to the request of further diagnostic tests including ultrasound imaging (11 patients) and endoscopy (7 patients). Conclusion In conclusion, PET-CT is a useful imaging tool in the diagnosis and monitoring of rheumatological inflammatory conditions. Despite a majority of patients taking corticosteroids at the time of scan, PET-CT remained an effective diagnostic adjunct. A large number of non-rheumatological imaging abnormalities were seen in our cohort; in most cases, the clinical significance was not immediately clear and further investigations were needed. Further guidance is needed to determine the characterisation and management of these incidental findings to avoid unnecessary, costly and sometimes invasive tests. Disclosure K. Biddle: None. K. Chaabo: None.

CARDIOGENIC SHOCK AND CRITICAL ILLNESS-RELATED CORTICOSTEROID INSUFFICIENCY: DID STEROIDS MAKE MY HEART GO ON?

CARDIOGENIC SHOCK AND CRITICAL ILLNESS-RELATED CORTICOSTEROID INSUFFICIENCY: DID STEROIDS MAKE MY HEART GO ON?

Does Dosage or Duration of Concurrent Oral Corticosteroid Influence Elevated Risk of Postoperative Complications After Total Joint Arthroplasty?

This report seeks to clarify whether the dosage and duration of preoperative concurrent corticosteroid use influence postoperative complications after primary total joint arthroplasty (TJA). This retrospective single institutional study enrolled 1128 primary TJA cases, including 905 total hip arthroplasties and 223 total knee arthroplasties at a minimum 6 months of follow-up. Mean follow-up period was 51.9±34.1 months (range 6-146). Of all joints, 120 joints (10.6%) were associated with chronic concurrent oral corticosteroid use. Multivariate analysis was performed to identify whether chronic concurrent oral corticosteroid use elevated the risk of postoperative complications including surgical site infection/periprosthetic joint infection, delayed wound healing, periprosthetic fracture, and implant loosening. For chronic concurrent oral corticosteroid user, we determined whether the dosage and duration of preoperative concurrent corticosteroid use influenced postoperative complications and have an effective threshold for postoperative complications using receiver operating characteristic curve analysis. The multivariate analysis revealed that American Society of Anesthesiologist Physical Status 3 was an independent risk factor for postoperative complications, while concurrent oral corticosteroid use was not an independent risk factor. When we compared joints with (n= 13) and without (n= 107) postoperative complications in chronic concurrent oral corticosteroid user, there was no statistical difference in the dosage (P= .97) and duration (P= .69) between the 2 groups. Area under the curve values for the oral corticosteroid dosages and duration were 0.482 and 0.549, respectively. This study revealed that neither dosage nor duration of concurrent oral corticosteroid use was predictive of postoperative complications after TJA. American Society of Anesthesiologist Physical Status 3 is a major factor in postoperative complications after TJA.

Abstract P4-11-33: Continuous glucose monitoring and hyperglycemia during chemotherapy for early-stage breast cancer

Abstract Background: There are a growing number of breast cancer (BC) survivors who are at risk for short and long-term treatment-related toxicities. BC survivors may be at higher risk of developing diabetes mellitus (DM), and chemotherapy may potentiate this risk due to concurrent corticosteroid use. DM is associated with both short and long-term treatment toxicities and worse BC outcomes. The prevalence of hyperglycemia (HG) during chemotherapy for early-stage BC (ESBC), and the association between HG during chemotherapy and treatment-related toxicities is unknown. Methods: We are conducting a single-arm pilot study to evaluate the prevalence of hyperglycemia among patients with ESBC during chemotherapy (NCT04473378). Patients are eligible if ≥18 years old, initiating chemotherapy with corticosteroid use, not receiving systemic steroids except as supportive care for chemotherapy, and known DM is allowed if patients are not treated with insulin. Within 7 days of chemotherapy initiation, the Freestyle Libre Pro (Abbott Diabetes Care) continuous glucose monitoring system is applied to the posterior arm of each participant. Patches are reapplied every 2-3 weeks and worn continuously until chemotherapy completion (duration per regimen). The Freestyle Libre Pro monitors interstitial glucose every 15 minutes via subcutaneous sensor filaments adhered to the skin without a finger prick. Data is downloaded using a wireless scan of the sensor by a reader. The primary endpoints are: 1) the prevalence of HG, defined as the number of participants who have ≥1 glucose value (fasting or non-fasting) of ≥140 mg/dL at any point from chemotherapy initiation to completion; 2) Among participants who develop HG, the proportion of time in which they have HG, measured as the number of hyperglycemic values (glucose value of ≥140 mg/dL) divided by the total number of glucose values recorded in an individual for the duration of chemotherapy. Secondary endpoints include the prevalence of impaired glucose tolerance (hemoglobin A1c [HgbA1c] ≥5.7%) prior to chemotherapy initiation in patients without a history of DM, and changes in glucose biomarkers (HgbA1c, fructosamine, and serum creatinine) during treatment. Results: Between December 2020 and April 2021, 7 patients were enrolled, with evaluable data for 5 patients. At baseline median age was 60 (range, 37-74) and median BMI was 33.0 (range, 24.6-41.6). Chemotherapy regimens were: docetaxel/cyclophosphamide (40%); docetaxel/cyclophosphamide/trastuzumab/pertuzumab (20%); weekly paclitaxel (20%); and paclitaxel followed by doxorubicin/cyclophosphamide (20%). All patients (100%) developed hyperglycemia. Of 18,768 sensor readings (281,265 minutes) the proportion of time participants were hyperglycemic (≥140 mg/dL) during the period of adjuvant/neoadjuvant chemotherapy was 22.1%, and the mean time from first corticosteroid administration to first hyperglycemic episode was 7.6 hours. Of three patients with no history of DM (including one patient with glucose intolerance), the proportion of time spent hyperglycemic (≥140 mg/dL) was 9.9% (range, 1.7-13.8%), and the mean daily glucose was 106.7 mg/dL (SD 10.3). Of the two patients with DM, the proportion of time spent hyperglycemic was 70.2% (range, 67.2-79.5%) and the mean daily glucose was 171.7 mg/dL (SD 3.1). Changes in glucose biomarkers will be presented with the full cohort. Conclusion: Hperglycemia during chemotherapy occurred in 100% of the cohort, including those without a history of DM or glucose intolerance. It is currently unknown if HG during chemotherapy is a modifiable risk factor for short and long-term BC treatment toxicities including neuropathy. Understanding glucose trends in this setting will help determine a successful intervention for HG during chemotherapy which may reduce short and long-term treatment toxicities. Citation Format: Melissa K Accordino, John H Spivack, Sophie Ulene, Erin Honan, Meghna S Trivedi, Katherine D Crew, Erik Harden, Cynthia Law, Dawn L Hershman. Continuous glucose monitoring and hyperglycemia during chemotherapy for early-stage breast cancer [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P4-11-33.

The Effect of Corticosteroids on Prostate Cancer Outcome Following Treatment with Enzalutamide: A Multivariate Analysis of the Phase III AFFIRM Trial.

The clinical impact of concurrent corticosteroid use (CCU) on enzalutamide-treated patients with metastatic castration-resistant prostate cancer (mCRPC) is unknown. We investigated the association of CCU with overall survival (OS), radiographic progression-free survival (rPFS), and time to prostate-specific antigen progression (TTPP) in post-chemotherapy, enzalutamide-treated patients with mCRPC. Post hoc analysis of AFFIRM (NCT00974311) with patients (n = 1,199) randomized 2:1 to enzalutamide 160 mg/day or placebo. Treatment group, CCU, and known prognostic factors were evaluated for impact on OS, rPFS, and TTPP using a multivariate Cox proportional hazards model. CCU was defined as "baseline" (use started at baseline) or "on-study" (baseline plus use that was started during the trial). Enzalutamide significantly improved OS, rPFS, and TTPP independent of baseline CCU but was associated with inferior clinical outcomes when compared with no baseline CCU, including a shorter OS [10.8 months vs. not reached (NR); HR for use vs. no use, 2.13; 95% confidence interval (CI), 1.79-2.54], rPFS (5.2 months vs. 8.0 months; HR, 1.49; 95% CI, 1.29-1.72], and TTPP (4.6 months vs. 5.7 months; HR, 1.50; 95% CI, 1.25-1.81). These findings held in a multivariate analysis adjusting for baseline prognostic factors wherein baseline CCU was independently associated with decreased OS (HR, 1.71; 95% CI, 1.43-2.04; P < 0.0001) and rPFS (HR, 1.28; 95% CI, 1.11-1.48; P = 0.0007). Patients with mCRPC benefited from enzalutamide treatment independent of CCU, but CCU was associated with worse baseline prognostic factors and outcomes.

Comparative Safety Profiles of Sedatives Commonly Used in Clinical Practice: A 10-Year Nationwide Pharmacovigilance Study in Korea.

This study aims to compare the prevalence and seriousness of adverse events (AEs) among sedatives used in critically ill patients or patients undergoing invasive procedures and to identify factors associated with serious AEs. Retrospective cross-sectional analysis of sedative-related AEs voluntarily reported to the Korea Adverse Event Reporting System from 2008 to 2017 was performed. All AEs were grouped using preferred terms and System Organ Classes per the World Health Organization—Adverse Reaction Terminology. Logistic regression was performed to identify factors associated with serious events. Among 95,188 AEs, including 3132 (3.3%) serious events, the most common etiologic sedative was fentanyl (58.8%), followed by pethidine (25.9%). Gastrointestinal disorders (54.2%) were the most frequent AEs. The most common serious AE was heart rate/rhythm disorders (33.1%). Serious AEs were significantly associated with male sex; pediatrics; etiologic sedative with etomidate at the highest risk, followed by dexmedetomidine, ketamine, and propofol; polypharmacy; combined sedative use; and concurrent use of corticosteroids, aspirin, neuromuscular blockers, and antihistamines (reporting odds ratio > 1, p < 0.001 for all). Sedative-induced AEs are most frequently reported with fentanyl, primarily manifesting as gastrointestinal disorders. Etomidate is associated with the highest risk of serious AEs, with the most common serious events being heart rate/rhythm disorders.

Corticosteroid use and its impact on the efficacy of immunotherapy in multiple tumor types.

e14583 Background: Studies have suggested that concurrent corticosteroid use may decrease the efficacy of immunotherapy for cancer treatment, however, the data remains limited. The purpose of this study is to expand upon the previous literature to analyze the outcomes of patients with the following cancer sites: renal cell, lung, melanoma, urothelial, head and neck, hepatocellular, or breast cancer who received immunotherapy and steroids concurrently. Our primary objective was to analyze the overall survival (OS) and objective response rate (ORR) of patients receiving immunotherapy with corticosteroids compared to immunotherapy alone. Methods: A retrospective cohort study was conducted of patients receiving immunotherapy plus corticosteroids compared to immunotherapy alone using University of Texas Medical Branch patients. Patients receiving nivolumab, pembrolizumab, atezolizumab, ipilimumab, durvalumab, or avelumab between January 1, 2012-August 2020 with one of the following cancers were included in the analysis: Renal cell carcinoma, lung carcinoma, melanoma, urothelial carcinoma, head and neck carcinoma, hepatocellular carcinoma, and breast cancer carcinoma. The resulting sample was then separated into two arms. The experimental sample received any of the following steroids either as part of their therapeutic regimen or for symptom management and within 30 days of immunotherapy initiation or at any time during the immunotherapy regimen: dexamethasone, prednisone, methylprednisolone, or hydrocortisone. The control did not receive steroids within 30 days of initiation or during the course of their immunotherapy regimen. Weibull regression models were then constructed to compute hazard ratios for OS at 6 months, 12 months, and 3 years. ORR - complete and partial response, stable disease, and disease progression - between the two arms was assessed using a chi-squared test. Results: Two hundred and sixty patients met inclusion criteria. Of this, 164 received corticosteroids. Our sample was primarily male (70.38%), white (66.54%), and had 0-1 comorbidities (83.08%), lung cancer (45%), and metastases (81.92%). There was no significant difference between the two arms regarding sex, age, number of comorbidities, ECOG score, cancer type, or race. There was no statistically significant difference in OS between the experimental and control arm at 6 months (HR: 1.01; 95%CI 0.63-1.62), 12 months (1.02; 95% CI 0.69-1.51), or 3 years (1.06; 95% CI 0.79-1.42). There was no significant difference in ORR at 6 months between the two arms (2 = 6.3, p=0.178). Conclusions: There was no statistically significant difference in OS or PFS between the two study arms. This study suggests that corticosteroid use does not affect immunotherapy efficacy as previous literature suggests. Larger studies are needed to assess the impact of corticosteroids on immunotherapy efficacy in patients with cancer.

1087. Evaluation of Risk Factors for Infection among Patients Receiving Ibrutinib

BackgroundIbrutinib is a small-molecule inhibitor of Bruton tyrosine kinase (BTK) approved for various B-cell malignancies and cGVHD. Rates of serious infection—defined as requiring hospitalization or parenteral antimicrobials— and invasive fungal infection (IFI) in patients on ibrutinib are as high as 11.4% and 4.2% respectively (Varughese T, et al. Clin Infect Dis 2018;67(5):687-92), which may be related to off-target inhibition of interleukin-2-inducible T-cell kinase or macrophage function.MethodsWe retrospectively reviewed infection complications in patients receiving ibrutinib at our institution between 06/01/2014 and 08/31/2019, including patients who received single-agent or combination ibrutinib. In this study, serious infection was defined as above, or a diagnosis of pneumonia regardless of hospitalization or parenteral antimicrobial therapy. Logistic regression was used to identify risk factors.ResultsBaseline characteristics of 134 included patients are in Table 1. Infection and serious infection occurred in 96 (72%) and 48 (36%) patients, respectively. When pneumonia was not included as a criterion for serious infection, the serious infection rate was 22%. Prior allogeneic stem cell transplant (allo-HSCT) (OR 4.50; 95% CI 1.19 – 17.00) and corticosteroid use (OR 5.42; 95% CI 1.49 – 19.82) were significant risk factors for serious infection without pneumonia (Table 2).Of 37 patients (28%) who received primary HSV/VZV prophylaxis with acyclovir, there was one case of suspected herpes zoster infection (3%). IFI developed in 7 patients (5%): 5 with Pneumocystis jirovecii pneumonia (PJP), 1 with invasive aspergillosis, and 1 with a filamentous fungus, species unknown. Other identified organisms are detailed in Figure 1. Classical risk factors for IFI, including diabetes, allo-HSCT, and concurrent corticosteroid use, were not significant predictors in this group.Table 1. Baseline Characteristics Table 2. Risk Factor Analysis Figure 1. Identified Organisms in Serious Infection ConclusionSerious infections developed at a higher rate than previously reported in the literature, with IFI rates similar to those previously described. Prior allo-HSCT and steroid use were found to be risk factors for serious infection without pneumonia. Treating physicians should have a high index of suspicion for pneumonia, IFI, and PJP in this population.Disclosures All Authors: No reported disclosures

S0733 Factors Associated With Ustekinumab Dose Escalation in Patients With Crohn's Disease

INTRODUCTION: Ustekinumab (UST) is a monoclonal antibody which inhibits both IL-12 and IL-23 activity and was approved for treatment of Crohn's disease (CD) in 2016. The current approved dosing is an initial intravenous weight-based loading dose followed by 90 mg subcutaneous maintenance injections every 8 weeks. Yet, patients frequently require dose escalation, most commonly to every 4 or 6 weeks. However, reasons for UST dose escalation and to which interval are poorly understood. METHODS: Retrospective cohort study of adult patients with CD who were treated with UST and underwent dose escalation between 1/1/2016 and 1/31/2019 at a tertiary referral center. Electronic health records were manually reviewed for demographic data, CD history, UST serum concentrations within 3 months prior to escalation and to identify primary reason for dose escalation. RESULTS: We identified 238 patients on UST for CD. Among these patients, 123 (51.7%) underwent escalation to every 4 (n = 64), 5 (n = 1), 6 (n = 55) or 7 (n = 3) weeks. UST serum concentrations were measured in 18/238 (14.6%) patients within 3 months prior to dose escalation with mean of 2.0 ug/ml and 1.3 ug/ml in patients escalated to 4 or 6 weeks, respectively (P = 0.54). Of the 123 patients, a total of 85 patients (69.1%) were escalated due to persistent clinical disease activity with Harvey Bradshaw Index (HBI) of 5 or greater. Among the 38 patients with HBI <5, primary reasons for escalation were as follows; early symptom recurrence (n = 10), concurrent corticosteroid use (n = 8), evidence of inflammation on endoscopy (n = 8), low UST drug concentrations (n = 3), elevated fecal calprotectin (n = 3), radiographic evidence of inflammation (n = 3), active perianal disease (n = 3) and patient preference (n = 1) (Figure 1). CONCLUSION: Among patients with CD who undergo UST dose escalation, nearly one fourth are escalated despite achieving remission as defined by HBI <5 without concurrent use of corticosteroids on standard UST dosing. The most common reasons for dose escalation among these patients are early recurrence of symptoms prior to next maintenance dose and evidence of inflammation on endoscopy. UST serum concentrations are uncommonly utilized to guide dose escalation and its utility remains unclear. Larger, prospective studies are needed to determine the long-term benefits and cost effectiveness of dose escalation of UST, as well as to further elucidate effectiveness of dose escalation primarily based on endoscopic findings in the absence of clinical symptoms.Figure 1.: Reasons for Ustekinumab Dose Escalation Among Patients with HBI <5 (n = 38).

Immune-Related Adverse Events and Corticosteroid Use for Cancer-Related Symptoms Are Associated With Efficacy in Patients With Non-small Cell Lung Cancer Receiving Anti-PD-(L)1 Blockade Agents.

Background: Immune-related adverse events (irAEs) have been associated with improved efficacy in advanced non-small cell lung cancer (NSCLC) patients receiving anti-PD-(L)1 blockade agents, while the concurrent use of corticosteroids seems to worsen it. We evaluated outcomes in advanced NSCLC patients treated with anti-PD-(L)1 blockade agents in relation to the presence of irAEs and the reasons for using corticosteroids: whether for palliative cancer-related reasons or for the management of irAEs.Methods: Clinical outcomes in advanced NSCLC patients treated with anti-PD-(L)1 blockade agents were calculated with regard to the presence of irAEs and the use of corticosteroids. A landmark analysis was performed to avoid immortal time bias due to the time-dependent nature of irAEs.Results: Out of a total of 267 patients, the 56.9% of patients who experienced irAEs had significantly improved outcomes. In the landmark analysis, median progression-free survival (PFS) was 12.4 months for patients with irAEs vs. 4.1 months for patients without irAEs (p < 0.001), while median overall survival (OS) was 28.2 vs. 12.5 months, respectively (p < 0.001). Likewise, objective response and disease control rates were significantly higher in patients experiencing irAEs: 48.6 vs. 22.8% and 77.1 vs. 39.6% (p < 0.001), respectively. Median OS was significantly shorter for patients receiving ≥10 mg of prednisone equivalent daily for cancer-related symptoms than for the rest of patients (<10 mg prednisone equivalent daily or for management of irAEs): 6 vs. 15.9 months (p < 0.001).Conclusions: IrAEs were associated with improved efficacy in advanced NSCLC patients when a landmark analysis was applied. Patients receiving corticosteroids had significantly poorer outcomes when they were used for cancer-related symptoms.

P105 Use of Infliximab or Adalimumab in Biologic-Naive Patients With Inflammatory Bowel Disease: Study of Patient Reported Outcomes in IBD Partners

BACKGROUND: We sought to compare Patient-Reported Outcomes Measurement Information System (PROMIS) measures and corticosteroid-free remission in biologic naive individuals with Crohn's disease (CD) or ulcerative colitis (UC) newly initiating therapy with adalimumab (ADA) or infliximab (IFX) in a large cohort of patients with inflammatory bowel disease (IBD). METHODS: Using data from the IBD Partners cohort from April 2014 to July 2019, we performed longitudinal analyses comparing the effects of initiation of ADA or IFX therapy on PROMIS measures and corticosteroid-free remission. We included adult IBD patients who were naive to biologics and who started ADA or IFX within 90 days of their baseline visit. Patients were required to have at least one follow-up visit 91-365 days later. Patients were excluded if they had prior exposure to biologic therapy at baseline, history of ileoanal pouch or end ileostomy, or if they failed to include a start date for initiation of their biologic therapy. We performed bivariate analyses by IFX or ADA subgroup, followed by logistic regression models to investigate factors associated with steroid-free remission, stratified by CD or UC disease subtype. RESULTS: A total of 256 biologic naive patients were included in our study. A total of 170 individuals started ADA (109 (64%) with CD and 61 (36%) with UC). Of the 86 patients initiating IFX, 51 (59%) had CD and 35 (41%) had UC. A majority of patients were female, Caucasian, and had similar mean age and disease duration at baseline. Overall, there were no significant differences at baseline of IBD-related hospitalization, prior IBD-related surgery, concurrent corticosteroid use, or immunomodulator (IMM) use between the ADA and IFX groups. No significant differences in anxiety, depression, fatigue, pain, sleep or social satisfaction were found at follow up between IFX and ADA groups overall, and for UC and CD subgroups. Reported rates of steroid-free remission at follow up were similar between biologic naive UC patients treated with ADA or IFX (37.1% vs 36.2%, P = 0.93). For UC, combination therapy with IFX and IMM had a higher rate of steroid-free remission as compared to IFX alone (53.8% vs 27.3%, P = 0.12), albeit not statistically significant. A similar trend was seen for ADA and IMM as compared to ADA alone (43.9% vs 35.3%, P = 0.20). Among biologic naive CD patients, rates of steroid-free remission at follow up were similar amongst groups (54.9% IFX vs 67.0% ADA, P = 0.14). Rates of steroid-free remission at follow up for combined therapy vs monotherapy were also similar for CD patients. In logistic regression models, only lack of steroid use at baseline was independently associated with steroid-free remission at follow up in CD patients (OR 0.37, 0.17-0.78). CONCLUSION(S): Among this cohort of biologic naive IBD patients, therapy with ADA or IFX resulted in similar rates of corticosteroid-free remission. Other PROs including PROMIS measures of anxiety, depression, fatigue, pain, sleep, and social satisfaction were also similar in ADA vs IFX treated patients. These findings suggest the comparative effectiveness of ADA and IFX are similar.

TL 18094 - Fluorquinolones and the risk of Achilles tendon disorders

Introduction: Achilles FQ-associated tendinopathy was first reported by Bailey et al. in 1983. Since then, nearly 200 case reports related to FQ-associated tendon injury have been published, as well as some case control and cohort studies. Today, drug-induced tendinopathy is accepted as a class effect of FQ. The Achilles tendon is affected in 90% of cases of FQ-related tendinopathy and rupture. Objective: To evaluate current evidence for the association between fluoroquinolones and Achilles tendinopathy and to identify associated risk factors that increase the incidence of this complication. Methods: We conducted a computerized search of the relevant scientific literature from 1988 to 2018 using electronic databases, including PubMed, Medline and Scopus. The search terms were fluoroquinolone-related tendinopathy. Eligible studies were any available reports of fluoroquinolone-related tendinopathy (tendinitis, tendon pain, or rupture); animal and human histologic studies were included. Data collected included any cases of fluoroquinolone-related tendinopathy, the particular tendon affected, type of FQ, dosage, and concomitant risk factors. Results: The references selected were reviewed by all authors and judged based on their contribution to the body of knowledge on this topic. The conduct and validity of any clinical studies were carefully considered, and the outcomes of management protocols were carefully scrutinized. Case reports mentioning a specific association with the condition that were thought to be relevant to the discussion were included. Only papers that made a significant contribution to understanding of this condition were included in the review. Thus, a total of 560 abstracts were screened, 79 of which were directly related to FQ-associated Achilles tendinopathy or tendon rupture. Conclusion: The association between the use of fluoroquinolone antibiotics and Achilles tendon disorders is well-established in the medical literature. We found that male gender, advanced age, normal BMI, chronic renal failure and concurrent use of corticosteroids increases the risk of Achilles tendon pathology. Caution should be exercised during the utilization of this antibiotic class in patients with these characteristics

Both the rituximab dose and maintenance immunosuppression in steroid-dependent/frequently-relapsing nephrotic syndrome have important effects on outcomes

Rituximab is an effective treatment for steroid-dependent/ frequently-relapsing nephrotic syndrome (SDFRNS) in children. However, the optimal rituximab regimen remains unknown. To help determine this we conducted an international, multicenter retrospective study at 11 tertiary pediatric nephrology centers in Asia, Europe and North America of children 1-18 years of age with complicated SDFRNS receiving rituximab between 2005-2016 for 18 or more months follow-up. The effect of rituximab prescribed at three dosing levels: low (375mg/m2), medium (750mg/m2) and high (1125-1500mg/m2), with or without maintenance immunosuppression (defined as concurrent use of corticosteroids, mycophenolate motile or calcineurin inhibition at first relapse or for at least six months following the rituximab treatment) was examined. Among the 511 children (median age 11.5 year, 67% boys), 191, 208 and 112 received low, medium and high dose rituximab, respectively. Within this total cohort of 511 children, 283 (55%) received maintenance immunosuppression. Renal biopsies were performed in 317 children indicating the predominant histology was minimal change disease (74%). Without maintenance immunosuppression, low-dose rituximab had a shorter relapse-free period and a higher relapse risk (8.5 months) than medium (12.7 months; adjusted hazard ratio, 0.62) and high dose (14.3 months; adjusted hazard ratio, 0.50; all significant). With maintenance immunosuppression, the relapse-free survival in low-dose rituximab (14 months) was similar to medium (10.9 months; adjusted hazard ratio, 1.23) and high dose (12.0 months; adjusted hazard ratio, 0.92; all non-significant). Most adverse events were mild. Thus, children receiving low-dose rituximab without maintenance immunosuppression had the shortest relapse-free survival. Hence, both rituximab dose and maintenance immunosuppression have important effects on the treatment outcomes.

Comprehensive B Cell Phenotyping Profile for Chronic Graft-versus-Host Disease Diagnosis

Previous studies have reported single B cell-related chronic graft-versus-host disease diagnostic (cGVHD) biomarkers, such as B cell-activating factor (BAFF), CD21low, and immature B cells, but research on the performance of biomarker combinations and the covariate effect of steroids is lacking. The primary objective of this study was to determine the most accurate combination of B cell populations using cell surface staining flow cytometry in an independent cohort of patients with cGVHD. Secondary objectives included assessing the effect of corticosteroid use at sample collection on the makeup and accuracy of the diagnostic panel and identifying the mechanism underlying low surface expression of BAFF receptor (BAFF-R) on B cells in cGVHD. Flow cytometry analysis was performed in an adult cohort of post-HCT patients with cGVHD onset (n = 44) and time-matched recipients without cGVHD (n = 63). We confirmed that the onset of cGVHD was associated with higher soluble BAFF (sBAFF) levels, elevated CD27-CD10-CD21low CD19+ B cell and classical switched memory B cell counts, and reduced transitional and naïve B cell counts. The highest single B cell population area under the receiver operating characteristic (ROC) curve (AUC) was .72 for transitional type 1 CD21low B cells. We also showed a significant inverse relationship between sBAFF and surface BAFF-R expression caused by sBAFF modulation of BAFF-R. Steroid use at sample collection influenced the significance of the sBAFF:B cell ratio, naïve and marginal zone-like B cells. The optimal combination of B cell subsets most significantly associated with cGVHD onset with or without concurrent corticosteroid use resulted in ROC AUCs of .87 and .84, respectively. Transitional and CD21low B cells were the only populations present in both panels; however, analyzing only these populations resulted in ROC AUCs of .79 and .78, respectively. This suggests that the inclusion of other populations and use of different panels depending on steroid use is necessary to achieve better accuracy. sBAFF was not a component of either panel. These novel B cell profiles could be tested prospectively in patients post-HSCT and could lead to focused mechanistic studies.

Case\u2013Control Study of Inflammatory Bowel Disease Patients with and without Clostridium difficile Infection and Poor Outcomes in Patients Coinfected with C. difficile and Cytomegalovirus

Background and AimsClostridium difficile infection (CDI) incidence and risk factors in patients with inflammatory bowel disease (IBD) have been extensively studied. However, data describing CDI in Chinese patients with IBD are limited. We investigated the cumulative incidence, risk factors, and outcomes of CDI in Chinese IBD patients.MethodsWe conducted a retrospective, case–control study of patients hospitalized with IBD and CDI at Peking Union Medical College Hospital from January 2010 to December 2015. CDI was diagnosed based on the presence of active symptoms and positive enzyme immunoassay-based stool test results for C. difficile toxin A or B (CDAB). Controls were selected from CDAB-negative patients with IBD and matched by age, gender, phenotypes of IBD and the same time period of CDAB testing at a 1:2 or 1:3 ratio.ResultsWe identified 60 (7.41%) cases of CDI among 810 patients with IBD, and 137 control cases were selected. Univariate analysis revealed that IBD patients with CDI had higher rates of concurrent corticosteroid use, proton pump inhibitor, antibiotic use, recent hospitalization, parenteral nutrition support, and cytomegalovirus (CMV) coinfection (P < 0.05). Multivariate analysis revealed that concurrent corticosteroid use (odds ratio [OR] = 6.803, 95% confidence interval [CI] = 2.901–15.954, P < 0.001) and hospitalization within 1 month (OR = 3.028, 95% CI = 1.225–7.480, P = 0.016) were associated with CDI. CMV and C. difficile coinfection (hazard ratio [HR] = 4.185, 95% CI = 1.492–11.736, P = 0.007) as well as disease severity (HR 2.070, 95% CI = 1.006–4.261, P = 0.048) were independently associated with colectomy following CDI.ConclusionsIBD patients with concurrent corticosteroid use and recent hospitalization are at a higher risk of CDI. CMV and C. difficile coinfection is associated with poorer outcomes.

Retrospective analysis of fatigue in men with metastatic castration-resistant prostate cancer treated with enzalutamide.

374 Background: Enzalutamide (E) improves survival in men with metastatic castration-resistant prostate cancer (mCRPC). Fatigue (F) while taking E is poorly understood and may limit the use of this life-prolonging drug. Methods: All men treated with E for mCRPC at Princess Margaret Cancer Centre from August 2010 and July 2016 were included. Relevant factors collected, include age, ECOG, Charleston Comorbidity Index, disease characteristics, prior therapies, concomitant medications, and details regarding E treatment and response. Univariate (UVA) and multivariate (MVA) analysis were performed using logistic regression. Results: 415 men started E for mCRPC during this period. Median age at diagnosis was 66 years (range 42-94) and median time to castration-resistance (TTCR) was 113 days. Prior therapies included docetaxel (21%) and abiraterone (26%). Bone was the most common site of metastasis (76%) followed by lymph nodes (45%) and visceral (20%). Concurrent corticosteroid use was 18% and PSA response (≥50%) rate was 55%. Median duration on E was 224 days. F on E occurred in 178 patients (43%) and 56 (13%) men required a dose-reduction due to F. 26 men (6%) stopped E due to F (Table). Conclusions: F is an important and common side effect of E in men with mCRPC. Duration of exposure to androgen deprivation, markers of systemic inflammation (such as increased NLR and platelets) and advanced age appear to be associated with E-related F and difficulty administering drug. There was no association between corticosteroid use and E-related F and difficulty administering drug. [Table: see text]