Rates Of Serious Infections Research Articles

697 Safety of Ustekinumab in Inflammatory Bowel Diseases: Integrated Safety Analysis of Results From Phase 2 and 3 Studies in Crohn's Disease and Ulcerative Colitis

INTRODUCTION: Ustekinumab (UST) is a well-established therapy in Crohn's disease (CD) and psoriatic diseases. UST was safe and effective in phase 3 ulcerative colitis (UC) studies. Pivotal studies of UST in CD (UNITI, IMUNITI) and UC (UNIFI) had similar designs, which allows for integrated analysis across both indications. We present an integrated safety analysis of UST in inflammatory bowel disease (IBD). METHODS: Data from 6 phase 2/3 studies were pooled, and safety was evaluated through 1 year of follow-up. In phase 3, pts received a single IV placebo (PBO) or UST (130 mg or ∼6 mg/kg) induction dose followed by SC maintenance doses of PBO or UST (90 mg q8w or q12w). Concomitant immunomodulators (IMM) and corticosteroids were permitted. All pts who received ≥1 dose of UST were included. Safety outcomes through 1 year are presented as the number of pts with events per 100 patient-years (PY) of follow-up. RESULTS: At induction baseline (2370 pts in pooled phase 3 IBD studies), median age was 38.0 years, 46.9% were receiving corticosteroids, 30.8% were receiving IMM, 53.0% had failed biologics, and 37.1% were naïve to biologics. In phase 3 IBD studies, through Wk8 of PBO-controlled induction, the frequency of key safety events was similar between UST and PBO (Table 1). In addition, through 1 year across phase 2/3 IBD studies (Table 2), numbers of pts per 100 PY with key safety events were similar between treatment groups. The most frequently occurring AEs (excluding diseases under study) were arthralgia (PBO 16.93 vs UST 16.56), headache (16.43 vs 16.50), nausea (13.25 vs 11.94), and abdominal pain (14.59 vs 11.54); infections were nasopharyngitis (16.26 vs 18.11) and upper respiratory tract infection (11.40 vs 11.36). For serious infections, the CD-specific event of anal abscess occurred in PBO 2.02 and UST 0.90 pts per 100 PY. When CD-specific events were excluded, overall rates of serious infections were similar between UC and CD. The only malignancy (excluding NMSC) reported in >1 UST-treated patient was prostate cancer; no lymphomas were reported through 1 year. Two pts receiving UST (0.12 per 100 PY; both had UC) died from events that investigators considered to be unrelated to study agent (esophageal varices hemorrhage and acute respiratory failure during thyroid surgery). CONCLUSION: The safety profile of UST in pts with UC and across integrated IBD indications through 1 year was favorable and consistent with the established safety profile in pts with CD and psoriatic disease.

Factors predictive of serious infections over time in systemic lupus erythematosus patients: data from a multi-ethnic, multi-national, Latin American lupus cohort.

The aim of this study was to identify factors predictive of serious infections over time in patients with systemic lupus erythematosus (SLE). A multi-ethnic, multi-national Latin American SLE cohort was studied. Serious infection was defined as one that required hospitalization, occurred during a hospitalization or led to death. Potential predictors included were sociodemographic factors, clinical manifestations (per organ involved, lymphopenia and leukopenia, independently) and previous infections at baseline. Disease activity (SLEDAI), damage (SLICC/ACR Damage Index), non-serious infections, glucocorticoids, antimalarials (users and non-users), and immunosuppressive drugs use; the last six variables were examined as time-dependent covariates. Cox regression models were used to evaluate the predictors of serious infections using a backward elimination procedure. Univariable and multivariable analyses were performed. Of the 1243 patients included, 1116 (89.8%) were female. The median (interquartile range) age at diagnosis and follow-up time were 27 (20-37) years and 47.8 (17.9-68.6) months, respectively. The incidence rate of serious infections was 3.8 cases per 100 person-years. Antimalarial use (hazard ratio: 0.69; 95% confidence interval (CI): 0.48-0.99; p = 0.0440) was protective, while doses of prednisone >15 and ≤60 mg/day (hazard ratio: 4.18; 95 %CI: 1.69-10.31; p = 0.0019) and >60 mg/day (hazard ratio: 4.71; 95% CI: 1.35-16.49; p = 0.0153), use of methylprednisolone pulses (hazard ratio: 1.53; 95% CI: 1.10-2.13; p = 0.0124), increase in disease activity (hazard ratio: 1.03; 95% CI: 1.01-1.04; p = 0.0016) and damage accrual (hazard ratio: 1.22; 95% CI: 1.11-1.34; p < 0.0001) were predictive factors of serious infections. Over time, prednisone doses higher than 15 mg/day, use of methylprednisolone pulses, increase in disease activity and damage accrual were predictive of infections, whereas antimalarial use was protective against them in SLE patients.

SUN-032 INCREASED RISK OF INFECTION IN SLE : RENAL INVOLVEMENT OR STEROID DOSAGE?

Systemic lupus erythematosus (SLE) is a serious, systemic inflammatory condition which carries a significant risk of mortality and morbidity. Patients with lupus nephritis (LN) are particularly susceptible to infection due to significant and aggressive immunosuppression requirement in the interest of end-organ preservation. In an Australian context, little data exist regarding the rate of serious infections in lupus patients, with or without LN.

Safety of selective IL-23p19 inhibitors for the treatment of psoriasis.

Psoriasis is a chronic disease that requires long‐term treatment. Consequently, understanding the safety and tolerability of any potential treatment over time is critical to effective prescribing. The biologic agents currently available for the treatment of psoriasis target a number of different inflammatory cytokines involved in psoriasis disease pathogenesis. The monoclonal antibodies tildrakizumab, guselkumab and risankizumab target the p19 subunit that is specific to interleukin (IL)‐23. This article reviews published data on the safety of these IL‐23p19 inhibitors in patients with psoriasis compared with other currently available biologic therapies. Data from randomized, placebo‐ and active‐controlled phase 3 clinical trials show tildrakizumab, guselkumab and risankizumab to have a favourable risk–benefit profile in patients with moderate to severe psoriasis. No significant safety concerns have been observed for any of these IL‐23p19 inhibitors in the data published to date. The most commonly reported adverse events (AEs) associated with these agents in phase 3 studies were upper respiratory tract infections. No increase was seen in rates of serious infections, malignancies or major adverse cardiovascular events, with no signals suggestive of an elevated risk of opportunistic infections, active tuberculosis or reactivation of latent tuberculosis infection, mucocutaneous Candida infections, triggering or worsening of inflammatory bowel disease, demyelinating disorders or suicidal ideation. Selectively targeting IL‐23p19 may help avoid AEs that have been associated with biologic agents with other mechanisms of action. Data from long‐term extension studies and patient registries will further establish the safety profile of IL‐23p19 inhibitors for the treatment of moderate to severe psoriasis in routine practice.

Prevalence, Safety and Long-Term Retention Rates of Biologics in Hong Kong from 2001 to 2015.

Biologic agents were initially introduced as treatment for rheumatoid arthritis (RA) but have since been used for other medical conditions. As new biologics become increasingly widespread in treatment regimens, it is important to understand their safety and utilization in the post-marketing context. The aim of this study was to investigate long-term prescribing patterns and the safety of biologics in real clinical settings in Hong Kong. This was a population-based drug utilization study in Hong Kong using a territory-wide electronic medical database Clinical Data Analysis and Reporting System (CDARS). Patients who received biologic treatments from 2001 to 2015 were identified and their corresponding demographic and clinical details retrieved from CDARS. The annual prevalence of biologic prescriptions, the long-term retention rates and incidence rates of infections associated with biologic treatments were evaluated. A total of 30,298 patients (male: 44%) prescribed biologic treatments were identified from CDARS from 2001 to 2015. The annual prevalence of biologic prescriptions increased from 0.1 to 16.1 per 100 persons for both sexes. Infliximab had the highest first-year retention rate of 95.6% among all biologics and continuously attained the highest retention rate from second to fifth year. The overall incidence rate of serious infections was less than five per 100 person-years. Specifically, the incidence rates of tuberculosis, upper and lower respiratory infections and herpes zoster were 0.52, 3.24, 4.99 and 1.01 per 100 person-years, respectively. This population-based study revealed an increasing prevalence of biologic prescribing. Results from the study described the long-term retention rates and incidence rates of serious infections of biologic treatments for all indications, and confirmed the safety of biologic treatments. Since this study provides an overview of all biologic utilization, further studies on cost effectiveness, safety and compliance of treatment in different patient groups are still warranted.

PB1898 SAFETY AND EFFECTIVENESS OF CHLORAMBUCIL‐OBINUTUZUMAB IN THE FRONT LINE TREATMENT OF UNFIT PATIENTS WITH CHRONIC LYMPHOCYTIC LEUKEMIA: REAL‐LIFE DATA FROM ANDALUSIAN LYMPHOID NEOPLASM GROUP (GRANEL)

Background:The Chlorambucil‐Obinutuzumab (CI‐O) is a therapeutic regimen for unfit patients with chronic lymphocytic leukemia (CLL), whether due to old age or with comorbidities that keep them from receiving intensive chemotherapeutic treatment. Results of the CLL11 clinical trial position this treatment as a first‐line alternative with 1A category because of its safety and efficacy among these patient.Aims:To analyze our real‐life experience in terms of safety and effectiveness in first‐line treatment with the CI‐O combination in elderly or unfit patients with CLL.Methods:This retrospective study included 69 unfit CLL patients from 12 hospitals from the GRANEL group (Andalusia, Spain) with first‐line treatment out of clinical trial from May 2016 to February 2019 following a CI‐O protocol. Before treatment, patients were assessed using the comorbidities scale CIRS (Cumulative Illness Rating Scale score). Demographic data, illness, complications, and responses to treatment are analyzed.Results:Baseline features are shown in table 1. At the time of analysis, 9 out of 69 patients of the series are still in treatment. From the remaining 60, 48 (80%) completed 6 programmed cycles, 2 (3.3.%) received 5 cycles, 3 (5%) received 4 cycles, 2 (3.3%) received 3 cycles and 5 (8.3%) only 1 cycle (2 deaths after the first cycle, 1 infusion reaction that led to ceasing treatment, 1 progression and later second‐line and a decision to stop treatment by the medical team due to stable illness after cycle 1). 69.6% of patients received treatment without infusion reaction. 21 infusion reactions occurred (30.4% of patients), 95% reported on the first day of the first cycle, being 90.4% of grade 1‐2. Only 1 suspension of treatment for infusion reaction grade 4 was reported, and 1 death occurred due to acute pulmonary edema on the second day in patient with severe heart failure prior to treatment. 55% of patients suffered some type of grade III‐IV toxicity: 40.5% neutropenia and 11.6% thrombocytopenia, 3 (4.3%) cases of grade III‐IV infection and 2 cases of liver toxicity (3%). Response at end of treatment (EOT) was assessed on 51 patients: overall responses (OR) rate was 90.2%. Complete remission (CR) 62.7% and partial remission (PR) 27.5%. 1 patient (2%) stable disease (SD) and 4 (7.8%) progressions occurred. Progression rate throughout the follow‐up was 21%. The median progression free survival (PFS) was not reached after a median follow‐up of 10 months. Estimated PFS at 12 months was 82% and 55.5% at 24 months. MRD in peripheral blood (PB) among 34 patients (49.3%) was evaluated at EOT: 64.7% negative and 35.3% positive. The median time to next treatment was not reached. 81% of patients continue without receiving second‐line treatment, and among the patients who progressed, 42% have still not initiated second line treatment. 7 deaths occurred (10%): 2 respiratory infections, 1 spontaneous bacterial peritonitis in a patient with HCV, 1 fulminating liver failure of unknown origin, 1 metastatic bladder cancer, 1 acute pulmonary edema, and 1 pulmonary thromboembolism. Median overall survival (OS) has not been reached. Estimated OS at 12 months is 90.2% and 83% at 24 months.Summary/Conclusion:Our data confirm the effectiveness of CI‐O regimen in fragile CLL patients in real‐life, with OR rates of 90%, and CR rates of 63%. 65% of patients achieved negative MRD at EOT in PB. Good safety profile and well‐tolerated regimen with low rate of serious infections and grade I‐II infusion‐related reactions which do not generally lead to treatment cessation.image

Risk of Serious Infection in Patients Receiving Systemic Medications for the Treatment of Psoriasis

There is a need for better understanding of the comparative safety of systemic medications used in the treatment of psoriasis. To compare the risk of serious infection associated with biologic and nonbiologic systemic medications in patients with psoriasis. An observational cohort study was conducted using medical and outpatient pharmacy claims from 2 large US health insurance claims databases from January 1, 2003, through September 30, 2015. We included patients with a diagnosis of psoriasis who were new users of systemic medications for psoriasis. Prescription claims for acitretin, adalimumab, apremilast, etanercept, infliximab, methotrexate, or ustekinumab. The primary outcome was serious infection, defined by inpatient discharge diagnosis International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes. Cox proportional hazards regression was used to compare rates of serious infection for each exposure (acitretin, adalimumab, apremilast, etanercept, infliximab, and ustekinumab) with the referent group (methotrexate). We used pairwise 1:1 propensity score (PS) matching to adjust for potential confounders, which were assessed during a 180-day baseline period prior to study drug initiation. Results from the 2 databases were pooled via fixed-effects analysis. The databases included 31 595 patients in the Optum Clinformatics Data Mart and 76 112 patients in Truven MarketScan who were new users of acitretin, adalimumab, apremilast, etanercept, infliximab, methotrexate, and ustekinumab. Users of acitretin, apremilast, infliximab, and methotrexate were older and had higher baseline comorbidity scores than subcutaneous biologic users (adalimumab, etanercept, and ustekinumab). The pooled PS-matched analysis yielded a decreased rate of overall serious infection in users of apremilast (hazard ratio [HR], 0.50; 95% CI, 0.26-0.94), etanercept (HR, 0.75; 95% CI, 0.61-0.93), and ustekinumab (HR, 0.65; 95% CI, 0.47-0.89) compared with methotrexate. We did not find a different rate of overall serious infection among users of acitretin, adalimumab, and infliximab compared with methotrexate. Subanalysis by type of serious infection showed a significantly increased risk of cellulitis among users of acitretin compared with methotrexate (PS-adjusted HR, 1.76; 95% CI, 1.11-2.80). Among patients with psoriasis treated with systemic medications in 2 large US claims databases, new users of apremilast, etanercept, and ustekinumab had a decreased rate of serious infection compared with methotrexate.

Su1850 – Rate of Serious Infection in Elderly Versus Non-Elderly Patients with Inflammatory Bowel Disease

Su1850 – Rate of Serious Infection in Elderly Versus Non-Elderly Patients with Inflammatory Bowel Disease

Mo1912 – Vedolizumab in Elderly Patients with Inflammatory Bowel Disease is Associated with Improved Disease Outcomes and Low Rates of Serious Infection: A Single Center Real World Experience

Mo1912 – Vedolizumab in Elderly Patients with Inflammatory Bowel Disease is Associated with Improved Disease Outcomes and Low Rates of Serious Infection: A Single Center Real World Experience

Changing rate of serious infections in biologic-exposed rheumatoid arthritis patients. Data from South American registries BIOBADABRASIL and BIOBADASAR

ObjectiveMost reports on serious infections (SI) in rheumatoid arthritis (RA) patients treated with biological disease-modifying antirheumatic drugs (bDMARDs) are from the USA and Western Europe. Data from other regions are largely missing. We report data from South American countries with different backgrounds and health-care systems but similar registries.MethodsWe merged 2010–2016 data from two registries, BIOBADABRASIL (Brazil) and BIOBADASAR (Argentina), which share the same protocol, online platform and data monitoring process. Patients with active RA were included when they began the first bDMARD or a conventional synthetic DMARD (csDMARD, control group). The SI incidence rate (IR) per 1000 patient/years and adjusted IR ratio (aIRR) were estimated for bDMARDs and csDMARDs.ResultsData were analysed for 3717 RA patients with an exposure of 13,380 patient/years. The 2591 patients treated with bDMARDs (64% tumour necrosis factor-α inhibitors (TNFi)) had a follow-up of 9300 years, and the 1126 treated with csDMARDs had an exposure of 4081 patient/years. The SI IR was 30.54 (CI 27.18–34.30) for all bDMARDs and 5.15 (CI 3.36–7.89) for csDMARDs. The aIRR between the two groups was 2.03 ([1.05, 3.9] p = 0.034) for the first 6 months of treatment but subsequently increased to 8.26 ([4.32, 15.76] p < 0.001). The SI IR for bDMARDs decreased over time in both registries, dropping from 36.59 (28.41–47.12) in 2012 to 7.27 (4.79–11.05) in 2016.ConclusionWhile SI remains a major concern in South American patients with RA treated with bDMARDs, a favourable trend toward a reduction was observed in the last years.Key Points• New comprehensive data on biologic drugs safety from international collaboration in South America.• First proposal for national registries data merging in South America.• Serious infections remain a major concern in RA patients treated with biologics.• A significant reduction of serious infections in RA patients exposed to biologics was observed over a 7 years period.

Neutropenia During Tocilizumab Treatment Is Not Associated with Infection Risk in Systemic or Polyarticular-course Juvenile Idiopathic Arthritis.

To determine whether neutropenia is associated with increased risk for infection in patients with systemic juvenile idiopathic arthritis (sJIA) and polyarticular-course juvenile idiopathic arthritis (pcJIA) treated with tocilizumab (TCZ). Data up to Week 104 from 2 phase III trials of intravenous TCZ in sJIA (n = 112; ClinicalTrials.gov, NCT00642460) and pcJIA (n = 188; ClinicalTrials.gov, NCT00988221) were pooled. Worst common toxicity criteria grade and lowest observed absolute neutrophil count (ANC) were identified for each patient. Associations between patient characteristics and lowest observed ANC were tested using univariate regression analysis. Infection and serious infection rates per 100 patient-years (PY) in periods associated with grades 1/2 and 3/4 neutrophil counts were compared with rates associated with normal neutrophil counts. ANC decreased to grade ≥ 3 in 25.0% and 5.9% of sJIA and pcJIA patients, respectively, and decreases were transient. Young age (p = 0.047) and methotrexate use (p = 0.012) were positively associated with neutropenia in patients with sJIA but not in patients with pcJIA. The rate of serious infections in patients with sJIA (10.9/100 PY; 95% CI 6.8-16.5) tended to be higher than in patients with pcJIA (5.2/100 PY; 95% CI 3-8.5). No increase in rates of serious or nonserious infections was observed during periods of neutropenia in either trial. Patients with JIA treated with TCZ experienced transient neutropenia that was not associated with an increased number of infections.

Infectious complications in lupus nephritis treatment: a systematic review and meta-analysis.

Infection is an important concern in lupus nephritis treatment, but few studies have focused on this complication. Available data suggest marked variation in occurrence and outcome. This meta-analysis and review aims to provide an overview of infective complications, focusing on the risk factors and outcomes. Original articles on lupus nephritis Class III/IV/V published in the period January 1980 to December 2016 were identified from the Pubmed/Medline electronic database. Meta-analysis of randomized controlled trials was performed to investigate total and serious infections at different phases of treatment and their associated factors. A descriptive review that included all studies was also performed, providing details on the types of infection, infection-related mortality, and potential impact of different eras on infection rates. A total of 56 studies (32 randomized controlled trials) were included. The incidence rates of overall and serious infections were higher during the induction than maintenance phase of therapy, with serious infections occurring at 8.2-50 and 3.5 per 100 patient-years, respectively. Recent data, predominantly from Asia, suggested lower rates of overall infections with induction regimens that included tacrolimus compared with mycophenolate (risk ratio 0.50, 95% confidence interval 0.33-0.76, p = 0.001). Mycophenolate as induction treatment was associated with lower overall infection risks than cyclophosphamide in non-Asians (risk ratio 0.60, 95% confidence interval 0.48-0.75, p < 0.001). The rates of serious infections were 4.1-25% in Asian and 4.4-8.5% in non-Asian countries; with infection-related mortality rates of 0-6.7% in Asian, compared to 0-2.1% in non-Asian locations. Infection remains a serious complication during treatment of lupus nephritis, but the reported rates and outcomes varied markedly. Mycophenolate was associated with lower infection risk than cyclophosphamide in non-Asians. Infection-related deaths appeared more common in Asian patients.

Antibiotic Prophylaxis in Cardiac Implantable Electronic Device Procedures: A Tale of Two Western Australian Hospitals

Australian guidelines recommend antibiotic prophylaxis (AP) for CIED procedures, however the level of adherence to these guidelines is currently unknown. This study aimed to investigate guideline adherence and the CIED infection rate in the two largest Western Australian public teaching hospitals. In a retrospective, observational study, medical records of patients who underwent CIED procedures at the two hospitals from January to December 2017 were reviewed. Adherence to the AP guidelines was assessed with respect to drug, dose, timing, route and frequency. CIED infection was identified using patient follow-up documentation. AP was administered in 589 (98.5%) of 598 procedures reviewed (Hospital A: n = 400, B: n = 198). Full guideline adherence was observed in 33.9% of procedures and differed significantly between the hospitals (A: 47.3% vs. B: 7.1%, p < 0.001). The most common reasons for non-adherence were timing of administration (A: 42.3% vs. B: 60.6% non-adherent, p < 0.001) and repeat dosing (A: 19.3% vs. B: 78.8% non-adherent, p < 0.001). Twenty infections were identified over 626.6 patient-years (PY) of follow-up (mean [SD] follow-up: 1.0 [0.3] years). The infection rate was 3.19 per 100 PY (p = 0.99 between the two hospitals). Two devices were removed; no patients died from CIED infection. There were no statistically significant associations between infection and any patient, procedure or AP-related factors. Infection occurred in 2.0% of AP guideline adherent and 4.1% of non-adherent cases (p = 0.27). Although the rate of serious infection was low, there was evidence of suboptimal antibiotic use, and notably potential overuse of AP in CIED procedures. Practices varied significantly between hospitals.

Antineutrophil Cytoplasmic Antibody-Associated Vasculitis in Korea: A Narrative Review.

Antineutrophil cytoplasmic antibody-associated vasculitis (AAV) is a group of systemic necrotising vasculitides, which often involve small vessels, and which lead to few or no immune deposits in affected organs. According to clinical manifestations and pathological features, AAV is classified into three variants: microscopic polyangiitis, granulomatosis with polyangiitis (GPA), and eosinophilic GPA. The American College of Rheumatology 1990 criteria contributed to the classification of AAV, although currently the algorithm suggested by the European Medicines Agency in 2007 and the Chapel Hill Consensus Conference Nomenclature of Vasculitides proposed in 2012 have encouraged physicians to classify AAV patients properly. So far, there have been noticeable advancements in studies on the pathophysiology of AAV and the classification criteria for AAV in Western countries. However, studies analysing clinical features of Korean patients with AAV have only been conducted and reported since 2000. One year-, 5 year-, and 10 year-cumulative patient survival rates are reported as 96.1, 94.8, and 92.8%. Furthermore, initial vasculitis activity, prognostic factor score, age and specific organ-involvement have been found to be associated with either all-cause mortality or poor disease course. The rate of serious infection is 28.6%, and 1 year-, 5 year- and 10 year-cumulative hospitalised infection free survival rates range from 85.1% to 72.7%. The overall standardised incidence ratio of cancer in AAV patients was deemed 1.43 compared to the general Korean population.

The Cost of a “Benign” Condition: Healthcare Utilization and Infectious Outcomes in Young Children with Autoimmune Neutropenia

Background:Autoimmune neutropenia (AIN) is the most common chronic neutropenia of childhood. Despite the expectation of a benign clinical course, many such patients undergo extensive evaluation to rule out congenital neutropenia or malignant disease, are followed within a subspecialty hematology clinic until resolution, and are given strict infectious precautions including emergency center (EC) assessment during febrile episodes. Data on healthcare utilization and rate of serious infections in young patients with AIN is limited.Objective:To evaluate the utilization of routine subspecialty and emergency healthcare and incidence of serious bacterial infections in young children with AIN at a large tertiary care children's hospital.Methods:All patients with a diagnosis code of leukopenia, neutropenia, or AIN followed within the outpatient hematology clinic of a large tertiary hospital from 2014 to 2016 were identified. Manual review of the electronic medical record was performed to assess patient eligibility and perform data collection. Patients age ≤5 years, with absolute neutrophil count (ANC) ≤500/µL persisting for ≥3 months, and a clinical diagnosis of AIN as determined by a hematology provider were included. Patients were excluded if they were lost to follow up prior to neutropenia resolution, had AIN secondary to underlying systemic autoimmune or immunologic disorder, neutropenia persisting beyond age 5 years, or if the etiology of neutropenia was unclear. Data on clinical assessment, laboratory parameters, immune and infectious evaluations, and total number of outpatient and EC assessments for fever were collected. Results of anti-neutrophil antibody testing were reviewed but no patients were included or excluded based on those results. EC visits for evaluation of fever in 3 representative patients were reviewed for charge capture data. All charges during the reviewed time period remained constant.Results:From 2014 to 2016, 46 patients (20 male [44%], median age at diagnosis 12 months) diagnosed with AIN met eligibility criteria and were followed in the outpatient hematology clinic for a total of 450 outpatient visits (Table 1). Median duration from initial identification of neutropenia to discharge from hematology clinic was 19 months (range 6 to 85 months). Thirteen patients (28%) had bone marrow evaluation to rule out infiltrative disease or marrow failure etiologies. Nine patients (20%) had genetic testing, the majority of which (n=6) were targeted sequencing for congenital neutropenia. Thirty-six patients (78%) had one or more EC encounters for evaluation of fever, and the cohort had a combined 125 such encounters. Of 155 blood cultures drawn, 3 returned positive. Positive cultures resulted in repeat blood cultures being drawn and hospital admission for antibiotics and clinical monitoring. However, all were determined to be contaminants that did not require treatment. Total charges associated with EC visits for the cohort are estimated at $471,375 based on a cost of $3771 per visit (Table 2). Those patients with ANC <500/µL at the time of presentation with isolated fever were admitted for observation per hospital policy, resulting in 29 inpatient hospitalizations after initial hematology visit.Conclusion:Over a 3-year period, no serious bloodstream or life-threatening infections were identified in a cohort of 46 young children with AIN presenting to the EC for assessment of fever at a single, large tertiary care children's hospital. A conservative estimate of EC charges for this cohort totaled just under half a million dollars for all visits in the study period. Costs would be expected to vary by center, and additional intangible costs include parental and patient anxiety, travel costs, and missed school or work. Further prospective research is needed to determine the potential for shifting toward a less intensive, more cost-effective management paradigm among young children with AIN without compromising patient safety. [Display omitted] DisclosuresDespotovic:Novartis: Research Funding; AmGen: Research Funding; Sanofi: Consultancy.

Use and effectiveness of rituximab in children and young people with juvenile idiopathic arthritis in a cohort study in the United Kingdom

ObjectivesRituximab (RTX) may be a treatment option for children and young people with JIA, although it is not licensed for this indication. The aim of this study was to describe RTX use and outcomes among children with JIA.MethodsThis analysis included all JIA patients within the UK Biologics for Children with Rheumatic Diseases study starting RTX. Disease activity was assessed at RTX start and at follow-up. The total number of courses each patient received was assessed. Serious infections and infusion reactions occurring following RTX were reported.ResultsForty-one JIA patients starting RTX were included, the majority with polyarthritis: polyarthritis RF negative [n = 14 (35%)], polyarthritis RF positive [n = 13 (33%)] and extended oligoarthritis [n = 9 (23%)]. Most were female (80%) with a median age of 15 years [interquartile range (IQR) 12–16] and a median disease duration of 9 years (IQR 5–11). The median improvement in the clinical Juvenile Arthritis Disease Activity Score (cJADAS; three-variable 71-joint JADAS) from RTX start was 9 units (n = 7; IQR −14–2). More than half reported more than one course of RTX. The median time between each course was 219 days (IQR 198–315). During follow-up, 17 (41%) patients reported switching to another biologic, including tocilizumab (n = 8), abatacept (n = 6) and TNF inhibitor (n = 3). Three patients (7%) reported a serious infection on RTX (rate of first serious infection 6.2/100 person-years). Four patients (10%) reported an infusion reaction.ConclusionsThis real-world cohort of children with JIA, the majority with polyarticular or extended oligoarticular JIA, showed RTX may be an effective treatment option for children who do not respond to TNF inhibitor, with a low rate of serious infections on treatment.

Risk of Serious Infections Associated with Biologic Agents in Juvenile Idiopathic Arthritis: A Systematic Review and Meta-Analyses

To assess whether treatment with biologic response modifying agents during clinical trial study periods increases the risk of serious infections in children with juvenile idiopathic arthritis (JIA). A systematic literature review using Medline, Embase, Cochrane library, and the clinical trial registry was performed up to July 2017. Random effects meta-analyses were used to compare rates of serious infections in children with JIA given biologic agents compared with controls, and the pooled relative risk calculated. Subanalyses were performed for different biologic agent classes. In total, 19 trials accounting for 21 individual studies were included (11 for tumor necrosis factor-alpha inhibitors [n = 814 patients], 3 for interleukin-6 inhibitors [n = 318], 6 for interleukin-1 inhibitors [n = 353], and 1 for selective T-lymphocyte costimulation modulators [n = 122]). Patients (68% female) had a mean age of 10.8 years. Seventeen serious infections were reported among 810 children receiving biologic agents and 15 among 797 controls. The most frequent infections were bronchopulmonary and varicella. No statistically significant difference in risk of serious infections was found between children receiving biologic agents compared with control groups (pooled relative risk = 1.13; 95% CI [0.63, 2.03]) during the trial study periods. The risk remained nonsignificant when evaluating the different classes of biologic agents separately. However, the analyses were underpowered to detect differences in the risk of serious infections overall or differences between classes of biologic agents. In this systematic review and meta-analyses, serious infections were uncommon and not significantly increased among patients with JIA receiving biologic agents compared with controls. However, the analyses were underpowered and study periods were relatively short. Ongoing careful monitoring for serious infections remains necessary for all patients with JIA, and particularly those receiving biologic agents.

Active Tuberculosis Complicates the Diagnosis and Treatment of Fibrostenosing Crohnʼs Disease

62-year-old male with Crohn's disease (CD), presented for abdominal pain and weight loss. Patient was initially diagnosed with CD based of CTE 2 years prior. He was started on 5-ASA and lost to follow up. Upon re-presentation patient reported lower abdominal pain, hematochezia and weight loss. Lab evaluation negative. Colonoscopy showed a hepatic flexure stricture which could not be traversed. Biopsy showed mild to moderate chronic colitis with focal severe ulceration. CTE showed a 7 cm thickening and a focal hyper-enhancement of the ascending colon. We elected to resect due to his obstructive symptoms, weight loss and cancer risk. Surgery was to be followed by biologic therapy. In preparation for therapy QuantiFERON gold was positive. An ill-defined right upper lobe mass was seen on CXR. AFB in sputum confirmed active pulmonary tuberculosis. Active TB raised the possibility of an alternative diagnosis for the colonic stricture. The patient was started on 4 drug therapy. Following 10 weeks of therapy patient was deemed non-infectious and underwent a successful laparoscopic right hemicolectomy. Path showed focal mild to moderate chronic colitis with focal ulceration. Negative AFB stains. Post-op biologic therapy was anticipated. However, his active TB postponed initiation until completion of antibiotic therapy. As such the final plan was to perform colonoscopy 6 months post-op to assess for recurrent inflammation and if so would consider starting biologic therapy. The diagnostic dilemma of gastrointestinal TB and Crohn's disease is a common occurrence in TB endemic areas. It often presents similar to Crohn's disease with abdominal pain, weight loss, hematochezia, has similar imaging and endoscopic findings. It is important to differentiate between the two as they have opposing treatments. The risk of biologic therapy and re-activation of latent tuberculosis is well documented and screening for and surveying for TB is standard of care. But consideration of how to manage a patient with complicated Crohn's disease recently treated for active TB presents a dilemma. Biologic therapy is warranted to prevent recurrence of anastomotic stricture. A risk vs benefit discussion must be had and a suitable therapy individualized for the specific patient must be chosen. Vedolizumab, a gut specific, monoclonal antibody against a4b7 Integrin is considered to have a favorable safety profile with low incidence rates of serious infections.2057_A Figure 1. Histology2057_B Figure 2. Colon Resection Specimen

Pelvic Actinomycosis. Autposy Finding

Background: Actinomycosis is a suppurative and granulomatous chronic infectious disease due to a gram positive, non-spore-forming, anaerobic bacteria, non-acid-alcohol resistant bacteria The organisms are indigenous in the oral cavity, pharynx, gastrointestinal tract, and genital tracts. There are at least 6 species that can affect the human, Actinomyces israelii is the most frequent. Methods & Materials: Autopsy is performed for alleged medical non-compliance to a 41-year-old woman with Paranoid Schizophrenia postpartum in treatment at the admission to the hospital she had normal vital parameters and standard physical examination, indirect anamnesis to parents reporting a different behavior in the last days. At necropsy, enlarged lungs are seen, with a yellowish, thick secretion. Abdomen hepatomegaly. Pelvic: left psoas with multiple abscesses. Is evidenced hypogastric plastron, involving uterus, small intestine, large intestine and bladder. To cut thick purulent brown material. Fallopian tubes and ovaries were not identified. Intrauterine contraceptive device is present. Pathologic diagnosis was: abscessed endometritis secondary to Actinomyces israelii with extension to cervix, appendages and pelvic organs with adherent plastron. Psoas abscesses with venous thrombosis. Pericarditis and lymphoplasmacytic myocarditis. Bronchopneumonia. Steatohepatitis with hemophagocytes. Disseminated intravascular coagulation. Cause of Death Organic Dysfunction Multiple-Shock Septic- abdominal-pelvic infection Endometritis by Actinomyces israelii. Results: Pelvic actinomycosis is an uncommon, opportunistic infection with a non-specific clinical course. It must be considered as a differential diagnosis in infiltrative processes suggestive of pelvic neoplasms. It presents a good evolution in the early diagnosis, with a response to beta-lactams. Schizophrenic patients show higher rates of serious infections than in the general population, since they are not aware of pain, which has an impact on morbidity and mortality, so it is suggested to perform interdisciplinary work and include in the medical controls the areas of hygiene, diet, activities, treatment of comorbid diseases and vaccines. Conclusion: The psychiatric pathology of the patient, caused that the evolution of the pathology is torpid in the absence of a clinical setting that guides tutors and doctors to the diagnosis.

Commentary on Complications of Immunosuppressive Treatments for Glomerulonephritis.

In this Evidence-Based Nephrology review, Jefferson ([1][1]) summarizes the potential complications and adverse effects of immunosuppressive therapies for GN. Organizing the results of major clinical trials by disease category and type of immunosuppressive therapy, he describes the frequency of