POS0293 TRheuMa REGISTRY PROVIDES FIRST EVIDENCE OF DIFFERENT COURSE OF RHEUMATIC IMMUNE-RELATED ADVERSE EVENTS AND TUMOUR RESPONSE RATES DEPENDING ON THE TUMOUR ENTITY

Background:Rheumatic immune-related adverse events (irAE) are associated with a better tumour response to immune checkpoint inhibitors (ICI). In contrast to other irAEs, their potentially chronic course may require long-term immunosuppressive treatment.Objectives:Our registry-based study analyses real-world data on the characteristics and outcome of rheumatic irAEs and underlying malignancy. Herein, we present first evidence that these parameters and the optimal clinical management may differ depending on the tumour entity.Methods:The TRheuMa registry is a prospective long-term observational study of a patient cohort suffering from rheumatic side effects of cancer therapies with focus on ICI. It is part of the MalheuR project initiated in July 2018 at the University Hospital Heidelberg to explore interrelations of malignancies and RMDs.Results:64 patients were recruited due to a rheumatic irAE under ICI treatment (nivolumab n=30, pembrolizumab n=33, ipilimumab n=12, PD-L1i n=5, ipi/nivo n=10) with a follow-up of up to 30 months. Of these, 47% had NSCLC and 41% melanoma. In local cohorts of patients receiving ICI, 4% of NSCLC (n total=888) and 13% of melanoma (n total=195) developed a rheumatic irAE. 7% of NSCLC and 23% of melanoma patients experienced a flare of a pre-existing RMD. De novo irAE mostly resembled phenotypes of spondyloarthritis both in NSCLC (43%) as well as in melanoma patients (33%). CRP levels were increased in 83% of NSCLC and 71% of melanoma patients. Almost all irAE patients showed autoantibody negativity and signs of inflammation in ultrasound examination (96%). Comparison of best responses to treatment in patients with and without rheumatic irAE in melanoma and without any irAE in NSCLC patients were as following: Complete remission (CR) in 48% vs. 4% of melanoma patients and partial remission (PR) in 68% vs. 41% of NSCLC patients. In accordance with our severity-based treatment algorithm, 25% of the melanoma patients in CR and 16% of the NSCLC patients in PR needed add-on DMARDs for sufficient irAE-treatment. ICI-treatment was discontinued in 7 cases (17% NSCLC, 8% melanoma)Conclusion:Prospective real-world data from the TRheuMa-registry provide first evidence that rheumatic irAE have distinct characteristics depending on the underlying malignancy. Oncological outcome was better with rheumatic irAE than in their absence and this effect was more pronounced in melanoma patients despite a larger use of immunosuppressants for irAE-treatment.Disclosure of Interests:Leonore Diekmann: None declared, Lea Daniello: None declared, Julia Kunz: None declared, Jan Leipe Consultant of: Pfizer; Novartis; Honoraria (self), Abbvie; Astra Zeneca; BMS; Celgene; Hospira; Janssen-Cilag; Gilead; LEO Pharma; Lilly; MSD; Roche; Sanofi; UCB., Grant/research support from: Research grant/Funding (self): Pfizer; Novartis; Honoraria (self), Hanns-Martin Lorenz Consultant of: Abbvie; BMS; MSD; Pfizer; Celgene; Roche; Chugai; Medac; GSK; Honoraria (self), Novartis; UCB; Janssen-Cilag; Astra Zeneca; Lilly, Grant/research support from: Research grant/Funding (institution): Abbvie; BMS; MSD; Pfizer; Celgene; Roche; Chugai; Medac; GSK; Honoraria (self), Research grant/Funding (institution), Novartis; UCB; Janssen-Cilag; Astra Zeneca; Lilly; Research grant/Funding (institution): Baxter; SOBI; Biogen; Actelion; Mundipharma; Bayer Vital; Octapharm; Sanofi; Hexal; Thermo Fischer; Shire., Jessica Hassel Consultant of: MDS; Honoraria (self): Roche; Novartis; Pierre Fabre., Grant/research support from: BMS; Honoraria (self), Karin Jordan Consultant of: Advisory/Consultancy: Amgen; Merck; MSD; Riemser; Helsinn; Tesaro; Kreussler; Voluntis; Pfizer; Pomme-med; Hexal., Petros Christopoulos Consultant of: advisory board/lecture fees from AstraZeneca, Boehringer Ingelheim, Chugai, Novartis, Pfizer, Roche, Takeda., Grant/research support from: research funding from AstraZeneca, Novartis, Roche, Takeda, Karolina Benesova Grant/research support from: Foundations and Awards” commission of the University of Heidelberg: University of Heidelberg; AbbVie; Novartis; Rheumaliga Baden-Württemberg e.V

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1362. Adding Insult to Injury: Association of Stigmatizing Language and Suboptimal Outcomes in People Who Inject Drugs

Open Forum Infectious Diseases ◽

10.1093/ofid/ofab466.1554 ◽

2021 ◽

Vol 8 (Supplement_1) ◽

pp. S767-S768

Author(s):

Joseph Carpenter ◽

Jillian S Catalanotti ◽

Melissa Notis ◽

Christopher J Brokus ◽

Timothy P Moran ◽

...

Keyword(s):

Best Practice ◽

Clinical Care ◽

Continuum Of Care ◽

Discharge Summary ◽

Infectious Complications ◽

Transitions Of Care ◽

Opioid Use ◽

Research Support ◽

Real World Data ◽

Research Grant

Abstract Background The National Academy of Medicine has identified stigma surrounding substance use disorders (SUDs) and infectious diseases (ID) as a key barrier to integration of opioid use disorder (OUD) and ID services. Prior literature on stigmatizing language in OUD clinical care focuses on surveys and theoretical scenarios rather than real-world data. As part of a larger study of patients admitted for infectious complications of injection drug use (CHOICE), we sought to determine how inpatient physicians describe persons with OUD, as well as associations of this language with outcomes along the OUD continuum of care. Methods CHOICE is a retrospective review of adults hospitalized with an infectious complication of OUD and IDU at four academic medical centers. Included patients were hospitalized between 1/1/2018-12/31/2018, had ICD9/10 diagnosis codes consistent with OUD and acute bacterial/fungal infection, and chart review verification of active infection associated with OUD. Data was abstracted regarding demographics, inpatient interventions, transitions of care, and outcomes 1 year after admission. Potentially stigmatizing language was identified based on the discharge summary. “Abuse” and “misuse” were considered potentially stigmatizing; “use disorder” was considered best practice. Associations of language and outcomes were analyzed via logistic generalized estimating equations. Results A total of 287 subjects met inclusion criteria; 119 (42%) were female and the median age was 40 years (IQR: 32 – 52). The most common terms used to describe OUD were “abuse” (190, 66%) and “IVDU” (119, 42%). “Use disorder” was noted in only 72 (25%) charts. In a regression analysis, any mention of “use disorder” was associated with not leaving against medical advice (OR 2.48, 95% CI 1.24 – 4.95), a plan for ongoing OUD treatment (OR 5.17, 95% CI 2.05-13.0), and addiction-specific follow up (OR 2.94, 95% CI 2.34-3.68). Conclusion In this multicenter retrospective study, inpatient physicians commonly referred to patients with OUD using stigmatizing language. When NIH-preferred language was used this was associated with improved outcomes along the OUD continuum of care, possibly reflecting increased awareness of best practices for treating patients with OUD. Disclosures Ellen Eaton, MD , Gilead (Grant/Research Support) Ellen Eaton, MD , Gilead (Individual(s) Involved: Self): Research Grant or Support Greer A. Burkholder, MD, MSPH, Eli Lilly (Grant/Research Support) Sarah Kattakuzhy, MD, Gilead Sciences (Scientific Research Study Investigator, Research Grant or Support) Elana S. Rosenthal, MD, Gilead Sciences (Research Grant or Support)Merck (Research Grant or Support)

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57. Evaluating the Utility of a Penicillin Allergy Reconciliation Program within an Infectious Diseases Consult Population in a Community Health System

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa439.102 ◽

2020 ◽

Vol 7 (Supplement_1) ◽

pp. S49-S50

Author(s):

Bruce M Jones ◽

Emily Plauche ◽

Susan E Smith ◽

Christopher M Bland

Keyword(s):

Infectious Diseases ◽

Health System ◽

Community Health ◽

Intervention Program ◽

Primary Outcome ◽

Panel Member ◽

Penicillin Allergy ◽

Secondary Outcome ◽

Research Support ◽

Research Grant

Abstract Background Penicillin allergy reconciliation is an important aspect of antimicrobial stewardship with ~10% of the population reporting a penicillin allergy. Our facility utilizes a Penicillin Allergy Reconciliation Program (PARP) led by an Infectious Diseases (ID) Pharmacist and pharmacy students to identify patients with penicillin allergies to reconcile and intervene when necessary. Information is collected by interview, electronic medical record (EMR) review, prescription outpatient fill history. This study evaluated reconciliations with and without a PARP in patients in a community health system. Methods This was a retrospective study that compared reconciliations performed on adult patients admitted at least once in 2019 with a self-reported penicillin allergy and ID physician consult at a hospital with a PARP (Institution 1) and one without a formal evaluation and intervention program (Institution 2) within the same community health system with same ID physicians. The primary outcome was documented reconciliation of a patient’s penicillin allergy during an inpatient visit in 2019. Reconciliation was defined as an edit or clarification (updating the severity, reaction, or comments section, as well as deleting) to a patient’s penicillin allergy in the EMR. The secondary outcome evaluated the percentage of total and ID consult patients with a penicillin allergy. Results There were 245 patients who met criteria and were included in the study, 113 from Institution 1 and 132 from Institution 2. For the primary outcome, there were 82 (72.6%) reconciliations at Institution 1 and 15 (11.4%) reconciliations at Institution 2 (p < 0.001). Interventions at Institution 1 and 2 resulted in 74 EMR updates and 8 removals and 14 EMR updates and 1 removal, respectively. Reconciliation was performed on the same visit as the ID consult in 59/82 patients (72%) at Institution 1 and 11/15 patients (73.3%) at Institution 2. All reconciliations at Institution 2 were made by pharmacist (10) or nurses (5). For the secondary outcome, 10.9% of patients with an ID consult and 12.6% of all patients admitted in 2019 had a penicillin allergy (p=0.027). Conclusion A PARP led by an ID pharmacist and students was an effective method to perform penicillin allergy reconciliations, even in the presence of active ID consultation. Disclosures Bruce M. Jones, PharmD, BCPS, ALK-Abello (Research Grant or Support)Allergan/Abbvie (Speaker’s Bureau) Christopher M. Bland, PharMD, FCCP, FIDSA, BCPS, ALK Abello, Inc. (Grant/Research Support)Biomerieux (Consultant)Merck (Consultant, Grant/Research Support, Advisor or Review Panel member, Speaker’s Bureau)Tetraphase (Speaker’s Bureau)

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AB1346-HPR REAL-WORLD EFFECTIVENESS AND PERCEIVED USEFULNESS OF SYMPTOM CHECKERS IN RHEUMATOLOGY: INTERIM REPORT FROM THE PROSPECTIVE MULTICENTER BETTER STUDY

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.1604 ◽

2020 ◽

Vol 79 (Suppl 1) ◽

pp. 1961.1-1961

Author(s):

J. Knitza ◽

J. Mohn ◽

C. Bergmann ◽

E. Kampylafka ◽

M. Hagen ◽

...

Keyword(s):

Diagnostic Accuracy ◽

Real World ◽

Search Engines ◽

Correct Diagnosis ◽

Perceived Usefulness ◽

Symptom Duration ◽

Research Support ◽

Link Type ◽

The Mean ◽

Research Grant

Background:Symptom checkers (SC) promise to reduce diagnostic delay, misdiagnosis and effectively guide patients through healthcare systems. They are increasingly used, however little evidence exists about their real-life effectiveness.Objectives:The aim of this study was to evaluate the diagnostic accuracy, usage time, usability and perceived usefulness of two promising SC, ADA (www.ada.com) and Rheport (www.rheport.de). Furthermore, symptom duration and previous symptom checking was recorded.Methods:Cross-sectional interim clinical data from the first of three recruiting centers from the prospective, real-world, multicenter bETTeR-study (DKRS DRKS00017642) was used. Patients newly presenting to a secondary rheumatology outpatient clinic between September and December 2019 completed the ADA and Rheport SC. The time and answers were recorded and compared to the patient’s actual diagnosis. ADA provides up to 5 disease suggestions, Rheport calculates a risk score for rheumatic musculoskeletal diseases (RMDs) (≥1=RMD). For both SC the sensitivity, specificity was calculated regarding RMDs. Furthermore, patients completed a survey evaluating the SC usability using the system usability scale (SUS), perceived usefulness, previous symptom checking and symptom duration.Results:Of the 129 consecutive patients approached, 97 agreed to participate. 38% (37/97) of the presenting patients presented with an RMD (Figure 1). Mean symptom duration was 146 weeks and a mean number of 10 physician contacts occurred previously, to evaluate current symptoms. 56% (54/96) had previously checked their symptoms on the internet using search engines, spending a mean of 6 hours. Rheport showed a sensitivity of 49% (18/37) and specificity of 58% (35/60) concerning RMDs. ADA’s top 1 and top 5 disease suggestions concerning RMD showed a sensitivity of 43% (16/37) and 54% (20/37) and a specificity of 58% (35/60) and 52% (31/60), respectively. ADA listed the correct diagnosis of the patients with RMDs first or within the first 5 disease suggestions in 19% (7/37) and 30% (11/37), respectively. The average perceived usefulness for checking symptoms using ADA, internet search engines and Rheport was 3.0, 3.5 and 3.1 on a visual analog scale from 1-5 (5=very useful). 61% (59/96) and 64% (61/96) would recommend using ADA and Rheport, respectively. The mean SUS score of ADA and Rheport was 72/100 and 73/100. The mean usage time for ADA and Rheport was 8 and 9 minutes, respectively.Conclusion:This is the first prospective, real-world, multicenter study evaluating the diagnostic accuracy and other features of two currently used SC in rheumatology. These interim results suggest that diagnostic accuracy is limited, however SC are well accepted among patients and in some cases, correct diagnosis can be provided out of the pocket within few minutes, saving valuable time.Figure:Acknowledgments:This study was supported by an unrestricted research grant from Novartis.Disclosure of Interests:Johannes Knitza Grant/research support from: Research Grant: Novartis, Jacob Mohn: None declared, Christina Bergmann: None declared, Eleni Kampylafka Speakers bureau: Novartis, BMS, Janssen, Melanie Hagen: None declared, Daniela Bohr: None declared, Elizabeth Araujo Speakers bureau: Novartis, Lilly, Abbott, Matthias Englbrecht Grant/research support from: Roche Pharma, Chugai Pharma Europe, Consultant of: AbbVie, Roche Pharma, RheumaDatenRhePort GbR, Speakers bureau: AbbVie, Celgene, Chugai Pharma Europe, Lilly, Mundipharma, Novartis, Pfizer, Roche Pharma, UCB, David Simon Grant/research support from: Else Kröner-Memorial Scholarship, Novartis, Consultant of: Novartis, Lilly, Arnd Kleyer Consultant of: Lilly, Gilead, Novartis,Abbvie, Speakers bureau: Novartis, Lilly, Timo Meinderink: None declared, Wolfgang Vorbrüggen: None declared, Cay-Benedict von der Decken: None declared, Stefan Kleinert Shareholder of: Morphosys, Grant/research support from: Novartis, Consultant of: Novartis, Speakers bureau: Abbvie, Novartis, Celgene, Roche, Chugai, Janssen, Andreas Ramming Grant/research support from: Pfizer, Novartis, Consultant of: Boehringer Ingelheim, Novartis, Gilead, Pfizer, Speakers bureau: Boehringer Ingelheim, Roche, Janssen, Jörg Distler Grant/research support from: Boehringer Ingelheim, Consultant of: Boehringer Ingelheim, Paid instructor for: Boehringer Ingelheim, Speakers bureau: Boehringer Ingelheim, Peter Bartz-Bazzanella: None declared, Georg Schett Speakers bureau: AbbVie, BMS, Celgene, Janssen, Eli Lilly, Novartis, Roche and UCB, Axel Hueber Grant/research support from: Novartis, Lilly, Pfizer, Consultant of: Abbvie, BMS, Celgene, Gilead, GSK, Lilly, Novartis, Speakers bureau: GSK, Lilly, Novartis, Martin Welcker Grant/research support from: Abbvie, Novartis, UCB, Hexal, BMS, Lilly, Roche, Celgene, Sanofi, Consultant of: Abbvie, Actelion, Aescu, Amgen, Celgene, Hexal, Janssen, Medac, Novartis, Pfizer, Sanofi, UCB, Speakers bureau: Abbvie, Aescu, Amgen, Biogen, Berlin Chemie, Celgene, GSK, Hexal, Mylan, Novartis, Pfizer, UCB

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FRI0052 INFLUENCE OF RHEUMATOID ARTHRITIS ON THE CLINICAL AND BIOLOGICAL PROFILE OF TYPE-2 DIABETES MELLITUS

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.5408 ◽

2020 ◽

Vol 79 (Suppl 1) ◽

pp. 601.2-602

Author(s):

J. Avouac ◽

M. Elhai ◽

M. Forien ◽

J. Sellam ◽

F. Eymard ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Insulin Resistance ◽

Type 2 Diabetes ◽

Insulin Requirement ◽

Multivariate Logistic Regression ◽

Biological Profile ◽

Research Support ◽

Insulin Resistant ◽

Research Grant

Background:Type-2 diabetes and rheumatoid arthritis (RA) are two chronic diseases characterized by tissue inflammation and insulin resistance. To date, no data have evaluated the influence of RA-induced joint and systemic inflammation on the course of type-2 diabetes.Objectives:To study the impact of RA on type-2 diabetesMethods:Observational, multicenter, cross-sectional usual-care study, including 7 rheumatology centers. This study included over a 24-month period consecutive patients with type-2 diabetes and RA, fulfilling the 2010 ACR / EULAR criteria, and diabetic controls with osteoarthritis (OA). The following data were collected: demographics, disease activity and severity indices, current treatment for RA and diabetes, history and complications of diabetes. A systematic blood test was performed, assessing inflammatory (CRP levels) and metabolic (fasting glycemia and insulin levels, HbA1c) parameters. The HOMA2%B (insulin secretion) and HOMA2%S (tissue insulin sensitivity) indices (HOMA calculator, © Diabetes Trials Unit, University of Oxford) were used to assess insulin resistance. Ra and OA patients were compared using parametric tests after adjusting for age and BMI. A multivariate logistic regression was performed ti identify factors independently associated with insulin resistance.Results:We included 122 RA patients (74% women, mean age 64+/-11 years, mean disease duration 15+/-11 11 years, 75% with positive ACPA antibodies and 64% with erosive disease) and 54 controls with OA. 64% of RA patients were treated with oral corticosteroids <10 mg/day, 65% received methotrexate and 53% received targeted biological therapies.The characteristics of type-2 diabetes in the 54 OA patients corresponded to severe insulin-resistant diabetes: age> 65 years, high BMI> 30 kg/m2, mean HbA1c 7.3%+/-11 1.3%, 30% of insulin requirement, high frequency of other cardiovascular risk factors, macroangiopathy found in almost half of patients and biological criteria of insulin resistance (elevation of HOMA2%B and decrease of HOMA2%S).RA patients with type-2 diabetes had a younger age (64+/-11 years vs. 68+/-12 years, p=0.031) and lower BMI (27.7+/-11 5.5 vs. 31.5+/-11 6.3, p<0.001). These patients also had severe diabetes (HbA1c 7.0%+/-11 1.2%, 29% of insulin requirement, 43% of macroangiopathy) with an insulin resistance profile identical to OA controls. After adjusting for age and BMI, RA patients had a significantly increased insulin secretion compared to OA patients (HOMA2%B: 83.1+/-11 65.2 vs. 49.3+/-11 25.7, p=0.023) as well as a significant reduction of insulin sensitivity (HOMA2%S: 61.1+/-11 31.6 vs. 92.9+/-11 68.1, p=0.016). This insulin resistance was associated with the inflammatory activity of RA, with a negative correlation between the HOMA2%S and the DAS28 (r=-0.28, p=0.027). The multivariate logistic regression confirmed the independent association between the HOMA2%S index and DAS28 (OR: 3.93, 95% CI 1.02-15.06), as well as high blood pressure (OR: 1.29, 95% CI 0.33-1.99 CI).Conclusion:RA patients with type-2 diabetes displayed severe, poorly controlled diabetes, highlighting the burden of comorbidities associated with RA. The clinical-biological profile of diabetic RA patients was severe insulin-resistant diabetes, with a biological profile of insulin resistance linked to the inflammatory activity of the disease. These findings may have therapeutic implications, with the potential targeting of insulin resistance through the treatment of joint and systemic inflammation.Acknowledgments:Société Française de Rhumatologie (research grant)Bristol Myers Squibb (research grant)Disclosure of Interests:Jérôme Avouac Grant/research support from: Pfizer, Bristol Myers Squibb, Consultant of: Sanofi, Bristol Myers Squibb, Abbvie, Boerhinger, Nordic Pharma, Speakers bureau: Sanofi, Bristol Myers Squibb Abbvie, MSD, Pfizer, Nordic Pharma, Muriel ELHAI: None declared, Marine Forien: None declared, Jérémie SELLAM: None declared, Florent Eymard Consultant of: Regenlab, Anna Moltó Grant/research support from: Pfizer, UCB, Consultant of: Abbvie, BMS, MSD, Novartis, Pfizer, UCB, Laure Gossec Grant/research support from: Lilly, Mylan, Pfizer, Sandoz, Consultant of: AbbVie, Amgen, Biogen, Celgene, Janssen, Lilly, Novartis, Pfizer, Sandoz, Sanofi-Aventis, UCB, Frédéric Banal: None declared, Joel Daminano: None declared, Philippe Dieudé: None declared, Yannick Allanore Shareholder of: Sanofi, Roche, Consultant of: Actelion, Bayer, BMS, Boehringer Ingelheim, Inventiva, Sanofi

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1104. Risk Factors and Outcomes of Refractory and/or Resistant Cytomegalovirus (CMV) Infection after Allogeneic Hematopoietic Stem Cell Transplantation

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa439.1290 ◽

2020 ◽

Vol 7 (Supplement_1) ◽

pp. S582-S583

Author(s):

Eleni Karantoni ◽

Yiqi Su ◽

Anat Stern ◽

Phaedon D Zavras ◽

Sergio Giralt ◽

...

Keyword(s):

Risk Factors ◽

Overall Survival ◽

T Cell ◽

Panel Member ◽

Multivariable Model ◽

Research Support ◽

Review Panel ◽

Material Support ◽

Advisory Boards ◽

Research Grant

Abstract Background The epidemiology of CMV end-organ disease (EOD) after Hematopoietic Cell Transplant (HCT) in the era of preemptive therapy (PET) is defined. In contrast, less data exists on refractory and/or resistant (R/R) CMV. We report on 1) the incidence; 2) risk factors and outcomes of R/R CMV by 1-year post HCT. Methods Retrospective review of 167 CMV seropositive (R+) recipients of first marrow or peripheral blood HCT from 1/2014 - 12/2017 managed by PET. Refractory CMV was defined as failure to achieve >1 log10 decrease in CMV viral load (VL) and having VL >1,000 IU/mL after ≥14 day of PET. Resistant CMV required genotypic confirmation of resistance mutation(s) in UL54 and/or UL97 genes. End organ disease (EOD) was defined by standard criteria. Patients (pts) were followed through 1-year post HCT and were categorized in two mutually exclusive groups as R/R and no R/R. Demographics, clinical characteristics and outcomes were extracted from medical records and hospital databases. Univariable and multivariable logistic models were used to identify risk factors for R/R CMV. Results Of 167 PET recipients, 91 (54.5%) received ex vivo T cell depleted (TCD) HCT; 40 (24.0%) had mismatched donor; and 26 (15.6%) had multiple myeloma. 66/167 (39.5%) pts developed refractory CMV (6 pts also had resistant CMV). Time from HCT to CMV viremia was shorter in R/R group: median (IQR) 21.5 (17.2-27.8) days compared to no R/R group: 26 (19-32) days (p=0.031). Maximum VL was higher for R/R compared to no R/R: median (IQR) 9,118 (2,849-18,456) and 868 (474-1,908), respectively (p< 0.001). In multivariable model, risk factors for R/R included TCD HCT (p< 0.0001) and higher VL at PET initiation (p=0.0002). In contrast, CMV seropositive donor (p=0.035) was protective (Figure 1). CMV EOD developed in 28.2% of R/R and 16.2% of no R/R groups (p=0.085) (Figure 2). Overall survival at 1 year was 59.1% for R/R compared to 83.1% for no R/R group (p=0.00027) (Figure 3). Figure 1. Adjusted odds ratio (OR) and 95% confidence interval (CI) from multivariable model evaluating risk factors of refractory/resistant (R/R) CMV. Figure 2. Cumulative incidence curves of CMV end-organ disease (EOD) at 1-year post HCT Figure 3. Kaplan-Meier survival curves of overall survival (OS) at 1-year post HCT Conclusion 1) Refractory and/or resistant CMV occurred in 39,5% of PET recipients. 2) T-cell depletion and higher CMV VL at PET initiation were risk factors for R/R CMV in multivariable models. 3) R/R CMV was associated with more EOD and worse overall survival. Disclosures Sergio Giralt, MD, Amgen (Advisor or Review Panel member, Research Grant or Support, Served an advisory board for Amgen, Actinuum, Celgene, Johnson & Johnson, JAZZ pharmaceutical, Takeda, Novartis, KITE, and Spectrum pharma and has received research support from Amgen, Actinuum, Celgene, Johnson & Johnson, and Miltenyi, Takeda.) Miguel-Angel Perales, MD, Abbvie (Other Financial or Material Support, Honoraria from Abbvie, Bellicum, Celgene, Bristol-Myers Squibb, Incyte, Merck, Novartis, Nektar Therapeutics, Omeros, and Takeda.)ASTCT (Other Financial or Material Support, Volunteer member of the Board of Directors of American Society for Transplantation and Cellular Therapy (ASTCT), Be The Match (National Marrow Donor Program, NMDP), and the CIBMTR Cellular Immunotherapy Data Resource (CIDR) Committee)Cidara Therapeutics (Advisor or Review Panel member, Other Financial or Material Support, Serve on DSMBs for Cidara Therapeutics, Servier and Medigene, and the scientific advisory boards of MolMed and NexImmune.)Kite/Gilead (Research Grant or Support, Other Financial or Material Support, Received research support for clinical trials from Incyte, Kite/Gilead and Miltenyi Biotec.) Genovefa Papanicolaou, MD, Chimerix (Research Grant or Support)Merck&Co (Research Grant or Support, Investigator and received funding and consulting fees from Merck, Chimerix, Shire and Astellas)

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913. Distribution of Respiratory Viral Pathogens in Infants Across Different Clinical Settings from December 2019 to April 2020

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa439.1101 ◽

2020 ◽

Vol 7 (Supplement_1) ◽

pp. S491-S492

Author(s):

Zaid Haddadin ◽

Danielle A Rankin ◽

loren lipworth ◽

Jon Fryzek ◽

Mina Suh ◽

...

Keyword(s):

Clinical Setting ◽

Respiratory Viruses ◽

Clinical Settings ◽

Research Support ◽

Viral Pathogens ◽

Abrupt Decrease ◽

Nasal Swabs ◽

Viral Testing ◽

Support Research ◽

Research Grant

Abstract Background Acute respiratory infections (ARI) are a major cause of morbidity and mortality in young children, with viral pathogens being the most common etiologies. However, due to limited and inconsistent clinical diagnostic viral testing in the outpatient (OP) setting compared to the inpatient (IP) setting, the actual burden and distribution of viral pathogens across these clinical settings remain largely underreported. We aimed to evaluate the frequency of common respiratory viruses in medically attended ARI in infants. Methods We conducted a prospective viral surveillance study in Davidson County, TN. Eligible infants under one year presenting with fever and/or respiratory symptoms were enrolled from OP, emergency department (ED), or IP settings. Nasal swabs were collected and tested for common viral pathogens using Luminex® NxTAG Respiratory Pathogen Panel and for SARS-CoV-2 using Luminex® NxTAG CoV extended panel. Results From 12/16/2019 to 4/30/2020, 364 infants were enrolled, and 361 (99%) had nasal swabs collected and tested. Of those, 295 (82%) had at least one virus detected; rhinovirus/enterovirus (RV/EV) [124 (42%)], respiratory syncytial virus (RSV) [101 (32%)], and influenza (flu) [44 (15%)] were the three most common pathogens detected. No samples tested positive for SARS-CoV-2. Overall, the mean age was 6.1 months, 50% were male, 45% White and 27% Hispanic. Figure 1 shows the total number of PCR viral testing results by month. RSV was the most frequent virus detected in the IP (63%) and ED (37%) settings, while RV/EV was the most common in the OP setting (Figure 2). Figure 3 displays viral seasonality by clinical setting, showing an abrupt decrease in virus-positive cases following the implementation of a stay-at-home order on March 23, 2020 in Nashville, TN. Distribution of Respiratory Viruses in Different Settings Distribution of Respiratory Viruses in Different Settings by Season Conclusion Most medical encounters in infants are due to viral pathogens, with RSV, RV/EV, and flu being the most common. However, distributions differed by clinical setting, with RSV being the most frequently detected in the IP and ED settings, and second to RV/EV in the OP setting. Continued active viral ARI surveillance in various clinical settings is warranted. Preventative measures such as vaccines and infection control measures deserve study to reduce viral ARI burden. Disclosures Zaid Haddadin, MD, CDC (Grant/Research Support, Research Grant or Support)Quidel Corporation (Grant/Research Support, Research Grant or Support)sanofi pasteur (Grant/Research Support, Research Grant or Support) Danielle A. Rankin, MPH, CIC, Sanofi Pasteur (Grant/Research Support, Research Grant or Support) Jon Fryzek, PhD, MPH, EpidStrategies (Employee) Mina Suh, MPH, International Health, EpidStrategies (Employee) Donald S. Shepard, PhD, Sanofi Pasteur (Grant/Research Support) Natasha B. Halasa, MD, MPH, Genentech (Other Financial or Material Support, I receive an honorarium for lectures - it’s a education grant, supported by genetech)Karius (Consultant)Moderna (Consultant)Quidel (Grant/Research Support, Research Grant or Support)Sanofi (Grant/Research Support, Research Grant or Support)

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1510. Infant Pneumonia and Subsequent Risk of Chronic Respiratory Disorders

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa439.1691 ◽

2020 ◽

Vol 7 (Supplement_1) ◽

pp. S758-S759

Author(s):

Stephen I Pelton ◽

Rotem Lapidot ◽

Matthew Wasserman ◽

Melody Shaff ◽

Ahuva Hanau ◽

...

Keyword(s):

Research Study ◽

Scientific Research ◽

Airway Disease ◽

Research Support ◽

Recurrent Wheezing ◽

Recurrent Pneumonia ◽

Respiratory Disorders ◽

Study Investigator ◽

Study Population ◽

Research Grant

Abstract Background Community-acquired pneumonia (CAP) in infancy (i.e., among children aged < 2 years) may have long-term consequences for the rapidly developing lung. We examined the impact of pneumonia in infancy on subsequent respiratory health. Methods A retrospective matched-cohort design and data from Optum’s de-identified Integrated Claims-Clinical dataset (2009-2018) were employed. Study population comprised children who were hospitalized for CAP before age 2 years (“CAP patients”) as well as matched comparators without evidence of pneumonia before age 2 years (“comparison patients”). CAP patients and comparison patients were matched (fixed 1:5 ratio, without replacement) using estimated propensity scores and a nearest-neighbor approach; those with evidence of selected medical conditions (e.g., extreme prematurity, congenital diseases, respiratory diseases) before age 2 years were excluded. Study outcomes included recurrent pneumonia and a composite of asthma, recurrent wheezing, and hyperactive airway disease. Rates of study outcomes from age 2 to 5 years were estimated for all CAP and comparison patients as well as subgroups of CAP patients (and corresponding comparison patients) stratified by etiology (bacterial, viral, unspecified). Results Study population totaled 1,343 CAP patients and 6,715 comparison patients. CAP patients and comparison patients were well-balanced on their baseline characteristics and mean duration of follow-up was 757 and 729 days, respectively. Rates of chronic respiratory disorders from age 2 to 5 years were significantly higher among CAP patients versus comparison patients. Analyses of subgroups stratified by etiology demonstrated higher rates of study outcomes among CAP patients across all strata. Rates of recurrent pneumonia and a composite of asthma, recurrent wheezing, and hyperactive airway disease from age 2 to 5 years among CAP patients and matched comparison patients Conclusion Infant CAP foreshadows an increase in subsequent risk of chronic respiratory disorders. Further studies are needed to determine whether this elevated risk is due to infant pneumonia or whether infant pneumonia is a marker of at-risk children. Disclosures Stephen I. Pelton, MD, Merck vaccine (Consultant, Grant/Research Support)Pfizer (Consultant, Grant/Research Support)Sanofi Pasteur (Consultant, Other Financial or Material Support, DSMB)Seqirus Vaccine Ltd. (Consultant) Rotem Lapidot, MD, MSCI, Pfizer (Consultant) Matthew Wasserman, MSc., Pfizer Inc. (Employee) Melody Shaff, BA, Pfizer, Inc. (Consultant, Grant/Research Support, Scientific Research Study Investigator, Research Grant or Support) Ahuva Hanau, BS, Pfizer, Inc. (Consultant, Grant/Research Support, Scientific Research Study Investigator, Research Grant or Support) Alexander Lonshteyn, PhD, Pfizer, Inc. (Consultant, Grant/Research Support, Scientific Research Study Investigator, Research Grant or Support) Derek Weycker, PhD, Pfizer Inc. (Consultant, Grant/Research Support, Scientific Research Study Investigator, Research Grant or Support)

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OP0211 TIME TO DISCONTINUATION OF TOFACITINIB AND TNF INHIBITORS IN RHEUMATOID ARTHRITIS PATIENTS WITH AND WITHOUT METHOTREXATE: DATA FROM A RHEUMATOID ARTHRITIS COHORT

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.1745 ◽

2020 ◽

Vol 79 (Suppl 1) ◽

pp. 131.2-132

Author(s):

M. Movahedi ◽

A. Cesta ◽

X. LI ◽

E. Keystone ◽

C. Bombardier

Keyword(s):

Rheumatoid Arthritis ◽

Propensity Score ◽

Best Practice ◽

Practice Research ◽

Research Support ◽

Real World Data ◽

Kaplan Meier ◽

Rheumatoid Arthritis Cohort ◽

Research Initiative ◽

Significant Difference

Background:Tofacitinib (TOFA) is an oral, small molecule drug used for rheumatoid arthritis (RA) treatment and is prescribed alone or with methotrexate (MTX). Tofa can be used as an alternative to biologic disease modifying antirheumatic drugs (bDMARDs) including tumor necrosis factor inhibitors (TNFi).Objectives:We aimed to evaluate the discontinuation rate of this drug, with and without concurrent MTX in comparison with TNFi, in patients with RA in the Ontario Best Practices Research Initiative (OBRI).Methods:RA patients enrolled in the OBRI initiating their TOFA or TNFi (adalimumab, certolizumab, etancercept, golimumab, and infliximab) within 30 days prior to or any time after enrolment between 1stJune 2014 (TOFA approval date in Canada) and 31stDec 2018 were included. Time to discontinuation (due to any reason) were assessed using Kaplan-Meier survival (adjusted for propensity score using inverse probability of treatment weight) to compare patients with and without MTX use at initiation of TOFA or TNFi.Results:A total of 565 patients initiated TOFA (n=208) or TNFi (n=357). Of those, 106 (51%) and 222 (62%) were treated with MTX in the TOFA and TNFi group, respectively and mean (SD) disease duration were 13.1 (9.4) and 9.5 (9.4) years. In the TOFA group, 86% were female and mean (SD) age at treatment initation was 60.4 (10.6) years. In the TNFi group 82% were female and mean age (SD) at treatment initation was 57.0 (12.6) years. The TOFA group was more likely to have prior biologic use (61.5%) compared with the TNFi group (31%). At treatment initiation, the mean (SD) clinical disease activcity index was 24.8 (12.1) in the TOFA group and 21.8 (12.0) in the TNFi group.Over a mean of 17.3 month follow-up, discontinuation was reported in 75 (36%) and 103 (29%) of all TOFA and TNFi patients, respectively. After adjusting for propensity score, patients treated with TNFi and MTX remained on treatment longer than those treated without MTX (Logrank p=0.002) while there was no significant difference in TOFA discontinuation in patients with and without MTX (Logrank p=0.31).Conclusion:In this real world data study, we found that TOFA retention is similar in patients with and without MTX, while patients treated with TNFi and MTX remained on treatment longer than those treated without MTX. Merging data with other RA registries in Canada is proposed to increase study power and to provide more robust results.Disclosure of Interests:Mohammad Movahedi Consultant of: Allergan, Angela Cesta: None declared, Xiuying Li: None declared, Edward Keystone Grant/research support from: AbbVie; Amgen; Gilead Sciences, Inc; Lilly Pharmaceuticals; Merck; Pfizer Pharmaceuticals; PuraPharm; Sanofi, Consultant of: AbbVie; Amgen; AstraZeneca Pharma; Bristol-Myers Squibb Company; Celltrion; F. Hoffman-La Roche Ltd.; Genentech, Inc; Gilead Sciences, Inc.; Janssen, Inc; Lilly Pharmaceuticals; Merck; Myriad Autoimmune; Pfizer Pharmaceuticals, Sandoz, Sanofi-Genzyme, Samsung Bioepsis., Speakers bureau: AbbVie; Amgen; Bristol-Myers Squibb; Celltrion; F. Hoffman-La Roche Ltd, Janssen, Inc; Merck; Pfizer Pharmaceuticals; Sanofi-Genzyme; UCB, Claire Bombardier Grant/research support from: Dr Bombardier reports sources of funding for Ontario Best Practice Research Initiative Research grants from Abbvie, Janssen, Amgen, Medexus, Merck, Pfizer, and Novartis outside of the submitted work. Consulting Agreements: Abbvie, Covance, Janssen, Merck, Pfizer, Sanofi and Novartis outside of the submitted work. Advisory Board Membership: Hospira, Sandoz, Merck, Pfizer and Novartis outside of the submitted work.

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108. Selective Decay of Intact HIV-1 Proviral DNA on Antiretroviral Therapy

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa439.418 ◽

2020 ◽

Vol 7 (Supplement_1) ◽

pp. S183-S183

Author(s):

Rajesh Gandhi ◽

Joshua Cyktor ◽

Ronald Bosch ◽

Hanna Mar ◽

Gregory Laird ◽

...

Keyword(s):

Antiretroviral Therapy ◽

Panel Member ◽

Plasma Viremia ◽

Research Support ◽

Review Panel ◽

Proviral Dna ◽

Hiv 1 ◽

Over Time ◽

Residual Plasma Viremia ◽

Research Grant

Abstract Background HIV-1 proviruses persist in people on antiretroviral therapy (ART) but most are defective and do not constitute a replication-competent reservoir. The decay of infected cells carrying intact compared with defective HIV-1 proviruses has not been well-defined in people on ART. Methods We separately quantified intact and defective proviruses (using an intact proviral DNA assay), residual plasma viremia, and markers of inflammation and activation in people on long-term ART. Longitudinal measurements were done at three timepoints: timepoint 1 was a median of 7.1 years on ART; timepoint 2 was a median of 3.7 years later; timepoint 3 was a median of 5.5 years after timepoint 1 and a median 12 years after starting ART (Figure 1). Figure 1: Study timepoints Results Among 40 participants tested longitudinally from a median of 7.1 years to 12 years after ART initiation, intact provirus levels declined significantly over time (median half-life 7.1 years; 95% confidence interval [CI], 3.9, 18), whereas defective provirus levels did not decrease. The median half-life of total HIV-1 DNA was 41.6 years (95% CI, 13.6, 75). When we evaluated the change in proviral DNA per year, intact proviral DNA declined significantly more (p< 0.001) than defective proviral DNA (the latter did not change) (Figure 2). The proportion of all proviruses that were intact diminished over time on ART, from about 10% at the first on-ART timepoint to about 5% at the last timepoint (Figure 3). At timepoint 1, intact provirus levels on ART correlated with total HIV-1 DNA and residual plasma viremia, but there was no evidence for associations between intact provirus levels and inflammation or immune activation. Figure 2: Percent change in HIV-1 proviral DNA per year Figure 3: Total HIV-1 proviruses (grey bars) and the percentage of intact proviruses (red lines, displaying median, Q1, Q3) by timepoint. Conclusion Cells containing intact, replication-competent proviruses are selectively lost during suppressive ART. Defining the mechanisms involved should inform strategies to accelerate HIV-1 reservoir depletion. Disclosures Rajesh Gandhi, MD, Merck (Advisor or Review Panel member) Gregory Laird, PhD, Accelevir Diagnostics (Shareholder, Other Financial or Material Support, Employee) Albine Martin, PhD, Accelevir Diagnostics (Shareholder, Other Financial or Material Support, Employee) Bernard Macatangay, MD, Gilead (Grant/Research Support) Joseph J. Eron, MD, Gilead Sciences (Consultant, Research Grant or Support)Janssen (Consultant, Research Grant or Support)Merck (Consultant)ViiV Healthcare (Consultant, Research Grant or Support) Janet Siliciano, PhD, Gilead (Advisor or Review Panel member)US Military HIV Research Program (Advisor or Review Panel member) John Mellors, MD, Abound Bio (Shareholder)Accelevir Diagnostics (Consultant)Co-Crystal Pharmaceuticals (Shareholder)Gilead (Consultant, Grant/Research Support)Merck (Consultant)

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SAT0039 ADAPTIVE DEEP LEARNING FOR THE PREDICTION OF INDIVIDUAL DISEASE ACTIVITY IN PATIENTS WITH RHEUMATOID ARTHRITIS

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.2712 ◽

2020 ◽

Vol 79 (Suppl 1) ◽

pp. 950.1-950

Author(s):

M. Hügle ◽

G. Kalweit ◽

U. Walker ◽

A. Finckh ◽

R. Muller ◽

...

Keyword(s):

Neural Network ◽

Rheumatoid Arthritis ◽

Disease Activity ◽

Deep Neural Networks ◽

Disease Duration ◽

Research Support ◽

Disease Characteristics ◽

Individual Disease ◽

Active Disease ◽

Research Grant

Background:Rheumatoid arthritis (RA) lacks reliable biomarkers that predict disease evolution on an individual basis, potentially leading to over- and undertreatment. Deep neural networks learn from former experiences on a large scale and can be used to predict future events as a potential tool for personalized clinical assistance.Objectives:To investigate deep learning for the prediction of individual disease activity in RA.Methods:Demographic and disease characteristics from over 9500 patients with 65.000 visits from the Swiss Quality Management (SCQM) database were used to train and evaluate an adaptive recurrent neural network (AdaptiveNet). Patient and disease characteristics along with clinical and patient reported outcomes, laboratory values and medication were used as input features. DAS28-BSR was used to predict active disease and future numeric individual disease activity by classification and regression, respectively.Results:AdaptiveNet predicted active disease defined as DAS28-BSR>2.6 at the next visit, with an overall accuracy of 75.6% and a sensitivity and specificity of 84.2% and 61.5%, respectively. Apart from DAS28-BSR, the most influential characteristics to predict disease activity were joint pain, disease duration, age and medication. Longer disease duration, age >50 or antibody positivity marginally improved prediction performance. Regression allowed forecasting individual DAS28-BSR values with a mean squared error of 0.9.Conclusion:Deep neural networks have the capacity to predict individual disease outcome in RA. Low specificity remains challenging and might benefit from alternative input data or outcome targets.References:[1] Hügle M, Kalweit G, Hügle T, Boedecker J. A Dynamic Deep Neural Network For Multimodal Clinical Data Analysis. Be Publ Stud Comput Intell Springer Verl. 2020.Figure 1.Examples of true disease activity and corresponding predictions of AdaptiveNet by regression analysis. Predictions are made step to step from the current to next visit.Disclosure of Interests:Maria Hügle Paid instructor for: Lilly, Gabriel Kalweit: None declared, Ulrich Walker Grant/research support from: Ulrich Walker has received an unrestricted research grant from Abbvie, Consultant of: Ulrich Walker has act as a consultant for Abbvie, Actelion, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, MSD, Novartis, Pfizer, Phadia, Roche, Sandoz, Sanofi, and ThermoFisher, Paid instructor for: Abbvie, Novartis, and Roche, Speakers bureau: Abbvie, Actelion, Bristol-Myers Squibb, Celgene, MSD, Novartis, Pfizer, Phadia, Roche, Sandoz, and ThermoFisher, Axel Finckh Grant/research support from: Pfizer: Unrestricted research grant, Eli-Lilly: Unrestricted research grant, Consultant of: Sanofi, AB2BIO, Abbvie, Pfizer, MSD, Speakers bureau: Sanofi, Pfizer, Roche, Thermo Fisher Scientific, Rudiger Muller Consultant of: AbbVie, Nordic, Sandoz, Almut Scherer: None declared, Joschka Boedecker: None declared, Thomas Hügle Grant/research support from: Abbvie, Novartis, Consultant of: Abbvie, Pfizer, Novartis, Roche, Lilly, BMS

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