scholarly journals 838. Drivers of empiric carbapenem use: How important is history of extended-spectrum beta-lactamase (ESBL) infection?

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S460-S460
Author(s):  
Tyler J Stone ◽  
James Beardsley ◽  
James Johnson ◽  
Christopher Ohl ◽  
Christopher Ohl ◽  
...  

Abstract Background CARs are first line agents for serious infections caused by ESBL producers. Likelihood of developing subsequent ESBL infection is unknown. In patients (pts) with a history (hx) of ESBL positive (ESBLP) culture, empiric therapy with a CAR has become common in hospitals. The purpose of this study was to evaluate the microbiology of subsequent infections (SI) among pts with hx of ESBLP culture and determine risk factors associated with ESBLP SI that may justify an empiric CAR. Methods This retrospective observational study was conducted at a multicenter health system. The electronic medical record (EMR) was used to generate a report of all E. coli (EC) or K. pneumoniae (KP) ESBLP cultures during 2017, an analogous report was generated for ESBL-negative (ESBLN) EC or KP. These were termed index cultures (IC). Pts were randomly selected from each report until 200 total pts were enrolled. Inpatients, outpatients, and all culture specimens were included. Pts with an ESBLP culture prior to 2017 were excluded. The EMR was reviewed up to 1 year after the IC. Pt and culture characteristics were recorded. The primary outcome was proportion of pts who developed an ESBLP SI. Risk factors associated with ESBLP SI were determined. Relapsed infection (same site, same bacteria) that occurred within 2 weeks of the IC was excluded. Results 200 pts were included, 100 with ESBLP IC and 100 with ESBLN IC. The mean age was 58 years, 84% were female, and 69% were outpatients. 86% of IC were EC and 86% were urine specimens. Within 1 year of IC, 100 pts (50%) developed a SI. 22 of these were ESBLP, 43 were ESBLN, and 35 had no or negative culture. The mean time since IC for ESBLP SI and ESBLN SI was 85 (26-226) days and 140 (15-363) days, respectively (p=0.014). When comparing time to SI, 21 (96%) ESBLP and 26 (61%) ESBLN occurred < 6 months after IC (p=0.003). Among SI with culture data (n= 65), the number of ESBLP SI was higher if the IC was ESBLP (22 vs 0, p< 0.001). Incidence of ESBLP or ESBLN SI in all pts with an ESBLP IC was similar (22 vs 18, p=0.428). Factors associated with ESBLP SI were hx of ESBLP IC, male gender, and time between IC and SI. Table 1. Index Culture Characteristics of Culture Positive Subsequent Infections Figure 1. Cumulative rate of ESBL-positive SI in 180 days (6 months) following IC Table 2. Univariate Analysis of Patient Characteristics Comparing ESBL-positive and ESBL-negative Culture Positive Subsequent Infections Conclusion Hx of positive culture for ESBL-producing EC or KP is associated with SI caused by ESBLP EC or KP. Pts presenting < 6 months after ESBLP IC are at increased risk for ESBLP SI, justifying empiric CAR therapy. Disclosures Tyler J. Stone, PharmD, Paratek (Research Grant or Support) Elizabeth Palavecino, MD, Paratek (Grant/Research Support)Paratek (Grant/Research Support) John Williamson, PharmD, Paratek (Research Grant or Support)

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 428-428
Author(s):  
Apurva Jain ◽  
Juhee Song ◽  
Milind M. Javle ◽  
Marina C. George

428 Background: Acute cholangitis due to malignant biliary obstruction is frequent in patients with pancreatic and hepatobiliary cancers. Recurrent cholangitis (RC) results in repeated hospitalization and delayed cancer care. The risk factors associated with RC are not yet defined. Methods: A pilot review was done on 146 patients admitted with a diagnosis of cholangitis from 2005 to 2014. We included demographics, cancer stage, details of first admission (FA) and interventions. Univariate and multivariate Fine-Gray models were used for statistical analysis. Results: The mean age at FA was 62 yrs, 84 (58%) were males and 99 (68%) were white. Most common cancer was pancreatic 100(69%) and 27(19%) pts had primary cholangitis at FA. During FA, interventions were performed in 114(78%), of whom 51 (45%) had percutaneous drainage (PTBD) and 63 (55%) had endoscopic drainage (ED). Readmission with cholangitis was noted in 35 (24%) cases. Univariate analysis did not show a difference between PTBD and ED. However, subgroup analysis showed external only PTBD and covered metallic stent ED had lower risk of RC. These variables remained significant on multivariate analysis (Subdistribution HR= 0.00, p<.0001 for both). Multiple previous PTBD (≥2) before FA was significantly associated with increased risk of RC (Subdistribution HR= 2.64, p= 0.01) on univariate analysis. Conclusions: Having multiple previous PTBD is associated with recurrent cholangitis. Though no significant difference was noted between PTBD and ED, the subgroups indicated a trend towards less recurrent cholangitis with covered metallic stent. [Table: see text]


2021 ◽  
Vol 33 (1) ◽  
Author(s):  
Moussa Kaboré ◽  
Brahima Kirakoya ◽  
Adama Ouattara ◽  
Clotaire Alexis Marie Kiemdiba Donega Yameogo ◽  
Stéphanie Dominique Amida Nama ◽  
...  

The objective of the study was to determine the risk factors for development of circumferential fistula. We carried out a crosssectional, multicentric and analytical study over 7 years period, from 1st January, 2010 to 31 December, 2016. We compared circumferential and non- circumferential fistula patients in order to determine the risk factors for circumferential fistula development. Circumferential fistula accounted for 20% (91/456) of all vesico-vaginal fistulas. The mean age of the 456 patients was 35.9 years±12.15 (min 15 years; max 72 years). On univariate analysis, factors associated with the risk of circumferential fistula were: residence (P=0.039; OR=1.7), parity (P=0.04; OR=0.47), marital status before fistula (P=0.002; 4.3), duration of labor (P=0.041; OR=2.7) and fistula aetiology (P=0.038; OR=2.54). In a logistic regression model, two factors remained significant: marital status before fistula (P=0.029; OR=0.13) and duration of labor (P=0.017; OR=0.26). Circumferential fistula occurs in urban, primiparous, unmarried women who have been in labor for more than 41 hours.


2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S366-S366
Author(s):  
Yasir Hamad ◽  
Katelin B Nickel ◽  
Yvonne Burnett ◽  
Margaret A Olsen

Abstract Background Vancomycin therapy is known to be associated with nephrotoxicity. Predictors of nephrotoxicity in outpatients are not well defined and have only been reported in relatively small studies. We examined the factors associated with incidence of nephrotoxicity during outpatient parenteral antimicrobial therapy (OPAT) using administrative data. Methods A large insurance claims database of privately insured patients (IBM-MarketScan) ages 18 - 64 from 2010 to 2016 was queried for patients discharged from the hospital on vancomycin OPAT. The primary endpoint was 42-day hospital readmission with acute kidney injury (AKI). A Chi-square test was used to examine associations with AKI. Factors with significant associations in univariate analysis were then incorporated into a multivariable logistic regression model. Results A total of 14,196 patients were included in the study, median age was 54 years and 53.8% were male. Hospital readmission with AKI occurred in 385 (2.7 %). Factors associated with AKI in univariate analysis included older age, living in a rural area, heart failure (CHF), chronic kidney disease (CKD), liver disease, diabetes, cancer, septicemia, MRSA infection, concomitant penicillin therapy, receiving therapy at home versus an infusion center, and infectious diseases consult during index hospitalization. In the multivariable model, septicemia, CHF, CKD, liver disease, and concomitant use of a penicillin family drug were independently associated with increased risk of acute kidney injury (Table). Conclusion Septicemia, use of penicillins and some comorbidities were associated with AKI in patients treated with vancomycin OPAT. Patients at high risk for vancomycin nephrotoxicity should be monitored closely and an alternative therapy should be considered. Table Disclosures Margaret A. Olsen, PhD, MPH, Merck (Grant/Research Support)Pfizer (Consultant, Grant/Research Support)


2012 ◽  
Vol 52 (5) ◽  
pp. 255
Author(s):  
Anak Agung Made Sucipta ◽  
Ida Bagus Subanada ◽  
Samik Wahab

Background Pneumonia is a health problem in developingcountries, often caused by bacterial agents. The 'Widespreaduse of cefotaxime, a third􀁒generation of cephalosporin, may leadto increased incidence of resistance to this antibiotic. Severalstudies have reported on risk factors associated v.ith resistanceto cefotaxime.Objective To identify risk factors for cefotaxime resistance inchildren 'With pneumonia.Methods We performed a case􀁒control study at Sanglah Hospitalbetween January 2006􀁒December 2010. The case group includedchildren with blood culture􀁒positive pneumonia and resistanceto cefotaxime by sensitivity test. The control group was selectedfrom the same population as the case group, but the bacteriaisolated from these subjects were sensitive to cefotaxime. Wetested the folloMng risk factors for resistance to cefotaxime:age :53 years, microorganism species, history of antimicrobialuse, and history of hospitalization within the prior 3 months.Chi square test and logistic regression analysis were performedto determine any associations between the four potential riskfactors and resistance to cefotaxime. A P<0.05 was consideredto be statistically significant.Results Univariate analysis showed that the risk factors forresistance to cefotaxime were history of antimicrobial use in theprior 3 months (OR 2.79; 95%CI 1.40 to 5.55; P􀁓O.OOI) andhistory of hospitalization Mthin the prior 3 months (OR 5.57;95%CI 1.95 to 15.87; P=<O.OOOl). By multivariate analysis,risk factors associated Mth resistance to cefotaxime were historyof antimicrobial use in the prior 3 months (OR 2.4; 95%CI 1.18to 4.86; P=0.015), history of hospitalization within the prior 3months (OR 4.7; 95%CI 1.62 to 13.85; P􀁓0.004), and historyof breast feeding for less than 2 months (OR 2.3; 95%CI 1.0 to5.4; P􀁓0.042).Conclusion History of antimicrobial use and history ofhospitalization within the prior 3 monthsweresignificantrisk factors for resistance to cefotaxime in children Mth pneumonia.[Paediatr Indanes. 2012;52:255-9].


2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 654-655
Author(s):  
K. Winthrop ◽  
L. Calabrese ◽  
F. Van den Bosch ◽  
K. Yamaoka ◽  
C. Selmi ◽  
...  

Background:Upadacitinib (UPA) is a selective and reversible Janus kinase (JAK) inhibitor with an approved dose of 15 mg once daily (QD) for the treatment of rheumatoid arthritis (RA). Patients (pts) receiving JAK inhibitors have been reported to be at increased risk of developing serious infection events (SIE) and opportunistic infections (OI).Objectives:To evaluate the incidence of SIEs and OIs in pts with RA receiving UPA and active comparators in the Phase 3 SELECT clinical trial program.Methods:The exposure-adjusted event rate (EAER) per 100 patient-years (E/100 PY) of SIEs and OIs was determined in pts receiving UPA in five randomized Phase 3 trials (SELECT-EARLY, SELECT-MONOTHERAPY, SELECT-NEXT, SELECT-COMPARE, and SELECT-BEYOND), of which four evaluated both UPA 15 mg and 30 mg QD doses and one (SELECT-COMPARE) evaluated only UPA 15 mg QD. Incidences of SIEs and OIs were also determined in pts receiving adalimumab (ADA) + methotrexate (MTX) in SELECT-COMPARE and MTX monotherapy in SELECT-EARLY. Data were analyzed descriptively, with no statistical comparisons between groups or doses. Risk factors for SIEs were determined using a univariate Cox regression model. The data cut-off was June 30, 2019.Results:Overall, 2629 pts who received UPA 15 mg, 1204 pts who received UPA 30 mg, 579 pts who received ADA + MTX, and 314 pts who received MTX monotherapy were included in this analysis. The EAERs (E/100 PYs [95% CI]) of SIEs were 3.2 (2.7–3.7) in the UPA 15 mg group, 5.7 (4.8–6.8) in the UPA 30 mg group, 3.9 (2.6–5.6) in pts receiving ADA + MTX, and 3.1 (1.7–5.2) in pts receiving MTX monotherapy. Pneumonia was the most common SIE, with EAERs (E/100 PYs [95% CI]) of 0.7 (0.5–1.0), 1.3 (0.9–1.9), 0.7 (0.2–1.5), and 0.7 (0.1–1.9) in the UPA 15 mg, UPA 30 mg, ADA + MTX, and MTX monotherapy groups, respectively. Rates of OIs (including oral candidiasis and disseminated herpes zoster [HZ]) (E/100 PYs [95% CI]) were 0.7 (0.5–1.0), 1.3 (0.9–1.9), 0.4 (0.1–1.1), and 0 (0–0) in the UPA 15 mg, UPA 30 mg, ADA + MTX, and MTX monotherapy groups, respectively. Oral candidiasis was the most frequent OI with EAERs (E/100 PYs [95% CI]) of 0.4 (0.2–0.6) in the UPA 15 mg group, 0.6 (0.3–1.0) in the UPA 30 mg group, 0.4 (0.1–1.1) in the ADA + MTX group, and 0 (0–0) in the MTX monotherapy group. Serious adverse events of HZ were only reported in the UPA groups (0.2 E/100 PYs [95% CI: 0.1–0.3] and 0.6 E/100 PYs [95% CI: 0.4–1.1] in the UPA 15 mg and 30 mg groups, respectively). Overall, there were 3 (4 coded events), 3, 1, and 0 pts who had active tuberculosis events in the UPA 15 mg, UPA 30 mg, ADA + MTX, and MTX monotherapy groups, respectively. Risk factors for SIEs are shown in the Figure. For both UPA doses, age ≥75 years and smoking were noted to have hazard ratios >1.Conclusion:The incidence rate of SIEs and OIs was higher in the UPA 30 mg group than the UPA 15 mg group. SIEs observed with UPA 15 mg were similar to that seen with ADA although the rates of HZ were higher on UPA. Pts with RA who are ≥75 years old and/or smokers may be at higher risk than other pts with RA for SIEs while receiving UPA.Figure.Univariate analysis of SIE risk factorsDisclosure of Interests:Kevin Winthrop Grant/research support from: Bristol-Myers Squibb, Consultant of: AbbVie, Bristol-Myers Squibb, Eli Lilly, Galapagos, Gilead, GSK, Pfizer Inc, Roche, UCB, Leonard Calabrese Consultant of: AbbVie, GSK, Bristol-Myers Squibb, Genentech, Janssen, Novartis, Sanofi, Horizon, Crescendo, and Gilead, Speakers bureau: Sanofi, Horizon, Crescendo, Novartis, Genentech, Janssen, and AbbVie, Filip van den Bosch Consultant of: AbbVie, Celgene Corporation, Eli Lilly, Galapagos, Janssen, Novartis, Pfizer, and UCB, Speakers bureau: AbbVie, Celgene Corporation, Eli Lilly, Galapagos, Janssen, Novartis, Pfizer, and UCB, Kunihiro Yamaoka Speakers bureau: AbbVie GK, Astellas Pharma Inc., Bristol-Myers Squibb, Chugai Pharmaceutical Co. Ltd, Mitsubishi-Tanabe Pharma Corporation, Pfizer Japan Inc., and Takeda Pharmaceutical Company Ltd, Carlo Selmi Grant/research support from: AbbVie, Janssen, MSD, Novartis, Pfizer, Celgene, and Leo Pharma, Consultant of: Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Novartis, Pfizer, Roche, and Sanofi-Regeneron, Speakers bureau: AbbVie, Aesku, Alfa-Wassermann, Bristol-Myers Squibb, Biogen, Celgene, Eli-Lilly, Grifols, Janssen, MSD, Novartis, Pfizer, Roche, Sanofi-Genzyme, UCB Pharma, Yanna Song Shareholder of: AbbVie Inc., Employee of: AbbVie Inc., Barbara Hendrickson Shareholder of: AbbVie Inc., Employee of: AbbVie Inc., Ivan Lagunes-Galindo Shareholder of: AbbVie Inc., Employee of: AbbVie Inc., Iain McInnes Grant/research support from: Bristol-Myers Squibb, Celgene, Eli Lilly and Company, Janssen, and UCB, Consultant of: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly and Company, Gilead, Janssen, Novartis, Pfizer, and UCB


2020 ◽  
Vol 148 ◽  
Author(s):  
Y. Yupiana ◽  
E. Vallée ◽  
P. Wilson ◽  
J. F. Weston ◽  
J. Benschop ◽  
...  

Abstract This study aimed to evaluate risk factors associated with shedding of pathogenic Leptospira species in urine at animal and herd levels. In total, 200 dairy farms were randomly selected from the DairyNZ database. Urine samples were taken from 20 lactating, clinically normal cows in each herd between January and April 2016 and tested by real-time polymerase chain reaction (PCR) using gyrB as the target gene. Overall, 26.5% of 200 farms had at least one PCR positive cow and 2.4% of 4000 cows were shedding Leptospira in the urine. Using a questionnaire, information about risk factors at cow and farm level was collected via face-to-face interviews with farm owners and managers. Animals on all but one farm had been vaccinated against Hardjo and Pomona and cows on 54 of 200 (27%) farms had also been vaccinated against Copenhageni in at least one age group (calves, heifers and cows). Associations found to be statistically significant in univariate analysis (at P < 0.2) were assessed by multivariable logistic regression. Factors associated with shedding included cattle age (Odds ratio (OR) 0.82, 95% CI 0.71–0.95), keeping sheep (OR 5.57, 95% confidence interval (CI) 1.46–21.25) or dogs (OR 1.45, 95% CI 1.07–1.97) and managing milking cows in a single as opposed to multiple groups (OR 0.45, 95% CI 0.20–0.99). We conclude that younger cattle were more likely to be shedding Leptospira than older cattle and that the presence of sheep and dogs was associated with an increased risk of shedding in cows. Larger herds were at higher risk of having Leptospira shedders. However, none of the environmental risk factors that were assessed (e.g. access to standing water, drinking-water source), or wildlife abundance on-farm, or pasture were associated with shedding, possibly due to low statistical power, given the low overall shedding rate.


2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S576-S577
Author(s):  
Thomas Holowka ◽  
Harry Cheung ◽  
Maricar F Malinis ◽  
Sarah Perreault ◽  
Iris Isufi ◽  
...  

Abstract Background Ibrutinib is a tyrosine kinase inhibitor used to treat hematologic malignancies that may increase the risk of serious infection including invasive fungal infections (IFI). In a study of 378 patients with hematologic malignancy on ibrutinib, serious infection and IFI occurred in 11% and 4% respectively (Varughese et al. Clin Infect Dis). The primary aims of our study were to determine the incidence of serious infection and associated risk factors in patients on ibrutinib. Methods We performed a retrospective analysis of patients with hematologic malignancy prescribed ibrutinib for ≥ 1 week at Yale New Haven Hospital from 2014 to 2019 to identify serious infections defined as those requiring inpatient management. We collected demographic, clinical and oncologic data. Chi-squared tests were used to determine factors associated with an increased risk of infection. Results A total of 254 patients received ibrutinib including 156 with CLL, 89 with NHL and 9 with other leukemias. Among these, 21 underwent HSCT, 9 complicated by GVHD. There were 51 (20%) patients with serious infections including 45 (17.7%) bacterial, 9 (3.5%) viral and 5 (2%) IFI (1 pulmonary cryptococcosis, 4 pulmonary aspergillosis). Anti-mold prophylaxis was prescribed to 7 (2.8%) patients, none of whom developed IFI. Risk factors associated with serious infection included ECOG score ≥ 2 (OR 4.6, p &lt; 0.001), concurrent steroid use (≥ 10 mg prednisone daily for ≥ 2 weeks; OR 3.0, p &lt; 0.001), neutropenia (OR 3.6, p &lt; 0.01), lymphopenia (OR 2.4, p &lt; 0.05) and maximum ibrutinib dose of 560 mg (OR 2, p &lt; 0.05). There was a dose dependent increase in infections based on number of chemotherapy regimens prior to ibrutinib initiation: 14.3% with 0, 19.7% with 1-2 and 28.7% with ≥ 3 prior treatments. Conclusion The incidence of serious infection in hematologic patients on ibrutinib was higher than previously reported (20% versus 11%) but the rate of IFI was lower (2% versus 4%). High ECOG score, leukopenia, steroids, and higher ibrutinib doses were associated with an increased risk for serious infection. Targeted antimicrobial prophylaxis should be considered for patients on ibrutinib with these risk factors. Improving functional status may also reduce the risk of infection in patients on ibrutinib. Disclosures All Authors: No reported disclosures


2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1961.1-1961
Author(s):  
J. Knitza ◽  
J. Mohn ◽  
C. Bergmann ◽  
E. Kampylafka ◽  
M. Hagen ◽  
...  

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


2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 54.1-54
Author(s):  
S. Benamar ◽  
C. Lukas ◽  
C. Daien ◽  
C. Gaujoux-Viala ◽  
L. Gossec ◽  
...  

Background:Polypharmacy is steadily increasing in patients with rheumatoid arthritis (RA). They may interfere with treatment response and the occurrence of serious adverse events. Medications taken by a patient may reflect active comorbidities, whereas comorbidity indices usually used include past or current diseases.Objectives:To evaluate whether polypharmarcy is associated with treatment response and adverse events in an early RA cohort and to establish whether polypharmacy could represent a substitute of comorbidities.Methods:We used data from the French cohort ESPOIR, including 813 patients with early onset arthritis. Patients included the current study had to start their first disease modifying anti-rheumatic drug (DMARD) within 24 months of inclusion in the cohort. Disease activity data were collected at one, five and ten years from the initiation of the first DMARD. For each patient, treatments were collected at baseline and at five years. Medications count included all specialties other than background RA therapy, analgesics/NSAIDs and topicals. Polypharmacy was defined as a categorical variable based on the median and tertiles of distribution in the cohort. Treatment response was assessed by achieving DAS28 ESR remission (REM) at 1 year, 5 years and 10 years from the initiation of the first DMARD. The occurrence of severe adverse events (SAE) was measured by the occurrence of severe infection, hospitalization, or death during the 10-year follow-up. The association between patient’s characteristics and achievement of REM and occurrence of SAE were tested in univariate analysis. A logistic regression model was used to evaluate associations between polypharmacy and REM at 1 year, 5 years and 10 years (we used baseline polypharmacy for the 1-year analysis and five years polypharmacy for the 5- and 10-years analyses). Multivariate adjustment was made for age, sex, BMI, duration of disease, initial DAS28 ESR, initial HAQ, smoking status, rheumatic disease comorbidity index (RDCI).Results:The proportion of patients who achieved REM one year after the initiation of the first DMARD was 32.1% in the polypharmacy according to the median group (patients taken ≥2 medication) versus 67.9% in the non-polypharmacy group (p=0.07). At 5 years after the first DMARD, the proportion of patients with REM was 45.0% in the polypharmacy group versus 56.3% in the non-polypharmacy group (p=0.03). At 10 years the proportion of patients with REM was 32.5% in the polypharmacy group versus 67.5% (p=0.06). Patients who take greater or equal to 2 medications had a 40% lower probability of achieving REM (OR = 0.60 [0.38-0.94] p = 0.03) at 5 years from the first DMARD (if RDCI index was not included in the model). At 10 years, patients receiving multiple medications had a 43% lower probability of achieving REM (OR = 0.57 [0.34-0.94] p = 0.02). SAE incidence was 61 per 1000 patient-years. For patients who developed SAE all causes 71.4% where in the polypharmacy group versus 57.8% were in the non-polypharmacy group (p = 0.03; univariate analysis). These results are no longer significant after adjustment for comorbidities indices.Conclusion:In this early RA cohort, polypharmacy is associated with a poorer treatment response and increased risk of adverse events. Polypharmacy may represent a good substitute of comorbidities for epidemiological studies.Acknowledgements:We are grateful to Nathalie Rincheval (Montpellier) who did expert monitoring and data management and all theinvestigators who recruited and followed the patients (F. Berenbaum, Paris-Saint Antoine; MC. Boissier, Paris-Bobigny; A. Cantagrel, Toulouse; B. Combe, Montpellier; M. Dougados, Paris-Cochin; P. Fardellone and P. Boumier, Amiens; B. Fautrel, Paris-La Pitié; RM. Flipo, Lille; Ph. Goupille, Tours; F. Liote, Paris- Lariboisière; O. Vittecoq, Rouen; X. Mariette, Paris-Bicêtre; P. Dieude, Paris Bichat; A. Saraux, Brest; T. Schaeverbeke, Bordeaux; and J. Sibilia, Strasbourg).The work reported on in the manuscript did not benefit from any financial support. The ESPOIR cohort is sponsored by the French Society for Rheumatology. An unrestricted grant from Merck Sharp and Dohme (MSD) was allocated for the first 5 years. Two additional grants from INSERM were obtained to support part of the biological database. Pfizer, Abbvie, Lilly and more recently Fresenius and Biogen also supported the ESPOIR cohort.Disclosure of Interests:Soraya Benamar: None declared, Cédric Lukas Speakers bureau: Abbvie, Amgen, Janssen, Lilly, MSD, Novartis, Pfizer, Roche-Chugai, UCB, Consultant of: Abbvie, Amgen, Janssen, Lilly, MSD, Novartis, Pfizer, Roche-Chugai, UCB, Grant/research support from: Pfizer, Novartis and Roche-Chugai, Claire Daien Speakers bureau: AbbVie, Abivax, BMS, MSD, Roche, Chugai, Novartis, Pfizer, Sandoz, Lilly, Consultant of: AbbVie, Abivax, BMS, MSD, Roche, Chugai, Novartis, Pfizer, Sandoz, Lilly, Cécile Gaujoux-Viala Speakers bureau: Abbvie, BMS, Celgene, Janssen, Medac, MSD, Nordic Pharma, Novartis, Pfizer, Sanofi, Roche-Chugai, UCB, Consultant of: Abbvie, BMS, Celgene, Janssen, Medac, MSD, Nordic Pharma, Novartis, Pfizer, Sanofi, Roche-Chugai, UCB, Grant/research support from: Pfizer, Laure Gossec Speakers bureau: AbbVie, Amgen, Biogen, Celgene, Janssen, Lilly, Novartis, Pfizer, Sandoz, Sanofi-Aventis et UCB, Consultant of: AbbVie, Amgen, Biogen, Celgene, Janssen, Lilly, Novartis, Pfizer, Sandoz, Sanofi-Aventis et UCB, Anne-Christine Rat Speakers bureau: Pfizer, Lilly, Consultant of: Pfizer, Lilly, Bernard Combe Speakers bureau: AbbVie; Bristol-Myers Squibb; Gilead; Janssen; Lilly; Merck; Novartis; Pfizer; Roche-Chugai; and Sanofi;, Consultant of: AbbVie; Bristol-Myers Squibb; Gilead; Janssen; Lilly; Merck; Novartis; Pfizer; Roche-Chugai; and Sanofi;, Grant/research support from: Novartis, Pfizer, and Roche-Chugai., Jacques Morel Speakers bureau: Abbvie, BMS, Lilly, Médac, MSD, Nordic Pharma, Pfizer, UCB, Consultant of: Abbvie, BMS, Lilly, Médac, MSD, Nordic Pharma, Pfizer, UCB, Grant/research support from: BMS, Pfizer


2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S582-S583
Author(s):  
Eleni Karantoni ◽  
Yiqi Su ◽  
Anat Stern ◽  
Phaedon D Zavras ◽  
Sergio Giralt ◽  
...  

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 &gt;1 log10 decrease in CMV viral load (VL) and having VL &gt;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&lt; 0.001). In multivariable model, risk factors for R/R included TCD HCT (p&lt; 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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