FRI0141 CHARACTERIZATION OF SERIOUS INFECTIONS WITH UPADACITINIB IN PATIENTS WITH RHEUMATOID ARTHRITIS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 654-655
Author(s):  
K. Winthrop ◽  
L. Calabrese ◽  
F. Van den Bosch ◽  
K. Yamaoka ◽  
C. Selmi ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Risk Factors ◽  
Cox Regression ◽  
Opportunistic Infections ◽  
Oral Candidiasis ◽  
Univariate Analysis ◽  
Janus Kinase ◽  
Research Support ◽  
Phase 3 ◽  
Increased Risk

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

scholarly journals Incidence and risk factors for herpes zoster in patients with rheumatoid arthritis receiving upadacitinib: a pooled analysis of six phase III clinical trials

2021 ◽  
Vol 81 (2) ◽  
pp. 206-213
Author(s):  
Kevin L Winthrop ◽  
Peter Nash ◽  
Kunihiro Yamaoka ◽  
Eduardo Mysler ◽  
Nasser Khan ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Risk Factors ◽  
Herpes Zoster ◽  
Cox Regression ◽  
Janus Kinase ◽  
Phase Iii ◽  
Cox Regression Analysis ◽  
Increased Risk ◽  
History Of ◽  
Event Rates

BackgroundUpadacitinib (UPA) is an oral Janus kinase (JAK) inhibitor approved for the treatment of rheumatoid arthritis (RA). JAK inhibitors have been associated with an increased risk of herpes zoster (HZ) in patients with RA.ObjectivesTo evaluate the incidence and risk factors for HZ in UPA-treated patients with RA from the UPA phase III clinical trial programme.MethodsExposure-adjusted incidence/event rates for HZ were determined in patients receiving UPA (monotherapy or combination therapy) in six randomised phase III trials (data cut-off on 30 June 2020). HZ incidence and event rates were also determined in patients receiving methotrexate (MTX) monotherapy or adalimumab (ADA) + MTX. Multivariable Cox regression analysis was used to identify HZ risk factors in UPA-treated patients.ResultsA total of 5306 patients were included in this analysis. The incidence rate of HZ/100 patient-years (95% CI) was 0.8 (0.3 to 1.9), 1.1 (0.5 to 1.9), 3.0 (2.6 to 3.5) and 5.3 (4.5 to 6.2), in the MTX monotherapy, ADA + MTX, UPA 15 mg and UPA 30 mg groups, respectively. The majority of HZ cases with UPA (71%) involved a single dermatome. Prior history of HZ and Asian region were HZ risk factors in UPA-treated patients.ConclusionIn the UPA phase III RA clinical programme, HZ incidence and event rates were higher with UPA versus ADA + MTX or MTX monotherapy, and higher with the 30 mg versus 15 mg dose. Patients from Asia and those with a history of HZ may be at increased risk of HZ while receiving UPA.

scholarly journals OP0098 POLYPHARMACY IS ASSOCIATED WITH A POORER TREATMENT RESPONSE AND INCREASED RISK OF ADVERSE EVENTS IN EARLY RHEUMATOID ARTHRITIS

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 54.1-54
Author(s):  
S. Benamar ◽  
C. Lukas ◽  
C. Daien ◽  
C. Gaujoux-Viala ◽  
L. Gossec ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Adverse Events ◽  
Treatment Response ◽  
Univariate Analysis ◽  
Group Versus ◽  
Biological Database ◽  
Lower Probability ◽  
Research Support ◽  
Early Ra ◽  
Increased Risk

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

scholarly journals Risk of venous thromboembolism associated with Janus kinase inhibitors for rheumatoid arthritis: case presentation and literature review

2021 ◽  
Author(s):  
Shunsuke Mori ◽  
Fumihiko Ogata ◽  
Ryusuke Tsunoda
Keyword(s):  
Rheumatoid Arthritis ◽  
Diabetes Mellitus ◽  
Risk Factors ◽  
Pulmonary Embolism ◽  
Venous Thromboembolism ◽  
Disease Activity ◽  
Janus Kinase ◽  
Advanced Age ◽  
Jak Inhibitors ◽  
Increased Risk

AbstractJanus kinase (JAK) inhibitors have been developed as disease-modifying antirheumatic drugs. Despite the positive therapeutic impacts of JAK inhibitors, concerns have been raised regarding the risk of venous thromboembolism (VTE), such as deep vein thrombosis (DVT) and pulmonary embolism (PE). A recent post hoc safety analysis of placebo-controlled trials of JAK inhibitors in rheumatoid arthritis (RA) reported an imbalance in the incidence of VTE for a 4-mg daily dose of baricitinib versus placebo. In a recent postmarketing surveillance trial for RA, a significantly higher incidence of PE was reported in treatment with tofacitinib (10 mg twice daily) compared with tofacitinib 5 mg or tumor necrosis factor inhibitors. We also experienced a case of massive PE occurring 3 months after starting baricitinib (4 mg once daily) for multiple biologic-resistant RA. Nevertheless, the evidence to support the role of JAK inhibitors in VTE risk remains insufficient. There are a number of predisposing conditions and risk factors for VTE. In addition to the known risk factors that can provoke VTE, advanced age, obesity, diabetes mellitus, hypertension, hyperlipidemia, and smoking can also contribute to its development. Greater VTE risk is noted in patients with chronic inflammatory conditions, particularly RA patients with uncontrolled disease activity and any comorbidity. Prior to the initiation of JAK inhibitors, clinicians should consider both the number and strength of VTE risk factors for each patient. In addition, clinicians should advise patients to seek prompt medical help if they develop clinical signs and symptoms that suggest VTE/PE. Key Points• Patients with rheumatoid arthritis (RA) are at increased risk of venous thromboembolism (VTE), especially those with uncontrolled, high disease activity and those with comorbidities.• In addition to the well-known risk factors that provoke VTE events, advanced age and cardiovascular risk factors, such as obesity, diabetes mellitus, hypertension, hyperlipidemia, and smoking, should be considered risk factors for VTE.• Although a signal of VTE/pulmonary embolism (PE) risk with JAK inhibitors has been noted in RA patients who are already at high risk, the evidence is currently insufficient to support the increased risk of VTE during RA treatment with JAK inhibitors.• If there are no suitable alternatives, clinicians should prescribe JAK inhibitors with caution, considering both the strength of individual risk factors and the cumulative weight of all risk factors for each patient.

The Association Between Serum Leptin Levels and Cardiovascular Events in Patients with Rheumatoid Arthritis

2020 ◽  
Vol 52 (1) ◽  
pp. 86-92 ◽  
Author(s):  
Jiliang Chen ◽  
Zhiping Xie ◽  
Zou Bin
Keyword(s):  
Rheumatoid Arthritis ◽  
Prognostic Factor ◽  
Cox Regression ◽  
Univariate Analysis ◽  
Elevated Serum ◽  
Confounding Factors ◽  
Serum Leptin ◽  
Cox Regression Analysis ◽  
Kaplan Meier ◽  
Increased Risk

Abstract Objective Cardiovascular diseases (CVDs) are important complications for patients with rheumatoid arthritis (RA). The study aimed to explore whether serum leptin is associated with a increased risk of cardiovascular (CV) events in patients with RA. Methods Two hundred twenty-three patients with RA were followed for a mean of 40 (range = 8-42) months. Serum leptin levels were measured at baseline. Cox regression analysis was performed to assess the association between leptin levels and the risk of CV events. Results The univariate analysis showed that patients with RA with higher serum leptin levels had higher rates of CV events and CV mortality, respectively (P <.001). The logistic regression model showed that leptin was independently related to CVD history (odds ratio = 1.603, 95% confidence interval [CI], 1.329–2.195; P =.005) after adjusting for confounding factors in patients with RA at baseline. The multivariate Cox proportional hazard model suggested that leptin was an independent prognostic factor for CV events in patients with RA after adjustments were made for clinical confounding factors (hazard ratio = 2.467, 95% CI, 2.019–4.495; P <.001). The Kaplan-Meier analysis showed that compared with patients with RA with leptin levels below the median value (≤15.4 mg/L), patients with leptin above the median value (>15.4 μg/L) had a higher rate of CV events (P <.001). Conclusion Leptin was significantly associated with CV events in patients with RA. Elevated serum leptin levels may be a reliable prognostic factor for predicting CV complications in patients with RA.

Multivariate Analysis of Risk Factors for Clinically Overt Hemorrhagic Cystitis after Allogeneic Hematopoietic Stem Cell Transplantation.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 5295-5295
Author(s):  
Kanger Zhu ◽  
Chunhui Ma ◽  
Tao Zhang ◽  
Juan Zhong
Keyword(s):  
Risk Factors ◽  
Multivariate Analysis ◽  
Cox Regression ◽  
Hemorrhagic Cystitis ◽  
Univariate Analysis ◽  
Male Gender ◽  
Gvhd Prophylaxis ◽  
Increased Risk ◽  
Grade Ii ◽  
Grade Iii

Abstract Objective: To analyze the risk factors of clinically overt hemorrhagic cystitis (HC) (grade ≥II) in 114 patients undergoing allo-HSCT to predict the occurrence of HC. Methods: We retrospectively analyzed 29 cases of clinically overt HC from a series of 114 patients given allo-HSCT from April 1997 to December 2004. The time of follow-up began from the day of initiating conditioning to day 180 post-transplant. The 11 clinical parameters were selected for univariate analysis using a Cox regression: age, sex, underlying disease, conditioning regimen, disease status at transplant, aGVHD, donor type, use of ATG, GVHD prophylaxis, platelet and neutrophil engraftment. Factors that were significant at the 0.1 level on univariate analysis were evaluated by multivariate analysis using a Cox regression. The cumulative incidence of grade ≥ II HC within the day 180 after transplantation was calculated by the method of Kaplan and Meier. Results: 29 out of 114 patients (26%) developed HC with grade II in 12/29 cases (41.4%), grade III in 11/29 cases (37.9%) and grade IV in 6/29 cases (20.7%). The following factors were associated with an increased risk of HC by univariate analysis: male gender (RR=2.885, P=0.021),younger than 26 years (RR=3.265, P=0.007),grade III~IV aGVHD (RR=4.039, P=0.002),unrelated doner (RR=4.347, P=0),intense GVHD prophylaxis (RR=2.218, P=0.045),advanced disease (RR=2.668, P=0.009). These risk factors were entered into a multivariate model. Only male gender (RR=2.993, 95% CI 1.218–7.358; P=0.017) and unrelated donor (RR=4.478, 95% CI 2.049–9.786; P=0.000) were identified as being significantly associated with the occurrence of hemorrhagic cystitis. Conclusion: We found that in multivariate analysis, patients were at increased risk of HC if they were male or had received graft from unrelated donors.

scholarly journals 20. Risk Factors for Breakthrough Cytomegalovirus (CMV) Infection and De Novo Resistance in Hematopoietic Cell Transplantation (HCT) Recipients Receiving Letermovir Prophylaxis

2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S13-S14
Author(s):  
Danniel Zamora ◽  
Garrett Perchetti ◽  
Melinda Biernacki ◽  
Hu Xie ◽  
Jared L Castor ◽  
...  
Keyword(s):  
Risk Factors ◽  
Cox Regression ◽  
De Novo ◽  
Resistance Testing ◽  
Cmv Infection ◽  
Research Support ◽  
Material Support ◽  
Increased Risk ◽  
Clinically Significant ◽  
Cmv Reactivation

Abstract Background Subclinical CMV reactivation on letermovir prophylaxis may be important for CMV-specific immune reconstitution after HCT (Zamora et al. Blood 2021) but concerns remain regarding the development of antiviral resistance. Here we analyze risk factors associated with breakthrough CMV infection on letermovir and describe the incidence of de novo letermovir resistance. Methods All CMV-seropositive, allogeneic HCT recipients who received letermovir prophylaxis from 10/2018-2020 were analyzed. Weekly proportions and cumulative incidences of CMV reactivation in the first 100 days post-HCT were calculated at different levels. Clinically significant CMV infection was treated preemptively with (val)ganciclovir or foscarnet. Univariable/multivariable Cox regression models for breakthrough CMV reactivation at each viral threshold were performed. Patients with CMV reactivation ≥ 200 IU/mL were tested by UL56 sequencing to identify de novo letermovir resistance. Results Two hundred thirty HCT recipients who received letermovir prophylaxis were identified. Weekly proportions and cumulative incidences of CMV reactivation are shown in Figure 1. Nine of 15 patients with CMV reactivation had sufficient serum for letermovir resistance testing. One C325Y mutation was identified in an umbilical cord blood transplant recipient who developed 4 weeks of CMV DNAemia with a peak of 2512 IU/mL. The patient received 56 days of letermovir prior to reactivation and responded to treatment initially with foscarnet (due to cytopenias) followed by ganciclovir. Greater cumulative steroid exposure was associated with increased risk of CMV reactivation and the association remained statistically significant at any level (adjusted Hazard Ratio [aHR] 10.8 mg/kg*days, 95% confidence interval [CI] 5.18-22.7) and ≥ 150 IU/mL (aHR 15.9 mg/kg*days, 95% CI 7.07-35.6) after adjusting for underlying disease and GVHD prophylaxis (Figure 2). Conclusion Letermovir prophylaxis was effective at preventing clinically significant CMV infection but subclinical reactivation continued to occur. Cumulative steroid exposure was the strongest risk factor for reactivation while on letermovir. Development of de novo letermovir resistance on prophylaxis occurred infrequently. Disclosures Michael Boeckh, MD PhD, AlloVir (Consultant)Ansun Biopharma (Grant/Research Support)Astellas (Grant/Research Support)EvrysBio (Consultant, Other Financial or Material Support, Options to acquire equity, but have not exercised them)Gilead Sciences (Consultant, Grant/Research Support)GlaxoSmithKline (Consultant)Helocyte (Consultant, Other Financial or Material Support, Options to acquire equity, but have not exercised them)Janssen (Grant/Research Support)Kyorin (Consultant)Merck (Consultant, Grant/Research Support)Moderna (Consultant)Symbio (Consultant)Takeda (formerly known as Shire) (Consultant, Grant/Research Support)VirBio (Consultant, Grant/Research Support) Alexander L. Greninger, MD, PhD, Abbott (Grant/Research Support)Gilead (Grant/Research Support)Merck (Grant/Research Support)

scholarly journals Risk factors of damage in early diagnosed systemic lupus erythematosus: results of the Italian multicentre Early Lupus Project inception cohort

Rheumatology ◽  
2019 ◽  
Vol 59 (9) ◽  
pp. 2272-2281 ◽  
Author(s):  
Matteo Piga ◽  
Alberto Floris ◽  
Gian Domenico Sebastiani ◽  
Imma Prevete ◽  
Florenzo Iannone ◽  
...  
Keyword(s):  
Risk Factors ◽  
Lupus Erythematosus ◽  
Cox Regression ◽  
Univariate Analysis ◽  
Damage Index ◽  
Inception Cohort ◽  
Damage Development ◽  
Increased Risk ◽  
Time Varying Covariates ◽  
Improve Patient

Abstract Objective To investigate risk factors for damage development in a prospective inception cohort of early diagnosed SLE patients. Methods The Early Lupus Project recruited an inception cohort of patients within 12 months of SLE classification (1997 ACR criteria). At enrolment and every 6 months thereafter, the SLICC/ACR Damage Index was recorded. The contribution of baseline and time-varying covariates to the development of damage, defined as any SLICC/ACR Damage Index increase from 0 to ≥1, was assessed using univariate analysis. Forward-backward Cox regression models were fitted with covariates with P < 0.05 to identify factors independently associated with the risk of damage development. Results Overall, 230 patients with a mean (s.d.) age of 36.5 (14.4) years were eligible for this study; the mean number of visits per patient was 5.3 (2.7). There were 51 (22.2%) patients with SLICC/ACR Damage Index ≥1 after 12 months, 59 (25.6%) after 24 months and 67 (29.1%) after 36 months. Dyslipidaemia [P = 0.001; hazard ratio (HR) 2.9; 95% CI 1.5, 5.6], older age (P = 0.001; HR 3.0; 95% CI 1.6, 5.5), number of organs/systems involved (P = 0.002; HR 1.4; 95% CI 1.1, 1.8) and cardiorespiratory involvement (P = 0.041; HR 1.9; 95% CI 1.0, 3.7) were independently associated with an increased risk of developing damage. Risk profiles for damage development differed for glucocorticoid-related and -unrelated damage. HCQ use (P = 0.005; HR 0.4; 95% CI 0.2, 0.8) reduced the risk of glucocorticoid-unrelated damage. Conclusion We identified risk factors of damage development, but little effect of glucocorticoids, in this early SLE cohort. Addressing modifiable risk factors from the time of SLE diagnosis might improve patient outcomes.

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 ◽  
...  
Keyword(s):  
Risk Factors ◽  
Univariate Analysis ◽  
Research Support ◽  
Factors Associated ◽  
Negative Culture ◽  
Increased Risk ◽  
Culture Characteristics ◽  
The Mean ◽  
Culture Positive ◽  
Research Grant

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)

Venous Thromboembolism Requiring Extended Anticoagulation Among HIV-Infected Patients in a Rural, Resource-Constrained Setting in Western Kenya

2017 ◽  
Vol 51 (5) ◽  
pp. 380-387 ◽  
Author(s):  
John Kanyi ◽  
Rakhi Karwa ◽  
Sonak Dinesh Pastakia ◽  
Imran Manji ◽  
Simon Manyara ◽  
...  
Keyword(s):  
Risk Factors ◽  
Venous Thromboembolism ◽  
Opportunistic Infections ◽  
Univariate Analysis ◽  
Retrospective Chart Review ◽  
International Normalized Ratio ◽  
Western Kenya ◽  
Adjusted Analysis ◽  
Healthcare Data ◽  
Increased Risk

Background: HIV-infected patients are at an increased risk of developing venous thromboembolism (VTE), and minimal data are available to describe the need for extended treatment. Objective: To evaluate the frequency of and determine predictive risk factors for extended anticoagulation of VTE in HIV-infected patients in rural, western Kenya. Methods: A retrospective chart review was conducted at the Anticoagulation Monitoring Service affiliated with Moi Teaching and Referral Hospital and the Academic Model Providing Access to Healthcare. Data were collected on patients who were HIV-infected and receiving anticoagulation for lower-limb deep vein thrombosis. The need for extended anticoagulation, defined as receiving ≥7 months of warfarin therapy, was established based on patient symptoms or Doppler ultrasound–confirmed diagnosis. Evaluation of the secondary outcomes utilized a univariate analysis to identify risk factors associated with extended anticoagulation. Results: A total of 71 patients were included in the analysis; 27 patients (38%) required extended anticoagulation. The univariate analysis showed a statistically significant association between the need for extended anticoagulation and achieving a therapeutic international normalized ratio within 21 days in both the unadjusted and adjusted analysis. Patients with a history of opportunistic infections required an extended duration of anticoagulation in the adjusted analysis: odds ratio = 3.42; 95% CI = 1.04-11.32; P = 0.04. Conclusions: This study shows that there may be a need for increased duration of anticoagulation in HIV-infected patients, with a need to address the issue of long-term management. Guideline recommendations are needed to address the complexity of treatment issues in this population.

Siblings of patients with rheumatoid arthritis are at increased risk of acute coronary syndrome

2019 ◽  
Vol 78 (5) ◽  
pp. 683-687 ◽  
Author(s):  
Helga Westerlind ◽  
Marie Holmqvist ◽  
Lotta Ljung ◽  
Thomas Frisell ◽  
Johan Askling
Keyword(s):  
Rheumatoid Arthritis ◽  
Risk Factors ◽  
Acute Coronary Syndrome ◽  
General Population ◽  
Cox Regression ◽  
Significant Risk ◽  
Coronary Syndrome ◽  
Risk Increase ◽  
Increased Risk ◽  
The Impact

ObjectivesTo investigate a potential shared susceptibility between rheumatoid arthritis (RA) and acute coronary syndrome (ACS) by estimation of the risk of ACS among full siblings of patients with RA.MethodsBy linking nation-wide Swedish registers, we identified a cohort of patients with new-onset RA 1996–2016, age- and sex-matched (5:1) general population comparator subjects, full siblings of RA and comparator subjects, and incident ACS events through 31 December 2016. We used Cox regression to estimate the HR of ACS among patients with RA and the siblings of patients with RA versus the general population, overall and stratified by RA serostatus. We explored the impact of traditional cardiovascular (CV) risk factors on the observed associations.ResultsWe identified 8109 patients with incident RA, and 11 562 full siblings of these. Compared with the general population, the HR of ACS in RA was 1.46 (95% CI 1.28 to 1.67) and 1.22 (95% CI 1.09 to 1.38) among their siblings. The increased risks seemed confined to seropositive RA (patients: 1.52 [1.30 to 1.79], their siblings: 1.27 [1.10 to 1.46]); no significant risk increase was observed among siblings of patients with seronegative RA (HR 1.13 [95% CI 0.92 to 1.39]). Adjustment for 19 traditional CV risk factors did not appreciably alter these associations.ConclusionSiblings of patients with RA are at increased risk of ACS, suggesting shared susceptibility between RA and ACS, indicating the need and potential for additional cardio-preventive measures in RA (and their siblings).

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