Dashboard-Driven Accelerated Infliximab Induction Dosing Increases Infliximab Durability and Reduces Immunogenicity

2022 ◽  
Author(s):  
Marla C Dubinsky ◽  
Michelle L Mendiolaza ◽  
Becky L Phan ◽  
Hunter R Moran ◽  
Stacy S Tse ◽  
...  
Keyword(s):  
Primary Outcome ◽  
Multivariate Analyses ◽  
C Reactive Protein ◽  
Reactive Protein ◽  
Protocol Population ◽  
Kaplan Meier ◽  
Antidrug Antibody ◽  
Inflammatory Bowel ◽  
The Impact ◽  
Trough Levels

Abstract Background and Aims Accelerated infliximab (IFX) induction is often based on clinical parameters as opposed to pharmacokinetics (PK). We aimed to investigate the impact of dashboard-guided optimized induction dosing on IFX durability and immunogenicity in a real-world inflammatory bowel disease (IBD) setting. Methods Pediatric and adult IBD patients were enrolled in a prospective single arm intervention trial. Cumulative data from each infusion (INF), weight, albumin, C-reactive protein, IFX dose, IFX trough level, and antidrug antibody presence were used to inform subsequent INF dosing. Forecasts driven by adaptive Bayesian modeling were generated to maintain trough levels for the third (INF3) and fourth (INF4) infusions of 17 μg/mL and 10 μg/mL, respectively. The primary outcome was proportion of patients prescribed accelerated dosing (AD) intervals by INF3 (<22 days) or INF4 (<49 days). Secondary outcomes included week 52 clinical and PK outcomes. Multivariate analyses and Kaplan-Meier curves compared outcomes based on adherence to dashboard forecasts. Results Of the 180 per-protocol population, AD was forecast for 41% (INF3) and 69% (INF4) of patients with median intervals of 17 (INF3) and 39 (INF4) days. Baseline age >18 years, albumin >3.5 g/L, and 10-mg/kg dose were independently associated with lower rates of AD by INF4. Nonadherence with the INF4 forecast (n = 39) was an independent predictor of antidrug antibody (P < .0001) and IFX discontinuation (P = .0006). A total of 119 of 123 patients on IFX at week 52 were in steroid-free remission. Conclusions The application of a PK dashboard during induction can optimize dosing early to improve IFX durability and immunogenicity.

scholarly journals Leucine-Rich Alpha-2 Glycoprotein May Be Predictive of the Adalimumab Trough Level and Antidrug Antibody Development for Patients with Inflammatory Bowel Disease: A Sub-Analysis of the PLANET Study

Digestion ◽  
2021 ◽  
pp. 1-9
Author(s):  
Shunichi Yanai ◽  
Shinichiro Shinzaki ◽  
Katsuyoshi Matsuoka ◽  
Shinta Mizuno ◽  
Hideki Iijima ◽  
...  
Keyword(s):  
Trough Level ◽  
Fecal Calprotectin ◽  
Negative Group ◽  
C Reactive Protein ◽  
Multicenter Observational Study ◽  
Reactive Protein ◽  
Antidrug Antibody ◽  
Inflammatory Bowel ◽  
Using Data ◽  
Prospective Multicenter Observational Study

<b><i>Introduction:</i></b> The aim of this study was to examine whether biomarkers are predictive of the adalimumab (ADA) trough level and antidrug antibody development in patients with Crohn’s disease (CD) and ulcerative colitis (UC). <b><i>Methods:</i></b> Using data obtained in a prospective, multicenter, observational study (PLANET), we assessed serial changes in a novel biomarker – leucine-rich alpha-2 glycoprotein (LRG) – during ADA treatment for patients with active CD and UC. We measured serum LRG, C-reactive protein (CRP), and fecal calprotectin (fCAL) at weeks 0, 12, 24, and 52. The ADA trough level and anti-ADA antibody (AAA) were also measured at weeks 12 and 52. Correlations between the ADA trough level, AAA, and biomarkers were examined. <b><i>Results:</i></b> In all, 34 patients with CD and 47 patients with UC were enrolled. The ADA trough level at week 12 or at the time of ADA withdrawal was 8.5 ± 3.9 in the AAA-negative group (<i>n</i> = 70) and 2.9 ± 2.7 μg/mL in the AAA-positive group (<i>n</i> = 8) (<i>p</i> &#x3c; 0.0001). The ADA trough level at week 12 or at the time of ADA withdrawal was associated with pretreatment LRG (<i>p</i> = 0.0437 and <i>r</i> = −0.23). <b><i>Conclusion:</i></b> LRG, rather than CRP or fCAL, may be a marker for predicting the trough level of ADA for patients with CD and UC treated with ADA.

scholarly journals Predictors for inpatient mortality during the first wave of the SARS-CoV-2 pandemic: A retrospective analysis

PLoS ONE ◽  
2021 ◽  
Vol 16 (5) ◽  
pp. e0251262
Author(s):  
Daniel Sammartino ◽  
Farrukh Jafri ◽  
Brennan Cook ◽  
Lisa La ◽  
Hyemin Kim ◽  
...  
Keyword(s):  
Incomplete Data ◽  
Primary Outcome ◽  
Early Death ◽  
Inpatient Mortality ◽  
C Reactive Protein ◽  
Medical Interventions ◽  
Reactive Protein ◽  
Process And Outcome ◽  
The Impact ◽  
Analyze Data

Background The coronavirus disease 2019 (COVID-19) pandemic overwhelmed healthcare systems, highlighting the need to better understand predictors of mortality and the impact of medical interventions. Methods This retrospective cohort study examined data from every patient who tested positive for COVID-19 and was admitted to White Plains Hospital between March 9, 2020, and June 3, 2020. We used binomial logistic regression to analyze data for all patients, and propensity score matching for those treated with hydroxychloroquine and convalescent plasma (CP). The primary outcome of interest was inpatient mortality. Results 1,108 admitted patients with COVID-19 were available for analysis, of which 124 (11.2%) were excluded due to incomplete data. Of the 984 patients included, 225 (22.9%) died. Risk for death decreased for each day later a patient was admitted [OR 0.970, CI 0.955 to 0.985; p < 0.001]. Elevated initial C-reactive protein (CRP) value was associated with a higher risk for death at 96 hours [OR 1.007, 1.002 to 1.012; p = 0.006]. Hydroxychloroquine and CP administration were each associated with increased mortality [OR 3.4, CI 1.614 to 7.396; p = 0.002, OR 2.8560, CI 1.361 to 6.160; p = 0.006 respectively]. Conclusions Elevated CRP carried significant odds of early death. Hydroxychloroquine and CP were each associated with higher risk for death, although CP was without titers and was administered at a median of five days from admission. Randomized or controlled studies will better describe the impact of CP. Mortality decreased as the pandemic progressed, suggesting that institutional capacity for dynamic evaluation of process and outcome measures may benefit COVID-19 survival.

scholarly journals Sarcopenia, severe anxiety and increased C-reactive protein are associated with severe fatigue in patients with inflammatory bowel diseases

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Laura Tasson ◽  
Fabiana Zingone ◽  
Brigida Barberio ◽  
Romina Valentini ◽  
Pamela Ballotta ◽  
...  
Keyword(s):  
Fecal Calprotectin ◽  
Healthy Population ◽  
C Reactive Protein ◽  
Reactive Protein ◽  
Severe Fatigue ◽  
High Prevalence ◽  
Bowel Diseases ◽  
Moderate Fatigue ◽  
Inflammatory Bowel ◽  
Severe Anxiety

AbstractPatients with inflammatory bowel disease (IBD) report fatigue more frequently than healthy population, but the precise mechanisms underlying its presence are unknown. This study aimed to evaluate the prevalence of fatigue in IBD and its relation with potential causative factors. A survey on fatigue, depression, anxiety, sleep disorders, and the presence of sarcopenia and malnutrition, was sent by email to 244 IBD outpatients of the Gastroenterology Unit of Academic Hospital of Padua. Demographics and clinical data, including the levels of fecal calprotectin (FC) and C-reactive protein (CRP), and current pharmacological treatments were obtained from patients’ medical records. Ninety-nine (40.5%) subjects answered the survey. Ninety-two (92.9%) patients reported fatigue, with sixty-six having mild to moderate fatigue and twenty-six severe fatigue. Multivariate analysis showed that abnormal values of CRP (OR 5.1), severe anxiety (OR 3.7) and sarcopenia (OR 4.4) were the factors independently associated with severe fatigue. Fatigue has a high prevalence in subject affected by IBD. Subjects with altered CRP, sarcopenia and severe anxiety appear more at risk of severe fatigue.

scholarly journals POS1012 HOW IMPORTANT WOULD BE THE IMPACT OF SPONDYLOARTHRITIS ON MILITARY POPULATION’S WORKING LIFE?

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 774.2-774
Author(s):  
T. Mehmli ◽  
R. Dhahri ◽  
M. Slouma ◽  
E. Hannech ◽  
B. Louzir ◽  
...  
Keyword(s):  
Ankylosing Spondylitis ◽  
Disease Activity ◽  
Activity Index ◽  
Productivity Loss ◽  
Young Patients ◽  
Work Productivity ◽  
C Reactive Protein ◽  
Reactive Protein ◽  
Military Patients ◽  
The Impact

Background:Spondyloarthritis is a group of chronic inflammatory diseases involving axial and peripheral joints. It mainly affects young patients typically of working age. Therefore, its impact on work outcomes may be considerable particularly in military patients.Objectives:The aim of this study was to evaluate the impact of spondyloarthritis on work ability and productivity in military patients, and to assess relationship between work productivity loss and disease activity.Methods:Thirty Three patients diagnosed with spondyloarthritis in the militay hospital of Tunis were included in the study. Age, gender and C-reactive protein were recorded. Data related to duration of the disease, Ankylosing Spondylitis Disease Activity Score (ASDAS) and Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) were also recorded. Employed patients completed Work Productivity and Activity Impairment (WPAI) questionnaire witch assesses four subscales: presenteism, absenteism, overall work impairemend and daily activity impairement in the 7 past days.Results:Among the thirty three patients, 63 % were men and 37% were women. The average age was 43,7 ± 13,5. The average duration of disease was 8,5 ± 7,75 years. Mean C-Reactive protein was 27,5 ± 39,3. Mean ASDAS and BASDAI were 3,12 ± 1,39 and 4,26 ± 1,78 respectively. 22 patients (66%) had an active disease and 11 (33%)were in remission. 48,4% of patients were using NSAIDs, 48,4% were under DMARDs and 42% were under biologics (12 patients using TNF-alpha blockers and 2 patients were given IL-17 inhibitors). Among this patients, 27 were employed. Three patients (11%) had a total work disability and were retired from work and two have been outplaced.Employed patients worked an average of 35,6 ± 10,3 hours per week and missed an average of 3,48 ± 6,49 hours per week. The mean rates of absenteeism, presenteeism and work productivity loss were 8,8 ± 16,9 %, 48,4 ± 19,9 % and 48,6 ± 19,7 %.There was a statistically significant correlation between BASDAI and work missed hours (p<0,05, r=0,48), absenteeism (p<0,05, r=0,48), presenteeism (p<0,01, r=0,669), work impairement (p<0,01, r=0,669), activity impairement (p<0,05, r=0,475) and work productivity loss (p<0,05, r=0,475), as well as between ASDAS CRP and presenteeism (p<0,05, r= 0,593), work impairement (p<0,05, r=0,593), activity impairement(p<0,05, r=0,460) and work productivity loss (p<0,05, r=0,460). No relation was found between WPAI indexes and C-reactive protein.Conclusion:This study demonstrates that spondyloarthritis has a major impact on military patients’ work productivity with a significant correlation between WAPI indexes and disease activity scores (ASDAS CRP and BASDAI). No relation was found with C-reactive protein.Disclosure of Interests:None declared.

Anti-TNF-α Treatment Reduces the Baseline Procoagulant Imbalance of Patients With Inflammatory Bowel Diseases

2021 ◽  
Author(s):  
Armando Tripodi ◽  
Luisa Spina ◽  
Laura Francesca Pisani ◽  
Lidia Padovan ◽  
Flaminia Cavallaro ◽  
...  
Keyword(s):  
Inflammatory Bowel Diseases ◽  
Coagulation Factors ◽  
Infliximab Treatment ◽  
C Reactive Protein ◽  
Reactive Protein ◽  
Thrombosis Risk ◽  
Bowel Diseases ◽  
Inflammatory Bowel ◽  
Factor Α

Abstract Background Inflammatory bowel diseases (IBD) are characterized by an increased thrombosis risk of uncertain etiology. Coagulation derangement arising from inflammation may be a triggering factor. We hypothesized that strong inflammation inhibitors (eg, anti-tumor necrosis factor-α drugs) may affect coagulation. Methods Forty patients with IBD were compared with 57 control patients for coagulation factors and endogenous thrombin potential (ETP), the latter being the most sensitive marker of in vivo pro- and anticoagulation balance. We measured ETP in the presence and absence of thrombomodulin (the physiologic protein C [PC] activator). Coagulation at different timepoints was also assessed for 28 of these patients during infliximab treatment. Results The median ETP (nM thrombin × minutes) and range (minimum-maximum) were each higher in patients at baseline than in control patients in both the absence (2120 [1611-3041] vs 1865 [1270-2337]) and the presence (1453 [464-2522] vs 831 [104-1741]) of thrombomodulin. The ETP ratio (with/without thrombomodulin) was high at baseline (0.73 [0.21-0.90] vs 0.45 [0.07-0.85]). The ETP and ETP ratio declined during treatment and were significantly lower at the end than at baseline. Factor (F) VIII and fibrinogen, which were high at baseline, decreased during treatment and at the end were significantly lower than at baseline. The FVIII/PC ratio, which was high in patients at baseline, declined during treatment and at the end was lower than at baseline. C-reactive protein recorded at the end of treatment was lower than at baseline. Conclusions Patients with IBD have a procoagulant imbalance as shown by increased ETP at baseline. The ETP decreases during treatment with infliximab, which is related to decreased FVIII and FVIII/PC ratio. This effect is also related to the improvement of inflammation as shown by decreased fibrinogen and C-reactive protein.

scholarly journals The Impact of Diet and Fibre Fractions on Plasma Adipocytokine Levels in Prediabetic Adults

Nutrients ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 487
Author(s):  
Margarita S. Dodevska ◽  
Sladjana S. Sobajic ◽  
Vesna D. Dragicevic ◽  
Ivan Stankovic ◽  
Nevena Dj. Ivanovic ◽  
...  
Keyword(s):  
Dietary Intervention ◽  
Polynomial Regression ◽  
Body Weight Loss ◽  
C Reactive Protein ◽  
Resistin Level ◽  
Reactive Protein ◽  
Obese Subjects ◽  
The Impact ◽  
Necrosis Factor ◽  
Recommended Level

The impact of diet and fibre fractions on adipocytokines in obese subjects with a risk of diabetes has not been investigated in detail yet. The purpose of the study is to evaluate the effects of a 12-month lifestyle intervention with different fibre profiles (resistant starch (RS)—rich fibre, or ordinary food fibre profiles) on adipocytokine levels. Fifty participants are divided into two groups (RS group and Fibre group). The groups differ only in the percentage of the recommended level of the RS consumed as a fraction of the same total fibre amount. The applied dietary intervention includes intake of 7531 KJ/daywith a total fibre portion of 25–35 g/dayfor both groups that includes 15 g/day of RS for the RS group only. The levels of leptin, adiponectin, apelin, resistin, tumor necrosis factor (TNF)-alpha and C-reactive protein (CRP) are measured, and their relationship to anthropometric and biochemical parameters is estimated. Along with significant body weight loss, only leptin is significantly reduced by 13% in the RS group while in the Fibre group, apelin levels are significant (−21%). Polynomial regression shows a negative correlation between RS intake and adiponectin (R2 = 0.145) and resistin level (R2 = 0.461) in the RS group. This study indicates the possibility that fibre fractions differently influence the outcome of lifestyle interventions, as well as their adipocytokine levels, in obese prediabetic adults.

scholarly journals Impact of Matrix Metalloproteinase-9 during Periodontitis and Cardiovascular Diseases

Molecules ◽  
2021 ◽  
Vol 26 (6) ◽  
pp. 1777
Author(s):  
Gaetano Isola ◽  
Alessandro Polizzi ◽  
Vincenzo Ronsivalle ◽  
Angela Alibrandi ◽  
Giuseppe Palazzo ◽  
...  
Keyword(s):  
Matrix Metalloproteinase ◽  
Healthy Subjects ◽  
Multivariate Regression Analysis ◽  
Matrix Metalloproteinase 9 ◽  
C Reactive Protein ◽  
Reactive Protein ◽  
Hs Crp ◽  
The Impact ◽  
Negative Predictor ◽  
Metalloproteinase 9

Matrix metalloproteinase-9 (MMP-9) has been shown to play a key role in endothelial function and perhaps pivotal in the correlation between periodontal disease and cardiovascular disease (CVD). For the study, the impact of MMP-9 of periodontitis and CVD on serum and saliva concentrations was analyzed. For the study patients with periodontitis (n = 31), CVD (n = 31), periodontitis + CVD (n = 31), and healthy patients (n = 31) were enrolled. Clinical and demographic characteristics as well as serum and salivary MMP-9 were evaluated. MMP-9 concentrations in serum and saliva were statistically elevated in patients with CVD (p < 0.01) and in patients with periodontitis plus CVD (p < 0.001) compared to patients with periodontitis and healthy subjects. Multivariate regression analysis showed that c-reactive protein (hs-CRP) was the only significant predictor for MMP-9 serum (p < 0.001), whereas hs-CRP (p < 0.001) and total cholesterol (p = 0.029) were the statistically significant salivary MMP-9 predictors. This study evidenced that patients with CVD and periodontitis + CVD presented elevated MMP-9 concentrations in serum and saliva compared to patients with periodontitis and healthy subjects. Furthermore, hs-CRP was a negative predictor of serum and salivary MMP-9.

scholarly journals Fecal Calprotectin, CRP and Leucocytes in IBD Patients: Comparison of Biomarkers With Biopsy Results

2020 ◽  
Author(s):  
Barry D Kyle ◽  
Terence A Agbor ◽  
Shajib Sharif ◽  
Usha Chauhan ◽  
John Marshall ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Fecal Calprotectin ◽  
Dependent Manner ◽  
Ascending Colon ◽  
C Reactive Protein ◽  
Concentration Dependent Manner ◽  
Reactive Protein ◽  
Inflammatory Bowel ◽  
Descending Colon ◽  
Active Inflammation

Abstract Background This study aimed to compare fecal calprotectin (FC) levels with other commonly used parameters as part of patient care during evaluation for inflammatory bowel disease (IBD). Methods We recruited adult IBD patients with ulcerative colitis (UC) and Crohn’s disease (CD) and compared the results of the patient’s biopsy results (i.e., inflamed versus noninflamed) for six sites (i.e., ileum, ascending colon, transverse colon, descending colon, sigmoid colon, rectum) with concentrations of C-reactive protein (CRP), total leucocytes and fecal calprotectin (FC). Results We found that FC was significantly elevated in a concentration-dependent manner that correlated with the number of active inflammation sites reported in biopsy. Although CRP and leucocyte measurements trended upwards in line with inflammation reported from biopsy, the results were highly variable and highlighted poor reliability of these biomarkers for indicating IBD inflammation. Conclusions These results strongly suggest that FC correlates best with biopsy reports and is a superior marker than CRP and leucocytes.

Abstract P181: Contribution of C-Reactive Protein to Racial Disparities in Incident Hypertension: The REasons for Geographic And Racial Differences in Stroke Study (REGARDS)

Circulation ◽  
2018 ◽  
Vol 137 (suppl_1) ◽  
Author(s):  
Timothy B Plante ◽  
D L Long ◽  
George Howard ◽  
April P Carson ◽  
Virginia J Howard ◽  
...  
Keyword(s):  
Racial Differences ◽  
Medication Use ◽  
Dietary Factors ◽  
C Reactive Protein ◽  
Incident Hypertension ◽  
Black And White ◽  
Reactive Protein ◽  
Stroke Study ◽  
Diet Pattern ◽  
The Impact

Introduction: In the US, blacks are at higher risk of hypertension than whites. The single largest contributor to this disparity is the Southern Diet pattern. Inflammation biomarkers are associated with risk of hypertension, and C-reactive protein (CRP) is higher in blacks than whites. We studied whether elevated CRP in blacks relative to whites contributes to the racial disparity in hypertension in blacks. Methods: We included 6,548 black and white men and women age ≥45 years from the REGARDS cohort without hypertension at baseline ('03-'07) and who completed visit 2 in '13-'16. Incident hypertension was defined as BP ≥140/90 mm Hg or hypertension medication use at visit 2. Using logistic regression, the black:white odds ratio (OR) for incident hypertension was calculated adjusting for age, sex, race, and baseline SBP. We assessed the percent change in the black:white OR for incident hypertension after adding CRP. The 95% CI was calculated using 1,000 bootstrapped samples. We determined the impact of known hypertension risk factors and anti-inflammatory medications on the percent mediation by CRP. Results: Hypertension developed in 46% of blacks and 33% of whites. Adjusting for demographics, the black:white OR (95% CI) was 1.51, which was reduced to 1.46, a 9.3% reduction (95% CI 5.4%, 13.2%) by CRP (Table). In models including exercise, waist circumference, BMI, and depressive symptoms, the percent mediation by CRP was 3.7% (1.0%, 6.4%). Similar patterns were seen for models incorporating socioeconomic factors and medication use. After adding Southern diet pattern and dietary Na/K ratio, CRP no longer attenuated the association (1.3% mediation; -1.5, 4.1). Conclusions: CRP significantly attenuated the black-white difference in incident hypertension; however, once dietary factors were accounted for, CRP had no impact on the black:white difference in incident hypertension. Thus, inflammation as measured by CRP, may be part of the reason that dietary factors influence the black:white disparity in incident hypertension.

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