Super Responders Research Articles

Super and Nonresponders to Catheter Ablation for Atrial Fibrillation: A Quality-of-Life Assessment Using Patient Reported Outcomes.

[Figure: see text].

Clinical implications and predictive values of early PASI responses to tildrakizumab in patients with moderate-to-severe plaque psoriasis

Objective To evaluate whether early Psoriasis Area Severity Index (PASI) improvements can predict week 28 tildrakizumab responders and nonresponders. Methods Psoriasis patients pooled from two tildrakizumab phase 3 trials randomized to receive tildrakizumab 100 mg at weeks 0, 4, 16, and 28 were included. Patients were grouped by week 28 PASI responses (<50, 50–74, 75–89, and 90–100). PASI improvements from baseline at weeks 4 and 16 were analyzed for each response group. Results Of 575 patients included, 8.3%, 14.3%, 23.8%, and 53.6%, respectively, achieved PASI <50, 50–74, 75–89, and 90–100 at week 28. Of patients with PASI <50 at week 16, 85% did not achieve PASI ≥75 at week 28 (nonresponders). Rapid response, defined as PASI ≥50 at week 4 (after a single tildrakizumab dose), was observed in 41% of patients. Of these patients, 87% were week 28 responders (PASI ≥75); 67% were ‘super responders’ (PASI 90–100). Among week 28 responders and super responders, 45% and 50% achieved PASI ≥50 at week 4, respectively. Conclusions Tildrakizumab week 28 nonresponders can be identified by week 16 PASI response. PASI improvements as early as week 4 can predict patients’ week 28 PASI improvement status.

66361 TL1 Team Approach to Predicting Response to Spinal Cord Stimulation for Chronic Low Back Pain

ABSTRACT IMPACT: Understanding how spinal cord stimulation works and who it works best for will improve clinical trial efficacy and prevent unnecessary surgeries. OBJECTIVES/GOALS: Spinal cord stimulation (SCS) is an intervention for chronic low back pain where standard interventions fail to provide relief. However, estimates suggest only 58% of patients achieve at least 50% reduction in their pain. There is no non-invasive method for predicting relief provided by SCS. We hypothesize neural activity in the brain can fill this gap. METHODS/STUDY POPULATION: We tested SCS patients at 3 times points: baseline (pre-surgery), at day 7 during the trial period (post-trial), and 6 months after a permanent system had been implanted. At each time point participants completed 10 minutes of eyes closed, resting electroencephalography (EEG) and self-reported their pain. EEG was collected with the ActiveTwo system and a 128-electrode cap. Patients were grouped based on the percentage change of their pain from baseline to the final visit using a median split (super responders &gt; average responders). Spectral density powerbands were extracted from resting EEG to use as input features for machine learning analyses. We used support vector machines to predict response to SCS. RESULTS/ANTICIPATED RESULTS: Baseline and post-trial EEG data predicted SCS response at 6-months with 95.56% and 100% accuracy, respectively. The gamma band had the highest performance in differentiating responders. Post-trial EEG data best differentiated the groups with feature weighted dipoles being more highly localized in sensorimotor cortex. DISCUSSION/SIGNIFICANCE OF FINDINGS: Understanding how SCS works and who it works best for is the long-term objective of our collaborative research program. These data provide an important first step towards this goal.

Diastolic dyssynchrony in patients with LV only fusion pacing CRT without RV lead

Abstract Funding Acknowledgements Type of funding sources: None. Background CRT improves both systolic and diastolic function, thus increasing cardiac output. However, less data is available concerning diastolic dyssynchrony and fusion pacing CRT. The aim of our study was to assess the outcome of LV diastolic asynchrony in a population of fusion pacing CRT without right ventricular (RV) lead. Methods Prospective data were collected from a cohort of patients (pts) with right atrium/left ventricle leads (RA/LV CRT). Baseline and every 6 months follow-up included standard ETT and classical dyssynchrony parameter measurements. Diastolic dyssynchrony was done by offline speckle-tracking derived TDI timing assesment of the simultaneity of E" and A" basal septal and lateral wall 4 chamber view. New parameters were introduced: E" and respectively A" time (E"T / A"T) as the time difference between E" (respectively A" ) peaks septal and lateral wall. Exercise tests, drugs optimization and device individual programmimg were systematically performed in order to maintain constant fusion and improve CRT response. Patients were divided in three groups: super-responders (SR), responders (R) and non responders (NR). Results Sixty-two pts (35 male) aged 62 ± 11 y.o. with idiopathic DCM implanted with a RA/LV CRT were analyzed: 34%SR / 61%R / 5%NR. Baseline initial characteristics: QRS 164 ± 18 ms; EF 27 ± 5.2; 29% had type III diastolic dysfunction (DD), 63% type II DD, 8% type I DD. Average follow-up was 45 ± 19 months; mean LVEF at the last follow-up was 37 ± 7.9%. The E"T decreased from 90 ± 20 ms to 25 ± 10 ms in SR with significant LV reverse remodelling (LV end-diastolic volume 193.7 ± 81 vs 243.2 ± 82 ml at baseline, p &amp;lt; 0.0028) and lower LV filling pressures (E/E" 13.2 ± 4.6 vs 11.4 ± 4.5, p =0.0295). DD profile improved in 65% of R with a reduction in E/A ratio (1.46 ± 5.3 vs. 0.82 ± 3.9 at baseline, p= 0.4453). Non-sudden cardiac death occurred in 3 NR pts (2%) with type III DD, severe LA volume and larger E" T /A"T (E"T&amp;gt; 85 msec A"T &amp;gt; 30 msec). Significant cut off value calculated by ROC curve for LV diastolic dyssynchrony is E"T &amp;gt; 80 ms and A"T of &amp;gt; 25 msec. Conclusions Fusion pacing CRT without RV lead showed a positive outcome; improving LV diastolic dyssynchrony in responders and super-responders patients is obvious. Larger randomized studies are needed to define the role of diastolic asynchronism as a predictor of favorable response in fusion pacing. Abstract Figure. Typical TDI patterns in LV fusion pacing

What can we learn from hyper-responders to cardiac resynchronisation therapy (CRT)? Characteristics and predictors of super response to CRT. An Algerian single centre experience

In some patients with dilated cardiomyopathy (DCM) and left bundle branch block (LBBB), cardiac resynchronisation therapy (CRT) has been shown to reverse almost completely left ventricular (LV) function. Determine the proportion of super responders among patients with DCM and attempt to determine their profile. Consecutive patients with DCM (LV ejection fraction (LVEF) < 35%, LV end-diastolic diameter > 60 mm) and LBBB implanted with a CRT were prospectively followed. Patients were considered super-responders if they fulfilled two criteria: class NYHA I/II and LVEF ≥ 50%. Among the 98 DCM patients, 19 (19.5%) were found to be super-responders following CRT (LVEF increased from 29.89 ± 4.44 to 53.37 ± 3.76%, P < 0.001). In the 79 (81%) remaining patients, there was a significant increase in LVEF from 26.49 ± 4.67 to 37.27 ± 7.20, P < 0.001). At baseline, there were no significant differences between super-responders and other patients, except that super-responders were female, had no hospitalisation for heart failure before implantation and no renal deficiency. Super responders had also less severe LVEF and lower pulmonary artery systolic pressure. CRT-P (OR: 5.47; 95% CI: 1.48–20.27; P = 0.007), lower left ventricular end-diastolic dimension (OR: 0.97; 95% CI: 0.95–0.0.99; P = 0.0002) and lower pulmonary artery systolic pressure (OR: 0.92; 95% CI: 0.87, 0.96; P < 0.001) were independent predictors of super-response to CRT (see Table 1 ). Among patients with DCM and LBBB, Patients in earlier phases of the cardiomyopathy, with a less altered ventricular geometry, seem to have a greater probability of becoming super-responders.

15280 Characterization of super responders to guselkumab treatment in moderate to severe psoriasis: Results from the VOYAGE 1 and 2 clinical trials

Background: Guselkumab (GUS) is effective in treating moderate to severe psoriasis. Here, we characterized the baseline profile of patients with moderate to severe psoriasis achieving superresponse (defined as patients who achieved a Psoriasis Severity and Area Index [PASI] 100 response at both weeks 20 and 28) with GUS treatment.

Symptomatic endpoint responder rates to BAROSTIM Therapy

Abstract Background Patients with heart failure with reduced ejection fraction (HFrEF) have varying responses to symptomatic endpoints with device-based HF therapies. Purpose Evaluate the symptomatic response to baroreflex activation therapy (BAT) at six months. Methods In a trial of subjects with NYHA Class II (recently III) or III HFrEF, left ventricular EF≤35%, guideline directed medical HF therapy (GDMT), no indication for cardiac resynchronization therapy, and NT-proBNP&amp;lt;1600 pg/ml, 264 subjects were randomized to BAROSTIM therapy plus GDMT (BAT group) or GDMT alone (Control group). Six-minute hall walk (6MHW), Minnesota Living with HF (QOL) and NYHA Class were analyzed. Clinically relevant responders were defined by 6-month improvement in 6MHW&amp;gt;10%, QOL&amp;gt;5 points or improvement in at least one NYHA class; super responders were defined by 6-month improvement in 6MHW&amp;gt;20%, QOL&amp;gt;10 points or improvement to NYHA class I. Results Both clinically relevant and super responders were significantly higher in BAT versus Control subjects for all symptomatic endpoints. In BAT subjects, 72% had clinically relevant improvements in ≥2 endpoints compared to 29% of Control subjects (p&amp;lt;0.001), and 28% of BAT subjects had super responder improvements in ≥2 endpoints versus 10% of Control subjects (p&amp;lt;0.001). Conclusion Among subjects with symptomatic HFrEF, treatment with BAT resulted in clinically relevant and super responder rates. The BAT clinically relevant and super responder rates are similar to those seen with CRT, in CRT-indicated patients. Funding Acknowledgement Type of funding source: Private company. Main funding source(s): CVRx, Inc.

A novel non-invasive electrical synchrony method to improve cardiac resynchronization therapy responders

Abstract Introduction Cardiac resynchronization therapy (CRT) has emerged as an important treatment for patients with heart failure and reduced ejection fraction (EF) despite optimal pharmacological therapy. Some studies showed non-responders rate near 30%. Nowaday there is no gold standard method for selection, evaluation and follow up on this group of patients. Multiple techniques used and operator dependence made echocardiogram failed. Synchromax 2 is a device designed to evaluate non-invasive electrical synchrony. It is fast, reproducible and non-operator dependent. Synchromax was evaluated and correlated with other techniques in previous studies. Objective Evaluate CRT response rate guided by electrical synchrony during the device implantation and follow up. Material and methods 43 patients were evaluated in an institution in Buenos Aires. A ICD-CRT was implanted in all patients due dilated cardiomyopathy, low EF (less than 35%) and left bundle branch block (LBBB). Non-invasive electrical synchrony evaluation (Synchromax 2) was performed in all patients in baseline condition, during device implantation and the follow up. Synchrony index and curves were analyzed. Curve type 4 and index between 0,4 and 0,7 were considered synchronous. Curve type 6 and 10 and index more than 0.7 were considered disynchronous. Interventricular intervals were modified to achieve the best curve and synchrony index. Super responders were considered when EF increased &amp;gt;50%. Baseline and 6 month after implantation echocardiogram were performed. Results Mean age 64 years. 39% females. Non-coronary dilated cardiomyopathy was main aetiology (63,1%). EF baseline average was 27%. A baseline index more than 0,7 was in 73,3% of the patients. Curve 6 was the most frequent (55,2%). Follow up average EF was 39% (increased 12%), the super responders rate was 18,6% (8 patients). Type 4 curve and index between 0,4 and 0,7 were achieved in 28 cases (65,1%). EF increased from 23% (baseline) to 42% (follow up). Average 19%. Type 4 curve was not achieved in 15 patients (34,9%). In this group, EF increased from 29% (baseline) to 34% (follow up). Average 5%. Conclusion Electrical synchrony evaluation using Synchromax 2 during ICD-CRT device implantation improves responders rate. When synchronous type 4 curve is achieved EF improves significantly. If type 4 curve is not found results will be unsuccessfully. Synchromax is fast, simple and non-operator dependent. Funding Acknowledgement Type of funding source: None

Long-Term Therapy Response to Anti–IL-5 Biologics in Severe Asthma—A Real-Life Evaluation

Patients with severe eosinophilic asthma show different responses to various anti-IL-5 biologics, ranging from super response to nonresponse. Residual disease manifestations observed in partial responders may prompt physicians to switch between biologics. More data on response, switches, and residual disease manifestations are needed to improve personalized treatment. To assess (1) prevalences and predictors of super, partial, and nonresponders to long-term anti-IL-5 treatment, (2) frequency and reasons for switches between anti-IL-5 biologics, and (3) nature of residual disease manifestations. In this 2-year follow-up study, patients with severe asthma were included who initiated an anti-IL-5 biologic (mepolizumab, reslizumab, benralizumab) (n= 114). Patient characteristics (clinical, functional, inflammatory) and comorbidities were collected at baseline and 2-year follow-up. "Super responders" showed no residual disease manifestations at 2-year follow-up, "partial responders" experienced residual disease manifestations, and "nonresponders" discontinued anti-IL-5 treatment after less than 2 years because of clinical worsening. After 2-year anti-IL-5 treatment, 14% of patients were super responders, 69% partial responders, and 11% nonresponders. Super response was predicted by shorter asthma duration and higher FEV1, and tended to be associated with adult-onset asthma, absence of nasal polyps, and lower body mass index. Switches between anti-IL-5 biologics occurred frequently (41%). After 2-year treatment, most common residual disease manifestations included impaired lung function (59%), uncontrolled sinonasal disease (58%), and uncontrolled asthma symptoms (48%). After 2 years of anti-IL-5 treatment, a favorable response was found in 83% of patients with severe asthma, including a super response in 14%. Most partial responders show impaired lung function or uncontrolled sinonasal disease, causing physicians to switch between biologics.

ENSIFENTRINE ADDED TO TIOTROPIUM OVER 4 WEEKS PROVIDES ADDITIONAL IMPROVEMENT IN COPD QUALITY OF LIFE

SESSION TITLE: Obstructive Lung Disease Posters SESSION TYPE: Original Investigation Posters PRESENTED ON: October 18-21, 2020 PURPOSE: Ensifentrine (RPL554) is an investigational, first-in-class, inhaled dual inhibitor of PDE 3 and 4 that combines bronchodilator and anti-inflammatory actions in a single compound. Results from a dose-ranging study demonstrated that twice-daily nebulised ensifentrine delivered clinically meaningful and significant improvements vs placebo (tiotropium) in lung function and quality of life when added to once-daily tiotropium over 4 weeks. This abstract reports on the effect on quality of life (St. George’s Respiratory Questionnaire for COPD patients; SGRQ-C) of ensifentrine when added to tiotropium. METHODS: This double-blind, placebo-controlled, parallel-group study enrolled COPD patients 40-80 years old, current and former smokers with a smoking history of ≥10 pack years, post-albuterol FEV1 30-70% predicted and FEV1/FVC ≤0.7. Following a 2-week run-in on tiotropium, symptomatic patients (mMRC≥2) with FEV1 30-70% predicted were randomized to receive once-daily tiotropium (Spiriva® Respimat®) plus nebulised ensifentrine (0.375, 0.75, 1.5, or 3 mg) or placebo twice daily for 4 weeks. SGRQ-C responses were collected at randomization and weeks 2 and 4. Means were calculated for the total and sub-domain scores and responder analyses for the proportion of patients that met specific minimal clinically important difference (MCID) were performed. RESULTS: Clinically meaningful and statistically significant improvements in SGRQ-C were observed over tiotropium alone (placebo), exceeding the MCID of 4 units at week 4 with the placebo-corrected change from baseline for the highest doses (1.5 mg: -4.755, p=0.0121; 3 mg: -4.047, p=0.0328). Placebo-corrected change from baseline in week 4 SGRQ-C subscales scores showed significant improvements in the impacts (1.5 mg: -4.396, p=0.0328; 3 mg: -4.981, p=0.0164) and activity (3 mg: -5.141, p=0.0466) scores. A week 4 analysis in patients that improved by at least 4, 8 and 12 units showed higher proportion of responders with at least 4 and 8 units improvement. However, in the analysis for responders with at least 12 units improvement, the difference was much more pronounced in favor of ensifentrine (0.375 mg: 24.3%, p= 0.0119; 0.75 mg: 12.9%; 1.5 mg: 13.9%; 3 mg: 20.5%) compared to placebo (tiotropium alone, 9.8%). CONCLUSIONS: Combined with a significant and clinically meaningful bronchodilator effect, ensifentrine also shows positive trends in COPD symptoms, activity and impacts related to COPD when added onto tiotropium, including a marked improvement in SGRQ-C Total Score of ≥12 units (so-called super responders) in >20% of patients treated with ensifentrine 3 mg added on to tiotropium compared to less than 10% in patients treated with placebo + tiotropium. CLINICAL IMPLICATIONS: Data demonstrates that ensifentrine added to tiotropium over 4 weeks provides additional improvement in COPD quality of life in symptomatic COPD patients. DISCLOSURES: Consultant relationship with Verona Pharma Please note: $5001 - $20000 Added 06/01/2020 by Thomas Bengtsson, source=Web Response, value=Consulting fee Employee relationship with Verona pharma Please note: >$100000 by Tara Rheault, source=Admin input, value=Stock Employee relationship with Verona Pharma Please note: >$100000 Added 05/20/2020 by Kathleen Rickard, source=Web Response, value=Salary

Aqueous Cytokine Expression and Higher Order OCT Biomarkers: Assessment of the Anatomic-Biologic Bridge in the IMAGINE DME Study

To identify biomarkers for predicting response to anti-vascular endothelial growth factor (VEGF) therapy in diabetic macular edema (DME) and evaluate any links between cytokine expression and optical coherence tomography (OCT) phenotype. The IMAGINE is a post hoc image analysis and cytokine expression assessment of the Efficacy & Safety Trial of Intravitreal Injections Combined With PRP for CSME Secondary to Diabetes Mellitus (DAVE) randomized clinical trial. Subjects were categorized as anatomical responders or nonresponders, and within the responder group as rebounders and non-rebounders based on quantitative, longitudinal OCT criteria. Retinal layer and fluid features were extracted using an OCT machine-learning augmented segmentation platform. Responders were further sub-classified by rapidity of response. Aqueous concentrations of 54 cytokines were measured at multiple timepoints. Expression was compared between responder groups and correlated with OCT imaging biomarkers. Of the 24 eyes studied, 79% were anatomical responders with 38% super responders, 17% early responders, and 25% slow responders. Twenty-one percent were nonresponders. Super responders had increased baseline vascular endothelial growth factor (VEGF) (880.0 pg/mL vs 245.4 pg/mL; P= .012) and decreased monocyte chemotactic protein-1 (MCP-1) (513.3 pg/mL vs 809.5 pg/mL; P= .0.042) concentrations compared with nonresponders. Interleukin-6 (-24.9 pg/mL vs 442.8 pg/mL; P= .032) concentrations increased among nonresponders during therapy. VEGF concentrations correlated with central subfield thickness (r= 0.49; P= .01). Panmacular retinal volume correlated with increased interleuckin-6 (r= 0.47; P= .02) and decreased MCP-1 (r=-0.45; P= .03). Matrix metallopeptidase-1 correlated with subretinal fluid volume (r= 0.50; P= .01). OCT imaging biomarkers correlated with both intraocular cytokines and responsiveness to anti-VEGF therapy, which indicated a possible link to underlying pathways and their relevance to DME prognosis. Baseline concentrations of VEGF and MCP-1 are associated with anatomic response to anti-VEGF therapy.

Real-World Effectiveness of Benralizumab in Severe Eosinophilic Asthma

Benralizumab is an IL5-receptor monoclonal antibody licensed for the treatment of severe eosinophilic asthma (SEA). It has demonstrated efficacy in clinical trials in reducing asthma exacerbation rates and maintenance oral corticosteroids (mOCSs). What is the real-world effectiveness of benralizumab and what baseline characteristics are associated with response to therapy? We assessed outcomes in all SEA patients who began benralizumab treatment at our specialist center. At each dosing visit, exacerbation history, mOCS dose, spirometry, and Asthma Control Questionnaire (ACQ6) and Mini-Asthma Quality of Life Questionnaire (mAQLQ) scores were recorded. Response to treatment was defined as a reduction of≥ 50%in annualized exacerbation rate (AER) or in mOCS dose after 48weeks of treatment. Super response was defined as zero exacerbations and no mOCSs for asthma. One hundred thirty patients were included in the analysis. At 48weeks, a 72.8%reduction in AER was noted, from 4.92 ± 3.35 per year in the year preceding biologic treatment to 1.34 ± 1.71 per year (P< .001), including 57 patients (43.8%) who were exacerbation-free with benralizumab. In those receiving mOCSs (n= 74 [56.9%]), the median daily prednisolone dose fell from 10mg (interquartile range, 5-20mg) to 0mg (interquartile range, 0-5mg; P< .001), and 38 of 74 patients (51.4%) were able to discontinue mOCS therapy. Clinically and statistically significant improvements were found in ACQ6 scores, mAQLQ scores, and FEV1. Overall, 51 patients (39%) met the super responder definition and 112 patients (86%) met the responder definition. The optimal regression model of super responders vsother responders included baseline characteristics associated with a strongly eosinophilic phenotype and less severe disease. Eighteen patients (13.8%) were nonresponders to benralizumab. Evidence of chronic airway infection was observed in 6 of 18 patients, and an increase in the blood eosinophil count consistent with the development of anti-drug antibodies was observed in 5 of 18 patients. In a large real-world SEA cohort, benralizumab led to significant improvements in all clinical outcome measures. A lack of response was seen in a minority of patients and should be a focus for future investigation.

Relationship of septal flash with electromechanical dyssynchrony and super-response to cardiac resynchronization therapy

Objectives - to identify a relationship of septal flash (SF) with a super-response to cardiac resynchronization therapy (CRT), apical rocking (AR) and signs of left bundle brunch block (LBBB) in patients with congestive heart failure (CHF). Material and methods. The study included 38 patients (92.1% men; mean age 54.3±9.4 years) with II-IV NYHA functional class CHF. Left bundle brunch block (LBBB) was diagnosed according to 3 criteria: American Heart Association (AHA) 2009, European Society of Cardiology (ESC) 2013, Strauss. Septal flash (SF, mechanical anomaly of interventricular septum (IVS) movement) is determined according to speckle tracking echocardiography (STE) and tissue Doppler imaging (TDI). The patients were divided into two groups: with SF (I group, n=8) and without SF (II group, n=30). Mean follow-up was 34.5 [13.8;55.3]. Results. At baseline the groups did not differ in main clinical characteristics including QRS. The left ventricular (LV) ejection fraction (EF) was higher in group I (33.1%±1.7 and 30.0%±4.0; p=0.044). Basal segment of IVS longitudinal strain (LS) delay by STE (258.0 [144.0;294.0] ms vs 323.5 [273.3;385.0] ms; р=0.024) and LS delay by TDI (176.0 [146.8;287.3] ms vs 415.5 [315.8;493.5] ms; р30%); 53.1% of patients in group II were super responders (р

A retrospective study evaluating clinical and molecular predictors of duration of response (DoR) to immune checkpoint inhibitors (ICI) in patients with advanced non-small cell lung cancer (NSCLC).

e21581 Background: ICI with/without chemotherapy has become the standard of care for the treatment of advanced NSCLC. Little is known about the clinical and molecular predictors of DoR to these agents. We previously reported clinical predictors of DoR to ICI in NSCLC patients (pts). Here we report the correlation of molecular alterations with DoR and clinical/molecular characteristics of super responders (DoR ≥ 2yr) to ICI. Methods: A retrospective chart review of pts with advanced NSCLC treated with ICI based therapy between 2015-2018 at Karmanos Cancer Institute was conducted. Clinical, tumor, and molecular characteristics data were collected. DoR was grouped into: &lt; / = 6 weeks, &gt; 6weeks-6months, &gt; 6mo-1yr, &gt; 1yr, and super responders. Results: Of 147 pts, 68% had adenocarcinoma, 61% received prior radiation, 21% had brain metastasis (mets), 26% developed irAEs, 33% were on statin, 27% were on aspirin, 83% were current or former smokers, 55% had right sided primary tumor, ICI was 1st line treatment (tx) in 20% and 2nd line tx in 52%. Overall median DoR was 168 days (95% CI, 132-231 days). Pts with right sided primary tumors and those who received ICI as 1st line tx had longer DoR (p = 0.012 and p = 0.017; respectively). Other aforementioned covariates, including brain mets, had no significant relationship with DoR. Molecular profile (MP) of 592 genes was available for 57 (38.8%) pts. PD-L1 ≥50%, CDKN2A and NOTCH1 mutations were associated with statistically significant longer DoR. Mutations/alterations in EGFR, ALK, ROS1, MET, RET, HER2, KRAS, STK11 and TP53 did not appears to have an impact on the DoR, although some of the analysis was limited because of very small number of pts. Of the 10 super responders, majority had adenocarcinoma, received prior radiation and were current/former smokers. Two had brain mets. Most did not have concurrent use of anti-inflammatory agents (statin or ASA). Only 2 of the super responders had MP available with negative NOTCH1 and CDKN2A mutations. Conclusions: Receiving ICI as 1st line of therapy and having right sided primary tumors predicted longer DoR. Presence of brain mets did not adversely affect the DoR. Super responders were more likely to have adenocarcinoma, prior radiation therapy, and current/former smoking history. PD-L1 expression ≥ 50%, CDKN2A, and NOTCH1 were associated with longer DoR. Presence of actionable genomic alterations, STK11, KRAS and TP53 did not appear to impact DoR to ICI.

Real-World Effectiveness and the Characteristics of a “Super-Responder” to Mepolizumab in Severe Eosinophilic Asthma

Mepolizumab was the first licensed anti-IL5 monoclonal antibody for severe eosinophilic asthma (SEA). To date there are few data to confirm its efficacy in the real-world setting or assessment of baseline characteristics associated with response. How do patients with severe eosinophilic asthma respond to mepolizumab in the real world setting and which characteristics are associated with a super-response to this therapy? We conducted a retrospective review of all patients who received at least 16weeks of treatment with mepolizumab (100mg subcutaneously) for SEA at our regional asthma center in the United Kingdom. Clinical data were collected at each 4-week visit. At 16, 24, and 52weeks, patients were classified as "responders" or "nonresponders." A response was defined as≥50%reduction in exacerbations; for patients whose condition requires maintenance oral corticosteroids (mOCS), a response was defined as≥50%reduction in prednisolone dose. Super responders were defined as exacerbation-free and off mOCS at one year. Ninety-nine patients were included in the analysis. Asthma exacerbations decreased from a baseline of 4.04 ± 2.57 to 1.86 ± 2.17 per year at one year (54%reduction; P< .001). Sixty-eight patients were receiving mOCS at the time of commencing mepolizumab. By one year, the daily median dose fell from 10mg (interquartile range, 10 to 15) to 0mg (interquartile range, 0 to 10; P< .001). Fifty-seven percent of them were able to discontinue mOCS; 72.7%(95%CI, 63.0 to 80.7) of the patients were classified as responders, and 28.3%(95%CI, 20.2 to 38.0) of the patients were classified as super responders. Baseline characteristics associated with responder and super responder status included the presence of nasal polyposis (P= .012), lower baseline Asthma Control Questionnaire 6 (P= .006), a lower BMI (P= .014), and, in those patients receiving mOCS, a significantly lower prednisolone dose at baseline (P= .005). At 16weeks, the one-year responder status was correctly identified in 80.8%patients; by 24weeks, this status rose to 92.9%. In a real-world SEA cohort, treatment with mepolizumab reduced exacerbation frequency and mOCS requirements. Nasal polyposis, a lower BMI, and a lower maintenance prednisolone requirement at baseline were associated with better outcomes. Twelve-month response was identifiable in >90%of patients by week24.

Plasma Galectin-3 and urine proteomics predict FEV1 improvement in omalizumab-treated patients with severe allergic asthma: Results from the PROXIMA sub-study

BackgroundPatients with severe allergic asthma (SAA) when treated with omalizumab may exhibit different extent of response. Identifying biomarkers that can predict the extent of treatment effectiveness in patients can be useful in personalizing omalizumab treatment. MethodsPatients from the longitudinal phase of the PROXIMA study were selected for this ancillary study. After 12 months of omalizumab treatment, patients were categorized according to their response to treatment as: "clinical responder" (Asthma Control Questionnaire [ACQ] total score <1 at Month 12 and/or with a reduction in number of exacerbation versus the previous year); "functional responder" (an increment of ≥0.1 L in forced expiratory volume in 1 s [FEV1] at Month 12 versus baseline); and "super responder" (among clinical responders group, who also showed a functional response). Plasma galectin-3 (GAL-3) levels were quantified using a micro titer plate-based enzyme linked immunosorbent assay kit. ResultsThe Majority of patients (86.36%) in sub-study population were identified as clinical responders. Of the total patients identified as clinical responders, 64.86% were identified as super responders. A statistically significant difference in the baseline plasma GAL-3 levels between responders and non-responders was observed only in the functional responders group (P = 0.0446). Patients with plasma GAL-3 level of ≥11 ng/mL had a greater probability of being a super responder (P = 0.0118) or a functional responder (P = 0.0032). ConclusionOur findings support the use of plasma GAL-3 as a predictive marker to stratify responders and identify super responders and functional responders to omalizumab treatment in patients with severe allergic asthma using less invasive sample like plasma.

Cardiac electrical and mechanical synchrony of super-responders to cardiac resynchronization therapy.

BackgroundSuper-responders (SRs) to cardiac resynchronization therapy (CRT) regain near-normal or normal cardiac function. The extent of cardiac synchrony of SRs and whether continuous biventricular (BIV) pacing is needed remain unknown. The aim of this study was to evaluate the cardiac electrical and mechanical synchrony of SRs.MethodsWe retrospectively analyzed CRT recipients between 2008 and 2016 in 2 centers to identify SRs, whose left ventricular (LV) ejection fraction was increased to ≥50% at follow-up. Cardiac synchrony was evaluated in intrinsic and BIV-paced rhythms. Electrical synchrony was estimated by QRS duration and LV mechanical synchrony by single-photon emission computed tomography myocardial perfusion imaging.ResultsSeventeen SRs were included with LV ejection fraction increased from 33.0 ± 4.6% to 59.3 ± 6.3%. The intrinsic QRS duration after super-response was 148.8 ± 30.0 ms, significantly shorter than baseline (174.8 ± 11.9 ms, P = 0.004, t = −3.379) but longer than BIV-paced level (135.5 ± 16.7 ms, P = 0.042, t = 2.211). Intrinsic LV mechanical synchrony significantly improved after super-response (phase standard deviation [PSD], 51.1 ± 16.5° vs. 19.8 ± 8.1°, P < 0.001, t = 5.726; phase histogram bandwidth (PHB), 171.7 ± 64.2° vs. 60.5 ± 22.9°, P < 0.001, t = 5.376) but was inferior to BIV-paced synchrony (PSD, 19.8 ± 8.1° vs. 15.2 ± 6.4°, P = 0.005, t = 3.414; PHB, 60.5 ± 22.9° vs. 46.0 ± 16.3°, P = 0.009, t = 3.136).ConclusionsSRs had significant improvements in cardiac electrical and LV mechanical synchrony. Since intrinsic synchrony of SRs was still inferior to BIV-paced rhythm, continued BIV pacing is needed to maintain longstanding and synchronized contraction.

P3801The impact of the type of response to cardiac resynchronization therapy in the survival of patients with advanced heart failure

Abstract Fundamental Cardiac resynchronization therapy (CRT) reduces total mortality in patients (pt) with advanced heart failure (HF). However, the impact of this reduction is unknown in the different types of response. Objective To describe the survival of responders and super responders pt to CRT in a retrospective cohort. Methods 250 pt who underwent a CRT were retrospectively evaluated. All presented in functional class (FC) III/ IV (NYHA). The criteria of response to CRT were: improvement of FC (&gt;1); increase in ejection fraction (EF) &gt;10% and decrease in left ventricular end-systolic diameter (LVESD) – &gt;15%. They were divided into three groups: Group I – 73/250 pt (33%): responder only by the criterion of FC improvement. Group II - 57/250 pt (24%): responder was defined by three criteria (clinical and echocardiographic). Grupo III - super responder – 48/250 pt (20%): decrease &gt;30% in LVESD and/or EF &gt;45%. The survival and clinical outcomes were analyzed in the 3 groups. Results In group I, the mean age was 68.7 years; 75% were male; left bundle branch block (LBBB) was observed in 93% and average QRS duration was 164 ms; EF: 26%; average LVESD and left ventricular end-diastolic diameter (LVEDD): 46 and 57.7 mm, respectively. BIV-ICD was observed in 72% of pt. The mean post-implant survival was 30.8 months (CI95%: 25.06–36.54). In group II, the mean age was 70 years; 82% were male; left bundle branch block (LBBB) was observed in 98% and average QRS duration was 166 ms; EF: 27.5%; average LVESD and LVEDD: 52 and 67 mm, respectively. BIV-ICD was observed in 75% of pt. The mean post-implant survival was 45.4 months (CI95%: 38.96–51.84). In group III, the mean age was 71 years; 65% were male; left bundle branch block (LBBB) was observed in all pt (100%) and average QRS duration was 176 ms; EF: 29.2%; average LVESD and LVEDD: 54 and 68 mm, respectively. BIV-ICD was observed in 70% of pt. The mean post-implant survival was 53 months (CI95%: 45.96–60.04). The total mortality observed was 11%, 17% and 6.25%, respectively (48%: neoplasia; 24%: stroke; 19%: terminal HF; 9%: sepsis). Conclusion In the present study, the survival of responders pt to CRT varied according to the type of response, being significantly higher in the super responders and in those who presented echocardiographic criteria of response to CRT. These findings present significant clinical relevance and should be evaluated in future studies.

Contrast-enhanced harmonic endoscopic ultrasonography for evaluating the response to chemotherapy in pancreatic cancer

Background and aimsContrast-enhanced harmonic endoscopic ultrasonography (CH-EUS) is used for the diagnosis of pancreatic cancer (PC). Here, we examined the usefulness of CH-EUS for evaluating therapeutic responses in PC. MethodsThe study included 23 patients with PC who received chemotherapy. Patients underwent contrast-enhanced computed tomography (CE-CT) and CH-EUS before chemotherapy and at the time of evaluation of the therapeutic response. Patients with a ≧50% reduction in serum carbohydrate antigen 19–9 levels after chemotherapy were defined as “super responders”. The incidence of an avascular area in the tumor on CH-EUS after chemotherapy was compared between “super responders” and non-super responders. ResultsNine patients were included in the “super responders” group.Tumor reduction rates did not differ significantly between CE-CT and CH-EUS in the “super responders”. The appearance of an avascular area was detected in 7 of 9 super responders (77.8%) and in 4 of 14 non-super responders (28.6%), and the difference was significant (P = 0.036). The mean survival time of patients with an avascular area after chemotherapy was longer than that of without an avascular area. ConclusionsDetection of avascular areas by CH-EUS after chemotherapy may predict long-term survival of patients with PC.

Echocardiographic markers of dyssynchrony as predictors of super-response to cardiac resynchronisation therapy \u2013 a pilot study

BackgroundSome patients with congestive heart failure have greater improvement of cardiac remodelling after cardiac resynchronisation therapy (CRT) and they are identified as super-responders (SRs). It remains unclear if echocardiographic markers of dyssynchrony could accuratelly predict super-response to CRT. The aim of this study is to evaluate potential echocardiographic predictors associated with super-response to CRT.MethodsFifthy nine CRT patients (mean age 52.9 ± 9.0 years, 88% men) with congestive heart failure (54% ischaemic and 46% non-ischaemic aetiology) II-IV NYHA functional class were enrolled. To assess mechanical dyssynchrony we evaluated interventricular mechanical delay, the maximum delay between peak systolic velocities of the septal and posterior walls of left ventricle, duration of left ventricular pre-ejection period (LVPEP), left ventricular and interventricular dyssynchrony by tissue Doppler imaging and systolic dyssynchrony index by 3D echocardiography. After six months the patients were assessed for response and classified as SRs (reduction in left ventricular end-systolic volume (LVESV) ≥30%, n = 20) and non-SRs (reduction in LVESV < 30%, n = 39) and baseline data were analyzed to identify the predictors.ResultsBoth groups demonstrated significant improvement in NYHA functional class, increase in left ventricular ejection fraction and reduction in LVESV. All parameters of mechanical dyssynchrony at baseline were significantly higher in SR group. Multiple logistic regression analysis showed that LVPEP (HR 1.031; 95% CI 1.007–1.055; p = 0.011) was an independent predictor for CRT super-response. In ROC curve analysis LVPEP with a cut-off value of 147 ms demonstrated 73.7% sensitivity and 75% specificity (AUC = 0.753; p = 0.002) for the prediction of super-response to CRT.ConclusionGreater mechanical dyssynchrony is associated with super-response to CRT in patients with congestive heart failure. It is probable that an LVPEP > 147 ms can be used as independent predictor of super-response.