Real-life Cohort Of Patients Research Articles

HLA-DQA1*05 Was Not Associated With Primary Nonresponse or Loss of Response to First Anti-TNF in Real-World Inflammatory Bowel Disease Patients.

We lack predictors of response to biologics in the management of patients with inflammatory bowel disease (IBD). A recent study has shown a significant association between HLA-DQA1*05 carriers and the development of loss of response to anti-tumor necrosis factor (TNF) mediated by immunogenicity. Retrospective single-center cohort study including IBD patients who had received anti-TNF therapy as a first biologic and whose HLA-DQA1*05 had been determined. Primary nonresponse and secondary failure (assessed by survival analysis) have been evaluated as well as safety outcomes. A total of 199 IBD patients (161 [81%] with Crohn's disease and 38 [19%] with ulcerative colitis) were included. A total of 42.4% were HLA-DQA1*05 carriers and 60% received combination therapy at the start of anti-TNF treatment. Median follow-up was 24 (interquartile range, 11-66) months. No statistically significant differences were found in primary nonresponse to anti-TNF (89.3% vs 87.8%; P = .825), depending on HLA carriers and noncarriers. No differences in secondary loss of response according to HLA variant in any of the analyses performed (full cohort, according to IBD or anti-TNF type) were observed. Again, no differences were observed in patients treated with combination therapy. In terms of safety, no significant differences were found in the rate of infusion reactions or serious adverse events. In our real-life cohort of IBD patients treated for the first time with anti-TNF, being an HLA-DQA1*05 carrier did not act as a predictor of response failure, either primary or secondary. The safety of anti-TNF treatment has also not been influenced by the variant.

Systemic Immunosuppressive Therapies for Children with Refractory Atopic Dermatitis: A Large Real-Life Cohort Study.

Systemic immunosuppressants are used off-label to treat paediatric patients with moderate-to severe atopic dermatitis (AD) for whom topical treatment has failed. A large real-life cohort of paediatric patients with AD treated with systemic immunosuppressive treatments is described in order to guide dermatologists’ prescribing practices when faced with a moderate to-severe AD paediatric patient who has failed or has a contraindication to topical treatment, phototherapy, biological agents or Janus kinase inhibitors.

Health-related quality of life and clinical complexity of a real-life cohort of patients with advanced HR+/HER2- breast cancer treated with CDK4/6 inhibitors and endocrine therapy.

Advanced breast cancer (ABC) is characterized by multidimensional clinical complexity that is usually not considered in randomized clinical trials. In the present real-life study, we investigated the link between clinical complexity and quality of life of patients with HR+/HER2- ABC treated with CDK4/6 inhibitors. We evaluated multimorbidity burden assessed with the Cumulative Illness Rating Scale (CIRS), polypharmacy and patient-reported outcomes (PROs). PROs were assessed at baseline (T0), after 3 months of therapy (T1), and at disease progression (T2) using EORTC QLC-C30 and QLQ-BR23 questionnaires. Baseline PROs and changes between T0 and T1 were evaluated amongst patients with different multimorbidity burden (CIRS <5 and ≥5) and polypharmacy (<2 or ≥2 drugs). From January 2018 to January 2022, we enrolled 54 patients (median age 66 years, IQR 59-74). The median CIRS score was 5 (IQR 2-7), whilst the median number of drugs taken by patients was 2 (IQR 0-4). No changes in QLQ-C30 final scoring between T0 and T1 were observed in the overall cohort (p=0.8944). At T2, QLQ-C30 global score deteriorated with respect to baseline (p=0.0089). At baseline, patients with CIRS ≥5 had worse constipation than patients without comorbidities (p<0.05) and a lower trend in the median QLQ-C30 global score. Patients on ≥2 drugs had lower QLQ-C30 final scores and worse insomnia and constipation (p<0.05). No change in QLQ-C30 final score from T0 to T1 was observed (p>0.05). Multimorbidity and polypharmacy increase the clinical complexity of patients with ABC and may affect baseline PROs. The safety profile of CDK4/6 inhibitors seems to be maintained in this population. Further studies are needed to assess clinical complexity in patients with ABC.This article is part of the Tackling clinical complexity in breast cancer Special Issue: https://www.drugsincontext.com/special_issues/tackling-clinical-complexity-in-breast-cancer/.

The impact of transsphenoidal surgery on pituitary function in patients with non-functioning macroadenomas

PurposeTranssphenoidal surgery for non-functioning pituitary adenomas (NFPAs) can alter pituitary function. We assessed the rates of improvement and deterioration of pituitary function by axis and searched for predictive factors of these outcomes.MethodsWe reviewed consecutive medical files from patients having had transsphenoidal surgery for NFPA between 2004 and 2018. Pituitary functions and MRI imaging were analyzed prior and after surgery. The occurrence of recovery and new deficit were documented per axis. Prognostic factors of hormonal recovery and new deficits were searched.ResultsAmong 137 patients analyzed, median tumor size of the NFPA was 24.8 mm and 58.4% of patients presented visual impairment. Before surgery, 91 patients (67%) had at least one abnormal pituitary axis (hypogonadism: 62.4%; hypothyroidism: 41%, adrenal insufficiency: 30.8%, growth hormone deficiency: 29.9%; increased prolactin: 50.8%). Following surgery, the recovery rate of pituitary deficiency of one axis or more was 46% and the rate of new pituitary deficiency was 10%. Rates of LH-FSH, TSH, ACTH and GH deficiency recovery were 35.7%, 30.4%, 15.4%, and 45.5% respectively. Rates of new LH-FSH, TSH, ACTH and GH deficiencies were 8.3%, 1.6%, 9.2% and 5.1% respectively. Altogether, 24.6% of patients had a global pituitary function improvement and only 7% had pituitary function worsening after surgery. Male patients and patients with hyperprolactinemia upon diagnosis were more likely to experience pituitary function recovery. No prognostic factors for the risk of new deficiencies were identified.ConclusionIn a real-life cohort of patients with NFPAs, recovery of hypopituitarism after surgery is more frequent than the occurrence of new deficiencies. Hence, hypopituitarism could be considered a relative indication for surgery in patients with NFPAs.

Impact of gender on the utilization of cardiac implantable devices and outcome: results from the German DEVICE registry

Abstract Funding Acknowledgements Type of funding sources: None. Background Implantable cardioverter defibrillators (ICDs) and cardiac resynchronization therapy (CRT) are widely used in patients with life-threatening cardiac arrhythmias or systolic heart failure. Real world data regarding gender impact on ICD and CRT implantation and outcome is scarce. Purpose To investigate the impact of gender-specific differences on cardiac devices implantation and outcomes. Methods The German DEVICE registry is a nationwide prospective multicentre database of ICD and CRT devices implantation. A total of 5451 patients were prospectively enrolled in 44 centres between March 2007 and February 2014 and were monitored for a median of 17 months. Results A minority of patients in this registry was female 1050 (19.3%; mean age 64.4 ± 14.6 years; median BMI 27.2) while men represented 80.7% (mean age 65.5 ± 12.4 years; median BMI 26.8). Female patients were less likely to have a LVEF &amp;lt;35% (70.6% vs. 77.7%; p&amp;lt;0.0001) and more likely to have a LVEF &amp;gt;55% (13.3% vs. 6.6%; p&amp;lt;0.0001). Moreover, women were less likely to have coronary artery disease (42.3% vs. 64.7%; p&amp;lt;0.0001), history of myocardial infarction, percutaneous coronary intervention, and coronary artery bypass graft (p&amp;lt;0.0001 for all). The rate of CRTs was significantly higher in women than in men (33.4% vs. 28.7%; p=0.0036). In terms of secondary prevention implantations, women were more likely to have history of ventricular fibrillation (VF; 50.7% vs. 37.2%; p&amp;lt;0.0001) but less likely to have history of ventricular tachycardia (VT; 34.5% vs. 47.5%; p&amp;lt;0.0001). The rates of major periprocedural complications and in-hospital complications were higher in women (3.3% vs. 1.7%; p=0.002 and 5.6% vs. 3.7%; p=0.0208). The Kaplan-Meier estimated 1-year all-cause mortality was 5.4% for women and 7.4% for men, while the overall mortality during follow-up was 10% for women and 14% for men (p=0.0004), with no gender differences in terms of death cause. Significantly less women received device shocks (14.2% vs. 17.5%; p=0.0260), while more women needed device revision during follow-up (10.9 % vs. 8.2%; p=0.0246). Similar rates of primary and secondary prevention indication were noted for female and male patients (p=0.9717). There was no difference between the groups regarding the need of postprocedural system revision (p=0.7884), as well as in-hospital death, cardiac death, or sudden cardiac death. The non-fatal complications during follow-up were comparable for men and women. Moreover, similar rates and durations of all cause and cardiac rehospitalizations were found (p=0.1644 and p= 0.1816). Conclusion In this real-life patient cohort only a minority of female patients were enrolled. Female patients were more likely to undergo CRT implantation and had a higher risk for acute major periprocedural complications and in-hospital complications but a lower overall mortality in 1-year follow-up. However, the differences in baseline characteristics should be considered as potential confounders.

P140Cap inhibits β-Catenin in the breast cancer stem cell compartment instructing a protective anti-tumor immune response

The p140Cap adaptor protein is a tumor suppressor in breast cancer associated with a favorable prognosis. Here we highlight a function of p140Cap in orchestrating local and systemic tumor-extrinsic events that eventually result in inhibition of the polymorphonuclear myeloid-derived suppressor cell function in creating an immunosuppressive tumor-promoting environment in the primary tumor, and premetastatic niches at distant sites. Integrative transcriptomic and preclinical studies unravel that p140Cap controls an epistatic axis where, through the upstream inhibition of β-Catenin, it restricts tumorigenicity and self-renewal of tumor-initiating cells limiting the release of the inflammatory cytokine G-CSF, required for polymorphonuclear myeloid-derived suppressor cells to exert their local and systemic tumor conducive function. Mechanistically, p140Cap inhibition of β-Catenin depends on its ability to localize in and stabilize the β-Catenin destruction complex, promoting enhanced β-Catenin inactivation. Clinical studies in women show that low p140Cap expression correlates with reduced presence of tumor-infiltrating lymphocytes and more aggressive tumor types in a large cohort of real-life female breast cancer patients, highlighting the potential of p140Cap as a biomarker for therapeutic intervention targeting the β-Catenin/ Tumor-initiating cells /G-CSF/ polymorphonuclear myeloid-derived suppressor cell axis to restore an efficient anti-tumor immune response.

Timely course of SARS-CoV-2 infections and vaccinations in patients with hemato-oncological diseases: analysis of a real-life cohort

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has particularly impacted patients with hemato-oncological malignancies, as they showed not only a higher propensity for severe courses but also weaker immune responses after vaccination. Still, data on the influence of pandemic waves and vaccinations on outcomes are rare. This study aimed to analyze the timely course of infections and vaccinations in a real-life cohort of patients with hemato-oncological diseases. In this cohort study, 1817 patients with hemato-oncological diseases from 1 February 2020 to 15 December 2022 at the 'Franz Tappeiner' Hospital in Merano/Meran, Italy, were followed for SARS-CoV-2 infections and vaccinations. Of 1817 patients with hemato-oncological malignancies, 735 (40.5%) were infected at least once with SARS-CoV-2, and 1614 (88.8%) received one or more doses of the approved vaccinations. Patients receiving antineoplastic treatment had a lower SARS-CoV-2 infection rate [35.1% versus 41.0%; odds ratio (OR) 0.78, 95% confidence interval (CI) 0.64-0.95], but higher risk of hospitalization (13.4% versus 6.9%; OR 2.11, 95% CI 1.25-3.69) compared with untreated patients. Overall, the case fatality rate (CFR) was 3.4%. Unvaccinated patients were more prone to severe coronavirus disease 2019 (COVID-19) courses requiring hospitalization (OR 2.34, 95% CI 1.25-4.36) and had a higher CFR (7.3% versus 1.6%; OR 4.98, 95% CI 2.16-12.98) than their vaccinated counterparts. In the Delta wave, patients with two vaccinations had a lower infection risk (OR 0.18, 95% CI 0.10-0.35) and tendentially lower hospitalization rates (OR 0.25, 95% CI 0.05-1.29) than unvaccinated patients. In the Omicron wave, 345/1198 (28.8%) patients with three or more vaccinations had breakthrough infections, resulting in a similar risk for infection (OR 0.88, 95% CI 0.60-1.30) but numerically lower risk for hospitalization (24/345, 7.0%) than unvaccinated individuals (4/40, 10.0%). Scheduled visits were postponed in 128/335 (38.2%) patients due to COVID-19, and deferrals correlated with pandemic wave (P= 0.002) and vaccination status (P < 0.001). SARS-CoV-2 infections and outcomes differ between distinct phases of the pandemic. Vaccination with variant-specific vaccines should be prioritized as general protective measures are increasingly lifted.

Pre-treatment comorbidities, C-reactive protein and eosinophil count, and immune-related adverse events as predictors of survival with checkpoint inhibition for multiple tumour entities.

The development of immune-related adverse events (irAEs) may be associated with clinical efficacy of checkpoint inhibitors (CPIs) in patients with cancer. We therefore investigated the effect of irAEs and pre-treatment parameters on outcome in a large, real-life patient cohort. We performed a single-centre, retrospective, observational study including patients who received CPIs from 2011 to 2018 and followed until 2021. The primary outcome was overall survival, and the secondary outcome was the development of irAEs. In total, 229 patients with different tumour entities (41% non-small cell lung cancer [NSCLC], 29% melanoma) received a total of 282 CPI treatment courses (ipilimumab, nivolumab, pembrolizumab or atezolizumab). Thirty-four percent of patients developed irAEs (of these 17% had CTCAE Grade ≥3). Factors independently associated with mortality were pre-treatment CRP ≥10 mg/L (hazard ratio [HR] 2.064, p = 0.0003), comorbidity measured by Charlson comorbidity index (HR 1.149, p = 0.014) and irAEs (HR 0.644, p = 0.036) (age-adjusted, n = 216). Baseline eosinophil count ≤0.2 × 109 /L was a further independent predictor of mortality (age-, CRP-, CCI- and irAE-adjusted HR = 2.252, p = 0.002, n = 166). Anti-CTLA-4 use (p < 0.001), and pre-treatment CRP <10 mg/L were independently associated with irAE occurrence (p = 0.037). We found an independent association between irAE occurrence and improved overall survival in a real-life cohort spanning multiple tumour entities and treatment regimens. Pre-treatment comorbidities, CRP and eosinophil count represent potential markers for predicting treatment response.

Clinical risk factors for ascites in metastatic pancreatic cancer

Malignant ascites is common in metastatic pancreatic cancer (mPC) and its management still remains a clinical challenge. Early identification of patients at risk for ascites development may support and guide treatment decisions. Data of patients treated for mPC at the Medical University of Vienna between 2010 and 2019 were collected by retrospective chart review. Ascites was defined as clinically relevant accumulation of intraperitoneal fluid diagnosed by ultrasound or computer tomography scan of the abdomen. We investigated the association between general risk factors, metastatic sites, liver function, systemic inflammation as well as portal vein obstruction (PVO) and ascites development. Among 581 patients with mPC included in this study, 122 (21.0%) developed ascites after a median of 8.7 months after diagnosis of metastatic disease. The occurrence of ascites led to an 8.9-fold increased risk of death [confidence interval (CI) 7.2-11, P < 0.001] with a median overall survival of 1 month thereafter. Clinical risk factors for ascites were male sex [hazard ratio (HR) 1.71, CI 1.00-2.90, P= 0.048], peritoneal carcinomatosis (HR 6.79, CI 4.09-11.3, P < 0.001), liver metastases (HR 2.16, CI 1.19-3.91, P= 0.011), an albumin-bilirubin (ALBI) score grade 3 (HR 6.79, CI 2.11-21.8, P= 0.001), PVO (HR 2.28, CI 1.15-4.52, P= 0.019), and an elevated C-reactive protein (CRP) (HR 4.19, CI 1.58-11.1, P= 0.004). Survival after diagnosis of ascites is very limited in mPC patients. Male sex, liver and peritoneal metastases, impaired liver function, PVO, as well as systemic inflammation were identified as independent risk factors for ascites development in this uniquely large real-life patient cohort.

Exposure-response analyses of BRAF- and MEK-inhibitors dabrafenib plus trametinib in melanoma patients.

Dabrafenib and trametinib are currently administered at fixed doses, at which interpatient variability in exposure is high. The aim of this study was to investigate whether drug exposure is related to efficacy and toxicity in a real-life cohort of melanoma patients treated with dabrafenib plus trametinib. An observational study was performed in which pharmacokinetic samples were collected as routine care. Using estimated dabrafenib Area Under the concentration-time Curve and trametinib trough concentrations (Cmin), univariable and multivariable exposure-response analyses were performed. In total, 140 patients were included. Dabrafenib exposure was not related to either progression-free survival (PFS) or overall survival (OS). Trametinib exposure was related to survival, with Cmin ≥ 15.6ng/mL being identified as the optimal threshold. Median OS was significantly longer in patients with trametinib Cmin ≥ 15.6ng/mL (22.8 vs. 12.6months, P = 0.003), with a multivariable hazard ratio of 0.55 (95% CI 0.36-0.85, P = 0.007). Median PFS in patients with trametinib Cmin levels ≥ 15.6ng/mL (37%) was 10.9months, compared with 6.0months for those with Cmin below this threshold (P = 0.06). Multivariable analysis resulted in a hazard ratio of 0.70 (95% CI 0.47-1.05, P = 0.082). Exposure to dabrafenib and trametinib was not related to clinically relevant toxicities. Overall survival of metastasized melanoma patients with trametinib Cmin levels ≥ 15.6ng/mL is ten months longer compared to patients with Cmin below this threshold. This would theoretically provide a rationale for therapeutic drug monitoring of trametinib. Although a high proportion of patients are underexposed, there is very little scope for dose increments due to the risk of serious toxicity.

Efficacy and tolerance of methotrexate in a real-life monocentric cohort of patients with giant cell arteritis

ObjectivesTo assess the indications, efficiency and tolerance profiles of methotrexate (MTX) in patients with giant cell arteritis (GCA) in a real-life setting. MethodsFrom a monocentric database of >500 GCA patients, we retrospectively selected 49 patients who received MTX between 2010 and 2020. Cumulative glucocorticoid (GC) doses, the number of relapses and GC-related adverse events were recorded before, during and after MTX. We separately analyzed the 3 main indications of MTX, i.e., disease relapse, GC-sparing strategy, and GCA presentation. ResultsWith a median follow-up of 84 [10–255] months, 25 (51%) and 18/41 (44%) patients relapsed during MTX treatment and after its discontinuation, respectively. Among the 40 patients who relapsed before MTX, 26 (65%) experienced a new relapse after MTX introduction. Once MTX was introduced, 24 (49%) patients were able to discontinue GC after 20.5 [7–64] months. No significant difference in cumulative GC doses were noted before and after MTX introduction with a total GC dose of 14.7 [1.05–69.4] grams. At the last follow-up, MTX was discontinued in 41 patients, including 13 (32%) due to clinicobiological remission, 12 (30%) due to treatment failure and 15 (36%) due to side effects. ConclusionOur real-life study showed a modest beneficial effect of MTX on relapse in patients with GCA. However, we did not observe any GC-sparing effect in this study. Other studies are needed to assess the GC-sparing effect in patients in whom GC management is adapted from recent recommendations.

PIK3CA and PIK3R1 tumor mutational landscape in a pan-cancer patient cohort and its association with pathway activation and treatment efficacy

There is little data concerning the implications of PIK3CA mutations outside of the known hotspots described in ER+/HER2− metastatic breast cancer (mBC). Similarly, PIK3R1 mutations could also lead to activation of PI3K pathway, but are poorly described. We determined the incidence and type of all somatic PIK3CA and PIK3R1 mutations by whole exome sequencing (WES) in a pan-cancer cohort of 1200 patients. Activation of the PI3K pathway was studied using phospho-AKT immunohistochemistry. Associations between PIK3CA/PIK3R1 mutations and response to chemotherapy were studied in mBC cases. We found 141 patients (11.8%) with a PIK3CA and/or PIK3R1 mutation across 20 different cancer types. The main cancer subtype was mBC (45.4%). Eighty-four mutations (62.2%) occurred in the three described hotspots; 51 mutations occurred outside of these hotspots. In total, 78.4% were considered activating or probably activating. Among PIK3R1 mutations, 20% were loss of function mutations, leading to a constitutional activation of the pathway. Phospho-AKT quantification in tumor samples was in favor of activation of the PI3K pathway in the majority of mutated tumors, regardless of mutation type. In ER+/HER2− mBC, first line chemotherapy efficacy was similar for PIK3CA-mutated and PIK3CA-WT tumors, whereas in triple negative mBC, chemotherapy appeared to be more effective in PIK3CA-WT tumors. In this large, real-life pan-cancer patient cohort, our results indicate that PIK3CA/PIK3R1 mutations are widely spread, and plead in favour of evaluating the efficacy of PI3K inhibitors outside of ER+/HER2− mBC and outside of hotspot mutations.

Advanced Cutaneous Squamous Cell Carcinoma: Italian Multicentric Retrospective Analysis of Patient Profiles and Therapeutic Approaches

Background: Advanced cutaneous squamous cell carcinoma (aCSCC) represents an area of unmet clinical need, with no standardized treatments until the recent approval of immune checkpoint inhibitors (ICIs). Objectives: The aim of the study was to describe clinical characteristics and therapeutic strategies of a real-life Italian cohort of aCSCC patients managed at the beginning of cemiplimab approval as compassionate use in Italy. Methods: A multicenter retrospective study was performed by 10 Italian centers in the period January 1, 2018–May 31, 2020. Patients aged ≥18 years and diagnosed with aCSCC (locally aCSCC and metastatic CSCC) were eligible for the study. Analysis of patients’ characteristics and treatment strategies was performed. Results: 239 patients were initially recruited in the study: 19 patients were excluded due to incomplete data collection, yielding a final cohort of 220 patients, of which 191 and 220 were included for patients’ clinical characteristics and therapeutic intervention analysis, respectively. Median age at the time of diagnosis was 81 years (range: 72–86); nodal metastases were detected in 64/220 (29%) patients, and distant metastatic spread was reported in 33/220 (15%) patients. Most of our patients referred chronic occupational and/or recreational sun exposure, experienced ≥1 sunburn during their lifetime, never wore hats or used photoprotective filters, and presented with signs of cumulative sun damage (solar lentigines and/or actinic keratosis). Majority of our cohort received at least one intervention directed to the primary tumor (n = 212, 96.3%); surgery and radiotherapy were the most common therapeutic choices. Immunotherapy was administered to a small number of patients as compassionate use, especially in the metastatic setting. Conclusions: Our study outlines the complex and heterogeneous clinical and therapeutic landscape of aCSCC patients at the beginning of ICI era, highlighting the need of a standardized care for this fragile and high-need patient population.

Clinical factors influencing long-term survival in a real-life cohort of early stage non-small-cell lung cancer patients in Spain.

Current prognosis in oncology is reduced to the tumour stage and performance status, leaving out many other factors that may impact the patient´s management. Prognostic stratification of early stage non-small-cell lung cancer (NSCLC) patients with poor prognosis after surgery is of considerable clinical relevance. The objective of this study was to identify clinical factors associated with long-term overall survival in a real-life cohort of patients with stage I-II NSCLC and develop a prognostic model that identifies features associated with poor prognosis and stratifies patients by risk. This is a cohort study including 505 patients, diagnosed with stage I-II NSCLC, who underwent curative surgical procedures at a tertiary hospital in Madrid, Spain. Median OS (in months) was 63.7 (95% CI, 58.7-68.7) for the whole cohort, 62.4 in patients submitted to surgery and 65 in patients submitted to surgery and adjuvant treatment. The univariate analysis estimated that a female diagnosed with NSCLC has a 0.967 (95% CI 0.936 - 0.999) probability of survival one year after diagnosis and a 0.784 (95% CI 0.712 - 0.863) five years after diagnosis. For males, these probabilities drop to 0.904 (95% CI 0.875 - 0.934) and 0.613 (95% CI 0.566 - 0.665), respectively. Multivariable analysis shows that sex, age at diagnosis, type of treatment, ECOG-PS, and stage are statistically significant variables (p<0.10). According to the Cox regression model, age over 50, ECOG-PS 1 or 2, and stage ll are risk factors for survival (HR>1) while adjuvant chemotherapy is a good prognostic variable (HR<1). The prognostic model identified a high-risk profile defined by males over 71 years old, former smokers, treated with surgery, ECOG-PS 2. The results of the present study found that, overall, adjuvant chemotherapy was associated with the best long-term OS in patients with resected NSCLC. Age, stage and ECOG-PS were also significant factors to take into account when making decisions regarding adjuvant therapy.

Changes in the Treatment Strategy Following Intracoronary Pressure Wire in a Contemporaneous Real-Life Cohort of Patients With Intermediate Coronary Stenosis. Results From a Nationwide Registry

BackgroundIntracoronary pressure wire is useful to guide revascularization in patients with coronary artery disease. AimsTo evaluate changes in diagnosis (coronary artery disease extent), treatment strategy and clinical results after intracoronary pressure wire study in real-life patients with intermediate coronary artery stenosis. MethodsObservational, prospective and multicenter registry of patients in whom pressure wire was performed. The extent of coronary artery disease and the treatment strategy based on clinical and angiographic criteria were recorded before and after intracoronary pressure wire guidance. 12-month incidence of MACE (cardiovascular death, non-fatal myocardial infarction or new revascularization of the target lesion) was assessed. Results1414 patients with 1781 lesions were included. Complications related to the procedure were reported in 42 patients (3.0 %). The extent of coronary artery disease changed in 771 patients (54.5 %). There was a change in treatment strategy in 779 patients (55.1 %) (18.0 % if medical treatment; 68.8 % if PCI; 58.9 % if surgery (p < 0.001 for PCI vs medical treatment; p = 0.041 for PCI vs CABG; p < 0.001 for medical treatment vs CABG)). In patients with PCI as the initial strategy, the change in strategy was associated with a lower rate of MACE (4.6 % vs 8.2 %, p = 0.034). ConclusionsThe use of intracoronary pressure wire was safe and led to the reclassification of the extent of coronary disease and change in the treatment strategy in more than half of the cases, especially in patients with PCI as initial treatment.

Low-Intensity Extracorporeal Shock Wave Treatment (LI-ESWT) efficacy treating a cohort of real-life patients with erectile dysfunction

Low-Intensity Extracorporeal Shock Wave Treatment (LI-ESWT) efficacy treating a cohort of real-life patients with erectile dysfunction

P593 Impact of immunomodulating treatment modalities, active smoking and (repeated) COVID19 vaccination on S-antibody seroconversion in IMID patients. Results of the BELCOMID study: BELgian Cohort study of COVID-19 in Immune Mediated Inflammatory Diseases (IMID)

Abstract Background Targeted Immune-Modulating Therapies (TIMT) and immunomodulators (IMM) for Immune Mediated Inflammatory diseases (IMID) theoretically interfere with humoral responses against COVID19. However, IMID patients and particularly patients receiving immunosuppressive treatment were excluded from phase-3 COVID19 vaccination efficacy trials. Real-world observational data is therefore required to provide more insight into the efficacy of COVID19 vaccination in IMID patients. Methods The BELCOMID study is a multidisciplinary, prospective observational cohort study performed at two university hospitals and set up with the intention to explore the interaction between IMIDs, immune-modulating treatment modalities and SARS-CoV-2 infection and vaccination in a real-life patient cohort. Consecutive patients seen between 17/12/2020 and 28/02/2021 during routine follow-up for IMIDs of the gut, joints and skin were invited to participate. Both patient data and serological samples were collected at 3 predefined periods (Figure 1: before vaccination, after start of the national vaccination campaign before booster vaccination, after booster vaccination). Spike (S) protein antibodies were analysed with the Abbott ArchitectTM assay. R version 4.0.2 was used to perform analyses. Results At inclusion period 2, 2065 patients (Table 1) participated of whom 1547 had received complete baseline vaccination (2 doses mRNA-1273, BNT162b2, ChadOx1 nCoV-19 or 1 dose JN78436735). S-antibody seroconversion rate was 91.2%. At inclusion period 3, data was available for 1566 patients of whom 74.7% had received 1 booster (BNT162b2 or mRNA-1273) vaccination leading to a S-antibody seroconversion rate of 98.3%. In 130 patients who had received 2 boosters, S-antibody seroconversion rate was 100%. At period 3, 37 patients had refused all vaccinations. Although 23 of these had experienced confirmed COVID19 since previous inquiry, no S-antibody seroconversion was found in 15 of them. Logistic regression analyses revealed that the odds of no S-antibody seroconversion were significantly higher in IMID patients treated with IMM, combination of IMM+TIMT, systemic steroids and smoking patients at both inclusion periods (Table 2). TIMT monotherapy did not influence seroconversion rates at inclusion period 3 but was associated with higher odds of the lowest S-antibody titre quartile (OR2.32, P&amp;lt;0.001). Among TIMT options, rituximab had higher odds of S-seronegativity. Conclusion S-antibody seroconversion rate in this real-life IMID population was high after baseline vaccination and increased further proportionally with booster vaccination, highlighting the value of repeated vaccination. However, the serologic response may be blunted due to different IMID treatment modalities and smoking.

P563 Monitoring of vedolizumab drug levels in a treat to target strategy for moderate-severe IBD (MOVE-IBD)

Abstract Background Vedolizumab is an effective drug in moderate-severe ulcerative colitis (UC) and Crohn’s disease (CD). A previous link between drug exposure and clinical response has been suggested in the literature making therapeutic drug monitoring (TDM) for vedolizumab an attractive idea to try and optimize patient outcomes. Recent data from the ENTERPRET induction study in UC presented at Digestive Diseases 2022 suggest no advantage to dose optimizing based on vedolizumab levels. Thus, there is discordance in the literature regarding the clinical relevance of vedolizumab drug levels. We aimed to clarify the utility of proactive TDM of vedolizumab trough levels in our cohort of maintenance vedolizumab patients using objective markers of disease activity in a treat to target strategy. Methods A single-centre retrospective cross sectional cohort study using proactive TDM was performed on 84 patients with moderate to severe IBD on vedolizumab maintenance therapy. All patients were receiving standard vedolizumab dosing of 300 mg every eight weeks. A vedolizumab trough drug level was paired with clinical and objective markers of disease activity. The two endpoints examined were steroid free clinical remission and objective remission. Objective remission targets were individualized for each patient using a treat to target strategy and benchmarked against a baseline abnormal test. Steroid free clinical remission was defined in Crohn’s disease as a Crohn’s disease activity index (CDAI) of &amp;lt; 150 and in ulcerative colitis as a partial MAYO score of &amp;lt; 1 in a patient off steroids. Objective remission was defined as faecal calprotectin &amp;lt; 150 ug/g, normal bowel wall thickness on intestinal ultrasound or magnetic resonance imaging without associated features of inflammation or absence of ulceration on colonoscopy or sigmoidoscopy within 3 months of the vedolizumab level. Results Median trough vedolizumab levels for patients were numerically higher but not statistically different in patients who had achieved steroid free clinical remission (13.3 ug/ml vs 8.89 ug/ml p = 0.544) or objective remission (15.22 ug/ml vs 10.28 ug/ml p = 0.139). See Figures 1. In addition, quartile analysis showed no statistically significant difference between quartiles of vedolizumab levels and clinical or objective remission (p = 0.822). Conclusion Trough serum vedolizumab levels in our real-life cohort of maintenance moderate severe IBD patients were not associated with clinical or objective remission. Caution should be applied to basing treatment decisions off vedolizumab maintenance levels until more data becomes available to support its routine use in clinical practice.

P627 HLA DQA1*05 was not associated to primary non-response or loss of response to first anti-TNF in real world Inflammatory Bowel Disease patients.

Abstract Background Biologics have been a breakthrough in the management of patients with inflammatory bowel disease (IBD). However, we lack predictors of response to these drugs. A recent study has shown a significant association between HLA DQA*105 mutations and the development of loss of response to anti-TNF mediated by immunogenicity. The high quality of the study and the wide differences found, have led to its quick practical implementation in the choice of biological agent. However, the supporting evidence is limited in clinical practice. Methods Retrospective cohort study, carried out at the Miguel Servet Hospital, Zaragoza, Spain. We included IBD patients who had received anti-TNF therapy as first biologic and whose HLA DQA1*05 had been determined. Primary non-response and secondary failure (assessed by survival analysis) has been evaluated as well as safety outcomes. Results 199 IBD patients [161 (81%) Crohn′s disease (CD) 38 (19%) ulcerative colitis (UC)] were included. 42.4% had HLA DQA1*05 mutation and 60% received combination therapy with immunomodulators at the start of anti-TNF treatment. Median follow-up was 24 months (IQR 11-66). No statistically significant differences were found in primary non-response to anti-TNF (87,8% vs 12,2%, p = 0,825), depending on the presence or absence of HLA mutation. No differences in secondary loss of response according to HLA mutation in any of the analyses performed (full cohort, according to IBD or anti TNF type) were observed (Figure 1). Secondary loss of response has also been assessed according to the use or non-use of concomitant immunomodulator. Again, no differences were observed in this analysis (Figure 2). Multivariate analysis, like the univariate analyses, showed that the presence of the HLA-DQA1*05 mutation was not associated with a higher rate of secondary loss of response or shorter time to failure. In terms of safety, no significant differences were found in the rate of infusion reactions or serious adverse events between carrier and non-carrier patients. Conclusion In our real-life cohort of IBD patients treated for the first time with anti-TNF, the presence of the HLA-DQA1*05 mutation did not act as a predictor of response failure, either primary or secondary. The safety of anti-TNF treatment has also not been influenced by the mutation. More data is needed to incorporate HLA DQA1*05 determination into routine clinical practice as a key factor in individual decision making.

Kinetics and predictive value of HBcrAg, HBV RNA and anti-HBc during bulevirtide treatment of chronic HDV-infected patients.

The entry inhibitor bulevirtide (BLV) is a new treatment option for patients with chronic hepatitis D virus (HDV) infection and compensated liver disease. The aim of this study was to investigate the kinetic and predictive value of markers reflecting HBV cccDNA transcriptional activity and host immune response activity during BLV treatment in a real-life cohort of HDV infected patients. Levels of HDV RNA, HBV RNA, hepatitis B core related antigen (HBcrAg) and hepatitis B core antibodies (anti-HBc) were measured in 16 patients before (BL), after three (3M) and six (6M) months of treatment with BLV. All patients received nucleos(t)ide analogue treatment. HDV RNA declined in all patients during treatment. 38% (6/16) showed ≥ 2 log HDV RNA decline from BL to 6M and 11 patients (69%) normalized ALT levels. HBV RNA levels were low and only detectable in two to four patients. HBcrAg levels declined in 75% (12/16) of patients. Median HBcrAg levels declined significantly from BL to 6M (3.75 logU/ml (IQR 2.93-4.78) vs. 3.4 logU/ml (IQR 2-4.68), p=0.002). A similar trend was shown for anti-HBc between BL and 6M. Levels of HBcrAg or anti-HBc did not differ significantly between patients with or without ≥ 2 log HDV RNA decline from BL to 6M.After 6 months treatment with BLV, levels of HBcrAg showed a significant decline, while HBV RNA and anti-HBc levels did not change. Reduction of HBV cccDNA transcriptional activity and immunological effects of antiviral treatment might explain these changes.