Real-world Observational Study Research Articles

Response to Arendt-Nielsen et al. (Methodology considerations for the paper by Hosted et al. 2023).

Response to Arendt-Nielsen et al. (Methodology considerations for the paper by Hosted et al. 2023).

Adjuvant dabrafenib and trametinib for patients with resected BRAF-mutated melanoma: DESCRIBE-AD real-world retrospective observational study.

BRAF and MEK inhibitor, dabrafenib plus trametinib, adjuvant therapy is effective for high-risk resected melanoma patients with BRAF-V600 mutations. However, real-world evidence is limited. We aimed to determine the feasibility of this therapy in routine clinical practice. DESCRIBE-AD, a retrospective observational study, collected real-world data from 25 hospitals in Spain. Histologically confirmed and resected BRAF-mutated melanoma patients aged ≥18 years who were previously treated with dabrafenib plus trametinib adjuvant therapy, were included. The primary objectives were treatment discontinuation rate and time to discontinuation. The secondary objectives included safety and efficacy. From October 2020 to March 2021, 65 patients were included. Dabrafenib and trametinib discontinuation rate due to treatment-related adverse events (TRAEs) of any grade was 9%. Other reasons for discontinuation included patients' decisions (6%), physician decisions (6%), unrelated adverse events (3%), disease progression (5%), and others (5%). The median time to treatment discontinuation was 9 months [95% confidence interval (CI), 5-11]. G3-4 TRAEs occurred in 21.5% of patients, the most common being pyrexia (3%), asthenia (3%), and diarrhoea (3%). Unscheduled hospitalisations and clinical tests occurred in 6 and 22% of patients, respectively. After 20-month median follow-up (95% CI, 18-22), 9% of patients had exitus due to disease progression, with a 12-month relapse-free survival and overall survival rates of 95.3% and 100%, respectively. Dabrafenib and trametinib adjuvant therapy proved effective for melanoma patients in a real-world setting, with a manageable toxicity profile. Toxicity frequencies were low leading to low incidence of unscheduled medical visits, tests, and treatment discontinuations.

A real-world observational study of dupilumab treatment in adult patients with prurigo nodularis

BackgroundPrurigo nodularis (PN) is a chronic inflammatory skin condition that has a significant unmet needs for effective treatment options. ObjectiveTo assess the efficacy and safety of dupilumab in adult patients with PN refractory to traditional therapies. MethodsThis ongoing, real-life study examined dupilumab treatment in 8 adult patients diagnosed with PN for at least 6 months. The included patients were prescribed 300 mg dupilumab biweekly for at least 16 weeks. Efficacy was the primary outcome by means of multiple standardized scale measurements while safety was also reported. ResultsPN patients treated with dupilumab showed notable clinical improvement. After 16 weeks of dupilumab treatment, the mean Investigator Global Assessment (IGA) score reduced from 3.75 to 1.50. Patients mean Numerical Rating Scale Itch Intensity (NRSI), Dermatology Life Quality Index (DLQI), and Hospital Anxiety and Depression Scale (HADS) ratings reduced from 8.625, 15.13, and 14.50 to 1.563, 4.625, and 1.000 respectively. The majority of the patients (87.5%) reported dupilumab as effective while no adverse events have been reported. Study limitationsThis study was limited to a small cohort of adult PN patients and a short-time observation period. ConclusionsDupilumab is effective and tolerable in adult PN patients with significant improvement in skin lesions, itching, and quality of life.

Effectiveness and Safety of Belimumab in Chinese Lupus Patients: A Multicenter, Real-World Observational Study.

Objective: The effectiveness and safety of belimumab in Chinese lupus patients with different disease activities were investigated in a real-world setting. Method: Patients who received 10 mg/kg belimumab intravenously on weeks 0, 2, and 4, and then every 4 weeks on a background of standard-of-care (SoC) therapy and had a follow-up of more than 6 months were enrolled from four centers in China. They were stratified according to the Safety of Estrogens in Lupus Erythematosus National Assessment-SLE Disease Activity Index (SELENA-SLEDAI) score at baseline as the moderate/severe (SELENA-SLEDAI > 6) or mild subgroups (SELENA-SLEDAI ≤ 6). Attainment of the Lupus Low Disease Activity State (LLDAS) or remission on treatment was analyzed in all patients. The SLE Responder Index 4 (SRI-4) and SELENA-SLEDAI Flare Index (SFI) were evaluated for patients with moderate/severe disease and mild disease, respectively. Patients in the control arm with SoC alone from previous metformin lupus trials were selected by propensity score matching (PSM) as the reference group. Results: 224 SLE patients with a mean follow-up of 11.7 months receiving belimumab were enrolled in this observational study, of which 126 and 98 were in the moderate/severe and mild subgroup, respectively. At 12 months, 54.76% of the patients attained LLDAS and 28.57% attained remission. Lower daily prednisone at baseline were independently associated with 12-month LLDAS. Further, 87% of the subgroup with moderate/severe disease achieved SRI-4 at 12 months and a high SLEDAI at baseline was its predictive factor. For the mild subgroup, a reduced flare rate was observed compared with PSM reference (17.5%, vs. 38.6%, p = 0.021). Infection events, particularly viral infections and pneumonia were recorded in 7 and 6 patients, respectively. Conclusion: Our real-world data supported the effectiveness and safety of belimumab in Chinese lupus patients.

P009 A real-world prospective observational multi-national study in adult patients with breast cancer treated with extended adjuvant neratinib: NERLYFE study

P009 A real-world prospective observational multi-national study in adult patients with breast cancer treated with extended adjuvant neratinib: NERLYFE study

A PROSPECTIVE OBSERVATIONAL STUDY OF PREDICTORS OF POOR OUTCOMES IN PATIENTS WITH CEREBRAL SINUS VENOUS THROMBOSIS AT A TERTIARY CARE CENTER IN INDIA

Objective: The objective of this study was to evaluate the factors associated with poor outcome in cerebral sinus venous thrombosis (CSVT) patients at 3 and 6 months. Methods: This was a prospective observational study in which CSVT patients hospitalized at a tertiary care center in Davangere, India during November 2016–October 2018 were included and followed up for 6 months. CSVT diagnosis was confirmed with imaging findings of computed tomography, magnetic resonance imaging, and magnetic resonance venography. Modified Rankin Scale score of 0–1 was considered indicative of “good outcome,” while that of ≥2 indicated “poor outcome.” Results: Data of 44 patients were collected, of which 59% (n=26) were male, 68.2% of the patients belonged to the age group 25–45 years (mean age: 34.91±11.23 years). Fifteen patients (34.09%) had acute, 24 patients (54.55%) had sub-acute, and five patients (11.36%) had chronic symptom duration. At 3 months, age >45 years (p=0.008), focal seizure (p<0.001), hemiparesis (p<0.001), cerebellar signs (p<0.008), infarct (p=0.006), hemorrhage (p=0.049), edema (p=0.012) and midline shift (p=0.007), involvements of straight sinus (p=0.035), inferior sagittal sinus (p=0.007), frontal lobe (p=0.038), and Glasgow coma scale (GCS) score of 8–12 (p=0.008) were significantly associated with “poor outcome.” At 6 months, patients with focal seizures (p=0.001), hemiparesis (p=0.008), hemorrhage (p=0.044), midline shift (p=0.013), involvement of parietal lobe (p=0.025), presence of hemorrhage (p=0.044), and GCS score of 8–12 (p=0.001) significantly higher rate of “poor outcome.” Conclusion: This real-world observational study identifies the clinicodemographic and neuroimaging variables significantly associated with “poor outcome” in CSVT patients.

Assessing patiromer utilization and associated serum potassium changes in US veterans with prior sodium polystyrene sulfonate exposure.

Untreated chronic hyperkalemia is associated with an increased risk of mortality. Novel potassium binders (e.g., patiromer) are new additions to the clinician's armamentarium. Prior to their approval, clinicians often considered trialing sodium polystyrene sulfonate. The study objective was to assess patiromer utilization and associated changes in serum potassium (K+) in US veterans with prior sodium polystyrene sulfonate exposure. This was a real-world observational study of US veterans with chronic kidney disease and a baseline K+ ≥ 5.1 mEq/L, initiated on patiromer between January 1, 2016, and February 28, 2021. The primary endpoints were patiromer utilization (dispensations and treatment courses), and K+ change at 30-, 91-, and 182-day follow-up (FU) intervals. Patiromer utilization was described using Kaplan-Meier probabilities and the proportion of days covered. Descriptive changes in population average K+ were obtained from a pre-post design using single-arm within-patient pre-post lab pairs and paired t tests. Two hundred five veterans met the study criteria. We observed an average of 1.25 (95% CI, 1.19-1.31) treatment courses and a median treatment duration of 64 days. Fifty veterans (24.4%) had >1 course, and 17.6% of patients remained on their initial patiromer treatment course until the end of the 180-day FU. The mean K+ value was 5.73 mEq/L (5.66-5.79) at baseline, 4.95 mEq/L (95% CI, 4.86-5.05) at the 30-day interval, 4.93 mEq/L (95% CI, 4.84-5.03) at the 91-day interval, and 4.9 mEq/L (95% CI, 4.8-4.99) at the 182-day interval. Novel potassium binders (e.g., patiromer) are newer chronic hyperkalemia management tools for clinicians. The average population K+ decreased to <5.1 mEq/L at all follow-up intervals. Patiromer appeared to be well tolerated with nearly 18% of patients remaining on their initial treatment course during the entire 180-day FU period. The median treatment duration was 64 days and approximately 24% of patients initiated a second course during FU.

Lower limb cutaneous melanoma surgery: location matters

The anatomical location of cutaneous melanoma is a relevant independent prognostic factor in melanoma. The aim of the study is to know the prognosis of lower limb cutaneous melanoma related to their location within the limb, regardless of the histological type, and if there are any other influencing variables. A real-world data observational study was developed. The lesions were divided depending on the location of the melanoma (thigh, leg and foot). Bivariate and multivariate analysis were performed, and melanoma-specific survival and disease-free survival rates were calculated. When these analysis were done, the results showed that, in melanomas of the lower limb, location on the foot presented a lower melanoma-specific survival rate compared to more proximal locations, and only the anatomical location presents statistical significance to discriminate cases with a higher mortality risk and a lower disease-free survival rate among distal melanomas (mainly on the foot). In conclusion, this study confirms that a more distal location of lower limb cutaneous melanoma is a relevant prognostic factor.Trial registration number NCT04625491 retrospectively registered.

Characteristics of COVID-19 vaccinated and unvaccinated patients admitted to Careggi University Hospital, Florence, Italy

More than 11.5 billion COVID-19 vaccine doses have been administered around the world. Although vaccine effectiveness for severe infections is reported to be 89.0%, breakthrough infections are common and may lead to severe outcome in fragile population. We conducted a real-world observational study on 420 COVID-19 admitted patients from July 2021 to January 2022 in a tertiary level Italian hospital. We collected patient’s vaccination and SARS-CoV-2 serological status, SARS-CoV-2 treatments, oxygen supports, intensive (ICU) and subintensive (sub-ICU) care unit admissions, length of staying (LoS) and in-hospital mortality. One-hundred-seventy-two vaccinated and 248 unvaccinated patients were admitted during the study period. Vaccinated group (Vg) had a significantly more elevated Charlson Comorbidity Index than Unvaccinated group (UVg), and no statistical differences were found in terms of in-hospital mortality, LoS or ICU and sub-ICU admissions. Among Vg, anti-S antibodies were detected in 86.18% of patients (seropositives). Vaccinated seronegative patients’ in-hospital mortality was significantly higher than vaccinated seropositive patients (33.33% vs 10.69%, p = 0.0055): in particular, mortality rate in 45–69 years old population was higher in vaccinated seronegative group, and comparable in patients ≥ 70 years old. No differences in terms of outcome were registered between Vg and UVg, taking into account that Vg was considerably older and with more comorbidities. In line with other recent observations, higher mortality rate was evidenced for seronegative vaccinated patients. Primary prophylaxis and early treatments result to be necessary, especially for older and immunosuppressed populations.

Comparative cardiovascular effects of GLP-1 agonists using real-world data.

There is limited research using real-world data to evaluate protective cardiovascular effects of glucagon-like peptide-1 (GLP-1) agonists among adults with type 2 diabetes (T2D) early in treatment. We conducted a retrospective, active comparator cohort study using 2011-2015 administrative claims data to compare cardiovascular disease (CVD) event rates following initiation of exenatide extended-release (E-ER), exenatide immediate-release (E-IR) or liraglutide in T2D adults who previously received no other antidiabetic medication (ADM) except metformin. The primary outcome was time to first major adverse CVD event (ischaemic heart disease, stroke, congestive heart failure or peripheral arterial disease) after starting GLP-1. Cox proportional hazards regression was used to model the association between index GLP-1 and CVD events, adjusting for baseline patient, prescriber and plan characteristics. Primary analyses included all patients with ≥2 prescription fills for the index GLP-1, regardless of subsequent refill adherence or initiation of other ADM after index date. Compared with liraglutide, neither E-ER nor E-IR was associated with risk of composite major CVD events (hazard ratios [HRs] for E-ER and E-IR: 1.33 [95% C.I. 0.73-2.39] and 1.30 [0.81-2.09]). No associations were observed between event rates for individual CVD components. The HR for an ischaemic event with E-IR relative to liraglutide was 1.85 (95% C.I. 0.97-3.53). Adjusting for time-varying exposure to other ADM and CVD medications after index date produced similar results. Initiating either immediate or extended-release exenatide rather than liraglutide was not associated with significant differences in CVD risk in this observational real-world study.

Predictors of response to galcanezumab in patients with chronic migraine: a real-world prospective observational study.

Despite high efficacy and tolerability, not all patients with chronic migraine benefit from anti-CGRP monoclonal antibodies. We aimed to identify the clinical predictors of the response to galcanezumab treatment in patients with chronic migraine from real-world data. We prospectively recruited patients with CM who underwent galcanezumab injections between December 2019 and February 2022. Treatment response was determined after three months of follow-up and was defined as ≥ 50% reduction in monthly headache days. The migraine characteristics, comorbidities, and other treatment responses were compared between the responder and non-responder groups. Of 238 patients with CM, 153 (64.3%) showed treatment response. The responder group was younger, had lower frequency of baseline headache days, and had more accompanying symptoms such as nausea, vomiting, and photophobia. Better triptan response and less depression were also observed in the responder group. Multivariable regression analysis revealed that the everyday headache (OR = 0.351, 95% CI = 0.133-0.874, p = 0.017), depression (OR = 0.439, 95% CI = 0.216-0.896, p = 0.024) and absence of accompanying symptoms (OR = 0.314, 95% CI = 0.118-0.834, p = 0.020) were significantly associated with response to galcanezumab treatment. Our real-world data showed the efficacy of galcanezumab in patients with CM, regardless of medication overuse. Everyday headache, presence of depression, and absence of accompanying symptoms of migraine were significant predictors of a poor response.

SPADE: Design of a real-world observational study of avelumab first-line (1L) maintenance in advanced urothelial carcinoma (UC) in the Asia-Pacific (APAC) region.

TPS577 Background: UC is a common cancer, with &gt;200,000 new cases reported in the APAC region in 2020. In the global phase 3 JAVELIN Bladder 100 trial, avelumab 1L maintenance + best supportive care (BSC) significantly prolonged overall survival (OS) and progression-free survival (PFS) vs BSC alone in patients with advanced UC that had not progressed with 1L platinum-containing chemotherapy (median OS, 23.8 vs 15.0 months [p=0.0036]; median PFS, 5.5 vs 2.1 months [p&lt;0.0001]), leading to regulatory approvals worldwide and incorporation into international treatment guidelines with level 1 evidence. The objectives of the SPADE noninterventional study are to evaluate real-world patient characteristics, treatment patterns, patient-reported outcomes (PROs) and treatment outcomes with avelumab maintenance administered in patients with advanced UC without disease progression after 1L platinum-based chemotherapy in the APAC region. Methods: SPADE is a multicenter, prospective, observational study ongoing in Australia, Hong Kong, India, Japan, Republic of Korea, Singapore, Taiwan, and other countries. Overall, 286 patients with unresectable locally advanced or metastatic (stage IV) measurable UC of any histology that has not progressed with 1L platinum-containing chemotherapy, for whom avelumab 1L maintenance therapy is planned, will be enrolled. All patients will receive avelumab 800 mg intravenously every 2 weeks (or per local marketing authorization) and will be followed up for 12 months or until avelumab is discontinued. The decision to start avelumab treatment should be made in advance by the treating physician and per local clinical practice. Data collected will include patient demographics (ECOG performance status, renal function, history of UC, primary tumor location, location of metastases, and prior therapy), treatment details for 1L platinum-based chemotherapy (regimen, cycles, and response per RECIST), treatment details for avelumab 1L maintenance (interval from end of chemotherapy until initiation, duration of avelumab treatment, and planned subsequent treatment), and treatment outcomes with avelumab 1L maintenance (6- and 12-month OS and health-related quality of life). Data sources will include medical records collected during routine clinical care. Data for baseline treatment patterns will be summarized using descriptive statistics. OS will be analyzed using the Kaplan-Meier method. Health-related quality of life, including changes over time, will be measured using the EQ-5D-5L and National Comprehensive Cancer Network/Functional Assessment of Cancer Therapy Bladder Symptom Index (NCCN/FACT FBISI-18) questionnaires. An interim analysis is planned after ~30% of patients have been enrolled.

A UK real-world observational study of avelumab + axitinib (A + Ax) in advanced renal cell carcinoma (aRCC): 24-month interim results.

631 Background: Combination therapy with A + Ax in patients with previously untreated aRCC has shown superior progression-free survival (PFS) and objective response rate (ORR) vs sunitinib across all International Metastatic RCC Database Consortium (IMDC) risk groups. This study reports 24-month real-world outcomes in patients with aRCC receiving A + Ax in the UK. Methods: Patients were recruited from 9 UK sites. Inclusion criteria were diagnosis of aRCC, initiation of A + Ax on or after August 1, 2019, via the Early Access to Medicines Scheme, and age ≥18 years. The primary endpoints were overall survival (OS), PFS, ORR, and best response at 24 months post-A + Ax initiation. Data were analyzed descriptively. Total recruitment was 130 patients. Follow-up will continue until July 2023. Results: This analysis includes 78 patients with a minimum follow-up of 24 months. Median age at baseline was 66.6 years (range, 39.8-84.1 years); 76% (n=59) of patients were male, 63% (n=49) were White, 5% (n=4) were Asian/Asian British, and ethnicity was not recorded in 32% (n=25); 91% (n=71) had an Eastern Cooperative Oncology Group score of 0 or 1. IMDC risk status was favorable in 42% (n=33) of patients, intermediate in 41% (n=32), and poor in 17% (n=13). Median time between aRCC diagnosis and A + Ax initiation was 2.5 months (range, 0.03-90.4 months; n=77). Clear cell histology was the most prevalent (81% [n=63]); 68% (n=53) of patients had undergone nephrectomy, and 74% (n=58) had 1 or 2 metastatic sites at the index date. The OS rate at 24 months was 60% (95% CI, 49.4%-71.1%). The OS rates by IMDC risk status were: favorable, 76% (95% CI, 61.1%-90.4%); intermediate, 63% (95% CI, 45.7%-79.3%); and poor, 15% (95% CI, 0%-35.0%). The PFS rate at 24 months was 31% (95% CI, 20.5%-41.0%); median PFS was 9.1 months (95% CI, 7.9-13.4 months). ORR (n=76) at 24 months was 59% (95% CI, 48.2%-70.3%), with 4% (n=3) achieving complete response (CR) and 55% (n=42) partial response (PR). Best responses observed within 24 months were CR in 4% (n=3), PR in 54% (n=42), stable disease in 29% (n=23), and progressive disease in 10% (n=8) (2 not recorded). Median duration of response was 11.9 months (range, 0.4-23.7 months). Median time to discontinuation (TTD) of either A or Ax was 5.5 months (range, 0.5-20.5 months; n=50). Median TTD of A + Ax combined was 5.6 months (range, 0.8-20.5 months; n=43). Of 78 patients, 62 experienced an adverse event (AE) due to A + Ax treatment, 8 of whom had 14 serious AEs in total. The most common AEs were diarrhea (n=31), fatigue (n=22), and rash or oral mucositis (n=18 each); 3 patients discontinued Ax due to AEs including diarrhea (n=2), abnormal hepatic function (n=1), and abdominal pain (n=1). Conclusions: This UK-based real-world study of A + Ax treatment reports 24-month clinical outcomes in patients with aRCC. OS, PFS, ORR, and best response were in line with findings from prior clinical trials, with no new emerging AEs.

Effect of dulaglutide injection on weight beyond glycemic control: real-world observational study

Dulaglutide is an effective Glucagon-like Peptide-1 (GLP-1) Receptor Agonist (RA) in optimizing weight and glycemic control in obese patients with Type 2 Diabetes Mellitus (T2DM). The study's objective was the real-world evaluation of the metabolic effect of Dulaglutide on weight and glycemic control in patients with T2DM from Southern Iraq. This study is a six-month observational prospective longitudinal evaluation of 185 obese individuals with T2DM. They were initiated on Dulaglutide as an add-on drug with Oral Antidiabetic (OAD) or insulin therapy. General characteristics of the patients, glycated hemoglobin (HbA1c), blood glucose, lipid profile, and side effects profile were evaluated at the enrollment and the end of the study. The enrolled 185 obese patients with T2DM, had a T2DM duration (2 -14 years) and initial HbA1c range (6 - 19.5%), with different treatment modalities, including insulin, OADs, or both. The study showed a significant reduction in weight, HbA1c, and serum cholesterol, with minimal hypoglycemic events in 5% of patients (n=9). The gastrointestinal side effects were mild to moderate and self-limited in &gt;96% of patients (n=178), while they were so severe in 4% (n=7) and caused discontinuation of Dulaglutide. Therefore, the insulin regimen was either stopped (n=28), changed (n=7), or reduced (n=9). No change on oral medications was performed in 141 patients. In conclusion, Dulaglutide 1.5 mg administered once a week significantly reduced the weight, HbA1c, Self-Monitoring of Blood Glucose (SMBG), and cholesterol levels with minimal hypoglycemic risk.

Long-Term Results with Everolimus in Advanced Hormone Receptor Positive Breast Cancer in a Multicenter National Real-World Observational Study

Everolimus is the first oral targeted therapy widely used in advanced HR+/HER2- breast cancer. We sought to evaluate the impact of everolimus-based therapy on overall survival in the ESME-MBC database, a national metastatic breast cancer cohort that collects retrospective data using clinical trial-like methodology including quality assessments. We compared 1693 patients having received everolimus to 5928 patients not exposed to everolimus in the same period. Overall survival was evaluated according to treatment line, and a propensity score with the inverse probability of treatment weighting method was built to adjust for differences between groups. Crude and landmark overall survival analyses were all compatible with a benefit from everolimus-based therapy. Adjusted hazard ratios for overall survival were 0.34 (95% CI: 0.16-0.72, p = 0.0054), 0.34 (95% CI: 0.22-0.52, p < 0.0001), and 0.23 (95% CI: 0.14-0.36, p < 0.0001) for patients treated with everolimus in line 1, 2, and 3 and beyond, respectively. No clinically relevant benefit on progression-free survival was observed. Causes for everolimus discontinuation were progressive disease (56.2%), adverse events (27.7%), and other miscellaneous reasons. Despite the limitations inherent to such retrospective studies, these results suggest that adding everolimus-based therapy to the therapeutic sequences in patients with advanced HR+/HER2- breast cancer may favorably affect overall survival.

Diabetes Technology and Therapy in the Pediatric Age Group.

Diabetes Technology and Therapy in the Pediatric Age Group.

P523 Quality, safety and equity of care outcomes for inflammatory bowel disease patients at four tertiary referral centres in Australia using a cloud based management system Crohn’s Colitis Care (CCCare): A real world observational study.

Abstract Background Inflammatory bowel disease (IBD) is a global problem and Australia has amongst the highest prevalence rates. This study looked to assess the quality, safety and equity of care across four specialised IBD centres in Australia over a 12-month period using the cloud-based IBD clinical management system called Crohn’s Colitis Care (CCCare). This study aimed to define existing care at each centre and the range of performance across each centre to propose potential benchmarks for optimal quality IBD care. Methods The study was conducted across four tertiary IBD centres in Australia (Centres A, B, and C were public hospitals and D was a private centre). De-identified data within the backend CCCare research registry was audited between 1st of July 2021 to 31st August 2022. People with IBD who had a clinical assessment documented within the platform during this 12-month period were included. We assessed quality of IBD care using disease activity based on patient reported outcome measures (PROMs), biomarkers and endoscopy; surgery rates; health maintenance indicators including vaccination and skin cancer screening rates and; key performance indicators including steroid use, smoking rates and current opioid use. Safety of care was assessed using adverse events from therapy and hospital admission due to therapeutic complications. Equity of care examined education levels and ethnicity. Results A total of 1889 patients were included. 63% had Crohn’s disease and 37% had ulcerative colitis. 51% of the cohort was female. The median age was 39 years (IQR 30-53) and the median disease duration was 8.4 years (IQR 3.3-15.7) (Table 1). Current steroid use was between 6% to 15.4%. Faecal calprotectin (FCP) remission rates (250μg/mg) were between 65-84% and patient reported outcome (PRO-2) remission rates were between 76-88% with the highest rates observed at Centre D (Figure 1). 74 patients underwent a surgical procedure. COVID-19 vaccination rates were between 40.1% to 88.8% with the highest rates once again observed at Centre D. 3% of the cohort was documented as currently using opioid medications. 12.2% were recorded as currently smoking at Centre A compared to 2.6% at Centre D. 55 medication related adverse events were recorded and 94 patients had a hospital admission during the study period. Conclusion This study showcases how CCCare can readily provide researchers with granular, real-world data to audit the quality of IBD care at 4 specialised centres in Australia over a 12-month period. While there were some differences (higher vaccination rates, lower smoking and steroid use rates at Centre D), quality and safety of care was still fairly uniform across the various sites and can serve as a standard of care for IBD patients in Australia.

P387 Different rate of transmural remission between first and second line of biologic treatment in Crohn's disease

Abstract Background Transmural remission in Crohn’s disease (CD) has been associated with improved long-term clinical outcomes including reduced hospitalization, surgery, escalation of treatment, and a decrease in clinical relapse over endoscopic remission alone. Albeit transmural remission rate (TRR) in CD patients treated with anti-TNF drugs in first line has been well explored, data on TRR using vedolizumab (VDZ) or ustekinumab (UST) as second-line therapy for CD are still scarce. The aim of this study was to evaluate the TRR in CD patients in maintenance treatment, comparing adalimumab (ADA) in first line with VDZ/UST in second line. Methods From 2018 to 2021 we performed a real world observational longitudinal study evaluating the TRR in all consecutive CD patients in a 2-years maintenance treatment with ADA in first line compared with those treated by VDZ or UST in second line. HBI, fecal calprotectin (FC), SES-CD, and bowel wall thickness (BWT) at ultrasound were analyzed in all patients at the baseline (T0) and after 2 years of maintenance treatment (T1). Clinical remission was defined when HBI was &amp;lt;4. Endoscopic remission was defined when SES-CD was &amp;lt;2. Transmural remission was defined when BWT was &amp;lt;3 mm at a “per-patient” analysis. In accordance with recent literature, laboratory remission was defined when FC was &amp;lt;94 ug/gr. Results One hundred and forty-one CD patients (78 ADA, 31 VDZ, 32 UST) were included in the study. At T1, transmural remission rate was recorded in 39.7% of CD patients treated in first line with ADA, and in 22.5% and 18.7% for VDZ and UST, respectively, in second line (ADA vs VDZ/UST: p&amp;lt;0.05; VDZ vs UST: p 0.7). Endoscopic remission rate was 50% for patients treated in first line with ADA, and 32.2% and 31.2% for second line VDZ and UST, respectively (ADA vs VDZ/UST: p&amp;lt;0.05; VDZ vs UST: p 0.9). Laboratory remission rate was 53.8% for patients treated in first line with ADA, and 29% and 37.5% for VDZ and UST in second line, respectively (ADA vs VDZ/UST: p&amp;lt;0.05; VDZ vs UST: p 0.4). Clinical remission rate was 58.9% for patients treated in first line with ADA, and 45.1% and 40.6% for second line VDZ and UST, respectively (ADA vs VDZ/UST: p=0.057; VDZ vs UST: p=0.7). Conclusion Our findings showed that in CD patients in maintenance treatment with biologics, ADA in first line showed a higher TRR compared with VDZ/UST in second line. Moreover, VDZ and UST showed similar TRR and other outcomes when used in second line.

P631 Long-term safety of vedolizumab versus other biologic agents in ulcerative colitis (UC) and Crohn’s Disease (CD): Results from a large multinational prospective observational study

Abstract Background Vedolizumab (VDZ) is a gut-selective humanised monoclonal anti-α4β7 integrin antibody for treatment of UC and CD. This post-authorization safety study (PASS) compared long-term safety in patients (pts) treated with VDZ or other biologics for UC or CD. Methods This was a prospective, observational, multicentre, cohort study in pts with UC or CD starting treatment with VDZ or other biologics (NCT02674308, EUPAS6469). Pts were biologic naïve (VDZ=35%, Other biologic=65%) or had prior exposure to biologics other than VDZ and were followed for up to 7 yrs. Pts were treated under usual standard of care as directed by their physician with no discontinuation from the study due to physician-directed treatment changes. The primary safety outcome was serious infections and was compared between cohorts using a Cox proportional hazards model adjusted by propensity score (with other biologics as reference). Secondary safety outcomes were adverse events (AE) of special interest (AESI) as listed in Tables 2 and 3. Results In total, 5208 patients were enrolled across 21 countries between Mar 2015 and Jul 2019. The full analysis set comprised 5008 pts (VDZ=2502; other biologic=2506) and mean (SD) study duration was 37.4 (14.1) months. Consistent with the observational nature of the study and the current standard of care, the baseline characteristics in the two cohorts were imbalanced (Table 1). The overall treatment-emergent Adverse Event (AE) rate was 61.3% (VDZ) and 59.5% (other biologic), with serious AEs in 27.5% (VDZ) and 25.7% (other biologic), respectively. In UC pts, the incidence rate (IR) of serious infections were: 0.014 (95% CI: 0.010, 0.019) [VDZ] and 0.015 (0.010, 0.023) [other biologic], with a hazard ratio (HR) of 1.018 (0.931, 1.114), p=0.70 (Table 2). In CD pts, corresponding findings were 0.012 (95% CI: 0.008, 0.017) [VDZ] and 0.006 (95% CI: 0.004, 0.009) [other biologic] with HR of 1.035 (0.959, 1.117), p=0.38 (Table 3). The incidence of primary and secondary safety outcomes is reported in Table 2 for UC and Table 3 for CD. There were no safety issues relating to pregnancy and no cases of PML observed. There were 19 deaths in the VDZ cohort (1 case of pneumonia deemed as treatment-related); and 13 deaths in the other biologic cohort, 2 cases deemed treatment-related (one case septic shock and pneumonia; one case non-small cell lung cancer). Clinical outcomes and quality of life (QoL) measures were comparable between cohorts. Conclusion In this long-term, prospective, real-world observational study of a large multinational population under routine standard of care there was no new safety signal identified in relation to VDZ. Results are consistent with the known safety profile of VDZ.

Bevacizumab versus Ramucirumab in EGFR-Mutated Metastatic Non-Small-Cell Lung Cancer Patients: A Real-World Observational Study.

The combination of bevacizumab or ramucirumab with epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) therapy, chemotherapy, or immunotherapy for non-small-cell lung cancer (NSCLC) patients with EGFR mutations could have survival benefits. However, no study, to date, has been conducted to compare the efficacy and safety of these two antiangiogenic therapies (AATs). Stage IIIB to IV EGFR-mutated NSCLC patients who received first-line EGFR-TKIs between January 2014 and May 2022 were enrolled. These patients were divided into two groups: those receiving bevacizumab and those receiving ramucirumab as a combination therapy in any line of treatment. Ninety-six patients were enrolled in this study's final analysis. The progression-free survival (PFS) of patients who received front-line AATs combined with EGFR-TKI therapy was longer than that of patients receiving later-line AATs combined with other therapies (19.6 vs. 10.0 months, p < 0.001). No difference in overall survival (OS) was observed between front-line and later-line therapy (non-reach vs. 44.0 months, p = 0.261). Patients who received these two different AATs did not differ in PFS (24.1 vs. 15.7 months, p = 0.454) and OS (48.6 vs. 43.0 months, p = 0.924). In addition, these two AATs showed similar frequencies of the T790M mutation (43.6% vs. 38.2%; p = 0.645). Multivariate Cox regression analysis indicated several AAT cycles as an independent good prognostic factor in OS. The incidence of some adverse events such as bleeding and hepatitis was higher for bevacizumab than for ramucirumab but it was not significant. Front-line AAT and EGFR-TKI combination therapy improved the PFS of stage IV EGFR-mutated NSCLC patients. The effectiveness and safety of the two AATs were similar.