Prospective Real-world Study Research Articles

Outcomes of switching from crizotinib to alectinib in patients with advanced non-small cell lung cancer with anaplastic lymphoma kinase fusion.

BackgroundAlectinib and crizotinib have been approved as first-line therapies for advanced non-small cell lung cancer (NSCLC) with anaplastic lymphoma kinase (ALK) gene fusion. However, the therapeutic efficacy and side effects are still largely unknown of patients who switched to next-generation ALK tyrosine kinase inhibitors (ALK-TKIs), such as alectinib, after experiencing no disease progression with initial crizotinib treatment.MethodsThis prospective real-world study enrolled patients who were treated with alectinib after experiencing no disease progression with initial crizotinib treatment. The patients’ baseline characteristics, objective response rate (ORR) of crizotinib and alectinib, size change of target tumor lesions, treatment regimen and adverse events (AEs) were collected and analyzed.ResultsThe study included 53 patients, the majority of whom (96.2%) had non-squamous NSCLC. The median age was 51 (range, 31–80) years old. The ORR of first-line crizotinib was 54.7%. The ORR of sequential alectinib was 73.6%, and 90.5% of patients showed further tumor shrinkage after the alectinib treatment. The median progression-free survival was not reached, and 90.5% of patients were still enrolled in the study at the last follow-up. Among them, 34.0% of patients switched to alectinib treatment due to the toxicity. Crizotinib was associated with a higher frequency of AEs of grades 3 and 4 than alectinib (15.1% vs. 0%). Neither group had any AEs resulting in death.ConclusionsSwitching to alectinib might be an option for patients who do not experience disease progression with initial crizotinib therapy, and may promote better treatment compliance.

Camrelizumab in combination with TACE for the treatment of unresectable hepatocellular carcinoma (HCC): A multicenter, single-arm, prospective real-world study.

e16114 Background: Transcatheter arterial chemoembolization (TACE) is considered to be the first-line topical therapy for unresectable hepatocellular carcinoma (HCC). However, the long-term efficacy of single TACE treatment is poor, with a five-year survival rate of 8%-43%. This study aims to investigate the efficacy and safety of TACE combined with camrelizumab in the treatment of unresectable HCC. Methods: This is a single-arm, prospective real-word study conducted in 14 hospitals in Jiangsu, China. Patients diagnosed with HCC received Camrelizumab (200mg, i.v. Q2W or Q3W) with or without antiangiogenic therapy (apatinib, lenvatinib, sorafenib, or regorafenib) at any stage of the TACE treatment. The primary endpoint was progression-free survival (PFS). Secondary endpoints were overall survival (OS), objective response rate (ORR), disease control rate (DCR), and safety. Kaplan-Meier method was used for survival analysis. This study was registered with ChiCTR.org.cn, number ChiCTR1900026163. Results: From September 2019 to January 2021, 151 patients were enrolled, of whom most were males and younger than 65 years, 92 (60.93%) had extrahepatic metastasis and 120 (79.47%) suffered from HBV infection, 59 (39.07%) had an AFP concentration of 400 ng/mL or higher, 150 (99.34) had an ECOG PS of 0 or 1, a Child-Puph score of A or B, and were classified as BCLC Stage B or C. In addition to TACE, 52 patients received camrelizumab alone, while the others also received antiangiogenic therapy. Most (139, 92.06%) of the patients received camrelizumab 200mg every 3 weeks. Of the 112 patients who were available for efficacy evaluation, 4 patients achieved CR, 25 achieved PR, and 53 achieved SD, resulting in an ORR of 25.89% and DCR of 73.21%. The median PFS was 4.27 months (95% CI, 3.45 to 7.36 months) and the median OS was 14.0 months (95% CI, 10.6 to NE months). The safety data were obtained from 140 patients. Treatment-related adverse events (TRAEs) occurred in 130 (92.86%) patients, with the commonest types including increased alanine and aspartate aminotransferases (65%), thrombocytopenia (57.86%), hypoalbuminemia (54.29%), hyperbilirubinemia (48.57%), anemia (42.86%), leukopenia (42.14%), neutropenia (37.14%) and proteinuria (20.71%). Severe AEs occurred in 52 (37.14%) patients, with the commonest types including thrombocytopenia (17.14%), increased alanine and aspartate aminotransferases (13.57%), neutropenia (8.57%) and hyperbilirubinemia (7.14%). Conclusions: The treatment strategy of TACE in combination with camrelizumab with or without antiangiogenic therapy showed encouraging clinical efficacy and manageable toxicity profile in treating unresectable HCC, which provided a new treatment option for HCC. Clinical trial information: ChiCTR1900026163.

OP0262-HPR THE NEURO-QOL UPPER EXTREMITY FUNCTION SCALE: NEW OPPORTUNITIES TO MORE RELIABLY AND PRECISELY MEASURE SELF-REPORTED HAND FUNCTION AND SELF-CARE ACTIVITIES IN PEOPLE WITH RA

Background:RA is an inflammatory disease that results in pain and loss of function, especially in the hands and wrists. Brief self-assessment tools that can reliably and precisely quantify hand/wrist function are needed to assess inflammatory activity when a physical exam is not feasible and to capture day-to-day experience of living with RA. Neuro-QoL is part of the PROMIS family of self-report measures created using a patient-centred approach and IRT methodology. The Neuro-Qol Upper Extremity Function (UEF) scale measures ability across fine motor and ADLs involving digital, manual and reach-related function and self-care. Little is known about its performance in RA.Objectives:To evaluate the validity and responsiveness of the 8-item Neuro-QoL UEF in RA. We hypothesized scores would be strongly (r>.70) associated with MHAQ, MD-HAQ, and PROMIS PF, moderately (r=.4 to .7) to symptoms, disease activity, and QoL indicators, and be responsive to change in disease activity and PF.Methods:Data were from the 0 and 6-month visits of adults with early RA (sx <1 yr) enrolled in the Canadian Early Arthritis Cohort, a prospective real-world study at 16 sites across Canada. Participants completed the Neuro-QoL UEF, MHAQ, MDHAQ, PROMIS-29, and PT Global at each visit. Rheumatologists recorded joint counts and MD Global. To evaluate content validity, we examined descriptive statistics across CDAI disease activity levels, and Pearson correlations between the Neuro-QOL UEF, legacy measures, CRP & ESR. Responsiveness was assessed by correlating change scores from visits 0-6 between Neuro-QoL UEF, disease activity and legacy PF scores.Results:The 262 participants were mostly white (83%) women (71%) with a mean (SD) age of 55 (13). Summary statistics at 6-months are shown in Table 1. Neuro-QOL UEF was moderately-strongly correlated with MHAQ, MDHAQ, PROMIS-PF (|r|=.63-.75) and moderately correlated with pain and stiffness, (|r|=.59, -.64), and CDAI, SDAI, PT&MD Global, TJ & SJ (|r|=.39-.58). Neuro-QOL UEF was moderately correlated with PROMIS QoL domains Pain, Fatigue, Anxiety, Depression, Sleep & Participation (|r|=.39-.60).Table 1.Summary statistics of physical function and RA disease activity indices at 6 months.MeanSDMdn25%75%(Min, Max)Physical FunctionNeuro-Qol UEF46.59.753.837.553.8(21.8, 53.8)MHAQ (0-3)0.290.430.130.000.38(0.00, 2.25)MD-HAQ (0-10)1.391.640.700.002.00(0.00, 8.00)PROMIS-PF46.48.546.239.556.0(23.3, 56.0)RA Disease ActivityCDAI9.39.96.03.013.0(0.0, 56.0)SDAI10.710.96.83.115.2(0.0, 57.0)Patient Global3.02.5315(0, 10)MD Global1.82.2103(0, 9)Swollen Joints (28)2.13.7002(0, 20)Tender Joints (28)2.43.9103(0, 24)Neuro-QOL scores decreased in a dose-response manner across worsening CDAI DA states reflecting increasing impairment (Table 2). Persons with HDA reported the highest disability, scoring nearly 0.5 SD lower on the Neuro-QoL UEF than PROMIS PF. Change from baseline to 6 months in Neuro-QoL UEF was moderately correlated with changes in PROMIS PF, MHAQ, PT Global, and CDAI (|r|=.44-.65). The mean change and range from 0-6 months in Neuro-QoL was significantly larger than in PROMIS (8.9 [95% CI 7.5, 10.4] vs. 5.4 [95% CI 4.4, 6.4])(see Figure).Table 2.Mean scores (95% CI) at 6 months by CDAI level.REMLDAMDAHADNeuroQol UEF52.8 (51.8, 53.7)48.1 (46.6, 49.7)42.0 (39.4, 44.6)33.8 (30.5, 37.1)MHAQ (0-3)0.05 (0.02, 0.09)0.19 (0.14, 0.24)0.45 (0.34, 0.57)0.90 (0.63, 1.17)MD-HAQ (0-10)0.31 (0.17, 0.46)1.11 (0.90, 1.32)2.15 (1.71, 2.59)3.56 (2.56, 4.56)PROMIS-PF52.8 (51.4, 54.2)46.8 (45.3, 48.2)42.3 (40.4, 44.2)38.0 (34.4, 41.6)Conclusion:Clinicians, researchers, and patients benefit from practical self-report tools that reliably and precisely monitor hand function in RA. Results offer initial evidence of validity and responsiveness and support use of Neuro-QoL UEF to self-assess inflammatory activity in the hands and day-to-day experiences of living with RA.Acknowledgements:The CATCH study was designed and implemented by the investigators and financially supported through unrestricted research grants from: Amgen and Pfizer Canada - Founding sponsors since January 2007; AbbVie Corporation and Hoffmann-LaRoche since 2011; Medexus Inc. since 2013;, Merck Canada since 2017, Sandoz Canada, Biopharmaceuticals since 2019,Gilead Sciences Canada since 2020 and Fresenius Kabi Canada Ltd. since 2021. Previously funded by Janssen Biotech from 2011-2016, UCB Canada and Bristol-Myers Squibb Canada from 2011-2018, Sanofi Genzyme from 2016-2017, and Eli Lilly Canada from 2016-2020.Disclosure of Interests:None declared

Predictive value of pentraxin-3 on disease severity and mortality risk in patients with hemorrhagic fever with renal syndrome

BackgroundHemorrhagic fever with renal syndrome (HFRS) caused by Hantaan virus is characterized by systemic immunopathological injury. Pentraxin-3 is an acute-phase reactant involved in the processes of inflammation and infection. This study aimed to investigate the levels of plasma pentraxin-3 and evaluate its predictive value on disease severity and mortality risk in patients with HFRS.MethodsThis was a prospective real-world observational study. The concentrations of plasma pentraxin-3 were measured by enzyme linked immunosorbent assay (ELISA) in 105 HFRS patients and 27 healthy controls. We analyzed the clinical relevance between pentraxin-3 and clinical subtyping, hospital stay and conventional laboratory parameters of HFRS patients. Considering the prognosis (death) as the primary endpoint, the levels of pentraxin-3 between survivors and non-survivors were compared, and its association with mortality was assessed by Kaplan-Meier survival analysis. The predictive potency of pentraxin-3 for mortality risk in HFRS patients was evaluated by receiver operating characteristic (ROC) curve analysis.ResultsThe levels of pentraxin-3 during the acute phase were increased with the aggravation of the disease, and showed the highest expression in critical-type patients (P < 0.05). Pentraxin-3 demonstrated significant correlations with conventional laboratory parameters (WBC, PLT, AST, ALB, APTT, Fib) and the length of hospital stay. Compared with the survivors, non-survivors showed higher levels of pentraxin-3 and worse expressions of conventional laboratory parameters during the acute phase. The Kaplan-Meier survival curves showed that high levels of pentraxin-3 during the acute phase were significantly associated with the death in HFRS patients. Pentraxin-3 demonstrated significant predictive value for the mortality risk of HFRS patients, with the area under ROC curve (AUC) of 0.753 (95%CI: 0.593 ~ 0.914, P = 0.003).ConclusionsThe detection of plasma pentraxin-3 might be beneficial to the evaluation of disease severity and to the prediction of mortality risk in HFRS patients.

Safety, effectiveness and costs of percutaneous mitral valve repair: A real-world prospective study.

AimsPercutaneous mitral valve leaflet repair is a treatment option for some people with severe mitral valve regurgitation for whom conventional mitral valve surgery is clinically inappropriate. This study aimed to determine the safety, efficacy, and costs of percutaneous mitral valve leaflet repair, using the MitraClip device in a UK setting.Methods and resultsThis was a prospective, single-armed registry with a follow-up of 2 years that reported a range of procedural, clinical and patient-orientated outcomes. Registry data were linked to routine data sources to allow for more comprehensive follow up concerning mortality and healthcare resource use. The registry received data for 199 mainly elective patients with mixed mitral regurgitation aetiology. A MitraClip device was implanted in 187 patients (94%), with a procedural success rate of 86%, with 8% of patients having a serious in-hospital adverse event (including 5% mortality). Percutaneous mitral valve leaflet repair reduced mitral regurgitation from 100% MR grade ≥ 3+ to 7% at discharge. There were corresponding improvements in New York Heart Association functional class, reducing from 92% (class ≥ 3) at baseline to 18% at 6 weeks. There were significant improvements in generic and disease specific quality of life indicators up to 2 years. The all-cause mortality rate was estimated to be 12.7% (95% CI 7.5 to 17.7%) at 1 year. Percutaneous mitral valve leaflet repair was associated with reduced hospital readmissions and potential cost-savings in post-procedural care.ConclusionThis study shows that percutaneous mitral valve leaflet repair using MitraClip is a relatively safe and effective treatment in patients unable to tolerate surgery and has the potential to reduce ongoing healthcare costs in the UK.

Implementation of Wearable Sensors and Digital Alerting Systems in Secondary Care: Protocol for a Real-World Prospective Study Evaluating Clinical Outcomes.

BackgroundAdvancements in wearable sensors have caused a resurgence in their use, particularly because their miniaturization offers ambulatory advantages while performing continuous vital sign monitoring. Digital alerts can be generated following early recognition of clinical deterioration through breaches of set parameter thresholds, permitting earlier intervention. However, a systematic real-world evaluation of these alerting systems has yet to be conducted, and their efficacy remains unknown.ObjectiveThe aim of this study is to implement wearable sensors and digital alerting systems in acute general wards to evaluate the resultant clinical outcomes.MethodsParticipants on acute general wards will be screened and recruited into a trial with a pre-post implementation design. In the preimplementation phase, the SensiumVitals monitoring system, which continuously measures temperature, heart, and respiratory rates, will be used for monitoring alongside usual care. In the postimplementation phase, alerts will be generated from the SensiumVitals system when pre-established thresholds for vital parameters have been crossed, requiring acknowledgement from health care staff; subsequent clinical outcomes will be analyzed.ResultsEnrolment is currently underway, having started in September 2017, and is anticipated to end shortly. Data analysis is expected to be completed in 2021.ConclusionsThis study will offer insight into the implementation of digital health technologies within a health care trust and aims to describe the effectiveness of wearable sensors for ambulatory continuous monitoring and digital alerts on clinical outcomes in acute general ward settings.Trial RegistrationClinicalTrials.gov NCT04638738; https://clinicaltrials.gov/ct2/show/NCT04638738.International Registered Report Identifier (IRRID)DERR1-10.2196/26240

High‐frequency spinal cord stimulation as rescue therapy for chronic pain patients with failure of conventional spinal cord stimulation

This study aims to evaluate the efficacy of 10-kHz high-frequency (HF10) devices as a rescue treatment in patients with failure of conventional spinal cord stimulation (SCS) therapy for chronic pain without the need to change the spinal hardware. In this real-world prospective study, patients with neuropathic pain treated with conventional tonic SCS in whom the therapy had failed, either during the trial phase or after a period of optimal functioning, were recruited throughout 2years for HF10-SCS therapy. Data on analgesia, functionality, analgesics use and treatment safety were collected 12months after treatment. Eleven of the 18 (61%) patients included in the study were successfully rescued with HF10-SCS. Of them, 5 out of 12 (45%) were in the trial phase and six out of six (100%) had previously functioning implants. A significant improvement in low-back and limb pain was obtained (p=0.003 and p=0.0001, respectively). Treatment success was significantly associated with gender (p=0.037), weight (p=0.014), body mass index (BMI) (p=0.007) and time of rescue (p=0.015). A linear regression test confirmed a significant association between treatment failure and BMI and gender (p=0.004). Our results suggest that analgesic rescue with HF10-SCS is an effective therapeutic option for non-responders to conventional SCS, although obesity might be a limiting factor for treatment success. Nevertheless, more comprehensive studies are needed to corroborate our findings. This study shows that high-frequency stimulation may be useful in patients with failure of conventional tonic stimulation for chronic pain, both in the trial phase and in previously implanted subjects. The novelty of this study lies in the use of the implanted epidural electrodes, which avoids the need for further surgery. The results in terms of pain control and recovery of functionality are satisfactory. In addition, variables such as male gender and high body mass index could be predictors of therapy failure.

A Real-World Prospective Study of the Safety and Effectiveness of the Loop Open Source Automated Insulin Delivery System.

Objective: To evaluate the safety and effectiveness of the Loop Do-It-Yourself automated insulin delivery system.Research Design and Methods: A prospective real-world observational study was conducted, which included 558 adults and children (age range 1–71 years, mean HbA1c 6.8% ± 1.0%) who initiated Loop either on their own or with community-developed resources and provided data for 6 months.Results: Mean time-in-range 70–180 mg/dL (TIR) increased from 67% ± 16% at baseline (before starting Loop) to 73% ± 13% during the 6 months (mean change from baseline 6.6%, 95% confidence interval [CI] 5.9%–7.4%; P < 0.001). TIR increased in both adults and children, across the full range of baseline HbA1c, and in participants with both high- and moderate-income levels. Median time <54 mg/dL was 0.40% at baseline and changed by −0.05% (95% CI −0.09% to −0.03%, P < 0.001). Mean HbA1c was 6.8% ± 1.0% at baseline and decreased to 6.5% ± 0.8% after 6 months (mean difference = −0.33%, 95% CI −0.40% to −0.26%, P < 0.001). The incidence rate of reported severe hypoglycemia events was 18.7 per 100 person-years, a reduction from the incidence rate of 181 per 100 person-years during the 3 months before the study. Among the 481 users providing Loop data at 6 months, median continuous glucose monitoring use was 96% (interquartile range [IQR] 91%–98%) and median time Loop modulating basal insulin was at least 83% (IQR 73%–88%).Conclusions: The Loop open source system can be initiated with community-developed resources and used safely and effectively by adults and children with type 1 diabetes.

Prospective observational study on Stelara (ustekinumab) assessing effectiveness in Crohn’s disease (PROSE): a 16-week follow-up

Background Prospectively and systematically collected real-world data on the effectiveness of ustekinumab (anti-interleukin-12/23) for treating Crohn’s disease (CD) are still limited. Aim To assess the short-term real-world effectiveness of ustekinumab in Swedish patients with active CD. Methods Prospective multicentre study of adult CD patients initiating ustekinumab according to recommended doses at 20 hospitals, between January 2017 and November 2018. Data were collected through an electronic case report form (eCRF) linked to the Swedish Inflammatory Bowel Disease Registry (SWIBREG). The primary outcomes were clinical response (≥3-point-decrease of Harvey–Bradshaw index (HBI)) and remission (HBI ≤4 points) at week 16. Secondary outcomes included C-reactive protein (CRP) and haemoglobin (Hb) at baseline compared to week 16. Results Of 114 included patients, 107 (94%) had failed ≥ 1 and 58 (51%) ≥ 2 biological agents (anti-tumour necrosis factor [aTNF] agents or vedolizumab). The 16-week ustekinumab retention rate was 105 (92%). Data on HBI at baseline were available for 96 patients. At week 16, response or remission was achieved in 38/96 (40%) patients (25/96 (26%) achieving clinical remission and 23/96 (24%) showing a clinical response). The median CRP concentration (N = 65) decreased from 6 to 4 mg/l (p = .006). No significant changes in Hb were observed. No incident malignancies or infections, requiring antibiotic treatment, were reported. Conclusions In this nation-wide prospective real-world study of adult patients with CD, ustekinumab was associated with clinical effectiveness when administered according to clinical practice and seemed to represent a safe treatment option.

Valuing Out-of-Pocket Expenditure and Health Related Quality of Life of COVID-19 patientsfrom Gujarat, India

Background: COVID-19 has financially burdened Government’s healthcare system as well as households with COVID-19 patients. Present study aims to value the out-of-pocket expenditure and health-related quality of life (HRQOL) using EQ-5D-5L among COVID-19 patients who sought treatment in COVID-19 center of a tertiary hospital in Vadodara, Gujarat. Methods: The present analysis is a prospective real-world study. The questionnaire included socio-demographic data, health status, out-of-pocket expenses associated with treatment of COVID-19, and EQ-5D-5L scale. The relationships of all factors and the scores of EQ-5D-5L were analyzed. All costs are reported in Indian Rupees and then converted to US dollars. Result: Out of total 138 participants included in the study, 108 (78.3%) participants had mild to moderate symptoms of COVID-19 infection and were admitted to COVID Care Centre (CCC) while 30 (21.7%) patients had severe disease and were admitted to COVID Intensive Care Unit (ICU). Mean total out of pocket expenditure for the patient admitted to COVID CCC and COVID ICU was INR 11,333.07 (31,707.68) and 27,374.17 (54,205.72) respectively. The respondents obtained a mean EQ-5D-5L index score of 0.755 (±0.180) for patients under COVID CCC and 0.513 (±0.378) for COVID ICU admitted patients. EQ-VAS index was 75.05 (±12.12) and 62 (±16.37) respectively, signifying the HRQoL from patient’s perspective. Conclusion: COVID-19 patients have suffered from significant physical and psychological impairment. It is essential to prospectively monitor the individuals who suffered from COVID-19 to understand the long term impact on HRQoL, as well as to inform prompt and efficient interventions to alleviate suffering.

Effectiveness and safety of iguratimod treatment in patients with active rheumatoid arthritis in Chinese: A nationwide, prospective real-world study

BackgroundThere is heterogeneity in the clinical manifestations and responses to drugs in RA patients due to variety of factors such as genes and environment. Despite advances in the treatment of rheumatoid arthritis (RA), approximately 40% of RA patients still do not achieve primary clinical outcomes in randomized trials, and its low remission rate and high economic consumption remain unresolved, especially in developing countries. Iguratimod (IGU) is a new disease-modifying anti-rheumatic drug (DMARD) with a low price that has demonstrated good efficacy and safety in clinical trials and was approved for active RA in China and Japan. As the most populous country in the Western Pacific region, it is warranted to conduct a study with a large scale of patients in a real-life setting. Our study confirms the new option for RA patients, which is potentially benificial for public health in developing countries. MethodsThis was a nationwide, prospective real-world study of IGU. Eligible subjects were active adult RA patients who aged 18 to 85 with or without multiple comorbidities such as hypertension and diabetes with DMARDs at a stable dosage for at least 12 weeks, or without ongoing DMARDs. A two-stage design was used for this study. In the first stage (the first 12 weeks), IGU 25 mg bid was added as monotherapy or to the background therapy, and in the second stage (the latter 12 weeks), adjustment of RA medicines other than IGU was allowed according to the participants’ disease activity. The primary endpoints were American College of Rheumatology 20% response (ACR20) 24 weeks and adverse events during 24 weeks. The secondary endpoints were ACR50 and ACR70 over 24 weeks, the changes of DAS28 and Health Assessment Questionnaire (HAQ) at week 12 and week 24 from baseline. The trial was registered with ClinicalTrials.gov, number NCT01554917. FindingsBetween March 2012 and January 2015, 1759 participants were enrolled, of whom 81•5% (1433/1759) completed the study. Notably, 1597 patients in the full analysis set were assessed for the effectiveness and 1751 patients were in the safety analysis set; 71•9% (1148/1597) of the patients achieved the primary endpoint of ACR20 response at week 24, and 51•7% (906/1751) patients had at least 1 adverse event (AE). The incidence of the clinical significant AE (grade≥3) of special interest was 3•4% (54 patients for grade 3 and 6 patients for grade 4), and 0•7% (13/1751) of patients developed SAEs associated with IGU. The most common clinical significant AEs were infection in 0•6% (10/1751) of the patients, abdominal discomfort in 0•5% (9/1751) of the patients including 0•2% (3/1751) gastric ulcer, fracture in 0•4% (7/1751), and increased alanine aminotransferase (ALT) in 0•2% (3/1751) of the patients. The secondary endpoint of ACR50 and ACR70 response rates at week 24 were 47•4% (757/1597) and 24•0% (384/1597). DAS28 was 4•11±1•27 and 3•75±1•32 at week 12 and 24, which was significantly decreased -1•40±1•10 and -1•75±1•26 compared with baseline (P<0•001) respectively. Changes in HAQ at week 12 and 24 from baseline were -7•4 ± 9•18 and -8•5 ± 9•97, respectively (all P<0•001). Stratified analysis results showed that the patients with shorter disease duration, male gender had better response to IGU. There was no significant difference in ACR20/50/70 responses between elderly patients(≥65 years) and younger patients(<65 years), IGU monotherapy or combined with other DMARDs. However, more fractures (1•1% vs 0•5%; P = 0•64) and infections (8•7% vs 7•9%; P = 0•69) were observed in elderly patients in our study. InterpretationOur results confirmed the effectiveness and safety of IGU as a new DMARD for active patients with RA as monotherapy or combination therapy. FundingThis study was supported by “the 11th Five-Year-Plan for Science and Technology Support Program (2012ZX09104-103-01)”.

Diabetes Knowledge and Metabolic Control in Type 1 Diabetes Starting With Continuous Glucose Monitoring: FUTURE-PEAK.

To investigate whether diabetes knowledge and health literacy impact glycemic control after 1 year of intermittently scanned continuous glucose monitoring (isCGM) in people with type 1 diabetes ≥ 16 years. In this prospective real-world cohort study, we assessed diabetes knowledge using a new 10-item questionnaire [Patient Education and Knowledge (PEAK)] and health literacy using the validated 6-item Newest-Vital Sign-D (NVS-D) questionnaire. Primary endpoint was association between PEAK score and change in hemoglobin A1c (HbA1c). Secondary endpoints were link between NVS-D score and change in HbA1c and that between time spent in/above/below range and PEAK/NVS-D scores. 851 subjects were consecutively recruited between July 2016 and July 2018. Median PEAK score was 8 (range: 0-10), and median NVS-D score was 6 (range 0-6). HbA1c evolved from 7.9% (7.8%-8.0%), 63 (62-64) mmol/mol, at start to 7.7% (7.6%-7.7%), 61 (60-61) mmol/mol (P < 0.001), at 6 months and to 7.8% (7.7%-7.9%), 62 (61-63) mmol/mol, at 12 months (P < 0.001). HbA1c only improved in subgroups with higher scores [PEAK subgroups with score 7-8 (P = 0.005) and 9-10 (P < 0.001) and NVS-D score 4-6 (P < 0.001)]. At 12 months, time spent below 70 mg/dL was reduced by 15% (P < 0.001), and time spent below 54 mg/dL was reduced by 14% (P < 0.001), irrespective of PEAK/NVS-D score. Multiple linear regression analysis demonstrated an association of PEAK score, scan frequency, and baseline HbA1c with evolutions in time in range and time in hyperglycemia. isCGM reduced time in hypoglycemia, and HbA1c evolved favorably. Our findings suggest that diabetes and health literacy affect glucometrics, emphasizing the importance of education.

P76.96 START: Real-world Prospective Study on Sequential Therapy with First-Line Afatinib in Chinese Patients with EGFRm+ Advanced NSCLC

P76.96 START: Real-world Prospective Study on Sequential Therapy with First-Line Afatinib in Chinese Patients with EGFRm+ Advanced NSCLC

Abstract OT-07-01: Guardant360® related clinical outcomes in patients who share medical records-breast cancer (GRECO-B)

Abstract Background: Cell free circulating tumor DNA (ctDNA) is a proven viable alternative to tissue molecular profiling with high sensitivity, specificity, and positive predictive value. However, there is limited data on the overall outcomes of patients following ctDNA testing. Guardant360® Related Clinical Outcomes in Patients who Share Medical Records - Breast Cancer (GRECO-Breast) is a novel, patient-centric approach to evaluate clinical data and outcomes. This real-world prospective observational study intends to assess the health outcomes of patients with advanced breast cancer who have undergone Guardant360 ctDNA testing by consenting patients through siteless methodologies to share their medical records and imaging studies documenting their clinical history. Trial design: This is an observational study to be conducted in the United States. Patients with a diagnosis of breast cancer and a completed Guardant360 test will consent to share their medical records. Patients will be recruited by telephone or email to determine interest in the study. Should patients be interested in contributing to this study, they will be asked to consent via an electronic signature platform (e-signature) and electronic informed consent form (e-consent). Enrolled participants will be required to sign an electronic medical records release form for data review and verification by the study team. A healthcare information management organization will abstract participant demographics, cancer-related therapies, and clinical outcomes directly from source data for final analysis. Eligibility criteria: Prospective participants will be adults (age 18+) with a diagnosis of breast cancer with a completed Guardant360 test who consent to be enrolled in the study. Endpoints: Primary endpoint: To measure event free survival (EFS, composite endpoint of overall survival, progression events, and subjects lost to follow-up) stratified by treatment and genomic biomarker. Secondary endpoints: 1) Assess the rate of biomarker discovery compared to tissue genotyping results, when available; 2) Time to Next Treatment (TTNT); 3) Real-world Time to Tumor Progression (rwTTP); defined and documented either clinically or radiologically 4) Real-world Overall Survival (rwOS); defined as either clinically recorded death or secondary validated sources; 5) Record completeness of data and data quality. Statistical methods: Descriptive statistics will be used to characterize the patient population. These will include frequency distributions, cross tabulations, and summary measures such as means, standard deviations, and ranges. Graphical displays will be employed, where appropriate, such as box plots, scatter plots, and survival curves for time-to-event endpoints. Present accrual and target accrual: GRECO-Breast opened for enrollment in June 2020 with a goal of enrolling up to 300 participants. Contact information: For more information, please visit: https://clinicaltrials.gov/ct2/show/NCT04436393 Citation Format: Aaron Fuchs, Matthew Muia, Vicky Ho, Kristi Ashton, Naveen Kumar, Enrique Marino, Junhua Yu, Kathryn Lang, Victoria M Raymond. Guardant360® related clinical outcomes in patients who share medical records-breast cancer (GRECO-B) [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr OT-07-01.

Incidence of chemotherapy-induced nausea and vomiting among cancer patients receiving moderately to highly emetogenic chemotherapy in cancer centers in Sichuan, China.

Nausea and vomiting are the most painful and feared side effects for patients during chemotherapy. Currently, most studies focus on the occurrence of CINV during the risk phase. We initiated this real-world study to understand the actual occurrence of CINV throughout all phases, to provide a basis to prevent CINV in patients during chemotherapy and improve their quality of life. This prospective real-world study was conducted at 17 major cancer centers in Sichuan, China. Cancer patients who were about to receive moderately/highly emetogenic chemotherapy were included in the study. Occurrences of nausea and vomiting were recorded using patient diaries, and physicians are responsible for recording patient clinical data. A total of 1,139 patients were included in this study between August 2018 and April 2019. In this study, the incidence of acute CINV was 55.3%, delayed CINV was 62.3%, and CINV beyond the risk period was 36%. All phases overall, the overall complete control (CC) rate of CINV was 30.1 and 32.1% for highly and moderately emetogenic chemotherapy regimens, respectively. The median CC time for CINV was 7days, but only 21.5% of these patients used antiemetic regimens according to the NCCN guideline. In the real world, the incidence of CINV is high in patients receiving chemotherapy, and nausea and vomiting may occur beyond the risk period; the low level of standardized antiemetic treatment in compliance with the guideline might have been the main reason for unsatisfactory prevention and control of CINV in this study.

Cancer diagnosis in a Spanish cohort of multiple sclerosis patients under dimethylfumarate treatment

BackgroundPotential increase of cancer incidence is one of the main safety concerns of the disease-modifying therapies employed in Multiple Sclerosis (MS). ObjectiveDetailed description of patients who developed cancer among a prospective cohort of Spanish MS patients on dimethyl fumarate (DMF) treatment. MethodsWe describe patients who developed cancer among a cohort of 886 MS patients on DMF treatment (2681 patient-years), with a median time of exposure of 39.5 months (IQR 23-51.5), who participated in a multicentre and prospective real-world study conducted in 16 Spanish National Health System hospitals from February 2014 to May 2019. Local researchers were periodically contacted by the investigation team to monitor safety issues. Cancer histories were collected from the medical records and the information was updated at July 30th 2020. ResultsEight Caucasian women developed cancer, which accounts for 0.9% and an accumulated malignancy rate of 298.39 cases per 100,000 patient-years of DMF exposure. At the time of cancer diagnosis, age was between 33 to 67 years and median time on DMF treatment 16.5 months (range 1-53). Two patients had familiar history of cancer. No specific cancer lines were found (breast cancer in 2 cases, thyroid in 3, urothelial carcinoma, cervix and a progression to leiomyosarcoma from a mitotically active leiomyoma). DMF was withdrawn during cancer treatment in 6 patients and reintroduced later. All cancers except one are in complete remission. The patient with leiomyosarcoma died by cancer progression. ConclusionA relationship between cancers and DMF is unlikely because the malignancy rate was similar to that of the age-and sex-matched general population, and because of the absence of specific tumour cell lines. Nevertheless, as with other immunosuppressive DMTs, clinicians treating MS should be aware of any potential cancer symptom and demand proper testing.

The Clinical and MRI Effect of TNF-α &amp;nbsp;Inhibitor in Spondyloarthritis Patients with Hip Involvement：A Real-World Prospective Clinical Study

Background: Hip involvement is an important cause of disability and poor prognostic in patients with spondyloarthritis (SpA). TNF-α inhibitor treatment had been demonstrated to be effective in SpA patients with hip arthritis, however, quantitative assessment with magnetic resonance imaging (MRI) in the long-term follow-up still needs further application. This study was performed to quantitatively assess the detailed clinical remission and MRI changes of hip involvement under the treatment of TNF-α inhibitor versus control in SpA patients. Methods: A total of 239 SpA patients with hip arthritis were involved in this study and MTX and SSZ were given as basic treatment. 165 of them received TNF-α inhibitor plus basic treatment and 74 patients in the control group received basic treatment only. The clinical symptoms were assessed at baseline, week 12, week 24, and week 52. The MRI performances of hip arthritis including bone marrow edema (BME) and synovitis were quantitatively assessed at baseline and week 52 using Hip MRI Inflammation Scoring System (HIMRISS). Findings: The clinical symptoms of ESR, CRP, BASDAI, Harris, and ASDAS-ESR of both groups got significant clinical remission at week 52 (p<0.001). However, the disease activity change levels at week 52 in control group were significantly worse than TNF group. In week 52, MRI performance showed significant remission trend in TNF-α inhibitor group versus baseline of which total HIMRISS scores decreased significantly ( 26.49±10.37 vs 20.59±9.41, p<0.001), but the control group only had slight improvement trend (p<0.05). Interpretation: TNF-α inhibitor could significantly improve the clinical and MRI manifestation of hip involvement in SpA patients, and the treatment effect was better than controls. Quantitative MRI assessment combined with clinical assessment could accurately and comprehensively evaluate the treatment effect of TNF for SpA patients with hip involvement , and it will help to guide accurate and targeted treatment. Funding: This work was supported by the National Basic Research Program of China (No. 2015CB553704) and National Natural Science Foundation of China(No.81871273). Declaration of Interest: We declare that all authors do not have a financial conflict of interest. Ethical Approval: The study was approved by the ethics committee of Xijing Hospital of China (instruction number: 20110303-7).

Histological Activity as A Predictor of Clinical Outcome in Ulcerative Colitis: A 1-Year Real-World Prospective Study

Histological Activity as A Predictor of Clinical Outcome in Ulcerative Colitis: A 1-Year Real-World Prospective Study

Efficacy and safety of insulin degludec in renal transplant recipients with pre-existing diabetes

IntroductionGlycemic control is important in renal transplant receptions with diabetes. In the early post-transplant period, recovering renal function and concomitant steroids and immunosuppressants increase the risk of dysglycemia which adversely impacts allograft and patient survival. We evaluated the short-term efficacy and safety of insulin degludec in diabetic renal transplant patients in early post-transplant period in outpatient settings. Materials and methodsA real world prospective observational study in 61 diabetes patients with ESRD who underwent renal transplant and were followed up for three months at Endocrinology OPD post discharge, as per routine clinical practice. All patients received standard and individualized treatment with insulin degludec. The primary outcome was change in glycosylated hemoglobin (HbA1c) and the secondary outcomes included changes in fasting (FPG)and post-prandial plasma glucose (PPPG) levels and body weight. Safety assessments included reports of hypoglycemia and changes in serum levels of creatinine and tacrolimus. ResultsMean age and duration of diabetes of the participants were 53.17 ± 8.77 years and 14.55 ± 5.71 years, respectively. During follow up, there were significant reductions in mean HbA1c (8.11 ± 1.94% to 6.96 ± 1.33%) and FPG (220.61 ± 79.42 mg/dL to 120.00 ± 37.80 mg/dL) and PPPG (303.97 ± 105.90 mg/dL to 164.25 ± 51.10 mg/dL) levels. A total of 43 patients (70.49%) achieved HbA1c target of <7%. Serum levels of creatinine and tacrolimus also reduced significantly during follow up. No significant reductions in body weight. Nocturnal hypoglycemia was reported in five patients and no patients reported severe hypoglycemia. ConclusionInsulin degludec was effective and safe in long standing diabetes patients undergoing renal transplant. Insulin degludec was well tolerated and was effective in lowering FPG, PPPG and HbA1C in early post-transplant OPD settings.

Depression in patients with chronic hepatitis-C treated with direct-acting antivirals: A real-world prospective observational study

BackgroundDirect-acting antiviral (DAAs) therapy showed high safety and efficacy profile in patients with chronic hepatitis C (CHC) particularly those with previous or current psychiatric illness. The aim of this study was to evaluate the incidence and potential risk factors of depression and psychological distress following DAAs therapy in CHC euthymic Egyptian patients with no previous or current diagnosis of any psychiatric disorders. MethodsThis is a prospective study that included 126 patients diagnosed with chronic hepatitis C virus genotype-4. Patients were candidate for DAAs therapy and were recruited consecutively (convenient sample) from the viral hepatitis center, Department of Endemic medicine, Kasr Al-Ainy Hospitals, Cairo University. Symptom Checklist 90-R, Beck Depression Inventory (BDI) and Structured Clinical Interview for DSM-IV (SCID IV) were performed at baseline and at 12 weeks post-treatment with DAAs. ResultsForty-seven patients were included in the final analysis. Depression severity increased after treatment as BDI scores increased significantly than baseline scores (p= < 0.001). About one third of patients (32%) had moderate to severe depression. All Symptom Checklist-90 scores showed significant increase after treatment. LimitationsDropout rate of patients for the 12 weeks post-treatment assessment was 33.8%. ConclusionDepression and psychological distress can occur with DAAs treatments. Close psychosocial assessment and patient monitoring are still needed.