Routine Clinical Care Setting Research Articles

Antiganglioside antibody frequency in routine clinical care settings.

Antiganglioside antibodies (AGAs) might be involved in the etiopathogenesis of many neurological diseases, such as Miller-Fisher syndrome (MFS) and Guillain-Barré syndrome (GBS). Available comprehensive reference data regarding AGA positivity rates and cross-responsiveness among AGAs (where one line immunoblot is positive for ≥1 AGA) during routine clinical care are scant. In this 10-year monocentric retrospective study, 3560 immunoglobulin (Ig) G and IgM line blots (GA Generic Assays' Anti-Ganglioside Dot kit) obtained using cerebrospinal fluid (CSF) and serum samples from 1342 patients were analyzed for AGA positivity in terms of 14 diagnosis categories and AGA cross-responsiveness. Of all 3560 line blots 158 (4.4%) and of all CSF samples 0.4% (4/924) CSF line blots were AGA positive. For serum IgG, blots with positivity rates higher than the standard deviation of 15.6% were associated with MFS (GD3, GD1a, GT1a and GQ1b) and acute motor axonal neuropathy (AMAN) (GM1, GD1a and GT1a). For serum IgM, blots with positivity rates higher than the standard deviation of 8.1% were associated with AMAN (GM2, GT1a and GQ1b), MFS (GM1, GT1a and GQ1b), multifocal motor neuropathy (MMN) (GM1, GM2 and GQ1b) and chronic inflammatory demyelinating polyneuropathy (CIDP) (GM1). Cross-responsiveness was observed in 39.6% of all positive serum AGA. Testing for AGAs during routine clinical care rarely led to positive findings, both in serum and even less in CSF, except for the diagnoses AMAN, MFS, MMN and CIDP. Nonspecific findings found as cross-responsiveness between different AGA samples occur frequently, impacting the positivity of most AGA subtypes.

Present and Future of Blood-Based Biomarkers of Alzheimer’s Disease: Beyond the Classics

The field of blood-based biomarkers for Alzheimer’s disease (AD) has advanced at an incredible pace, especially after the development of sensitive analytic platforms that can facilitate large-scale screening. Such screening will be important when more sophisticated diagnostic methods are scarce and expensive. Thus, blood-based biomarkers can potentially reduce diagnosis inequities among populations from different socioeconomic contexts. This large-scale screening can be performed so that older adults at risk of cognitive decline assessed using these methods can then undergo more complete assessments with classic biomarkers, increasing diagnosis efficiency and reducing costs to the health systems. Blood-based biomarkers can also aid in assessing the effect of new disease-modifying treatments. This paper reviews recent advances in the area, focusing on the following leading candidates for blood-based biomarkers: amyloid-beta (Aβ), phosphorylated tau isoforms (p-tau), neurofilament light (NfL), and glial fibrillary acidic (GFAP) proteins, as well as on new candidates, Neuron-Derived Exosomes contents (NDEs) and Transactive response DNA-binding protein-43 (TDP-43), based on data from longitudinal observational cohort studies. The underlying challenges of validating and incorporating these biomarkers into routine clinical practice and primary care settings are also discussed. Importantly, challenges related to the underrepresentation of ethnic minorities and socioeconomically disadvantaged persons must be considered. If these challenges are overcome, a new time of cost-effective blood-based biomarkers for AD could represent the future of clinical procedures in the field and, together with continued prevention strategies, the beginning of an era with a lower incidence of dementia worldwide.

Unmet Medical Needs Amongst Older Patients Aged ≥60 Years with Newly Diagnosed Acute Myeloid Leukemia Receiving Intensive Chemotherapy: Experience from a Predominately United States Community Setting

Background: Venetoclax (Ven) in combination with hypomethylating agents is approved for treatment in patients (pts) with newly diagnosed (ND) acute myeloid leukemia (AML) who are ≥75 years old or unfit for intensive chemotherapy (IC), based on the longer median overall survival (OS) with Ven+azacitidine (Aza) compared with Aza in combination with placebo in the Phase III VIALE-A study (NCT02993523). Several studies are now evaluating Ven-based regimens in pts eligible for IC, for example Ven+Aza compared with IC (NCT04801797). Additionally, Ven in combination with cladribine (CLAD) and low-dose cytarabine (LDAC) is currently under investigation in a Phase II single-arm study (NCT03586609) amongst older pts (aged ≥60 years) with ND AML. An interim analysis of this trial evaluated 60 pts where complete remission (CR) and CR with incomplete count recovery (CRi) was observed in 93% of pts, and the median OS, overall and by transplant status, was not reached; 1-year OS was 72.9% and 2-year OS was 63.5% (Kadia et al. J Clin Oncol 2022). The aim of this study is to better understand treatment outcomes amongst older pts (aged ≥60 years) with ND AML receiving IC in a routine clinical care setting in the United States (US). Methods: This was a retrospective cohort study using the Flatiron Health electronic health record-derived, US nationwide, de-identified database. Pts aged ≥60 years with ND AML who initiated IC within 60 days of AML diagnosis (Dx) between January 1, 2014, and November 30, 2022, with ≥2 visits recorded within 3 months of AML Dx, and ≥3 months of follow-up before study end date (February 28, 2023) were included. Clinical trial participants and pts with acute promyelocytic leukemia or core binding factor were excluded. Descriptive analysis on patient characteristics was conducted. The proportion of pts who achieved real-world response (defined as <5% bone marrow [BM] blasts), real-world CR/CRi (defined as <5% BM blast with either platelet count <100 x 10 9/L or absolute neutrophil count <1000 x 10 9/L) and received a stem cell transplant (SCT) post-remission were reported. Thirty-day mortality, 60-day mortality, 1-year real-world OS (rwOS), and 2-year rwOS were evaluated using Kaplan-Meier (KM) analyses. The starting points for KM analyses were IC treatment initiation (all pts), SCT (pts who underwent SCT post-remission), and remission (pts who did not undergo SCT post-remission). Pts were censored at the last activity date or SCT date (whichever occurred earliest) for the overall patient cohort, and the last activity date for pts with or without SCT post-remission. Results: A total of 1105 pts met the study criteria. The median (IQR) age was 67 (64-71) years, 57% were male, 27% had secondary AML, 48% had BM blast >50% at Dx, and 66% were treated in the community setting. Excluding 340 pts with unknown cytogenetic and molecular data, 19%, 32%, and 48% of pts had European LeukemiaNet 2017 favorable, intermediate, and adverse risk, respectively. At a median (IQR) follow-up of 13 (6-28) months from AML Dx, 74% (n=821) of pts achieved real-world response, including 66% (n=724) who achieved real-world CR/CRi. For all pts, the 30-day mortality was 3%, 60-day mortality was 6%, 1-year rwOS was 58%, 2-year OS was 34%, and the median rwOS was 14.3 months ( Figure A). A total of 37% (n=306/821) of pts underwent SCT post-remission; 98% (n=300/306) underwent allogeneic-SCT and 2% (n=6/306) underwent autologous-SCT. The median rwOS was 40.4 months for pts undergoing SCT post-remission, and 13.8 months for pts without SCT post-remission ( Figure B). Conclusions: In this large real-world data study, we observed older pts (aged ≥60 years) with ND AML receiving IC treatment had a median OS of <14 months and <35% of pts remained alive 2 years after IC initiation. Findings from this study suggest the need for other novel treatment options, including Ven based regimens, to improve OS in older pts (aged ≥60 years) with ND AML who are eligible for IC. Future studies are warranted to conduct randomized controlled trials to comparatively evaluate IC vs other novel treatment options in older pts (aged ≥60 years) with ND AML, or conduct the appropriate statistical adjustment to minimize confounding in indirect treatment comparisons from different studies.

The Cytogenetic and Molecular Testing Landscape in Patients with Newly Diagnosed Acute Myeloid Leukemia in Routine Clinical Practices in the United States

Background: The prognostic and treatment (Tx) landscape for newly diagnosed acute myeloid leukemia (ND AML) has evolved in recent years; several novel therapies have been recommended in Tx guidelines. Tx for patients (pts) with actionable IDH1, IDH2, or FLT3 mutations includes Venetoclax (Ven)-based regimens (i.e. Ven+hypomethylating agents [HMAs] and Ven+low-dose cytarabine), HMA monotherapy (i.e. Azacitidine [Aza] or decitabine), and targeted Tx (i.e. ivosidenib±Aza, enasidenib±Aza, sorafenib±HMAs, and gilteritinib+Aza). This study aims to better understand the cytogenetic and molecular testing landscape among pts with ND AML receiving first-line (1L) Tx in routine clinical settings in the United States (US). Methods: This retrospective cohort study used data from the Flatiron Health database: a US nationwide, electronic health record-derived de-identified database. Pts with ND AML, aged ≥18 years, diagnosed with AML between January 1, 2020, and December 31, 2022, with ≥2 visits recorded within 3 months of AML diagnosis (Dx), and 1L Tx initiated any time after AML Dx were included.Pts with secondary AML, acute promyelocytic leukemia or t(9;22) were excluded. Descriptive analyses evaluated the cytogenetic testing pattern, molecular testing pattern (including next generation sequencing [NGS] and polymerase chain reaction [PCR]), and 1L Tx pattern for pts harboring IDH1/2 or FLT3 mutations (categorized as Ven-based, HMA monotherapy, and targeted Tx). Results: A total of 1577 pts met the study criteria. Overall, 95% (n=1501) of pts received a cytogenetic test and 91% (n=1434) received molecular testing that corresponded to a positive or negative result from the first specimen collected. Of the pts with molecular testing, 70% (n=1005) were treated in the community setting, 27% (n=390) in the academic setting, and 3% (n=39) in both academic and community settings. NGS was the most used molecular testing technique in all settings (76%, 50%, and 61% in the community setting, academic setting, and both settings, respectively) vs PCR (11%, 34%, and 26%, respectively). Testing rates were relatively consistent from 2020 to 2022 ( Figure). Bone marrow aspirate alone was the most common specimen type used for molecular testing (82%, 65% and 72%, in the community setting, academic setting, and both settings, respectively), followed by blood only (14%, 25%, and 21%, respectively). A total of 78% of pts treated in the community setting had their first specimen collected at AML Dx for molecular testing (vs 63% in the academic setting and 59% in both settings). Overall, 85% of pts treated in the community setting had their first specimen collected for molecular testing before 1L Tx initiation (vs 75% in the academic setting and 90% in both settings), and 35% had repeated molecular testing (proxy by second specimen collected) after 2 weeks of 1L Tx initiation (vs 40% in the academic setting and 29% in both settings). Of the pts who received molecular testing, 25% (n=365) harbored IDH1/2 or FLT3 mutations. A total of 39% (n=142) of pts with IDH1/2 or FLT3 mutations received Ven-based Tx, 9% (n=34) received HMA monotherapy, 3% (n=12) received targeted Tx, and 49% (n=177) received chemotherapy excluding HMAs. Conclusions: This study found that cytogenetic and molecular testing have been integrated into routine clinical care settings for pts with ND AML receiving 1L Tx. The consistent testing rates in recent years, common use of NGS molecular testing technique, and the majority of pts having first specimen collected for molecular testing prior to 1L Tx initiation reflect physicians' intention to leverage molecular data to better inform Tx decisions. The subset of pts with second specimen collected for molecular testing after 2 weeks of 1L Tx initiation suggests some physicians' efforts to evaluate new and/or persistent targeted stable mutations. Although the rate of molecular testing was high, nearly half of pts harboring IDH1/2 or FLT3 mutations received Tx guideline recommended regimens, and Ven-based Tx was more commonly administered than HMA monotherapy or targeted Tx; suggesting physicians are more commonly choosing a mutation agnostic Tx approach in ND AML. Future studies are warranted to better understand potential barriers to the timely report of molecular testing results in routine clinical practice for pts with AML.

Treatment patterns, survival, and healthcare utilisation and costs in patients with locally advanced and metastatic bladder cancer in Denmark 2015–2020

Background Treatment patterns in locally advanced and metastatic urothelial bladder cancer (La/mUBC) is changing, but little is known about current treatment patterns, survival, and costs of these patients. Our aim was to describe treatment patterns, survival, and healthcare utilisation/costs in Danish La/mUBC patients in a routine clinical care setting. Methods Registry-based nationwide cohort study including all bladder cancer patients aged 18 years or older with a La/mUBC tumour in the pathology register and a concomitant bladder cancer diagnosis in the Danish National Patient Registry in the period 2015–2020. We categorised the patients according to (1) La/mUBC at time of first bladder cancer diagnosis (de novo La/mUBC) and (2) non-invasive or localised muscle-invasive bladder cancer at time of diagnosis which had progressed to La/mUBC. All patients were included at date of pathology-confirmed La/mUBC. Follow-up ended 30 September 2022. Results We identified 1278 patients (69% men) with La/mUBC and no other previous cancer. Of these, 212 (17%) had de novo La/mUBC, while 1066 (83%) had progressed to La/mUBC. Median age was 72 years. Patients were followed for a median of 13.0 months (interquartile range 4.7;32.0). During follow-up, 651 (51%) patients started first-line treatment, of these, 285 progressed to second-line treatment, and 112 also started third-line treatment. Median survival was 13.0 months from La/mUBC diagnosis, 12.1 months from start of first-line treatment, 9.8 months from start of second-line treatment, and 8.6 months from start of third-line treatment. The mean number of days admitted to hospital was 3.47, 3.97, and 4.07 per month following initiation of first-line, second-line, and third-line treatment, respectively. Conclusion Patients with La/mUBC have a poor prognosis, and in routine clinical care only around half of the patients received systemic anti-cancer treatment suggesting an unmet need for novel treatments. The overall costs only increased slightly from first to third-line treatment.

Mindfulness-enhanced internet-based cognitive behavioural therapy for anxiety and depression: Outcomes in routine care

BackgroundClinical trials support the efficacy of mindfulness-enhanced, internet-based cognitive behavioural therapies (CBT) in reducing anxiety and depression symptom severity. However, it is unclear how effective these interventions are when delivered in routine clinical care settings. This study investigated the utilisation and treatment outcomes of an online mindfulness-enhanced CBT program in the general Australian community. MethodsOver a one-year study period, 2187 adults commenced the online mindfulness-enhanced CBT program. The program consisted of six sequential lessons to be completed within 90 days. Participants (mean age= 39 ± 14 years, 68 % female) completed measures of symptom severity for anxiety, depression, and psychological distress at pre-, mid- and post-treatment. Treatment effects were assessed via intention-to-treat linear mixed models with Hedges' g effect size calculations. ResultsFrom pre- to post-treatment, the mindfulness-enhanced CBT program was associated with medium and large effect sized reductions in generalised anxiety symptom severity (g = 0.80, 95%CI: 0.74–0.86), depression symptom severity (g = 0.74, 95%CI: 0.68–0.80), and psychological distress (g = 0.97, 95%CI: 0.90–1.03). Program adherence was modest with approximately 30 % of participants completing all six lessons of the program. LimitationsThis study is limited by its lack of a comparator condition, longer-term follow-up, and assessment of the reasons for participant non-adherence. The relative acceptability and effectiveness of mindfulness versus CBT components was not examined. ConclusionThis study supports the effectiveness of mindfulness-enhanced iCBT for symptoms of anxiety and depression when delivered in a routine care setting under the supervision of community health care practitioners.

Stellate Ganglion Block and Intraarterial Spasmolysis in Patients with Cerebral Vasospasm: A Retrospective Cohort Study

BackgroundIn patients with symptomatic cerebral vasospasm (CV) following aneurysmal subarachnoid hemorrhage who do not respond to medical therapy, urgent treatment escalation has been suggested to be beneficial for brain tissue at risk. In our routine clinical care setting, we implemented stellate ganglion block (SGB) as a rescue therapy with subsequent escalation to intraarterial spasmolysis (IAS) with milrinone for refractory CV.MethodsIn this retrospective analysis from 2012 to 2021, patients with CV following aneurysmal subarachnoid hemorrhage who received an SGB or IAS were identified. Patients were assessed through neurological examination and transcranial Doppler. Rescue therapy was performed in patients with mean cerebral blood flow velocity (CBFV) ≥ 120 cm/s and persistent neurological deterioration/intubation under induced hypertension. Patients were reassessed after therapy and the following day. The Glasgow Outcome Scale was assessed at discharge and 6-month follow-up.ResultsA total of 82 patients (mean age 50.16 years) with 184 areas treated with SGB and/or IAS met the inclusion criteria; 109 nonaffected areas were extracted as controls. The mean CBFV decrease in the middle cerebral artery on the following day was − 30.1 (± 45.2) cm/s with SGB and − 31.5 (± 45.2) cm/s with IAS. Mixed linear regression proved the significance of the treatment categories; other fixed effects (sex, age, aneurysm treatment modality [clipping or coiling], World Federation of Neurological Surgeons score, and Fisher score) were insignificant. In logistic regression, the presence of cerebral infarction on imaging before discharge from the intensive care unit (34/82) was significantly associated with unfavorable outcomes (Glasgow Outcome Scale ≤ 3) at follow-up.ConclusionsStellate ganglion block and IAS decreased CBFV the following 24 h in patients with CV. We suggest SGB alone for patients with mild symptomatic CV (CBFV < 180 cm/s), while subsequent escalation to IAS proved to be beneficial in patients with refractory CV and severe CBFV elevation (CBFV ≥ 180 cm/s).

Telehealth-Based Health Coaching Produces Significant Weight Loss over 12 Months in a Usual Care Setting

Background: Telehealth-based health coaching in a usual care setting has yet to be examined. The purpose of this study was to incorporate the inHealth Lifestyle Therapeutics, Inc.’s Telehealth Enabled Approach to Multidisciplinary Care (TEAM) method within a real-world routine clinical care setting to reduce body weight in obese participants. Materials and Methods: n = 70 participants were recruited for this intervention (Age: 58.1 ± 14.6yrs, BMI: 35.5 ± 7.8 kg/m2, 32 males and 38 females). All participants self-selected participation in either the virtual health coaching (VHC) group or usual care (UC) group. VHC participants met with a medical doctor monthly and a certified health coach weekly for the first 12 weeks of the study, bi-weekly for the following 12 weeks, and monthly for the remaining 6 months. Data were analyzed using a two-sample student’s t-test to assess any changes from baseline for both VHC and UC groups. Results: A significant difference for weight-loss between VHC and UC groups (8.24 ± 9.8 vs. 0.16 ± 10.6 kg, respectively, p &lt; 0.05) was observed. In addition, there was a significant change in the mean percentage of body weight loss (6.5 ± 0.1% vs. 0.53 ± 1.45%, respectively, p &lt; 0.05) between groups. Conclusions: Incorporating innovative deliveries that are scalable, such as telehealth-based interventions, may help stem the tide of patient obesity related care. Furthermore, using a TEAM method in a usual care setting may be effective for inducing sustained weight loss at 12 months.

The Effectiveness and Tolerability of Glycopyrronium for Patients with Chronic Obstructive Pulmonary Disease in a Clinical Setting: GLARE-Taiwan.

Glycopyrronium (GLY) is a pharmacological maintenance treatment for chronic obstructive pulmonary disease (COPD). However, its effectiveness and tolerability for COPD patients in routine clinical practice have not been well-investigated. This study aimed to assess the effectiveness of GLY on health-related quality of life and its safety in patients with COPD in a routine clinical care setting. This multi-center, prospective, six-month observational study recruited patients diagnosed with COPD and treated with GLY at three medical centers in central Taiwan. The full analysis set (n = 102) had a significant improvement in the Clinical COPD Questionnaire total (mean ± SD = −0.39 ± 0.90, p = 0.002), symptoms (mean ± SD = −0.61 ± 0.90, p < 0.001) and mental state scores (mean ± SD = −0.54 ± 1.72, p = 0.021) but not the functional state score (mean ± SD = −0.10 ± 1.15, p = 0.529). During the observational period, 58 patients (52.73%) experienced adverse events; only one adverse event (dizziness) was suspected to be related to the study drug. Three patients (2.73%) discontinued the study and GLY treatment because of an adverse event. One patient (0.91%) died during the study period because of a cerebral infarction, which was judged to be not associated with GLY treatment. In conclusion, GLY could be effective in improving the health status and is safe for patients with COPD in a real-life setting.

Precision Implementation: An Approach to Mechanism Testing in Implementation Research.

Advancing mechanism-focused research in implementation science is a priority given its potential to improve tailoring and efficiency of implementation strategies. Experimental therapeutics, or experimental medicine, offers an approach for mechanism testing that has been promoted by the NIH Science of Behavior Change and endorsed by the National Institute for Mental Health. This approach has been applied across the translational spectrum - with initial applications to biological research and more recent applications to psychosocial treatment development research. We describe further advancement of experimental therapeutics along the translational spectrum and describe how it is ideally suited to inform precision experimental tests of implementation strategy mechanisms, which we term precision implementation. Such an approach to mechanism testing will allow for identification of causal dose-response relationships between implementation strategies, presumed mechanisms, and implementation outcomes. We discuss the tension between the scientific rigor required to conduct mechanism-focused research using experimental therapeutics and the "real world" conditions in which implementation research takes place. We provide a series of example studies that show "beginning to end" application of this framework in research focused on provider implementation of an evidence-based intervention in routine clinical care settings.

The future of CBT and evidence-based psychotherapies is promising.

The future of CBT and evidence-based psychotherapies is promising.

Effectiveness of Vortioxetine in Patients with Major Depressive Disorder in Real-World Clinical Practice: French Cohort Results from the Global RELIEVE Study.

AimFunctional recovery is an important treatment goal in patients with major depressive disorder (MDD). The Real-Life Effectiveness of Vortioxetine in Depression (RELIEVE) study assessed the effectiveness of vortioxetine in patients with MDD receiving treatment in routine clinical care settings in France, Italy, Canada, and the United States. This paper presents the study data for the cohort enrolled in France.MethodsRELIEVE was a 6-month, international, observational, prospective cohort study in outpatients initiating vortioxetine treatment for MDD at their physician’s discretion (NCT03555136). Patients were assessed at routine clinic visits at study entry (baseline) and after 12 and 24 weeks of vortioxetine treatment. The primary study outcome was patient functioning, assessed by the Sheehan Disability Scale (SDS). Secondary outcomes included depression severity (assessed by the Patient Health Questionnaire [PHQ-9]), cognitive symptoms (assessed by the Perceived Deficits Questionnaire-Depression [PDQ-D-5]), and cognitive performance (Digit Symbol Substitution Test [DSST]). Changes from baseline to week 24 were assessed using mixed models for repeated measures, adjusted for relevant confounders. Adverse events spontaneously reported by the patient or observed by the investigator were recorded.ResultsData are available for 184 patients in France (mean age, 50.2 years; 65.2% female). Overall, 67.9% of patients had at least one comorbidity and 46.2% reported current anxiety symptoms at baseline. Adjusted least-squares mean (standard error) change in SDS score from baseline to week 24 was −10.9 (0.6) points (P < 0.001). Respective changes for PHQ-9, PDQ-D-5 and DSST scores were −9.3 (0.5), −6.1 (0.4), and +6.9 (1.0) points (all P < 0.0001). Adverse events were reported by 29 patients (15.8%), most commonly nausea (11 patients, 6.0%).ConclusionClinically relevant and sustained improvements in overall functioning, depressive symptoms, cognitive symptoms, and cognitive performance were observed in patients with MDD treated with vortioxetine for 6 months in routine clinical practice settings in France.

127-LB: Effectiveness and Safety of Empagliflozin in Routine Care in Europe and East Asia: Results from the Empagliflozin Comparative Effectiveness and Safety (EMPRISE) Study

The EMPRISE study evaluates the effectiveness and safety of empagliflozin (EMPA) in a broader population of patients with T2D in routine clinical care across countries. The study included 67,140 pairs of 1:1 propensity score matched (PSM) patients ≥18 years with T2D newly initiating EMPA or any DPP-4i from large databases/registers in Israel, Finland, Germany, Spain, Sweden, South Korea, Taiwan and Japan. Mostly, PSM used 100+ baseline covariates (Table), and pooled HR with 95% CI were computed using random-effects meta-analysis models. EMPA compared to DPP-4i (Table), was associated with 27-47% lower risk of hospitalization for heart failure (HHF), stroke, all-cause mortality (ACM), and two composite outcomes: HHF & ACM; and myocardial infarction, stroke & ACM. Safety analyses associated EMPA with 46% lower risk of acute kidney injury requiring dialysis. EMPRISE study results showed that EMPA is associated with reduced risk of cardiovascular (CV) disease, incl HHF, in patients with T2D in routine clinical care settings in Israel, Europe and East Asia. These results complement the results from clinical trial EMPA-REG OUTCOME®, and are in line with the ADA/EASD 2019 consensus update to prescribe SGLT-2i for patients with T2D and high-risk, vascular or chronic kidney disease or heart failure to reduce HHF and major adverse CV events/deaths. Disclosure A. Karasik: Advisory Panel; Self; Boehringer Ingelheim International GmbH. Research Support; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Novo Nordisk A/S. Speaker’s Bureau; Self; AstraZeneca, Novo Nordisk A/S. S. Lanzinger: None. E. C. H. Tan: Consultant; Self; Boehringer Ingelheim Pharmaceuticals, Inc. D. Yabe: Research Support; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Novo Nordisk Pharma Ltd., Ono Pharmaceutical Co., Ltd., Taisho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Company Limited, Terumo Corporation. Speaker’s Bureau; Self; Boehringer Ingelheim Pharmaceuticals, Inc., MDS Co., Ltd., Novo Nordisk Pharma Ltd. D. Kim: None. W. Sheu: None. C. Melzer Cohen: None. R. W. Holl: None. K. Ha: None. T. Nystrom: Board Member; Self; Abbott, Lilly Diabetes, Sanofi. Research Support; Self; Boehringer Ingelheim International GmbH. Speaker’s Bureau; Self; AstraZeneca. L. K. Niskanen: Advisory Panel; Self; Boehringer Ingelheim International GmbH, Sanofi-Aventis. Speaker’s Bureau; Self; AstraZeneca, Novo Nordisk. Stock/Shareholder; Self; Boehringer Ingelheim Pharmaceuticals, Inc. M. Linnemann Jensen: Stock/Shareholder; Self; Novo Nordisk A/S. M. H. Kyaw: Employee; Self; Boehringer Ingelheim Pharmaceuticals, Inc. J. Nunez: Advisory Panel; Self; Novo Nordisk Pharma Ltd. Research Support; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc.

Safety and efficacy of nonacog alfa for the treatment of haemophilia B in children younger than 6 years of age in a routine clinical care setting: the EUREKIX registry study

European regulatory authorities request postmarketing safety and efficacy data for factor IX (FIX) products. Collect additional clinical data from routine nonacog alfa use in children aged <6years with haemophilia B. The EUREKIX registry included retrospective and prospective data collection phases. Safety was assessed via adverse drug reactions (ADRs)/adverse events (AEs) and events of special interest (ESIs) as the primary objective; efficacy was evaluated via annualised bleeding rates (ABRs). The retrospective phase comprised 37 subjects. Of these, 25 had severe haemophilia B. One subject experienced 2 ADRs; another experienced 4 ESIs of hypersensitivity. Median ABR in subjects receiving a predominantly on-demand regimen (prophylaxis <50% of time; n=11) was 2.0; median ABR was 3.8 in those receiving predominantly prophylactic treatment (prophylaxis ≥50% of time; n=24). Joint bleeding was infrequent (median ABR, 0.4; n=35). The prospective phase included 26 subjects, with 17 continuing from the retrospective phase. A total of 20 subjects had severe haemophilia B. Three subjects experienced 7 treatment-related AEs; 3 experienced 4 ESIs. Median ABR was 4.5 and 1.1 in subjects who received predominantly on-demand (n=5) or prophylactic treatment (n=19), respectively; the overall median ABR for joint bleeding events was 0.0. Overall, nonacog alfa treatment effectively controlled bleeding events, with no new safety signals identified. These data support the safety and efficacy of nonacog alfa in routine clinical settings in children aged <6years.

Intravenous tocilizumab in the management of rheumatoid arthritis: Clinical practice findings from a 6-month international, multicentre, observational study in Central America and the Caribbean

Tocilizumab (TCZ), an interleukin-6 receptor-α inhibitor, is indicated in patients with moderate to severe rheumatoid arthritis with inadequate response to disease modifying drugs. ACT UP is a multinational project collecting information from several post-marketing TCZ studies. AimTo determine the proportion of patients in the routine clinical care setting receiving intravenous TCZ after 6 months treatment. Identification of TCZ treatment patterns, efficacy, and safety were also recorded. MethodThis prospective non-interventional 6-month study, collected real-world information from 169 Central American and Caribbean patients. No interventional procedures or additional visits outside routine clinical care practice were performed. Statistical analysis was essentially descriptive. ResultsAdherence rate was 74.0%, with 97% of patients receiving TCZ as first biological therapy line and there were no deviations from the local label. Almost 85% of patients started with combination therapy, and the majority remained under this scheme throughout the study. A significant decrease in disease activity assessments and acute phase reactants values were detected during TCZ treatment. The percentage of patients that achieved improvement according to the different levels of the American College of Rheumatology (ACR) increased during the study, and relevant enhancements in quality of life were also accomplished. Adverse events (AEs) occurred in 35 patients, with metabolic and nutritional disorders being the most common. Serious AEs were reported in 3% of patients, and special interest AEs occurred in 6 patients. ConclusionTreatment adherence was mainly determined by follow-up and compliance with the administration schedule. Efficacy analysis showed better results than those reported in international literature. The incidence of AEs was also lower than in previously published data.

Intravenous tocilizumab in the management of rheumatoid arthritis: Clinical practice findings from a 6-month international, multicentre, observational study in Central America and the Caribbean

Tocilizumab (TCZ), an interleukin-6 receptor-α inhibitor, is indicated in patients with moderate to severe rheumatoid arthritis with inadequate response to disease modifying drugs. ACT UP is a multinational project collecting information from several post-marketing TCZ studies. AimTo determine the proportion of patients in the routine clinical care setting receiving intravenous TCZ after 6 months treatment. Identification of TCZ treatment patterns, efficacy, and safety were also recorded. MethodThis prospective non-interventional 6-month study, collected real-world information from 169 Central American and Caribbean patients. No interventional procedures or additional visits outside routine clinical care practice were performed. Statistical analysis was essentially descriptive. ResultsAdherence rate was 74.0%, with 97% of patients receiving TCZ as first biological therapy line and there were no deviations from the local label. Almost 85% of patients started with combination therapy, and the majority remained under this scheme throughout the study. A significant decrease in disease activity assessments and acute phase reactants values were detected during TCZ treatment. The percentage of patients that achieved improvement according to the different levels of the American College of Rheumatology (ACR) increased during the study, and relevant enhancements in quality of life were also accomplished. Adverse events (AEs) occurred in 35 patients, with metabolic and nutritional disorders being the most common. Serious AEs were reported in 3% of patients, and special interest AEs occurred in 6 patients. ConclusionTreatment adherence was mainly determined by follow-up and compliance with the administration schedule. Efficacy analysis showed better results than those reported in international literature. The incidence of AEs was also lower than in previously published data.

Translation, validation and cross-cultural adaptation of the Revised Fibromyalgia Impact Questionnaire (FIQR) in Nepali language.

To translate, cross-culturally adapt and test the psychometric properties of the Revised Fibromyalgia Impact Questionnaire (FIQR) in Nepali language (Nepali FIQR). The translation was performed following the methodological standards described by Beaton. Comprehensibility testing of the preliminary version was done in 40 fibromyalgia patients, and a pre-final version was prepared after making changes in the original version to maintain the equivalence with the target version. Psychometric testing was done in another group of 130 fibromyalgia patients to test for content validity and reliability. Construct validity was tested with visual analog score (VAS) for pain and Short Form (SF)-36. Nepali FIQR was comprehensible to 92.5% patients. The internal consistency was also acceptable with Cronbach's alpha of 0.900, 0.714 and 0.863 for function, overall and symptoms domain, respectively. Construct validity was also acceptable with a moderate correlation between Nepali FIQR and VAS and SF-36. Test-retest reliability of the total Nepali FIQR and of each item were acceptable with intraclass correlation coefficient (ICC) of >0.7 in all items except for question 1 of function domain (ICC: 0.65). Nepali FIQR is a comprehensible, reliable and valid tool for evaluation of the functional status of Nepalese patients with fibromyalgia and should be implemented in routine clinical care and research settings.

Regional variability in Canadian routine care of type 2 diabetes, hypercholesterolemia, and hypertension: Results from the The Cardio-Vascular and metabolic treatments in Canada: Assessment of REal-life therapeutic value (CV-CARE) registry

BackgroundRegional differences in the profile and treatment strategies of patients with cardiometabolic diseases have been studied in several different countries. The Cardio-Vascular and metabolic treatments in Canada: Assessment of REal-life therapeutic value (CV-CARE) registry was designed to evaluate patient profiles and medical management of cardiometabolic diseases in routine clinical care settings across Canada. Primary objectives were to (1) evaluate regional variability of patient profiles with cardiometabolic disease(s) and (2) assess treatment differences of patients treated for type 2 diabetes (T2D), hypercholesterolemia (HCh), and hypertension (HTN) across Canada. MethodsCV-CARE is a multi-center, observational, prospective registry that enrolled Canadian patients treated with metformin-extended release (MetER) for T2D, colesevelam (C) for HCh, azilsartan (AZI) for mild-to-moderate essential HTN and azilsartan/chlorthalidone (AZI/CHL) for severe, essential HTN. Patient characteristics and treatments were assessed at baseline. ResultsThe registry enrolled 6960 patients, with a total of 4194 patients making up the primary analysis population [MetER (n=995); C (n=1639); AZI (n=1364); AZI/CHL (n=498)]. First-line use of MetER was more common in British Columbia (BC; 45.5%) compared to Ontario (ON; 29.8%), and Quebec (QC; 12.9%). C treatment for HCh was used as monotherapy most readily in BC (68.7%) compared with QC (59.7%) and ON (35.8%). Dual action of low-density lipoprotein cholesterol and hemoglobin A1c reduction was the predominant reason for C add-on therapy (46.8%), with highest usage seen in ON (62.9%). AZI treatment for HTN was most frequently used in BC (43.8%), and AZI/CHL was most commonly used in ON (12.0%). First-line use of AZI was more common in QC (50%) vs. ON (34.9%) and BC (24.1%). The primary reason for switching to AZI and AZI/CHL from prior treatment was lack of efficacy across provinces. ConclusionThis is the first regional description of the CV-CARE cohort. Significant variations in both baseline profile and treatments were observed which could have an impact on long-term outcomes.

Effectiveness of ustekinumab in patients with psoriatic arthritis in a real-world, multicenter study.

To assess the effectiveness and survival of ustekinumab (UST) among patients with psoriatic arthritis (PsA) treated under routine clinical care. Multicenter study. Epidemiological and clinical data was collected through electronic medical records of all patients with PsA who started UST in 15 hospitals of Spain. Two hundred and one patients were included, 130 (64.7%) with 45mg and 71 (35.3%) with 90mg. One hundred and thirty one patients (65.2%) had previously received another biological therapy. The median baseline DAS 28 ESR was 3.99, and Psoriasis Area and Severity Index (PASI) was 3. Overall, there was a significant decrease in DAS66/68 CRP, swollen joint count (SJC), tender joint count (TJC), and PASI in the first month of treatment, with earlier improvement in skin (PASI) than joints outcomes. Survival was numerically lower in patients with UST 45mg (58.1%) than 90mg (76.1%), although significant differences were not found (p = 0.147). When comparing naïve and <1 TNF blocker versus > 2 TNF blocker-experienced patients, a significantly earlier response was seen in the former group regarding SJC (p = 0.029) at 1month. Fifty-one patients (25.3%) stopped UST due to joint inefficacy and 4 patients due to adverse events (1.9%). Drug survival was significantly better in patients with fewer lines of previous biological agents (p = 0.003 for < 1 TNF blocker versus > 2 TNF blocker users). UST was effective in PsA patients in a routine clinical care setting. Patients with UST 90mg and fewer lines of previous biologics achieved better and faster responses. Key Points • Largest cohort of patients with PsA in treatment with UST with specific rheumatological indication. • First cohort of patients with PsA comparing effectiveness of UST according to 45/90mg dose.

TREatment of ATopic eczema (TREAT) Registry Taskforce: protocol for a European safety study of dupilumab and other systemic therapies in patients with atopic eczema.

A long-term prospective observational safety study is essential to characterize fully the safety profile of systemic immunomodulating therapies for patients with atopic eczema. The TREatment of ATopic eczema (TREAT) Registry Taskforce offers a large platform to conduct such research using national registries that collect the same data using a predefined core dataset. To present a protocol for a safety study comparing dupilumab with other systemic immunomodulating therapies in children and adults with moderate-to-severe atopic eczema, to assess the long-term safety risk of these therapies in a routine clinical care setting. We describe a registry-embedded international observational prospective cohort study. Adult and paediatric patients who start treatment with dupilumab or another systemic immunomodulating agent for their atopic eczema will be included. The primary end point is the incidence of malignancies (excluding nonmelanoma skin cancer) compared between the treatment groups. Secondary end points include other serious adverse events and adverse events of special interest, such as eye disorders and eosinophilia. This protocol delineates a safety study for dupilumab in adult and paediatric patients with atopic eczema, using a standardized methodological approach across several national registries. The protocol could also be used for other novel systemic immunomodulating therapies, and could provide licensing and reimbursement authorities, pharmaceutical companies and clinicians with safety evidence from a routine clinical care setting. What's already known about this topic? There is a need for long-term data on the safety of systemic immunomodulating therapies in patients with atopic eczema. Regulatory bodies, such as the European Medicines Agency, increasingly stipulate the collection of such data as part of the licensing agreement for new treatments, to assess the new agent's long-term safety profile against established therapies. Large numbers of patients with a long duration of follow-up are necessary in order to detect rare events like malignancies. What does this study add? The TREAT Registry Taskforce offers a platform to conduct such research with a network of multiple national atopic eczema research registries. We present a protocol for an investigator-initiated multicentre safety study comparing dupilumab with other systemic immunomodulating therapies in adults and subsequently adolescents and children with moderate-to-severe atopic eczema. This protocol can be used as a framework for similar studies for other novel systemic immunomodulating therapies across both adult and paediatric populations.