Takeda (France)

To characterize patients with narcolepsy type 1 (NT1), narcolepsy type 2 (NT2), and idiopathic hypersomnia (IH), their diagnosis, and treatment journey using administrative health data.

To evaluate psychometric properties of the Functional Impacts of Narcolepsy Instrument (FINI) using data from two narcolepsy studies.

Subcutaneous immunoglobulin (SCIg) replacement therapy is indicated for patients with hypogammaglobulinemia caused by primary (PID) and secondary immunodeficiencies (SID). To compare healthcare resource utilization (HCRU) and related direct medical costs of patients in France treated with weekly conventional SCIg (cSCIg) vs monthly hyaluronidase-facilitated SCIg (fSCIg). This retrospective study of Ig-naïve patients with PID or SID newly receiving a SCIg between 2016 and 2018, extracted from the French National Healthcare reimbursement database (SNDS), analyzed the SCIg-related HCRU and reimbursed costs generated from in-hospital (hospitalizations and SCIg doses) or at-home (nurse visits [NV] and pump provider visits [PPV], drug doses) SCIg administration. Overall, 2,012 patients (PID:534; SID:1,478) were analyzed. The follow-up duration varied between 7.5 and 8.7 months according to sub-groups. Compared with fSCIg-treated patients, monthly mean rates of NV and PPV were respectively 2.5 and 3.1 times higher in PID, and 1.6 and 3.1 times higher in SID cSCIg-treated patients. Monthly mean rates for SCIg administration-related hospitalizations were lower overall, while their costs were 1.6 and 1.8 times higher for cSCIg than fSCIg subgroups, in PIDs and SIDs respectively; these results are due to more frequent hospitalizations with fSCIg being mainly shorter, without stayover. Total HCRU costs from the French NHI's perspective were estimated to be lower with fSCIg vs cSCIg, in PIDs and SIDs. This study provides real-world evidence of SCIg administration in a large French population. Patients with PID or SID treated with fSCIg had fewer at-home HCRU and lower overall costs for in-hospital or at-home SCIg administration compared with cSCIg-treated patients.

Abstract Background Biological therapy has revolutionized the treatment of inflammatory bowel disease (IBD); however, a subset of patients still requires therapy optimization to achieve therapeutic goals. This study aimed to identify patients who underwent biological therapy optimization (TO) and compare their characteristics with those who did not require such adjustments. Methods A retrospective study was conducted using data from the national patient registry of GEDIIB (Brazilian Crohn's and Colitis Organization). A total of 1,660 patients with Crohn's disease (CD) and 530 patients with ulcerative colitis (UC) undergoing biological therapy were included. The need for TO was determined based on clinical or endoscopic criteria specific to each participating center. Statistical analyses included association tests and Poisson regression. Results The need for TO was more frequent among patients with CD(33.3%) compared to those with UC (26.2%) (p=0.003). In CD, optimization was associated with younger age (p=0.016), stenosing (p=0.03) or penetrating behavior (p=0.015), perianal disease (p<0.001), presence of fistula (p=0.019), and prior surgery (p=0.044). Table 1 displays the adjusted frequency ratio (FR) for TO in CD patients. After adjusting for confounding factors, the most significant predictors for optimization in CD were younger age, perianal disease, and prior surgery. In UC, optimization was associated with younger age (p=0.013), pancolitis extent (p<0.001), previous surgery (p=0.037), hospitalization (p=0.025), and chronic liver disease (p=0.024). Table 2 presents the adjusted FR for therapy optimization in UC patients. After adjustment, the factors most strongly associated with optimization in UC were prior surgery and chronic liver disease. Conclusion Approximately 30% of patients required optimization of biological therapy. This need was associated with younger age, a more severe disease profile, and the presence of complications, such as perianal disease in CD, as well as a history of surgery and hospitalization in UC. References Papamichael K, Cheifetz AS, Melmed GY, Irving PM, Vande Casteele N, Kozuch PL, Raffals LE, Baidoo L, Bressler B, Devlin SM, Jones J, Kaplan GG, Sparrow MP, Velayos FS, Ullman T, Siegel CA. Appropriate Therapeutic Drug Monitoring of Biologic Agents for Patients With Inflammatory Bowel Diseases. Clin Gastroenterol Hepatol. 2019 Aug;17(9):1655-1668.e3. doi: 10.1016/j.cgh.2019.03.037. Fróes RSB, Andrade AR, Faria MAG, de Souza HSP, Parra RS, Zaltman C, Dos Santos CHM, Bafutto M, Quaresma AB, Santana GO, Luporini RL, de Lima Junior SF, Miszputen SJ, de Souza MM, Herrerias GSP, Junior RLK, do Nascimento CR, Féres O, de Barros JR, Sassaki LY, Saad-Hossne R. Clinical factors associated with severity in patients with inflammatory bowel disease in Brazil based on 2-year national registry data from GEDIIB. Sci Rep. 2024 Feb 21;14(1):4314. doi: 10.1038/s41598-024-54332-1.

Background/Objectives: Gaucher disease type 1 (GD1) is characterized by hepatosplenomegaly, thrombocytopenia, and disabling bone manifestations requiring regular MRI monitoring. The EIROS study assessed the real-world impact of velaglucerase alfa on GD1 bone disease, using MRI data collected in French clinical practice. Methods: MRIs collected retrospectively from treatment initiation and prospectively during follow-up (12-months) were analyzed centrally by a blinded expert radiologist to evaluate bone infiltration using the Bone Marrow Burden (BMB) score and a qualitative method (stable, improved or worsened for the spine and femur). Abdominal MRIs were also centrally analyzed to assess hepatosplenomegaly. Bone manifestations, hepatosplenomegaly, and hematologic parameters were analyzed from medical records. Results: MRI data were available for 20 patients: 6 treatment-naive patients and 14 patients who switched to velaglucerase alfa from another GD treatment. Interpretable MRIs for BMB scoring were available for seven patients for the spine and one patient for the femur. Qualitative assessments (n = 18) revealed stability in spine and femur infiltration in 100.0% and 84.6% of treatment-switched patients (n = 13), respectively, and improvements in 80.0% and 60.0% of treatment-naive patients (n = 5), respectively; no worsening of bone infiltration was observed. Liver, spleen, and hematologic parameters improved in treatment-naive patients and remained stable in treatment-switched patients. Conclusions: The qualitative real-world data support findings from clinical trials suggesting the long-term effectiveness of velaglucerase alfa on GD1 bone manifestations. When MRI assessment by radiologists with experience of GD is not possible, a simplified qualitative assessment may be sufficient in clinical practice for monitoring bone disease progression and treatment response.

Abstract Background Gaucher disease type 1 (GD1) is a rare autosomal recessive disorder characterized by hepatosplenomegaly, thrombocytopenia, and disabling bone manifestations that require regular MRI monitoring to assess disease progression and treatment responses. Velaglucerase alfa therapy results in long-term improvements in hematologic and visceral manifestations, but more real-world data on its impact on bone manifestations are needed. The EIROS study aimed to address this knowledge gap by using MRI data collected in daily practice in France to assess the impact of velaglucerase alfa on GD1 bone disease. Methods Patients with GD1 and bone MRI data from around the time of velaglucerase alfa initiation were eligible for inclusion. All MRIs collected retrospectively from treatment initiation and prospectively to the end of follow-up (12 months) were analyzed centrally by a blinded expert radiologist to evaluate bone infiltration using the Bone Marrow Burden (BMB) score and a qualitative method (scored for the spine and femur: stable, improved or worsened). Abdominal MRIs were also centrally analyzed to assess hepatosplenomegaly. Reports from bone MRIs, X-rays, and abdominal ultrasounds made by local radiologists were also collected. Clinical (acute and chronic bone pain) and biological parameters were analyzed from medical records. Results MRI data were available for 20 patients from 9 hospital centers: 6 treatment-naive patients and 14 patients who switched to velaglucerase alfa from another GD treatment. Readable MRIs for BMB scoring were only available for 7 patients for the spine and 1 patient for the femur. Qualitative assessments, performed for 18 patients, revealed stability in spine and femur infiltration in 100.0% and 84.6% of treatment-switched patients (n = 13), respectively, and improvements in 80.0% and 60.0% of treatment-naive patients, respectively; no worsening of bone infiltration was observed. Liver, spleen and hematologic parameters improved in treatment-naive patients and remained stable in treatment-switched patients. Conclusions This study provided real-world evidence suggesting the long-term effectiveness of velaglucerase alfa treatment in GD1, including bone manifestations. The data indicate that if MRI assessment by a radiologist with experience of GD bone manifestations is not possible, a simplified qualitative assessment provides sufficient evidence in clinical practice for monitoring bone disease progression and treatment response.

Introduction:Disparities in the recruitment of minority populations in research are well-documented. However, the degree of participation and retention of minorities following enrollment is less known, particularly in decentralized studies. Although decentralized clinical research methods may allow researchers to engage broader study populations with less participation burden, they may present different retention challenges. To evaluate racial and ethnic differences in the degree of participation after enrollment in a decentralized study, we analyzed data from a cohort of patients with inflammatory bowel diseases following COVID-19 immunization.Methods:We compared by race and ethnicity the following post-enrollment participation metrics: response to > 50% of follow-up surveys, donation of a blood sample for antibody testing, consent to use of bio samples for future research, and withdrawal prior to study completion.Results:Overall, we observed higher levels of post-enrollment study participation among non-Hispanic White (NHW) participants as compared to Black or Hispanic participants: 95% of NHW participants completed follow-up versus 87% of Black participants and 91% of Hispanic participants, 73% of NHW participants provided bio samples versus 64% Black participants and 67% Hispanic participants, and 65% of NHW participants provided consent for future research versus 62% of Black participants and 52% of Hispanic participants.Conclusions:Our findings demonstrate that the degree of study participation after enrollment in this decentralized study differed by race and ethnicity, indicating that attention to diversity, equity, and inclusion is needed not only in clinical research recruitment but also throughout study administration.

Regulation (EU) 2017/746 on in vitro diagnostic medical devices (IVDR) imposes several conditions on pathology institutes that develop and use in-house in vitro diagnostic medical devices (IH-IVDs). However, not all of these conditions need to be implemented immediately after the IVDR entered into force on 26May 2022. Based on an amending regulation of the European Parliament and the Council of the European Union, the requirements for IH-IVDs will be phased in. Conformity with the essential safety and performance requirements of annexI must be ensured from May2022. With this article, we would like to present the practical implementation of the currently valid conditions for IH-IVDs at the Institute of Pathology at the University Hospital of Heidelberg, in order to provide possible assistance to other institutions. In addition to the intensive work on the requirements for IH-IVDs, several guidance documents and handouts provide orientation for the implementation and harmonisation of the requirements for healthcare institutions mentioned in Article5(5). Exchange in academic network structures is also of great importance for the interpretation and practical implementation of the IVDR. For university and nonuniversity institutions, ensuring conformity with the IVDR represents afurther challenge in terms of personnel and time, in addition to the essential tasks of patient care, teaching and research and the further development of methods for optimal and targeted diagnostics, as well as the maintenance of the constantly evolving quality management system.

The standard treatment for advanced urothelial carcinoma includes platinum-based chemotherapy and programmed cell death protein 1 or programmed death ligand 1 inhibitors. However, urothelial carcinomas are often associated with both intrinsic and acquired resistance to these treatments. Paclitaxel, ifosfamide, and nedaplatin (TIN) chemotherapy has been proven to be effective as the second- or third-line treatment for platinum-resistant advanced urothelial cancer. Herein, we report two cases of patients with advanced bladder cancer resistant to platinum-based chemotherapy or pembrolizumab, who were treated with TIN chemotherapy. The first case was in a 66-year-old woman treated with gemcitabine and cisplatin (GC) chemotherapy followed by gemcitabine, paclitaxel, and cisplatin chemotherapy for multiple pulmonary metastases after radical cystectomy. Following reduction in pulmonary metastases after six courses of TIN treatment, metastasectomy and two courses of adjuvant TIN treatment were administered, with no recurrence for eight years. The other case was in a 70-year-old man treated with GC chemotherapy and pembrolizumab for invasive bladder cancer and multiple pulmonary metastases. We treated this patient with salvage pelvic exenteration. Pulmonary metastases significantly decreased after six courses of TIN chemotherapy. After a partial response for seven months; the patient died due to a novel cerebellar metastasis after six courses of TIN chemotherapy. Thus, we conclude that TIN chemotherapy can be considered as a third line treatment for advanced urothelial cancer resistant to platinum-based chemotherapy and pembrolizumab.