Efficacy and safety of tocilizumab in adult-onset Still's disease: Real-life experience from the international AIDA registry.

BACKGROUND/OBJECTIVES: Long-term efficacy and safety of tocilizumab (TCZ) in adult-onset Still's disease (AOSD) mostly derive from small case series. Herein we report a registry-based study investigating TCZ efficacy and safety in a cohort of patients with AOSD evaluated by clinical and serum inflammatory markers as well as drug retention rate analysis. METHODS: This is an international multicentre study analyzing data from patients with AOSD regularly enrolled in the AIDA registry. TCZ efficacy was evaluated between baseline and last follow-up assessment in terms of changes in the Pouchot score and laboratory findings. Drug-retention rate was estimated by the Kaplan-Meier method, while Cox-regression analysis was employed to detect potential predictive factors of treatment withdrawal. RESULTS: Data from 31 patients (15 men, 16 women) refractory to the conventional therapies and treated with TCZ were extracted from the AIDA registry. Mean ± SD time of treatment duration with TCZ was 24.32 ± 20.57 months. Median (IRQ) Pouchot score significantly decreased throughout the study period (p=0.001) with a significant difference between baseline [2.00 (4.00)] and 6 month-follow-up [0.00 (0.00)] (p=0.003) and between baseline and last follow-up assessment [0.00 (0.00)] (p=0.032), while no differences were observed between 6 month-evaluation and last follow-up assessment (p=0.823). Similarly, laboratory parameters significantly decreased from baseline to the last follow-up visit. With regard to drug survival, cumulative TCZ retention rate at 12-, 24-, and 36-month follow-up visit were 83.1%, 71.7% and 63.7%, respectively, without significant differences between biologic naïve patients and those previously treated with other biologics (p=0.329). Likewise, no significant differences were observed between chronic articular course of AOSD and other types of disease course (p=0.938) or between patients co-administered with conventional immunosuppressants and patients receiving TCZ as monotherapy (p=0.778). Cox-regression analysis identified no variable associated with a higher hazard of treatment withdrawal. Treatment was discontinued in 9 patients due to long-term remission (n=4), adverse events (n=2), loss of efficacy (n=1), non-medical reason (n=1) and unspecified cause (n=1). Mean glucocorticosteroids daily dose significantly decreased from baseline (18.36 ± 24.72 mg) to the last follow-up assessment (4.02 ± 4.99 mg, p=0.003). CONCLUSIONS: TCZ allows control of disease activity as well as normalization of serum inflammatory markers in both systemic and chronic articular form of AOSD. Additionally, TCZ displays an excellent drug retention rate while minimizing the risk of long-term exposure to corticosteroids.

Development and Implementation of the AIDA International Registry for Patients With Still's Disease.

Objective: Aim of this paper is to present the design, construction, and modalities of dissemination of the AutoInflammatory Disease Alliance (AIDA) International Registry for patients with systemic juvenile idiopathic arthritis (sJIA) and adult-onset Still's disease (AOSD), which are the pediatric and adult forms of the same autoinflammatory disorder. Methods: This Registry is a clinical, physician-driven, population- and electronic-based instrument implemented for the retrospective and prospective collection of real-world data. The collection of data is based on the Research Electronic Data Capture (REDCap) tool and is intended to obtain evidence drawn from routine patients' management. The collection of standardized data is thought to bring knowledge about real-life clinical research and potentially communicate with other existing and future Registries dedicated to Still's disease. Moreover, it has been conceived to be flexible enough to easily change according to future scientific acquisitions. Results: Starting from June 30th to February 7th, 2022, 110 Centers from 23 Countries in 4 continents have been involved. Fifty-four of these have already obtained the approval from their local Ethics Committees. Currently, the platform counts 290 users (111 Principal Investigators, 175 Site Investigators, 2 Lead Investigators, and 2 data managers). The Registry collects baseline and follow-up data using 4449 fields organized into 14 instruments, including patient's demographics, history, clinical manifestations and symptoms, trigger/risk factors, therapies and healthcare access. Conclusions: This international Registry for patients with Still's disease will allow a robust clinical research through collection of standardized data, international consultation, dissemination of knowledge, and implementation of observational studies based on wide cohorts of patients followed-up for very long periods. Solid evidence drawn from "real-life" data represents the ultimate goal of this Registry, which has been implemented to significantly improve the overall management of patients with Still's disease. NCT05200715 available at https://clinicaltrials.gov/.

Development and Implementation of the AIDA International Registry for Patients with Non-Infectious Scleritis.

INTRODUCTION: This article points out the design, methods, development and deployment of the international registry promoted by the AutoInflammatory Disease Alliance (AIDA) Network with the aim to define and assess paediatric and adult patients with immune-mediated scleritis. METHODS: This registry collects both retrospective and prospective real-world data from patients with non-infectious scleritis through the Research Electronic Data Capture (REDCap) tool and aims to promote knowledge and real-life evidence from patients enrolled worldwide; the registry also allows the collection of standardised data, ensuring the highest levels of security and anonymity of patients' data and flexibility to change according to scientific acquisitions over time. The communication with other similar registries has been also ensured in order to pursue the sustainability of the project with respect to the adaptation of collected data to the most diverse research projects. RESULTS: Since the launch of the registry, 99 centres have been involved from 20 countries and four continents. Forty-eight of the centres have already obtained a formal approval from their local ethics committees. At present, the platform counts 259 users (95 principal investigators, 160 site investigators, 2 lead investigators, and 2 data managers); the platform collects baseline and follow-up data using 3683 fields organised into 13 instruments, including patient's demographics, history, symptoms, trigger or risk factors, therapies and healthcare utilization. CONCLUSIONS: The development of the AIDA International Registry for patients with non-infectious scleritis will allow solid research on this rare condition. Real-world evidence resulting from standardised real-life data will lead to the optimisation of routine clinical and therapeutic management, which are currently limited by the rarity of this ocular inflammatory condition.

Development and Implementation of the AIDA International Registry for Patients with Non-Infectious Uveitis.

INTRODUCTION: The aim of this paper is to point out the design, development and deployment of the AutoInflammatory Disease Alliance (AIDA) International Registry for paediatric and adult patients with non-infectious uveitis (NIU). METHODS: This is a physician-driven, population- and electronic-based registry implemented for both retrospective and prospective collection of real-world demographics, clinical, laboratory, instrumental and socioeconomic data of patients with uveitis and other non-infectious inflammatory ocular diseases recruited through the AIDA Network. Data recruitment, based on the Research Electronic Data Capture (REDCap) tool, is thought to collect standardised information for real-life research and has been developed to change over time according to future scientific acquisitions and potentially communicate with other similar instruments. Security, data quality and data governance are cornerstones of this platform. RESULTS: Ninety-five centres have been involved from 19 countries and four continents from 24 March to 16 November 2021. Forty-eight out of 95 have already obtained the approval from their local ethics committees. At present, the platform counts 259 users (95 principal investigators, 160 site investigators, 2 lead investigators, and 2 data managers). The AIDA Registry collects baseline and follow-up data using 3943 fields organised into 13 instruments, including patient's demographics, history, symptoms, trigger/risk factors, therapies and healthcare utilization for patients with NIU. CONCLUSIONS: The development of the AIDA Registry for patients with NIU will facilitate the collection of standardised data leading to real-world evidence and enabling international multicentre collaborative research through inclusion of patients and their families worldwide.

Coherence of brain electrical activity: a quality of life indicator in Alzheimer's disease?

OBJECTIVE: To investigate the relationships between quality of life (QOL) and clinical and electroencephalogram (EEG) aspects in patients with Alzheimer's disease (AD). METHOD: Twenty-eight patients with mild or moderate AD, 31 with Parkinson's disease (PD), and 27 normal controls (NC) were submitted to: CERAD neuropsychological battery, Hamilton Depression and Anxiety Rating Scales, Functional Activities Questionnaire, QOL scale for patients with AD, and quantitative EEG measures. RESULTS: AD and PD patients had similar QOL (31.0 ± 5.8; 31.7 ± 4.8, respectively), worse than that of NC (37.5 ± 6.3). AD patients had lower global interhemispheric theta coherence (0.49 ± 0.04; 0.52 ± 0.05; 0.52 ± 0.05; respectively) than PD and NC. Multiple linear regression for QOL of AD patients revealed that global interhemispheric theta coherence, and Hamilton depression scores were significant factors (coefficients; 58.2 and -0.27, respectively; R2, 0.377). CONCLUSION: Interhemispheric coherence correlates with QOL regardless of cognitive and functional variables and seems to be a neurophysiological indicator of QOL in AD patients.

Coherence of brain electrical activity: a quality of life indicator in Alzheimer’s disease?Coerência da atividade elétrica cerebral: indicador da qualidade de vida na doença de Alzheimer?

Objective To investigate the relationships between quality of life (QOL) and clinical and electroencephalogram (EEG) aspects in patients with Alzheimer’s disease (AD). Method Twenty-eight patients with mild or moderate AD, 31 with Parkinson’s disease (PD), and 27 normal controls (NC) were submitted to: CERAD neuropsychological battery, Hamilton Depression and Anxiety Rating Scales, Functional Activities Questionnaire, QOL scale for patients with AD, and quantitative EEG measures. Results AD and PD patients had similar QOL (31.0 ± 5.8; 31.7 ± 4.8, respectively), worse than that of NC (37.5 ± 6.3). AD patients had lower global interhemispheric theta coherence (0.49 ± 0.04; 0.52 ± 0.05; 0.52 ± 0.05; respectively) than PD and NC. Multiple linear regression for QOL of AD patients revealed that global interhemispheric theta coherence, and Hamilton depression scores were significant factors (coefficients; 58.2 and -0.27, respectively; R2, 0.377). Conclusion Interhemispheric coherence correlates with QOL regardless of cognitive and functional variables and seems to be a neurophysiological indicator of QOL in AD patients. .

Objetivo Investigar relações entre qualidade de vida (QV) e aspectos clínico-eletrencefalográficos (EEG) em pacientes com doença de Alzheimer (DA). Método Vinte e oito pacientes com DA, 31 com doença de Parkinson (DP) e 27 controles normais (CN) foram submetidos a avaliações neurocognitivas, escala de depressão de Hamilton e de qualidade de vida para pacientes com DA, questionário de atividades funcionais e medidas do EEG. Resultados A QV foi similar nos grupos DA e DP (31,0 ± 5,8; 31,7 ± 4,8, respectivamente), mas inferior ao CN (37,5 ± 6,3). No grupo DA houve menor coerência inter-hemisférica global teta (CIGT) do que em DP e CN (p < 0,05). Regressão múltipla linear para QV no grupo DA revelou a CIGT e a escala de Hamilton como fatores significativos (coeficientes; 58,2; -0,27, respectivamente; R2, 0,377). Conclusão A CIGT correlaciona-se com a QV independentemente de variáveis cognitivas e funcionais e parece ser um indicador neurofisológico da QV em pacientes com DA. .