Dataset Information

A 5-year clinical follow-up study from the Italian National Registry for FSHD.

ABSTRACT:

Background

The natural history of facioscapulohumeral muscular dystrophy (FSHD) is undefined.

Methods

An observational cohort study was conducted in 246 FSHD1 patients. We split the analysis between index cases and carrier relatives and we classified all patients using the Comprehensive Clinical Evaluation Form (CCEF). The disease progression was measured as a variation of the FSHD score performed at baseline and at the end of 5-year follow-up (?FSHD score).

Findings

Disease worsened in 79.4% (112/141) of index cases versus 38.1% (40/105) of carrier relatives and advanced more rapidly in index cases (?FSHD score 2.3 versus 1.2). The 79.1% (38/48) of asymptomatic carriers remained asymptomatic. The highest ?FSHD score (1.7) was found in subject with facial and scapular weakness at baseline (category A), whereas in subjects with incomplete phenotype (facial or scapular weakness, category B) had lower ?FSHD score (0.6) p?ConclusionsThe progression of disease is different between index cases and carrier relatives and the assessment of the CCEF categories has strong prognostic effect in FSHD1 patients.

SUBMITTER: Vercelli L

PROVIDER: S-EPMC7815626 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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Publications

A 5-year clinical follow-up study from the Italian National Registry for FSHD.

Vercelli Liliana L Mele Fabiano F Ruggiero Lucia L Sera Francesco F Tripodi Silvia S Ricci Giulia G Vallarola Antonio A Villa Luisa L Govi Monica M Maranda Louise L Di Muzio Antonio A Scarlato Marina M Bucci Elisabetta E Maggi Lorenzo L Rodolico Carmelo C Moggio Maurizio M Filosto Massimiliano M Antonini Giovanni G Previtali Stefano S Angelini Corrado C Berardinelli Angela A Pegoraro Elena E Siciliano Gabriele G Tomelleri Giuliano G Santoro Lucio L Mongini Tiziana T Tupler Rossella R

Journal of neurology 20200819 1

<h4>Background</h4>The natural history of facioscapulohumeral muscular dystrophy (FSHD) is undefined.<h4>Methods</h4>An observational cohort study was conducted in 246 FSHD1 patients. We split the analysis between index cases and carrier relatives and we classified all patients using the Comprehensive Clinical Evaluation Form (CCEF). The disease progression was measured as a variation of the FSHD score performed at baseline and at the end of 5-year follow-up (ΔFSHD score).<h4>Findings</h4>Diseas ...[more]

PMID: 32813049

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Project description:Facioscapulohumeral muscular dystrophy type 1 (FSHD1) has been genetically linked to reduced numbers (? 8) of D4Z4 repeats at 4q35. Particularly severe FSHD cases, characterised by an infantile onset and presence of additional extra-muscular features, have been associated with the shortest D4Z4 reduced alleles with 1-3 repeats (1-3 DRA). We searched for signs of perinatal onset and evaluated disease outcome through the systematic collection of clinical and anamnestic records of de novo and familial index cases and their relatives, carrying 1-3 DRA.Italy.66 index cases and 33 relatives carrying 1-3 DRA.The clinical examination was performed using the standardised FSHD evaluation form with validated inter-rater reliability. To investigate the earliest signs of disease, we designed the Infantile Anamnestic Questionnaire (IAQ). Comparison of age at onset was performed using the non-parametric Wilcoxon rank-sum or Kruskal-Wallis test. Comparison of the FSHD score was performed using a general linear model and Wald test. Kaplan-Meier survival analysis was used to estimate the age-specific cumulative motor impairment risk.No patients had perinatal onset. Among index cases, 36 (54.5%) showed the first signs by 10 years of age. The large majority of patients with early disease onset (26 out of 36, 72.2%) were de novo; whereas the majority of patients with disease onset after 10 years of age were familial (16, 53.3%). Comparison of the disease severity outcome between index cases with age at onset before and over 10 years of age, failed to detect statistical significance (Wald test p value=0.064). Of 61 index cases, only 17 (27.9%) presented extra-muscular conditions. Relatives carrying 1-3 DRA showed a large clinical variability ranging from healthy subjects, to patients with severe motor impairment.The size of the D4Z4 allele is not always predictive of severe clinical outcome. The high degree of clinical variability suggests that additional factors contribute to the phenotype complexity.

Project description:Rabbit antithymocyte globulin (rATG, Thymoglobulin®) is the most common induction immunosuppression therapy in kidney transplantation. We applied a database integration strategy to capture and compare long-term (10-year) outcome data for US participants in a clinical trial of rATG versus FDA-approved basiliximab.Records for US participants in an international, 1-year, randomized clinical trial comparing rATG and basiliximab induction in deceased donor kidney transplantation were integrated with records from the US national Organ Procurement and Transplantation (OPTN) registry using center, transplant dates, recipient sex, and birthdates. The OPTN captures center-reported acute rejection, graft failure, death, and cancer events, and incorporates comprehensive death records from the Social Security Death Master File. Ten-year outcomes according to randomized induction regimen were compared by Kaplan-Meier analysis (two-sided P). Non-inferiority of rATG was assessed using a one-tailed equivalence test (a-priori equivalence margins of 0-10 %).Of 183 US trial participants, 89 % (n = 163) matched OPTN records exactly; the remainder were matched by extending agreement windows for transplant and birthdates. Matches were validated by donor and recipient blood types. By Kaplan-Meier analysis, 10 years post-transplant, freedom from acute rejection, graft failure, or death was 32.6 % and 24.0 % in the rATG and basiliximab arms, respectively (P = 0.09). The incidence of acute rejection with rATG versus basiliximab induction was 21.0 % versus 32.8 % (P = 0.07). Patient survival (52.8 % [Corrected] versus 52.2 %, P = 0.92) and graft survival (34.3 % versus 30.9 %, P = 0.56) rates were numerically and statistically similar for both arms. Comparison of the composite outcome meets non-inferiority criteria even with a 0 % equivalence margin (one-sided P = 0.04). With a 10 % equivalence margin, the odds that rATG is no worse than basiliximab for 10-year risk of the composite endpoint are >99 %.Ten years post-transplant, rATG induction has comparable efficacy and safety to FDA-approved basiliximab. Integration of clinical trial records with national registry data can enable long-term monitoring of trial participants in transplantation, circumventing logistical and cost barriers of extended follow-up.ClinicalTrials.gov NCT00235300.

Dataset Information

A 5-year clinical follow-up study from the Italian National Registry for FSHD.

Background

Methods

Findings

Publications

A 5-year clinical follow-up study from the Italian National Registry for FSHD.

Similar Datasets

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