Impact of Gender on the Characteristics of Patients with Idiopathic Pulmonary Fibrosis Included in the RaDiCo-ILD Cohort.

BACKGROUND: There is growing evidence of gender-specific phenotypic differences among patients with idiopathic pulmonary fibrosis (IPF), which may affect patient outcomes. OBJECTIVES: We present the characteristics of patients with IPF at inclusion in the French Rare Disease Cohort - Interstitial Lung Disease (RaDiCo-ILD) with the aim of characterizing gender-specific phenotypic differences. METHODS: Patients with IPF who were enrolled in the national, multicentre RaDiCo-ILD cohort were included. Demographic characteristics, comorbidities, health-related quality of life (HRQoL) scores, pulmonary function, chest imaging, and IPF treatment were collected at inclusion and described by gender. RESULTS: The cohort included 724 patients with IPF (54% of RaDiCo-ILD cohort), of whom 82.9% were male. The proportion of male and female patients with a prior history of smoking was 75.0% and 26.8%, respectively. Emphysema was present in 17.0% (95% confidence interval [CI]: 10.0, 24.0) of men and 5.4% (95% CI: 1.2, 9.6) of women. At inclusion, females had poorer HRQoL than males based on St. George's Respiratory Questionnaire scores (48.5 [95% CI: 43.9, 53.0] and 41.5 [39.4, 43.6], respectively). The mean forced vital capacity per cent predicted was 77.7% (95% CI: 76.2, 79.3) and 87.4% (83.4, 91.4) for males and females, respectively. Honeycombing on high-resolution computed tomography (HRCT) was present in 70.8% (95% CI: 61.0, 80.6) of males and 45.8% (95% CI: 35.1, 56.5) of females. CONCLUSIONS: This analysis of patients with IPF at inclusion in the RaDiCo-ILD cohort provides evidence that comorbid emphysema, lung volume reduction, and honeycombing on HRCT are more common characteristics of males than females.

Treatment of Idiopathic Pulmonary Fibrosis with Capsule or Tablet Formulations of Pirfenidone in the Real-Life French RaDiCo-ILD Cohort.

INTRODUCTION: Pirfenidone, an antifibrotic medication for idiopathic pulmonary fibrosis (IPF), is now available in France in two formulations: tablets since April 2018, and the initial capsules form. We conducted a cohort study to describe tolerance and acceptability of capsules and/or tablets of pirfenidone in patients with IPF. METHODS: This study was nested within the French, non-randomized, multicenter RaDiCo-ILD (Rare Disease Cohort-Interstitial Lung Diseases). Included patients with IPF received at least one dose of pirfenidone tablets or capsules from July 2017 to June 2019 in three populations: the inclusion population (patients treated at least once with pirfenidone during the study period, n = 288); the potential switch population (patients treated with pirfenidone during the switch period starting April 2018, n = 256); the newly treated population (patients who initiated pirfenidone during the study period, n = 162). Each of those last two populations included three subgroups (tablets, capsules, and substitution). RESULTS: In 288 patients treated, 162 newly initiated pirfenidone during the study period: there were no meaningful differences in the baseline characteristics with the 256 patients treated during the potential switch period. In the newly treated population, 30.3% started pirfenidone treatment with tablet formulation. In the potential switch population, 44.9% of patients shifted from capsule to tablet. Half of the patients shifted to tablet formulation within the first 10 months. The mean treatment duration was 21.5 months with a mean dose of 2106.7 mg/day; 46.5% of patients discontinued treatment, mainly because of adverse events. There were fewer discontinuations in the tablets and substitution subgroups than in the capsules-only subgroup. The most reported adverse event was skin rash (11.5%). No new adverse event was identified. CONCLUSIONS: This real-life cohort assessing the characteristics of the prescription of pirfenidone tablets and capsules suggests a good acceptability of the tablet formulation by patients with IPF. TRIAL REGISTRATION: Clinical trial registered with www.clinicaltrials.gov (NCT04238871).

Prediction of the age at onset in spinocerebellar ataxia type 1, 2, 3 and 6.

BACKGROUND: The most common spinocerebellar ataxias (SCA)--SCA1, SCA2, SCA3, and SCA6--are caused by (CAG)n repeat expansion. While the number of repeats of the coding (CAG)n expansions is correlated with the age at onset, there are no appropriate models that include both affected and preclinical carriers allowing for the prediction of age at onset. METHODS: We combined data from two major European cohorts of SCA1, SCA2, SCA3, and SCA6 mutation carriers: 1187 affected individuals from the EUROSCA registry and 123 preclinical individuals from the RISCA cohort. For each SCA genotype, a regression model was fitted using a log-normal distribution for age at onset with the repeat length of the alleles as covariates. From these models, we calculated expected age at onset from birth and conditionally that this age is greater than the current age. RESULTS: For SCA2 and SCA3 genotypes, the expanded allele was a significant predictor of age at onset (-0.105±0.005 and -0.056±0.003) while for SCA1 and SCA6 genotypes both the size of the expanded and normal alleles were significant (expanded: -0.049±0.002 and -0.090±0.009, respectively; normal: +0.013±0.005 and -0.029±0.010, respectively). According to the model, we indicated the median values (90% critical region) and the expectancy (SD) of the predicted age at onset for each SCA genotype according to the CAG repeat size and current age. CONCLUSIONS: These estimations can be valuable in clinical and research. However, results need to be confirmed in other independent cohorts and in future longitudinal studies. CLINICALTRIALSGOV, NUMBER: NCT01037777 and NCT00136630 for the French patients.

Biological and clinical characteristics of individuals at risk for spinocerebellar ataxia types 1, 2, 3, and 6 in the longitudinal RISCA study: analysis of baseline data.

BACKGROUND: Spinocerebellar ataxias (SCAs) are autosomal, dominantly inherited, fully penetrant neurodegenerative diseases. Our aim was to study the preclinical stage of the most common SCAs: SCA1, SCA2, SCA3, and SCA6. METHODS: Between Sept 13, 2008, and Dec 1, 2011, offspring or siblings of patients with SCA1, SCA2, SCA3, or SCA6 were enrolled into a prospective, longitudinal observational study at 14 European centres. To be eligible for inclusion in our study, individuals had to have no ataxia and be aged 18-50 years if directly related to individuals with SCA1, SCA2, or SCA3, or 35-70 years if directly related to individuals with SCA6. We did anonymous genetic testing to identify mutation carriers. We assessed participants with clinical scales, questionnaires, and performance-based coordination tests. In eight of the 14 centres, participants underwent MRI. We analysed relations between outcome variables and time from onset (defined as the difference between present age and estimated age at ataxia onset). This study is registered with ClinicalTrials.gov, number NCT01037777. FINDINGS: 276 participants met inclusion criteria and agreed to participate, of whom 12 (4%) were excluded from final analysis because DNA samples were missing or genotyping failed. Estimated time from onset was -9 years (IQR -13 to -6) in 50 carriers of the SCA1 mutation, -12 years (-15 to -9) in 31 SCA2 mutation carriers, -8 years (-11 to -6) in 26 SCA3 mutation carriers, and -18 years (-22 to -16) in 16 SCA6 mutation carriers. Compared with non-carriers of each mutation, SCA1 mutation carriers had higher median scores on the scale for the assessment and rating of ataxia (SARA; 0·5 [IQR 0-1·0] vs 0 [0-0]; p=0·0052), as did SCA2 mutation carriers (0·5 [0-2·0] vs 0 [0-0·5]; p=0·0037). SCA2 mutation carriers had lower SCA functional index scores than did non-carriers (-0·43 [-0·91 to -0·07] vs 0·09 [-0·30 to 0·56]; p=0·0007). SCA2 mutation carriers had worse composite cerebellar functional scores than did their non-carrier counterparts (0·915 [0·861-0·959] vs 0·849 [0·764-0·886]; p=0·0039). All other differences between carriers and non-carriers were non-significant. In SCA1 and SCA2 mutation carriers, SARA scores were increased in participants who were closer to the estimated age at onset (SCA1: r=0·36, p=0·0112; SCA2: r=0·50, p=0·0038). 83 individuals (30%) underwent MRI. Voxel-based morphometry showed grey-matter loss in the brainstem and cerebellum in SCA1 and SCA2 mutation carriers, and normalised brainstem volume was lower in SCA2 mutation carriers (median 0·015, range 0·012-0·016) than in non-carriers (0·019, 0·017-0·021; p=0·0107). INTERPRETATION: Preclinical SCA1 and SCA2 mutation carriers seem to have mild coordination deficits and abnormalities in the brain that are more common in carriers who are closer to the estimated onset of ataxia. Individuals in this early disease stage could be targeted in future preventive trials. FUNDING: ERA-Net E-Rare and Polish Ministry of Science and Higher Education.