Patients' and Healthcare Professionals' Experiences of Idiopathic Pulmonary Fibrosis Treatment with the Pirfenidone 801 mg Tablet Formulation: A Multinational Survey.

INTRODUCTION: Idiopathic pulmonary fibrosis (IPF) is a progressive, debilitating interstitial lung disease. Two antifibrotics, pirfenidone and nintedanib, are available for IPF treatment. Pirfenidone is available as 267 mg capsules and, more recently, as 267 mg and 801 mg tablets. The aim of this study was to examine the perceived benefits of the 801 mg formulation on patient quality of life (QoL), IPF management and pill burden. METHODS: Forty-seven patients with IPF and 170 healthcare professionals (HCPs; 150 physicians in France, Germany, Spain and the USA and 20 nurses in the USA) completed online questionnaires comprising 67 and 61 questions, respectively. Eligible patients had experience switching from the 267 mg pirfenidone tablet or capsule formulations to the 801 mg tablet formulation, and eligible HCPs were experienced in managing this switch. Questions included single and multiple responses and scalar questions with responses on a 7-point Likert scale. RESULTS: Patients received the 267 mg formulation for a median (range) of 6.0 (2.0-40.0) months prior to switching to the 801 mg formulation. Higher percentages of patients reported satisfaction with the 801 mg versus the 267 mg formulation for its convenience (64 vs. 17%) and number of dosage units (70 vs. 2%). More patients reported good emotional well-being on the 801 mg versus the 267 mg formulation (51 vs. 21%), and fewer patients reported missing a dose of pirfenidone (21 vs. 30%). More HCPs perceived high patient adherence with the 801 mg versus the 267 mg formulation (57 vs. 37%). Overall, 33% of physicians had experienced switching patients back to the 267 mg formulation. CONCLUSION: Patients and HCPs consistently favoured the 801 mg formulation across multiple domains, including convenience, patient QoL and adherence. The 801 mg formulation may provide an alternative to the 267 mg formulation in patients established on the recommended daily dose of pirfenidone.

Exploring predictors of work competence in schizophrenia: The role of theory of mind.

In schizophrenia employment rate is dramatically low, also among patients receiving job support interventions. Recent studies showed a direct relationship between neurocognitive deficits and work functioning, as well as proving the benefits of combined neurocognitive and work interventions. Current evidence also supports a role of Theory of Mind (ToM), on work functioning. However, the effect of integrated rehabilitation programmes including a social cognitive training on job outcome is still less explored. The aim of this pilot study is to investigate the relationship between work competence and clinical factors, neurocognitive and ToM abilities, as well as to explore the effect of neurocognitive and ToM treatments combined with work therapy. Thirty-seven outpatients with schizophrenia were assigned to either a Computer-assisted Cognitive Remediation (CACR) plus work therapy group (WTG) or to CACR and WTG added to ToM Intervention, both followed by a job support programme. All patients were assessed for psychopathology, neurocognition, ToM and work functioning. Work outcome was significantly predicted by age at onset, neurocognitive abilities and the degree of ToM improvement after the specific intervention. This study provides preliminary insight on predictors of work competence in schizophrenia, highlighting the importance of ToM abilities.

Measurement of respiratory function decline in patients with Duchenne muscular dystrophy: a conjoint analysis.

AIM: In Duchenne muscular dystrophy (DMD), little attention has been paid to severity of respiratory function decline (RFD) based on disease progression. We performed a conjoint analysis among 123 Italian clinicians to generate a scale for RFD in DMD patients. METHODS: Before the interview, 11 attributes were selected by discussion among experts. 32 'patient profiles' were generated. Each physician assessed the severity of RFD for each profile. Each level/attribute was assigned an estimated usefulness to understand its impact on RFD. RESULTS: The identified attributes were forced vital capacity, forced vital capacity decline, dysphagia, type of ventilation and peak cough flow. These results allowed the development of a scale for RFD severity. CONCLUSION: This scale can stratify DMD patients according to the severity of their RFD.

Unmet needs in the treatment of idiopathic pulmonary fibrosis-insights from patient chart review in five European countries.

BACKGROUND: Two antifibrotic drugs, pirfenidone and nintedanib, are approved by the European Medicines Agency and the US Food and Drug Administration for the treatment of idiopathic pulmonary fibrosis (IPF). In this analysis, treatment patterns of European patients with IPF were investigated to understand antifibrotic prescribing and identify unmet needs in IPF treatment practice. METHODS: Between February and March 2016, respiratory physicians from France, Germany, Italy, Spain, and the UK participated in an online questionnaire designed to collect information on IPF treatment patterns in patients under their care. Patients were categorized as treated (received approved antifibrotics) or untreated (did not receive approved antifibrotics, but may have received other unapproved therapies). Classification of IPF diagnosis (confirmed/suspected) and severity ('mild'/'moderate'/'severe') for each patient was based on the individual physician's report. Patients' perspectives were not recorded in this study. RESULTS: In total, 290 physicians responded to the questionnaire. Overall, 54% of patients with IPF did not receive treatment with an approved antifibrotic. More patients had a confirmed IPF diagnosis in the treated (84%) versus the untreated (51%) population. Of patients with a confirmed diagnosis, 40% did not receive treatment. The treated population was younger than the untreated population (67 vs 70 years, respectively; p ≤ 0.01), with more frequent multidisciplinary team evaluation (83% vs 57%, respectively; p ≤ 0.01). A higher proportion of untreated patients had forced vital capacity > 80% at diagnosis versus treated patients. Of patients with 'mild' IPF, 71% did not receive an approved antifibrotic versus 41% and 60% of patients with 'moderate' and 'severe' IPF, respectively. CONCLUSIONS: Despite the availability of antifibrotic therapies, many European patients with confirmed IPF do not receive approved antifibrotic treatment. Importantly, there appears to be a reluctance to treat patients with 'mild' or 'stable' disease, and instead adopt a 'watch and wait' approach. More education is required to address diagnostic uncertainty, poor understanding of IPF and its treatments, and issues of treatment access. There is a need to increase physician awareness of the benefits associated with antifibrotic treatment across the spectrum of IPF severity.

Qualitative European survey of patients with idiopathic pulmonary fibrosis: patients' perspectives of the disease and treatment.

BACKGROUND: 'Living with IPF and an exploration of Esbriet® - a new treatment' was an exploratory, qualitative, real-world survey of European patients with idiopathic pulmonary fibrosis (IPF) who were receiving treatment with pirfenidone prior to its commercial availability. The aim of the survey was to probe the impact of IPF on patients' quality of life; the role of healthcare professionals and caregivers; the information needs of both patients and their caregivers; and patients' perceptions of pirfenidone as a new treatment option for IPF. METHODS: Patients from the UK, Germany and Italy, with a diagnosis of IPF (duration >3 months), who were being treated with pirfenidone, were recruited from patient support groups, specialist centres and advocacy groups. Semi-structured, qualitative, in-depth patient interviews of 1-h duration were conducted by an independent researcher. Patients were initially asked about their experiences of living with IPF and then prompted to describe their experiences of taking pirfenidone. Techniques utilised included: the bubble-speech technique; the icon cards projective exercise; and the free association exercise. All interviews were transcribed and analysed by an independent researcher. RESULTS: Forty-five patients (71% male) were interviewed (mean age 68.5 years; mean time since diagnosis 3.5 years); 87% of patients reported that diagnosis took >1 year. Patients reported that IPF had a significant physical and emotional impact on their quality of life. The beneficial role played by caregivers and interstitial lung disease specialist nurses (where available) was specifically highlighted. Although most patients were keen for information on IPF, this was often of poor quality, out of date, or in English only. Patients' perceptions of pirfenidone were largely positive and associated with 'hope' but were also influenced by the level of side effects experienced. CONCLUSIONS: This survey highlights the impact of IPF on patients' lives, and the need to adequately support both patients and their caregivers. These findings demonstrate the value of seeking patients' perspectives of a chronic disease such as IPF and how this information can be used to guide improvements in care, to best support the needs of patients with this devastating condition.

Conversion of murine antibodies to human antibodies and their optimization for ovarian cancer therapy targeted to the folate receptor.

We previously developed murine and chimeric antibodies against a specific epithelial ovarian carcinoma (EOC) marker, named folate receptor (FR), and promising results were obtained in phase II trials. More recently, we successfully generated a completely human Fab fragment, C4, by conversion of one of the murine anti-FR antibodies to human antibody using phage display and guided selection. However, subsequent efforts to obtain C4 in a dimer format, which seems especially desirable for EOC locoregional treatment, resulted in a highly heterogeneous product upon natural dimerization and in a very poor production yield upon chemical dimerization by a non-hydrolyzable linker to a di-Fab-maleimide (DFM). We therefore designed, constructed and characterized a large Fab dual combinatorial human antibody phage display library obtained from EOC patients and potentially biased toward an anti-tumor response in an effort to obtain new anti-FR human antibodies suitable for therapy. Using this library and guiding the selection on FR-expressing cells with murine/human antibody chains, we generated four new human anti-FR antibody (AFRA) Fab fragments, one of which was genetically and chemically manipulated to obtain a chemical dimer, designated AFRA-DFM5.3, with high yield production and the capability for purification scaled-up to clinical grade. Overall affinity of AFRA-DFM5.3 was in the 2-digit nanomolar range, and immunohistochemistry indicated that the reagent recognized the FR expressed on EOC samples. (131)I-AFRA-DFM5.3 showed high immunoreactivity, in vitro stability and integrity, and specifically accumulated only in FR-expressing tumors in subcutaneous preclinical in vivo models. Overall, our studies demonstrate the successful conversion of murine to completely human anti-FR antibodies through the combined use of antibody phage display libraries biased toward an anti-tumor response, guided selection and chain shuffling, and point to the suitability of AFRA5.3 for future clinical application in ovarian cancer.