Clinical implications of nintedanib pharmacokinetics in patients with pulmonary fibrosis.

BACKGROUND: Nintedanib is used to treat both idiopathic and progressive pulmonary fibrosis (IPF/PPF). Evidence of both an exposure-response relationship and an exposure-toxicity relationship has been found, suggesting the potential value of therapeutic drug monitoring (TDM). We aimed to define the therapeutic window of nintedanib in a real-world cohort. METHODS: Data from two clinical studies were pooled for this analysis. To quantify exposure to nintedanib, a population-pharmacokinetic (PK) model was developed. Associations between PK and decline in forced vital capacity (FVC) and diffusing capacity (DLCO) were performed using linear-mixed-effect models (LMEM). The exposure-toxicity relationship was evaluated using a Cox proportional hazards model. RESULTS: In total, 911 PK samples from 99 patients were used to develop the PK model. The LMEM with random slopes and intercepts included 517 pulmonary function tests (PFT) from 81 patients. The average administered nintedanib dose was associated with the rate of FVC decline (p=0.002). Per 50 mg decrease of daily dosage, the rate of FVC decline increased by 53.5 mL/year. Neither nintedanib exposure nor dose significantly affected DLCO decline and they were also not significantly associated with the occurrence of a dose-limiting toxicity (DLT). This may be explained by a large inter- and intrapatient variability in nintedanib PK. CONCLUSION: Nintedanib dose was significantly associated with FVC loss. However, no significant relationship between nintedanib exposure and the occurrence of DLTs was found in this real-world population, and no therapeutic window could be established. The findings in this study indicate that nintedanib is an unsuitable candidate for performing TDM.

Needs, Perceptions and Education in Sarcoidosis: A Live Interactive Survey of Patients and Partners.

OBJECTIVES: Sarcoidosis is a chronic, multisystem disease with often a major impact on quality of life. Information on unmet needs of patients and their partners is lacking. We assessed needs and perceptions of sarcoidosis patients and their partners. METHODS: During patient information meetings in 2015 and 2017 in the Erasmus University Medical Center, we interviewed patients and partners using interactive voting boxes. Patients responded anonymously to 17 questions. Answers were projected directly on the screen in the room. RESULTS: 210 patients and 132 partners participated. Sarcoidosis has a subjective significant impact on lives of both patients and partners. The vast majority of patients and partners feel regularly misunderstood because of the general unawareness of sarcoidosis. Many patients and partners experience anxiety. Three-quarters of patients would like to see more attention and support for their psychological problems. Additionally, more supportive care for partners of sarcoidosis patients is warranted. Interactive interviewing was considered educational (91%) and pleasant (84%). DISCUSSION: This study improves awareness of needs and perceptions of patients with sarcoidosis and their partners. Sarcoidosis leads to anxiety and psychological distress and impairs well-being of patients and their partners. Attention for psychological support, better disease education, and more supportive care for partners is warranted.

A home monitoring program including real-time wireless home spirometry in idiopathic pulmonary fibrosis: a pilot study on experiences and barriers.

In idiopathic pulmonary fibrosis (IPF), home monitoring experiences are limited, not yet real-time available nor implemented in daily care. We evaluated feasibility and potential barriers of a new home monitoring program with real-time wireless home spirometry in IPF. Ten patients with IPF were asked to test this home monitoring program, including daily home spirometry, for four weeks. Measurements of home and hospital spirometry showed good agreement. All patients considered real-time wireless spirometry useful and highly feasible. Both patients and researchers suggested relatively easy solutions for the identified potential barriers regarding real-time home monitoring in IPF.

[Characteristics and treatment of tuberculosis patients in Dekkerswald, 2000-2005]. / Kenmerken en behandeling van tuberculosepatiënten in Dekkerswald, 2000-2005.

OBJECTIVE: To describe the patient population in Dekkerswald, Nijmegen, one of two tuberculosis (TB) centres in The Netherlands. DESIGN: Descriptive, retrospective study. METHOD: Examination of medical records for all TB patients hospitalised between 2000 and 2005, including demographic, social, clinical and follow-up data. RESULTS: Data from 166 patients were analysed. Tertiary referrals accounted for 98% of all hospitalisations. Most patients (68%) were referred for clinical reasons, and 32% were referred for social reasons. Drug resistance was encountered in 23% of patients; 9% had multidrug-resistant TB. Ten percent of patients were seropositive for HIV. Toxicity and side-effects of treatment often led to changes in treatment (40%). Patients had pulmonary TB (59%), extrapulmonary TB (23%) or both (17%). Overall, 141 patients (85%) completed treatment. The TB-related mortality rate was 5%. CONCLUSION: In Dekkerswald, there is a selected patient population that is characterised by drug-resistance, comorbidity, side-effects, extrapulmonary disease and social issues. Due to the low prevalence of TB in The Netherlands, knowledge and experience regarding complex types of TB are limited. Centralisation of patient care is important to preserve and optimise this expertise.