Effect of interferon gamma-1b on survival in patients with idiopathic pulmonary fibrosis (INSPIRE): a multicentre, randomised, placebo-controlled trial

Idiopathic pulmonary fibrosis is a fatal disease for which no effective treatment exists. We assessed whether treatment with interferon gamma-1b improved survival compared with placebo in patients with idiopathic pulmonary fibrosis and mild-to-moderate impairment of pulmonary function

Supplementary Material for: An Open-Label Study of the Long-Term Safety of Pirfenidone in Patients with Idiopathic Pulmonary Fibrosis (RECAP)

<p><b><i>Background:</i></b> RECAP (NCT00662038) was an open-label extension study in patients with idiopathic pulmonary fibrosis (IPF) who completed either the Assessment of Pirfenidone to Confirm Efficacy and Safety in Idiopathic Pulmonary Fibrosis (ASCEND) 016 phase 3 trial or the Clinical Studies Assessing Pirfenidone in Idiopathic Pulmonary Fibrosis: Research of Efficacy and Safety Outcomes (CAPACITY) 004/006 phase 3 trials. <b><i>Objective:</i></b> To obtain long-term safety data for pirfenidone in patients with IPF in RECAP. <b><i>Methods:</i></b> Of the 1,334 patients who participated in the phase 3 trials, 1,058 entered RECAP. The final analysis from enrollment (September 2008) to June 2015 is presented. <b><i>Results:</i></b> Mean (SD) and median (range) pirfenidone exposures in RECAP were 122 (98) weeks and 88 (>0 to 349) weeks, respectively, with a mean daily dose of 2,091.1 mg. Cumulative total exposure was 2,482 patient exposure years (PEY). The treatment-emergent adverse event (TEAE) rate was 701.9 per 100 PEY. The serious TEAE rate was 53.5 per 100 PEY, with the most common serious TEAE being IPF (11.1 per 100 PEY). Of the 231 deaths (9.3 per 100 PEY), the most common cause was IPF (5.4 per 100 PEY). The treatment discontinuation rate due to a TEAE was 17.9 per 100 PEY; discontinuations were due to IPF (7.2 per 100 PEY), pneumonia, respiratory failure, acute respiratory failure, rash (0.5 per 100 PEY each), and nausea (0.4 per 100 PEY). For patients from CAPACITY 004/006 who entered RECAP, the mean change in percent predicted forced vital capacity from RECAP baseline at 180 weeks was -9.6%. Median on-treatment survival from the first pirfenidone dose in RECAP was 77.2 months. <b><i>Conclusions:</i></b> RECAP provides long-term follow-up and safety data for pirfenidone that were consistent with the known profile, with no new safety signals observed.</p

Long-term safety of pirfenidone: results of the prospective, observational PASSPORT study

Real-world studies include a broader patient population for a longer duration than randomised controlled trials (RCTs) and can provide relevant insights for clinical practice. PASSPORT was a multicentre, prospective, post-authorisation study of patients who were newly prescribed pirfenidone and followed for 2 years after initiating treatment. Physicians collected data on adverse drug reactions (ADRs), serious ADRs (SADRs) and ADRs of special interest (ADRSI) at baseline and then every 3 months. Post hoc stepwise logistic regression models were used to identify baseline characteristics associated with discontinuing treatment due to an ADR. Patients (n=1009, 99.7% with idiopathic pulmonary fibrosis) had a median pirfenidone exposure of 442.0 days. Overall, 741 (73.4%) patients experienced ADRs, most commonly nausea (20.6%) and fatigue (18.5%). ADRs led to treatment discontinuation in 290 (28.7%) patients after a median of 99.5 days. Overall, 55 (5.5%) patients experienced SADRs, with a fatal outcome in six patients. ADRSI were reported in 693 patients, most commonly gastrointestinal symptoms (38.3%) and photosensitivity reactions/skin rashes (29.0%). Older age and female sex were associated with early treatment discontinuation due to an ADR. Findings were consistent with the known safety profile of pirfenidone, based on RCT data and other post-marketing experience, with no new safety signals observed

Coupled social and ecological outcomes of agricultural intensification in Costa Rica and the future of biodiversity conservation in tropical agricultural regions

Tropical ecosystem conversion to agriculture has caused widespread habitat loss and created fragmented landscapes composed of remnant forest patches embedded in a matrix of agricultural land uses. Non- traditional agricultural export (NTAE) crops such as pineapple are rapidly replacing multiuse landscapes characterized by a diverse matrix of pasture and smallholder crops with intensive, large-scale, monoculture plantations. Using an interdisciplinary approach, we conduct a case study to examine the coupled social and ecological implications of agricultural intensification in this region, with larger application to regions experiencing similar patterns of agricultural intensification. Guided by frameworks from both political and landscape ecology, we: (1) describe the social and economic implications of pineapple expansion, specifically the concentration of land, labor and financial resources, (2) quantify pineapple cultivation's spatial characteristics, and (3) assess the effects of pineapple expansion on surrounding forest ecosystems, on the agricultural matrix and on biodiversity conservation. Our results indicate that pineapple production concentrates land, labor, and financial resources, which has a homogenizing effect on the agricultural economy in the study region. This constrains farm-based livelihoods, with larger implications for food security and agricultural diversity. Landscape ecology analyses further reveal how pineapple production simplifies and homogenizes the agricultural matrix between forest patches, which is likely to have a negative effect on biodiversity. To offset the effects of pineapple expansion on social and environmental systems, we recommend developing landscape level land use planning capacity. Furthermore, agricultural and conservation policy reform is needed to promote landscape heterogeneity and economic diversity within the agricultural sector. Our interdisciplinary research provides a detailed examination of the social and ecological impacts of agricultural intensification in a tropical landscape, and offers recommendations for improvement relevant not only to our study region but to the many other tropical landscapes currently undergoing non-traditional agricultural export driven agricultural intensification. (Résumé d'auteur