Longitudinal clinical outcomes in a real-world population of patients with idiopathic pulmonary fibrosis: the PROOF registry

Abstract

BackgroundThe PROOF registry is an observational study initiated in October 2013 with the aim to monitor disease progression in a real-world population of patients with idiopathic pulmonary fibrosis (IPF). Here, we present longitudinal clinical outcomes from the PROOF registry.MethodsPatients with IPF were enrolled across eight centers in Belgium and Luxembourg. For all patients, clinical outcomes data were collected, including mortality, lung transplant, acute exacerbations, and pulmonary hypertension. For patients treated with pirfenidone at any time during follow-up (2013–2017), for any duration of treatment (the pirfenidone-treated population): pirfenidone treatment patterns were collected; changes in pulmonary function (forced vital capacity [FVC] and carbon monoxide diffusing capacity [DLco]) were reviewed up to 24 months post-inclusion; and time-to-event analyses from the time of registry inclusion were performed.ResultsThe PROOF registry enrolled a total of 277 patients. During follow-up, 23.1% of patients died, 5.1% received a lung transplant, 5.4% experienced an acute exacerbation, and 6.1% had comorbid pulmonary hypertension. In the pirfenidone-treated population (N = 233, 84.1%), 12.9% of patients had a temporary dose discontinuation and 31.8% had a temporary dose reduction; 4.3% of patients permanently discontinued pirfenidone due to an adverse drug reaction. Mean percent predicted FVC was 81.2% (standard deviation [SD] 19.0) at Month 0 and 78.3% (SD 25.0) at Month 24, and mean percent predicted DLco was 47.0% (SD 13.2) and 45.0% (SD 16.5), respectively. Rates of ≥ 10% absolute decline in percent predicted FVC and ≥ 15% absolute decline in percent predicted DLco over 24 months were 31.0% and 23.2%, respectively. Mean times from registry inclusion to categorical absolute decline in percent predicted FVC and percent predicted DLco were 20.1 (standard error [SE] 0.6) months and 23.4 (SE 0.5) months, respectively; mean time from registry inclusion to death was 31.0 (SE 0.9) months.ConclusionsThe PROOF registry is a source of European data characterizing longitudinal clinical outcomes of patients with IPF. Over 12 months of follow-up, pulmonary function remained largely stable in patients with IPF who received pirfenidone for any duration of treatment. Pulmonary function remained similar at 24 months of follow-up, although patient numbers were lower.Trial registrationPROOF is registered with the relevant authorities in Belgium and Luxembourg, with registration to Comité National d’Éthique et de Recherche (CNER) N201309/03–12 September 2013 and a notification to Comité National de Protection des Données (CNDP) for Luxembourg.

A multicentre retrospective observational study on Polish experience of pirfenidone therapy in patients with idiopathic pulmonary fibrosis: the PolExPIR study

“…The ADRs led to permanent treatment discontinuations in 16.61% of Polish patients which, despite median longer drug exposition, is in good agreement with the rates of pirfenidone discontinuations due to ADRs reported in the CAPACITY study (15%) [4] and the AS-CEND study (14.4%) [5]. Although, pirfenidone treatment discontinuation rates due to ADRs reported in the previous observational RWD studies vary significantly in the range of 1.7 to 31.8% [12,14,17,19,[25][26][27][28]. The majority of discontinuations in our study related to ADRs (84%) were gastrointestinal and skin-related which is consistent with previous pirfenidone tolerance data [35][36][37].…”

“…Surprisingly, only one patient in the PolExPIR cohort (0.33%) discontinued pirfenidone treatment due to lung transplantation. In the recently published results of an observational study of patients with IPF treated with pirfenidone in Belgium and Luxembourg (PROOF registry) the lung transplant rate for all patients during a study follow-up of 24 months was 5.6% (13 out of 233 patients) [28]. This finding confirms that improvement in cooperation between pulmonary centres and transplantation units in Poland is crucial for optimal patients outcomes in this matter.…”

“…Up to date, several RWD studies were published supplementing previous evidence of RCTs on the efficacy and safety of pirfenidone in the treatment of heterogenous IPF patients populations, however the scientific significance of many of those studies suffer from a small number of patients included for analysis (<100 patients) [11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30]. Moreover, no data exist describing the clinical efficacy and safety of long-term pirfenidone use in patients with IPF in Poland.…”

Baseline characteristics and survival of patients of idiopathic pulmonary fibrosis: a longitudinal analysis of the Swedish IPF Registry

“…Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive fibrosing interstitial lung disease (ILD) of unknown cause [1][2][3].The disease is characterized by an aberrant accumulation of fibrotic tissue in the lung parenchyma, resulting in extensive alterations of lung structure and function and leads finally to respiratory failure and death [2,4,5]. Long-term observational studies in clinically diverse IPF populations from all over the world are increasing [1,[6][7][8][9][10][11][12][13][14][15] and provide us with important information on disease behaviour, management, and effectiveness of approved treatments.…”

The world is not enough – the value of increasing registry data in idiopathic pulmonary fibrosis

“…Patients in registries tend to have a slightly worse health-related quality of life, more clinically important comorbidities, and may have a more severely impaired lung function as compared to patients who participated in clinical trials [18]. Real-world registries have proved to be an important source of information regarding disease behavior, use and long-term efficacy of anti-fibrotic medication, mortality, prevalence and impact of comorbidities, burden of disease, and various other topics [19][20][21][22][23]. Despite these advances, many more essential questions remain to be elucidated in the coming years [17].…”