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High-resolution CT scan of the chest showing features of UIP, including peripheral reticulation (open arrows) and honeycombing (closed arrow).
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Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial lung disease of unknown cause. Approximately 5,000 people are diagnosed with IPF in the UK every year. People with IPF suffer significant morbidity and, without any curative treatment at present, survival rates remain poor with a median survival of 3 years. While treatment remains la...
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Objective:
Clinical trials have shown that nintedanib 150 mg twice daily (bid) reduces disease progression in patients with idiopathic pulmonary fibrosis (IPF), with an adverse event profile that is manageable for most patients. Prior to the approval of nintedanib as a treatment for IPF in Brazil, an expanded access program (EAP) was initiated to...
Citations
... As there is no cure for ILD, aside from lung transplantation, medical therapies aim to slow or stop disease progression. 89 In general, ILD/IPF medical therapies are used for either their antifibrotic, anti-inflammatory, or immune suppressing effects. However, these medications come with risks of adverse events. ...
... Adverse events are the most common reason for patients to discontinue medications. 89 In general, medication-related gastrointestinal (GI) adverse events can be managed through dose adjustment, treatment interruption, and/or symptoms management. 90 Therefore, involvement of healthcare professionals to provide symptomatic and supportive care to patients in order to manage these medication-related adverse events is an important component of ILD/IPF management. ...
... 95 Pirfenidone Pirfenidone is an antifibrotic medication used in patients with IPF and acts to suppress the activity of fibrosisassociated pathways. 89,96 Pirfenidone is also used for its antioxidant and anti-inflammatory effects. 97 compiled from four randomized control trials of 623 patients suggest that patients who experience ≥5% weight loss in 1 year while on pirfenidone experience worse outcomes compared with patients that maintain their weight. ...
Restrictive lung disease is defined as a reduction in lung volume that may be due to intraparenchymal or extraparenchymal causes. Intraparenchymal causes falls under the umbrella term of interstitial lung disease (ILD) and includes idiopathic pulmonary fibrosis. This manuscript provides an overview of ILD and can be beneficial for all clinicians working with patients with ILD. Although not well documented, the prevalence of malnutrition in patients with ILD has been reported to be between ~9% and 55%. Body mass index has been shown to predict survival; but more recently, research has suggested that fat‐free mass has a larger influence on survival. There is insufficient evidence to support the use of antioxidant or vitamin supplementation to help diminish the chronic inflammatory process that is seen in this patient population. There are data from studies examining the vitamin D status in this patient population, but research on vitamin D supplementation appears to be lacking. Registered dietitian nutritionists should continue to advocate and play a more prominent role in the nutrition management of patients with ILD as part of standard of care.
... A number of studies [31][32][33] have investigated the efficacy of bosentan, imatinib, etanercept, interferon gamma, and prednisone, azathioprine and N-beta cysteine in the treatment of IPF. However, the results of the related studies show that the efficacy of each drug in the treatment of IPF is unsatisfactory. ...
Background
It is necessary to systematically evaluate the efficacy and adverse reactions of pirfenidone in the treatment of patients with idiopathic pulmonary fibrosis (IPF).
Methods
Pubmed et al. databases were searched up to March 15, 2021 for randomized controlled trials (RCT) of pirfenidone in the treatment of IPF. Two authors collected and compared the indicators including progression-free survival (PFS), vital capacity (VC), forced vital capacity (FVC), and adverse reactions. RevMan 5.3 software and Stata 15.0 software were used for meta-analysis.
Results
A total of 8 reports with 9 RCTs involving 1824 IPF patients were included. Meta-analysis results showed that compared with the control group, pirfenidone could prolong the PFS phase of IPF patients (HR = 0.65, 95% CI 0.55 ~ 0.76, P < 0.001), slow down the VC of IPF patients (SMD = 0.43, 95% CI 0.21 ~ 0.66, P < 0.001), and decrease FVC (SMD = 0.31, 95% CI 0.14 ~ 0.48, P < 0.001). The main adverse reactions of pirfenidone were gastrointestinal reactions, photosensitivity and skin rashes.
Conclusion
Pirfenidone is beneficial to prolong the PFS of IPF patients, improve lung function, and it is safe for clinical use. However, more high-quality RCTs are still needed to provide reliable evidence for the treatment of IPF.
... Nintedanib (Ofev or Vargatef ® ). These drugs provide substantial benefits by slowing disease progression, but they do not offer symptomatic relief or improvement in quality of life and are associated with various side effects and prohibitively high cost (17)(18)(19). Additionally, available treatments do not reverse lung damage incurred during fibrotic progression, necessitating early treatments prior to the destruction of normal lung architecture. ...
Rationale: Pulmonary fibrosis is a devastating lung disease with few therapeutic options. Chitinase 1 (CHIT1), an 18 glycosyl hydrolase family member, contributes to the pathogenesis of pulmonary fibrosis through regulation of Transforming Growth Factor (TGF)-β signaling and effector function. Therefore, CHIT1 is a potential therapeutic target of pulmonary fibrosis.
Objectives: This study aimed to identify and characterize a druggable CHIT1 inhibitor with strong antifibrotic activity and minimal toxicity for therapeutic application to pulmonary fibrosis.
Methods: Extensive screening of small molecule libraries identified the aminoglycoside antibiotic Kasugamycin as a potent CHIT1 inhibitor.
Measurements and Main Results: Elevated levels of CHIT1 were detected in the lungs of patients with pulmonary fibrosis. In vivo bleomycin- and TGF-β-stimulated murine models of pulmonary fibrosis, Kasugamycin showed impressive anti-fibrotic effects in both preventive and therapeutic conditions. In vitro studies also demonstrated that Kasugamycin inhibits fibrotic macrophage activation, fibroblast proliferation and myofibroblast transformation. Null mutation of transforming growth factor beta associated protein 1 (TGFBRAP1), a recently identified CHIT1 interacting signaling molecule, phenocopied antifibrotic effects of Kasugamycin in in vivo lungs and in vitro fibroblasts responses. Kasugamycin inhibits physical association between CHIT1 and TGFBRAP1 with decreased levels of SMAD4 association, suggesting that antifibrotic effect of Kasugamycin is mediated through regulation of TGFBRAP1, at least in part.
Conclusions: These studies demonstrate that Kasugamycin is a novel CHIT1 inhibitor with strong antifibrotic effect that can be further developed as an effective and safe therapeutic drug for pulmonary fibrosis.
... Patients choosing between two equally efficacious drugs that differ only in their lifestyle impact, boils down to the strength of information given by their clinicians [11,12]. Asking patients their priorities on quality of life can help in patient centered decision-making that rhymes with it [13]. ...
Introduction:
Idiopathic Pulmonary Fibrosis is a chronic, progressive lung disease characterized by worsening lung scarring and the radiological/histological pattern of usual interstitial pneumonia. Substantial progress has been made in the clinical management of IPF in the last decade. The two novel antifibrotics, Nintedanib and Pirfenidone have changed the landscape of IPF, by hindering disease progression; however, the drugs have significant discontinuation rates, due to adverse events and do not offer a definitive cure, as such IPF remains a deleterious disease with poor survival.
Areas covered:
In this review, the authors focus on the current and emerging pharmacological options in the treatment of IPF. They include a summary of the current approach including treatment of comorbidities and then discuss promising drugs in the drug pipeline.
Expert opinion:
IPF remains a disease with detrimental outcomes. The plethora of emerging pharmacological treatments brings hope for the future. The current pharmacological 'one fits all' approach has been proven effective in slowing disease progression. The future lies in an oncological approach with combination of therapies. We expect to see a change in clinical trial endpoints and a more inclusive approach for the diagnosis of IPF.
Abbreviation list:
AE: Acute ExacerbationA-SMA: a smooth muscle actinATX: AutotaxinCOPD: Combined Obstructive Pulmonary DiseaseCPFE: Combined Pulmonary Fibrosis and EmphysemaGER: Gastro-esophageal refluxFVC: forced vital capacityECMO: extracorporeal membrane oxygenationILD: Interstitial Lung DiseaseIPF: Idiopathic Pulmonary FibrosisNAC: N-acetylcysteineLPA: Lysophosphatidic acidPH: Pulmonary RehabilitationPR: Pulmonary rehabilitationRCTs: randomized placebo-controlled trialsUIP: usual interstitial pneumonia.
... 19,20 Factors that influence the selection of and treatment with antifibrotic therapy include patient preferences, potential adverse events (AEs), disease progression, and individual burden of comorbidities. 21,22 A patient's lifestyle and clinical conditions may influence the selection between pirfenidone and nintedanib. Gastrointestinal-related AEs are the most frequently reported AEs associated with both antifibrotic therapies. ...
Pirfenidone and nintedanib are oral antifibrotic agents approved for the treatment of idiopathic pulmonary fibrosis (IPF). Real-world data on factors that influence IPF treatment decisions are limited. Physician characteristics associated with antifibrotic therapy initiation following an IPF diagnosis were examined in a sample of US pulmonologists. An online, self-administered survey was fielded to pulmonologists between April 10, 2017, and May 17, 2017. Pulmonologists were included if they spent >20% of their time in direct patient care and had ≥5 patients with IPF receiving antifibrotics. Participants answered questions regarding timing and reasons for considering the initiation of antifibrotic therapy after an IPF diagnosis. A total of 169 pulmonologists participated. The majority (81.7%) considered initiating antifibrotic therapy immediately after IPF diagnosis all or most of the time (immediate group), while 18.3% considered it only some of the time or not at all (delayed group). Pulmonologists in the immediate group were more likely to work in private practice (26.1%), have a greater mean percentage of patients receiving antifibrotic therapy (60.8%), and decide to initiate treatment themselves (31.2%) versus those in the delayed group (16.1%, 30.5%, and 16.1%, respectively). Most pulmonologists consider initiating antifibrotic treatment immediately after establishing an IPF diagnosis all or most of the time versus using a “watch-and-wait” approach. Distinguishing characteristics between pulmonologists in the immediate group versus the delayed group included practice setting, percentage of patients receiving antifibrotic therapy, and the decision-making dynamics between the patient and the pulmonologist.
... It is widely acknowledged that the patient's perspective regarding medical therapy should play a central role in deciding upon treatment strategies [1][2][3][4][5][6][7][8][9][10][11]. Patients who perceive their medication to be ineffective, suffer from side effects, or experience difficulties with the administration of a medication, are less likely to be satisfied and take their medication as prescribed [12]. ...
Background
This study assessed the validity and reliability of the generic module of the recently developed Patient Experiences and Satisfaction with Medications (PESaM) questionnaire in a sample of patients in the Netherlands.
Methods
The generic module of the PESaM questionnaire consists of 18 items related to the domains effectiveness, side effects and ease of use of medications. It assesses patients’ experiences regarding the impact of the medication on daily life, health and satisfaction. In 2017, the PESaM questionnaire was sent out to idiopathic pulmonary fibrosis patients using pirfenidone or nintedanib, atypical haemolytic uraemic syndrome patients receiving eculizumab and patients using tacrolimus after kidney transplantation. Mean scores for each domain were calculated applying a scoring algorithm. Construct validity and reliability were assessed using recommended methods.
Results
188 participants completed the generic module, of whom 48% used pirfenidone, 36% nintedanib, 11% tacrolimus and 5% eculizumab. The generic module has good structural properties. Internal consistency values of the domains were satisfactory (i.e. Cronbach’s coefficient alpha above 0.7). Confirmatory factor analysis provided further evidence for construct validity, with good convergent and discriminant validity. The PESaM questionnaire also showed different scores for patients using different medications, in line with expectations, and was therefore able to differentiate between patient groups. Test–retest reliability of the items and domains were rated as moderate to fair (i.e. intraclass coefficients ranged between 0.18 and 0.76).
Conclusions
The PESaM questionnaire is a unique patient-reported outcome measure evaluating patient experiences and satisfaction with medications. It has been developed in conjunction with patients, ensuring coverage of domains and issues relevant from the patient’s perspective. This study has shown promising validity of the generic module of the PESaM questionnaire. Further research is recommended to assess reliability in greater detail as well as the responsiveness of the measure.
Trial registration
The study is registered in The Netherlands National Trial Register (Trial Code 5860).
... In idiopathic pulmonary fibrosis (IPF), no clinical solution has been found for this rather uncommon disease. (94,95) Its pathogenetics has not been fully clarified and its treatment options remain limited. Table 2B summarizes therapeutic effects of heparin in IPF (Table 2B). ...
Heparin is well known for its anticoagulant and anti-inflammatory properties. Inhaled heparin regimens are increasingly being used to manage lung disease. It has been used to treat cystic fibrosis, thromboembolism, and pulmonary fibrosis, as well as bronchial asthma and asthma-induced airway hypersensitivity. Several preclinical studies attained some useful effects of heparin-administered, parenterally and through inhalation, treatment of lung disease. Besides, recent clinical trials suggest that inhaled heparin for lung diseases is beneficial and safe, but such data remain to be limited. In 2005, the orphan designation was granted by the European Commission for heparin sodium (inhalation use) for the treatment of cystic fibrosis. The positive results of heparin in the pulmonary route necessitate a focus on the preparation and evaluation of heparin in advanced drug delivery systems, namely nano/microparticles and liposomes. Through this pulmonary delivery, heparin is protected from enzymatic degradation within the airway. Heparin is thus passively targeted into the lungs, and long-lasting localized treatment is achieved. On the other hand, these systems have encountered several problems as follows: (1) polymers, such as poly-L-lactide-glycolic acid, poly (lactic acid), and chitosan, used to prepare heparin-loaded microparticle/nanoparticle (MP/NP) systems have not been granted approval for lung application by the FDA and (2) liposomal and NP formulation stability is the main problem of formulation design. We propose that additional in vitro and in vivo research is necessary to assess the clinical applicability of this treatment strategy. The present article discusses heparin treatments for lung diseases and the use of heparin and/or heparin-loaded drugs in advanced delivery systems through the pulmonary route.
... These analyses have reached similar conclusions that both agents likely result in similar clinical and physiological results (Fig. 3). The availability of two effective agents with differing dosing regimens and tolerability profiles provides the patient and clinician with valuable therapeutic options that must be personalized 53 . The timing of initiation of therapy remains controversial 54 . ...
... These analyses have reached similar conclusions that both agents likely result in similar clinical and physiological results (Fig. 3). The availability of two effective agents with differing dosing regimens and tolerability profiles provides the patient and clinician with valuable therapeutic options that must be personalized 53 . The timing of initiation of therapy remains controversial 54 . ...
... As a consequence, potential side effects of these drugs need to be balanced with the treatment effect [33,34]. Evaluation of patient experiences can thus play a significant role when considering treatment approaches [35,36]. In The Netherlands, it is estimated that between 800 and 1600 people are diagnosed with IPF each year [37]. ...
Background:
The aim of this study was to develop, together with the Lung Foundation Netherlands and Dutch Kidney Patients Association, patients and clinicians, a measure to evaluate patient experiences with the orphan drugs pirfenidone (for idiopathic pulmonary fibrosis [IPF]) and eculizumab (for atypical haemolytic uraemic syndrome [aHUS]), as well as a generic measure of patient experiences and satisfaction with medications.
Methods:
Development of the Patient Experiences and Satisfaction with Medications (PESaM) questionnaire consisted of four phases: literature review (phase I); focus groups and individual patient interviews (phase II); item generation (phase III); and face and content validity testing (phase IV). Literature review aimed to identify existing disease-specific and generic patient experience measures to provide guidance on the domains of medication use relevant to patients, the number of items and type of response categories, and to generate an initial pool of items. Subsequent focus groups and patient interviews were conducted to gain insight into the perceived effectiveness of the therapies, the burden of side effects, and how the medication impacted on a patient's daily life. Focus groups and interviews were recorded and transcribed verbatim. Coding was carried out by highlighting passages in the text and assigning each passage a code representing the following predefined categories: (1) perceived effectiveness; (2) side effects; (3) ease of use; and (4) impact of medication. Using data from phase I and II, a panel of experts selected items relevant for inclusion in the questionnaire. Individual patient interviews with IPF and aHUS patients (n?=?18), using a retrospective verbal probing technique, were conducted to assess face validity, time needed to fill out the questionnaire, and content validity.
Results:
The PESaM questionnaire that was developed consisted of two disease-specific modules that assessed patient experiences with pirfenidone for the treatment of IPF, and eculizumab for the treatment of aHUS, a generic module, applicable to any medication, and a module to assess patient expectations. Review of the literature identified multiple disease- or medication-specific questionnaires and two generic patient satisfaction questionnaires. Common domains across most questionnaires were effectiveness, side effects, ease of use and overall satisfaction. Patient interviews revealed the social impact (e.g. unable to go outside) of side effects such as photosensitivity associated with pirfenidone and the risk of infection associated with eculizumab. Each PESaM module focuses on patients' perceived effectiveness of the medication, side effects, and ease of use, and the impact these aspects have on physical and emotional health and daily life. The generic module additionally includes items related to satisfaction with the medication. Individual interviews with patients in phase IV confirmed, in general, that questions and response options of the modules were clear and content validity was good. The mean time to complete the modules ranged from 6?min for the disease-specific (aHUS) module to 9?min for the generic module.
Conclusions:
We developed the PESaM questionnaire to quantitatively assess patient experiences and satisfaction with medications. A validation study is currently underway to examine the psychometric properties of the PESaM questionnaire.
