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Respiratory Research Sep 2019Idiopathic pulmonary fibrosis (IPF) is a progressive disease with a dismal prognosis. The average life expectancy of untreated patients with IPF is only 3 to 4 years.... (Review)
Review
Idiopathic pulmonary fibrosis (IPF) is a progressive disease with a dismal prognosis. The average life expectancy of untreated patients with IPF is only 3 to 4 years. Decline in forced vital capacity (FVC) in patients with IPF appears to be almost linear, with patients with well-preserved FVC at baseline experiencing the same rate of decline in FVC as patients with more advanced disease. Two antifibrotic therapies have been approved for the treatment of IPF: nintedanib and pirfenidone. These drugs slow decline in lung function and reduce the risk of acute respiratory deteriorations, which are associated with very high morbidity and mortality. Individual clinical trials have not been powered to show reductions in mortality, but analyses of pooled data from clinical trials, as well as observational studies, suggest that antifibrotic therapies improve life expectancy. Despite this, many individuals with IPF remain untreated. In many cases, this is because the physician perceives that the disease is stable and so does not warrant therapy, or has concerns over the potential side-effects of antifibrotic drugs. There remains a need to educate pulmonologists that IPF is a progressive, irreversible and fatal disease and that prompt treatment is critical to preserving patients' lung function and improving outcomes. Most individuals can tolerate antifibrotic therapy, and dose adjustment has been shown to be effective at reducing side effects without compromising efficacy. In addition to anti-fibrotic therapies, individuals with IPF benefit from a holistic approach to their care that includes symptom management and supportive care tailored to the needs of the individual. An animation illustrating the themes covered in this article will be available at: http://www.usscicomms.com/respiratory/maher/treatment-of-IPF .
Topics: Anti-Inflammatory Agents, Non-Steroidal; Clinical Trials as Topic; Humans; Idiopathic Pulmonary Fibrosis; Indoles; Protein Kinase Inhibitors; Pyridones; Time-to-Treatment
PubMed: 31492155
DOI: 10.1186/s12931-019-1161-4 -
Respirology (Carlton, Vic.) Aug 2017The real-world tolerability of pirfenidone and nintedanib in non-clinical trial patients is unknown. Many patients with pulmonary fibrosis have significant medical...
BACKGROUND AND OBJECTIVE
The real-world tolerability of pirfenidone and nintedanib in non-clinical trial patients is unknown. Many patients with pulmonary fibrosis have significant medical co-morbidities or baseline characteristics that exclude them from clinical trial participation.
METHODS
We conducted a retrospective chart review study on subjects prescribed nintedanib or pirfenidone for pulmonary fibrosis treatment (any aetiology) from September 2014 to February 2016. A total of 186 subjects were included: 129 received pirfenidone and 57 were prescribed nintedanib and followed up for mean observation periods of 52 ± 17 weeks for pirfenidone and 41 ± 15 weeks for nintedanib. The primary outcome was drug discontinuation as a result of an adverse event.
RESULTS
Subjects had significant respiratory impairment at baseline, 63% required home oxygen therapy and mean diffusion capacity of carbon monoxide (DLCO) was 36 ± 14% predicted. Drug discontinuation as a result of an adverse event occurred in 20.9% of subjects on pirfenidone and 26.3% on nintedanib. Drug discontinuation rates for both pirfenidone and nintedanib did not significantly differ from corresponding large clinical trials (ASCEND/CAPACITY and INPULSIS 1 and 2, respectively). Adverse events that occurred with highest frequency on pirfenidone were nausea (26.4%), rash/photosensitivity (14.7%) and dyspepsia/gastroesophageal reflux disease (GERD) (12.4%). Diarrhoea (52.6%) and nausea (29.8%) were reported most often with nintedanib therapy.
CONCLUSION
Patients with pulmonary fibrosis treated with nintedanib or pirfenidone in routine clinical practice had drug tolerability and adverse event profiles comparable with subjects enrolled in clinical trials despite having a greater degree of respiratory impairment and a high prevalence of co-morbid medical conditions.
Topics: Aged; Anti-Inflammatory Agents, Non-Steroidal; Enzyme Inhibitors; Female; Humans; Idiopathic Pulmonary Fibrosis; Indoles; Male; Middle Aged; Pyridones; Retrospective Studies; Treatment Outcome
PubMed: 28317233
DOI: 10.1111/resp.13024 -
Drugs Mar 2016Idiopathic pulmonary fibrosis (IPF) is an aging-associated, recalcitrant lung disease with historically limited therapeutic options. The recent approval of two drugs,... (Review)
Review
Idiopathic pulmonary fibrosis (IPF) is an aging-associated, recalcitrant lung disease with historically limited therapeutic options. The recent approval of two drugs, pirfenidone and nintedanib, by the US Food and Drug Administration in 2014 has heralded a new era in its management. Both drugs have demonstrated efficacy in phase III clinical trials by retarding the rate of progression of IPF; neither drug appears to be able to completely arrest disease progression. Advances in the understanding of IPF pathobiology have led to an unprecedented expansion in the number of potential therapeutic targets. Drugs targeting several of these are under investigation in various stages of clinical development. Here, we provide a brief overview of the drugs that are currently approved and others in phase II clinical trials. Future therapeutic opportunities that target novel pathways, including some that are associated with the biology of aging, are examined. A multi-targeted approach, potentially with combination therapies, and identification of individual patients (or subsets of patients) who may respond more favourably to specific agents are likely to be more effective.
Topics: Aging; Clinical Trials, Phase II as Topic; Drug Approval; Humans; Idiopathic Pulmonary Fibrosis; Indoles; Molecular Targeted Therapy; Pyridones
PubMed: 26729185
DOI: 10.1007/s40265-015-0523-6 -
Journal of Managed Care & Specialty... Mar 2017Maher has received grants, consulting fees, and speaker fees from GlaxoSmithKline and UCB and grants from Novartis. He has also received consulting fees and speaker fees... (Review)
Review
Maher has received grants, consulting fees, and speaker fees from GlaxoSmithKline and UCB and grants from Novartis. He has also received consulting fees and speaker fees from AstraZeneca, Bayer, Biogen Idec, Boehringer Ingelheim, Cipla, Lanthio, InterMune International AG (a wholly owned Roche subsidiary since 2014), F. Hoffmann-La Roche, Sanofi-Aventis, and Takeda. Maher is supported by a National Institute for Health Research Clinician Scientist Fellowship (NIHR Ref: CS:-2013-13-017). Dejonckheere is an employee of F. Hoffmann-La Roche. Nathan has received consulting fees from Roche-Genentech and Boehringer Ingelheim. He is also on the speakers bureau for Roche-Genentech and Boehringer Ingelheim and has received research funding from both companies. All authors contributed equally to study concept and design, data collection and analysis, and manuscript preparation.
Topics: Anti-Inflammatory Agents, Non-Steroidal; Humans; Hypertension, Pulmonary; Idiopathic Pulmonary Fibrosis; Indoles; Phosphodiesterase 5 Inhibitors; Pyridones; Survival Rate
PubMed: 28287348
DOI: 10.18553/jmcp.2017.23.3-b.s3 -
Annals of Dermatology May 2023A 75-year-old male was diagnosed with idiopathic pulmonary fibrosis and treated with pirfenidone. He presented with an erythematous thick scaly patch on his face, neck,...
A 75-year-old male was diagnosed with idiopathic pulmonary fibrosis and treated with pirfenidone. He presented with an erythematous thick scaly patch on his face, neck, and both hands and arms. He had a history of significant exposure to sunlight without using sunscreen. All lesions were restricted to sun-exposed areas and appeared one month ago. Histopathological examination revealed necrotic keratinocytes, epidermal spongiosis, liquefaction degeneration of the basal layer, interface dermatitis, solar elastosis, and upper dermal perivascular lympho-histiocytic infiltration. Based on clinical and histopathological findings, the skin lesion could be diagnosed as photosensitive drug eruption induced by pirfenidone. Pirfenidone was discontinued for a month, and the patient was treated with oral and topical corticosteroids. Consequently, the skin lesion almost fully cleared, leaving mild postinflammatory hyperpigmentation. Although there are many reports of photosensitivity reactions to pirfenidone, dermatologists are still not familiar with this drug. Through this case presentation, clinicians should be aware of the potential phototoxic effects of pirfenidone and provide the necessary precautionary information to patients who take pirfenidone.
PubMed: 37853864
DOI: 10.5021/ad.21.052 -
Respiratory Research Feb 2016Idiopathic pulmonary fibrosis (IPF) is an incurable lung disease with a poor prognosis. Fibroblasts and myofibroblasts are the key cells in the fibrotic process....
BACKGROUND
Idiopathic pulmonary fibrosis (IPF) is an incurable lung disease with a poor prognosis. Fibroblasts and myofibroblasts are the key cells in the fibrotic process. Recently two drugs, pirfenidone and nintedanib, were approved for clinical use as they are able to slow down the disease progression. The mechanisms by which these two drugs act in in vitro cell systems are not known. The aim of this study was therefore to examine the effects of pirfenidone and nintedanib on fibroblasts and myofibroblasts structure and function established from patients with or without IPF.
METHODS
Stromal cells were collected and cultured from control lung (n = 4) or IPF (n = 7). The cells were treated with pirfenidone and/or nintedanib and the effect of treatment was evaluated by measuring cell proliferation, alpha smooth muscle actin (α-SMA) and fibronectin expression by Western analysis and/or immunoelectron microscopy, ultrastructural properties by transmission electron microscopy and functional properties by collagen gel contraction and invasion assays.
RESULTS
Both pirfenidone and nintedanib reduced in vitro proliferation of fibroblastic cells in a dose dependent manner. The number of cells from control lung was reduced to 47 % (p = 0.04) and of IPF cells to 42 % (p = 0.04) by 1 mM pirfenidone and correspondingly to 67 % (p = 0.04) and 68 % (p = 0.04), by 1 μM nintedanib. If both drugs were used together, a further reduced proliferation was observed. Both pirfenidone and nintedanib were able to reduce the amount of α-SMA and the myofibroblastic appearance although the level of reduction was cell line dependent. In functional assays, the effect of both drugs was also variable.
CONCLUSIONS
We conclude that the ultrastructure and function of fibroblasts and myofibroblasts are affected by pirfenidone and nintedanib. Combination of the drugs reduced cell proliferation more than either of them individually. Human lung derived cell culture systems represent a potential platform for screening and testing drugs for fibrotic diseases.
Topics: Anti-Inflammatory Agents, Non-Steroidal; Cell Proliferation; Cells, Cultured; Dose-Response Relationship, Drug; Drug Therapy, Combination; Fibroblasts; Humans; Idiopathic Pulmonary Fibrosis; Indoles; Myofibroblasts; Pyridones; Treatment Outcome
PubMed: 26846335
DOI: 10.1186/s12931-016-0328-5 -
Respiratory Research Jul 2020Two antifibrotic drugs, nintedanib and pirfenidone, are available for treatment of idiopathic pulmonary fibrosis (IPF). Although efficacy and adverse events have been... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Two antifibrotic drugs, nintedanib and pirfenidone, are available for treatment of idiopathic pulmonary fibrosis (IPF). Although efficacy and adverse events have been well studied, little is known about patient experiences with these drugs. We aimed to systematically and quantitatively evaluate patient expectations, experiences, and satisfaction with nintedanib and pirfenidone. Furthermore, we assessed which factors were associated with overall patient satisfaction with medication.
METHODS
Outpatients with IPF prospectively completed the Patient Experiences and Satisfaction with Medication (PESaM) questionnaire before start, and after three and 6 months of antifibrotic treatment, as part of a randomized eHealth trial (NCT03420235). The PESaM questionnaire consists of an expectation module, a validated generic module evaluating patient experiences and satisfaction concerning the effectiveness, side-effects, and ease of use of a medication, and a disease-specific module about IPF. Satisfaction was scored on a scale from - 5 (very dissatisfied) to + 5 (very satisfied).
RESULTS
In total, 90 patients were included, of whom 43% used nintedanib and 57% pirfenidone. After 6 months, the mean overall score for satisfaction with medication was 2.1 (SD 1.9). No differences were found in experiences and satisfaction with medication, and the number and severity of side-effects between nintedanib and pirfenidone. Perceived effectiveness of medication was rated as significantly more important than side-effects and ease of use (p = 0.001). Expectations of patients regarding effectiveness were higher than experiences after 6 months. Self-reported experience with effectiveness was the main factor associated with overall medication satisfaction.
CONCLUSIONS
Patient experiences and satisfaction with antifibrotic treatment were fairly positive, and similar for nintedanib and pirfenidone. Systematic evaluation of patient expectations, experiences, and satisfaction with medication could enhance shared-decision making and guide drug treatment decisions in the future.
TRIAL REGISTRATION
NCT03420235 .
Topics: Aged; Anti-Inflammatory Agents, Non-Steroidal; Female; Humans; Idiopathic Pulmonary Fibrosis; Indoles; Male; Middle Aged; Motivation; Patient Satisfaction; Prospective Studies; Pyridones; Self Report; Surveys and Questionnaires; Treatment Outcome
PubMed: 32703201
DOI: 10.1186/s12931-020-01458-1 -
Scientific Reports Nov 2023Chronic kidney disease (CKD) is a comorbidity in idiopathic pulmonary fibrosis (IPF), and managing IPF with CKD is challenging due to limited options for antifibrotic...
Chronic kidney disease (CKD) is a comorbidity in idiopathic pulmonary fibrosis (IPF), and managing IPF with CKD is challenging due to limited options for antifibrotic therapy. The aim of this study was to examine the prevalence of CKD and prescription status of pirfenidone in IPF patients and to analyze its impact on mortality. Data from the Korean National Health Insurance Service (NHIS) database between October 2015 and September 2021 were used. IPF and CKD were defined based on both International Classification of Diseases 10th Revision (ICD-10) codes and Rare Intractable Disease (RID) codes. The risk of mortality was assessed based on accompanying CKD with or without antifibrotic therapy. Among 5038 patients with IPF, 8.4% had comorbid CKD and 83.3% with CKD did not receive renal replacement therapy (RRT). Patients with IPF and CKD were older, predominantly male, and had more frequent comorbidities such as cardiovascular disease and diabetes mellitus than subjects without CKD. Pirfenidone was prescribed to 105 (24.6%) of 426 CKD patients, and 89.5% of them did not receive RRT. Pirfenidone was also prescribed to 775 (16.8%) of 4612 IPF patients without CKD. Significant difference was not found in all-cause mortality between the IPF patients with or without CKD regardless of pirfenidone treatment. The use of antifibrotics in IPF patients with CKD is limited due to CKD severity; however, evidence is lacking. Mortality did not increase with accompanying CKD regardless of antifibrotic use. Further research on IPF and CKD is needed.
Topics: Humans; Male; Female; Idiopathic Pulmonary Fibrosis; Pyridones; Comorbidity; Renal Insufficiency, Chronic; Treatment Outcome
PubMed: 37935732
DOI: 10.1038/s41598-023-46506-0 -
European Journal of Hospital Pharmacy :... Nov 2020To assess the long-term effectiveness of pirfenidone in idiopathic pulmonary fibrosis (IPF) treatment and to establish its adverse effects profile. (Observational Study)
Observational Study
OBJECTIVES
To assess the long-term effectiveness of pirfenidone in idiopathic pulmonary fibrosis (IPF) treatment and to establish its adverse effects profile.
METHODS
Retrospective observational study in patients with IPF who initiated treatment with pirfenidone between 2011 and 2016. We collected demographic variables (age, sex); date of first and last treatment; reason for discontinuation; pulmonary function measures (forced vital capacity (FVC), carbon monoxide diffusion capacity (DLCO), and 6 min walk test (6MWT)) at treatment initiation (baseline) and at 1, 2 and 3 year follow-up; adherence to pirfenidone treatment; recorded adverse effects; and mortality.
RESULTS
Thirty-one patients treated with pirfenidone were included; mean±SD age was 69±8 years, 74% were men, and 59% had a smoking history. Mean baseline values were: FVC 2.43±0.66 L (61.8±12.1%); DLCO 46.1±19.4%; and 6MWT 334±125 m. Median duration of treatment was 14±13 months, and treatment was discontinued in 58% of patients. The most frequently observed adverse effects were gastrointestinal disturbances and photosensitivity. Twenty (65%) patients were evaluated at 1 year, when mean FVC was 2.41±0.86 L (64.7±20.3%); DLCO 50.8±26.8%; and 6MWT 341±139 m. At 2 years' follow-up, 11 patients (36%) who were still taking pirfenidone were evaluated. Mean FVC was 2.34±0.79 L (66.2±14.7%); DLCO 50.0±28.3%; and 6MWT 265±121 m. At 3 years, five patients were still taking the treatment. Mean FVC was 2.71±0.84 L (71.0±24.7%); DLCO 52.6±26.7%; and 6MWT 286±139 m. Nineteen per cent of patients were non-adherent to treatment.
CONCLUSIONS
Pirfenidone seems to be effective for long-term control of IPF despite substantial variability in response among individual patients. The most frequent adverse effects were digestive and cutaneous, prompting in some cases a reduction in dose or even discontinuation of the treatment.
Topics: Aged; Anti-Inflammatory Agents, Non-Steroidal; Exercise Test; Fatigue; Female; Follow-Up Studies; Humans; Idiopathic Pulmonary Fibrosis; Male; Middle Aged; Myalgia; Pyridones; Retrospective Studies; Treatment Outcome
PubMed: 33020058
DOI: 10.1136/ejhpharm-2018-001806 -
Respiratory Medicine and Research Nov 2023GAP (gender-age-physiology) and TORVAN are multi-parametric prognostication scores for idiopathic pulmonary fibrosis (IPF). We compared their prognostic value in...
BACKGROUND
GAP (gender-age-physiology) and TORVAN are multi-parametric prognostication scores for idiopathic pulmonary fibrosis (IPF). We compared their prognostic value in patients treated with nintedanib or pirfenidone and explored their effect on patient survival in relation to disease staging.
STUDY DESIGN AND PATIENTS
Retrospective evaluation of 235 naïve IPF patients (M = 179; mean age 69.8 yrs±7.1; 102 treated with nintedanib and 133 with pirfenidone), referred to two Italian academic centers between February 2012 and December 2019.
RESULTS
During a median follow-up of 4.2 years, the incidence rate of death was 14.5 per 100 person-years (95% CI: 12 to 17.4), with no differences between nintedanib and pirfenidone (log-rank p = 0.771). According to time-ROC analysis, GAP and TORVAN showed a similar discrimination performance at 1, 2, and 5 years. Survival of GAP-2/GAP-3 IPF patients treated with nintedanib was worse than that of patients in GAP-1 (HR 4.8, 95% CI: 2.2 to 10.5 and HR 9.4, 95% CI: 3.8 to 23.2). TORVAN I patients treated with nintedanib exhibited better survival than those in stages III (HR 3.1, 95% CI: 1.4 to 6.6) and IV (HR 10.5, 95% CI: 3.5 to 31.6). A significant treatment x stage interaction was observed for both disease staging indexes (p = 0.042 for treatment by GAP interaction and p = 0.046 for treatment by TORVAN interaction). A better survival was associated with nintedanib in patients with mild disease (GAP-1 or TORVAN I stage) and with pirfenidone in GAP-3 or TORVAN IV cases, although these findings did not always reach statistical significance.
CONCLUSIONS
GAP and TORVAN similarly perform in IPF patients on anti-fibrotic therapy. However, the survival of patients treated with nintedanib and pirfenidone appears to be differently affected by disease staging.
Topics: Humans; Aged; Retrospective Studies; Treatment Outcome; Idiopathic Pulmonary Fibrosis
PubMed: 37302161
DOI: 10.1016/j.resmer.2023.101013