scholarly journals Safety and tolerability of nintedanib in patients with systemic sclerosis-associated interstitial lung disease: data from the SENSCIS trial

2020 ◽  
Vol 79 (11) ◽  
pp. 1478-1484
Author(s):  
James R Seibold ◽  
Toby M Maher ◽  
Kristin B Highland ◽  
Shervin Assassi ◽  
Arata Azuma ◽  
...  
Keyword(s):  
Adverse Event ◽  
Systemic Sclerosis ◽  
Interstitial Lung Disease ◽  
Adverse Events ◽  
Lung Disease ◽  
Treatment Interruption ◽  
Common Adverse Event ◽  
Tolerability Profile ◽  
Trial Drug ◽  
The Impact

ObjectivesTo characterise the safety and tolerability of nintedanib and the dose adjustments used to manage adverse events in patients with systemic sclerosis-associated interstitial lung disease (SSc-ILD).MethodsIn the SENSCIS trial, patients with SSc-ILD were randomised to receive nintedanib 150 mg two times per day or placebo. To manage adverse events, treatment could be interrupted or the dose reduced to 100 mg two times per day. We assessed adverse events and dose adjustments over 52 weeks.ResultsA total of 576 patients received nintedanib (n=288) or placebo (n=288). The most common adverse event was diarrhoea, reported in 75.7% of patients in the nintedanib group and 31.6% in the placebo group; diarrhoea led to permanent treatment discontinuation in 6.9% and 0.3% of patients in the nintedanib and placebo groups, respectively. In the nintedanib and placebo groups, respectively, 48.3% and 12.2% of patients had ≥1 dose reduction and/or treatment interruption, and adverse events led to permanent discontinuation of the trial drug in 16.0% and 8.7% of patients. The adverse events associated with nintedanib were similar across subgroups defined by age, sex, race and weight. The rate of decline in forced vital capacity in patients treated with nintedanib was similar irrespective of dose adjustments.ConclusionsThe adverse event profile of nintedanib in patients with SSc-ILD is consistent with its established safety and tolerability profile in patients with idiopathic pulmonary fibrosis. Dose adjustment is important to minimise the impact of adverse events and help patients remain on therapy.

Immune-related adverse events for different age groups using the FDA Adverse Event Reporting System.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e14256-e14256
Author(s):  
Zin Myint ◽  
Ayman Qasrawi ◽  
Richard O'Neal ◽  
Chris Z Thomas ◽  
Susanne M. Arnold ◽  
...  
Keyword(s):  
Adverse Event ◽  
Interstitial Lung Disease ◽  
Adverse Events ◽  
Lung Disease ◽  
Reporting System ◽  
Adverse Event Reporting System ◽  
Age Groups ◽  
Adverse Event Reporting ◽  
Age Group ◽  
Event Reporting

e14256 Background: Understanding immune-related adverse events (irAEs) for different age groups is crucial in the era of immunotherapy. The aim of our study is to assess the irAE profiles in different age groups (≤65 and > 65 years) for drugs that target PD1/PDL1, CTLA4, and their combination. Methods: Data were obtained from the FDA Adverse Event Reporting System database from Jan 2014 to Sep 2018. We extracted the data based on reported irAEs and reviewed 30 different irAEs including, but not limited to colitis, pneumonitis, interstitial lung disease (ILD), myocarditis and pneumonitis. Cases with missing data, another drug reported with the PD1/PDL1 or CTLA4 combinations, and duplicate cases were excluded. We calculated the reporting odds ratio (ROR) for irAE associated with the use of PD1/PDL1, CTLA4 and combination, respectively. Results: A total of 6197 reported irAEs cases were included: 3140 cases from patients ≤65 years and 3057 from > 65 years old. Colitis was the most common irAEs in both groups. The RORs (95% CI) in patients using CTLA4 alone, PD1/PDL1 alone or the combination were 4.17 (3.47-5.02), 0.6 (0.5-0.72), 1.98 (1.64-2.39) for colitis; 0.21 (0.09-0.52), 2.94 (1.97-4.38), 2.2 (1.46-3.3) for diabetic ketoacidosis; 0.29 (0.09-0.92), 16.5 (6.54-41.9), 0.18 (0.04-0.73) for rheumatoid arthritis in ≤65 age group. In > 65 age group, the RORs (95% CI) in patients using CTLA4 alone, PD1/PDL1 alone or the combination were 4.79 (3.49-6.58), 0.56 (0.4-0.78), 2.84 (2.06-4) for hypophysitis; 0.12 (0.06-0.24), 28.53 (18.5-44), 0.17 (0.1-0.29) for interstitial lung disease (ILD); 0.38 (0.19-0.78), 2.87 (2.01-4.1), 2.41 (1.64-3.54) for myocarditis. When we compared all the studied irAEs between age groups (≤65 and > 65) by ROR, the only statistically significant irAE was ILD. The RORs (95%CI) for ILD associated with PD1/PDL1 in age≤65 and > 65 were 11.3 (7.65-16.8) & 28.53 (18.49-44.02). Conclusions: There was no significant difference between irAEs in different age groups except with ILD, which is more commonly seen in the > 65 age group. The ROR combination irAE profiles provide hypothesis generating information regarding association between irAEs and the use of various immune therapies.

scholarly journals Evaluation of Potential Complications of Interstitial Lung Disease Associated With Antiandrogens Using Data From Databases Reporting Spontaneous Adverse Effects

2021 ◽  
Vol 12 ◽  
Author(s):  
Hideki Nawa ◽  
Takahiro Niimura ◽  
Hirofumi Hamano ◽  
Kenta Yagi ◽  
Mitsuhiro Goda ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Adverse Event ◽  
Interstitial Lung Disease ◽  
Drug Use ◽  
Adverse Events ◽  
Lung Disease ◽  
Drug Event ◽  
Therapeutic Effects ◽  
Treat Prostate Cancer ◽  
Using Data

From 2002 to 2018, the number of patients with prostate cancer significantly increased from 679,023 to 1276,106 worldwide. Total prostatectomy (including robot-assisted prostatectomy), radiation therapy, and pharmacological treatment are commonly used to treat prostate cancer. The Chief of the Pharmaceutical Safety Division, that is, the Federation of Pharmaceutical Manufacturers’ Associations of Japan (FPMAJ), recently called for the revision of package inserts for ethical drugs. However, the pathogenesis of interstitial lung disease (ILD), a serious drug-induced adverse effect, remains unclear. Moreover, there have been no large-scale evaluations of potential complications associated with currently used antiandrogens, which are commonly employed to treat prostate cancer. Hence, ILD, as an adverse event, remains poorly understood. Therefore, we conducted a survey of reports in the Japanese Adverse Drug Event Report (JADER) database to investigate the potential association between the reporting of ILD and antiandrogen drug use in clinical practice. The occurrence of ILD was investigated by evaluating the relationship between antiandrogen drug use and ILD. Adverse event signals were detected with reporting odds ratios (RORs), using data from the JADER and FDA Adverse Event Reporting System (FAERS) databases, for the analysis of post-marketing adverse event reports. The JADER was used to examine the time profile of adverse event occurrence for each drug, whereas the FAERS was used to screen cases of unknown adverse events and analyze their trends of occurrence. The analysis of data from both databases revealed the 95% confidence interval lower limits of ROR for bicalutamide and flutamide to be > 1, and adverse event signals were detected following the use of either drug. While caution should be exercised for drugs that are new to the market, we conclude that drugs with similar therapeutic effects that have been in use for a long period should also be re-examined for potential adverse events.

scholarly journals Efficacy, Safety, and Tolerability of Treatments for Systemic Sclerosis-Related Interstitial Lung Disease: A Systematic Review and Network Meta-Analysis

2020 ◽  
Vol 9 (8) ◽  
pp. 2560
Author(s):  
Gian Luca Erre ◽  
Marco Sebastiani ◽  
Maria Antonietta Fenu ◽  
Angelo Zinellu ◽  
Alberto Floris ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
Interstitial Lung Disease ◽  
Adverse Events ◽  
Lung Disease ◽  
Fixed Effects ◽  
Randomized Clinical Trials ◽  
Meta Analysis ◽  
Lung Function Decline ◽  
Serious Adverse Events ◽  
Direct Head

Background: There is a paucity of head-to-head comparisons of the efficacy and harms of pharmacological treatments for systemic sclerosis-related interstitial lung disease (SSc-ILD). Methods: We conducted a network meta-analysis (NMA) in order to compare the effects of different treatments with the placebo on change in forced vital capacity (FVC), change in diffusion lung capacity for CO (DLCO), serious adverse events (SAEs), discontinuation for adverse events and mortality in SSc-ILD. Standardized mean difference (SMD) and log odds ratio were estimated using NMA with fixed effects. Results: Nine randomized clinical trials (926 participants) comparing eight interventions and the placebo for an average follow-up of one year were included. Compared to the placebo, only rituximab significantly reduced FVC decline (SMD (95% CI) = 1.00 (0.39 to 1.61)). Suitable data on FVC outcome for nintedanib were not available for the analysis. No treatments influenced DLCO. Safety and mortality were also not different across treatments and the placebo, although there were few reported events. Cyclophosphamide and pomalidomide were less tolerated than the placebo, mycophenolate, and nintedanib. Conclusion: Only rituximab significantly reduced lung function decline compared to the placebo. However, direct head-to-head comparison studies are required to confirm these findings and to better determine the safety profile of various treatments.

scholarly journals Pomalidomide in Patients with Interstitial Lung Disease due to Systemic Sclerosis: A Phase II, Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel-group Study

2017 ◽  
Vol 45 (3) ◽  
pp. 405-410 ◽  
Author(s):  
Vivien M. Hsu ◽  
Christopher P. Denton ◽  
Robyn T. Domsic ◽  
Daniel E. Furst ◽  
Maureen Rischmueller ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
Interstitial Lung Disease ◽  
Lung Disease ◽  
Statistical Significance ◽  
Tolerability Profile ◽  
Double Blind ◽  
Primary Endpoints ◽  
Recruitment Challenges ◽  
Parallel Group ◽  
Study Results

Objective.To evaluate the safety and efficacy of pomalidomide (POM) on forced vital capacity (FVC), modified Rodnan skin score (mRSS), and gastrointestinal (GI) symptomatology over 52 weeks of treatment in patients with interstitial lung disease due to systemic sclerosis (SSc).Methods.Twenty-three adult patients diagnosed with SSc were randomized 1:1 POM:placebo (PBO).Results.Mean change at Week 52 from baseline in predicted FVC% −5.2 and −2.8; mRSS −2.7 and −3.7; and UCLA Scleroderma Clinical Trial Consortium Gastrointestinal Tract (SCTC GIT 2.0) score 0.1 and 0.0, with POM and PBO, respectively. Statistical significance was not achieved for any of these 3 primary endpoints at 52 weeks.Conclusion.Because of recruitment challenges, subject enrollment was discontinued early. In an interim analysis, the study did not meet its Week 52 primary endpoints. Therefore, a decision was made to terminate all study phases. POM was generally well tolerated, with an adverse event profile consistent with the known safety and tolerability profile of POM in other diseases. Study results were neither positive nor negative because too few subjects were enrolled to make meaningful conclusions. Clinical Trials number: NCT01559129.

Quality of life in SSc-ILD patients: Understanding the impact of the ILD and the needs of the SSc-ILD patients and their need for caregivers in France

2021 ◽  
pp. 239719832110139
Author(s):  
Yannick Allanore ◽  
Joel Constans ◽  
Dominique Godard ◽  
Gerard de Pouvourville ◽  
Stephane Bouee ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Systemic Sclerosis ◽  
Interstitial Lung Disease ◽  
Lung Disease ◽  
Forced Vital Capacity ◽  
Vital Capacity ◽  
Disease Score ◽  
System P ◽  
The Impact

Objectives: The objectives of this study were to describe the impact of systemic sclerosis associated interstitial lung disease, on quality of life, to estimate the correlation between quality of life and severity of lung disease and to assess the impact of interstitial lung disease on caregivers. Methods: Seven investigators included systemic sclerosis associated interstitial lung disease patients from December 2019 to April 2020. Sociodemographics and clinical data were collected. Patients reported outcomes and questionnaires were used with 1 generic patients reported outcome (EQ-5D-5L), 1 specific PRO (Brief Interstitial Lung Disease) and 2 self-reported questionnaires on impact of SSc complications and impact on caregivers. The correlation between forced vital capacity and EQ-5D-5L score was estimated with a multivariate linear regression model adjusted on several covariates. Results: In all, 89 patients were included. 26.4% were males, mean age was 58.2 ± 14.5 years. Mean EQ-5D-5L score = 0.79 ± 0.22 (median = 0.85). Mean EQ-5D-5L visual analog scale score = 60.8 ± 20.4 (median = 61.5). Mean King’s Brief Interstitial Lung Disease score = 58.4 ± 12.7 (median = 58.0). After adjustment on covariates, a significant correlation between forced vital capacity and EQ-5D-5L score was found with an increase of 0.003 of the EQ-5D-5L score for a 1% increase of FVC (p = 0.0096). No significant correlation between forced vital capacity and the EQ-VAS and King’s Brief Interstitial Lung Disease score were found. The impact of SSc on other organs was significantly correlated with EQ- 5D-5L score, respectively, for the impact scores on the lung system (p = 0.0003), heart system (p = 0.0182), Raynaud’s syndrome (p = 0.0015), digestive system (p = 0.0032), joints/muscles (p = 0.0003), skin (p < 0.0001), kidney (p = 0.0052) and gastro-oesophageal reflux (p = 0.0063). Significant correlations between King’s Brief Interstitial Lung Disease score and lung system (p < 0.0001), heart system (p < 0.0001), digital ulcers (p = 0.058), digestive system (p < 0.0001), kidney (p = 0.0004), skin (p = 0.0499) and gastro-oesophageal reflux (p = 0.0033) scores were found 68.5% of patients reported their need for a caregiver to help them in their daily life activities. Conclusion: Our study highlighted the strong burden of systemic sclerosis associated interstitial lung disease` for patients, especially with an impact on quality of life, on other organs manifestations and need for caregivers in their daily life.

Sign in / Sign up

Export Citation Format

Share Document