Nintedanib in Patients With Autoimmune Disease–Related Progressive Fibrosing Interstitial Lung Diseases: Subgroup Analysis of the <scp>INBUILD</scp> Trial

Matteson, Eric L.; Kelly, Clive; Distler, Jörg H W; Hoffmann-Vold, A. M.; Seibold, James R.; Mittoo, Shikha; Dellaripa, Paul F.; Aringer, Martin; Pope, Janet; Distler, Oliver; James, Alexandra; Schlenker‐Herceg, Rozsa; Stowasser, Susanne; Quaresma, Manuel; Flaherty, Kevin R.

doi:10.1002/art.42075

Cited by 60 publications

(57 citation statements)

References 34 publications

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“…The pathobiology of progressive fibrosing ILD remains incompletely understood [ 27 ], but these findings support the proposition that fibrosing ILDs show commonalities in the pathobiological pathways that lead to progression of fibrosis [ 14 , 27 – 30 ] and that nintedanib slows the progression of pulmonary fibrosis irrespective of its aetiology [ 14 , 17 , 29 – 31 ]. Further support for this hypothesis is provided by subgroup analyses of data from the INBUILD trial that suggested that the effect of nintedanib on FVC decline was consistent irrespective of the underlying diagnosis [ 29 , 30 ]. Subgroup analyses have also shown that nintedanib has a consistent effect on reducing FVC decline in subjects of different ages and disease severities based on FVC, DLco, or staging systems such as the composite physiologic index or GAP index [ 32 – 37 ].…”

Section: Discussionmentioning

confidence: 86%

Meta-Analysis of Effect of Nintedanib on Reducing FVC Decline Across Interstitial Lung Diseases

et al. 2022

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Introduction The effect of nintedanib on slowing the rate of decline in forced vital capacity (FVC) has been investigated in randomized placebo-controlled trials in subjects with idiopathic pulmonary fibrosis (IPF), other progressive fibrosing interstitial lung diseases (ILDs), and ILD associated with systemic sclerosis (SSc-ILD). We assessed the consistency of the effect of nintedanib on the rate of decline in FVC over 52 weeks across four placebo-controlled phase III trials. Methods We used data on FVC decline from the INPULSIS-1 and INPULSIS-2 trials in subjects with IPF, the INBUILD trial in subjects with progressing fibrosing ILDs other than IPF, and the SENSCIS trial in subjects with SSc-ILD. In each trial, the primary endpoint was the annual rate of decline in FVC (mL/year) assessed over 52 weeks. We performed fixed effect and random effects meta-analyses based on the relative treatment effect of nintedanib versus placebo on the rate of decline in FVC (mL/year) over 52 weeks. Heterogeneity of the relative treatment effect of nintedanib across populations was assessed using the I 2 statistic, τ 2 and corresponding p value from a Q test for heterogeneity. Results The combined analysis comprised 1257 subjects treated with nintedanib and 1042 subjects who received placebo. Nintedanib reduced the rate of decline in FVC (mL/year) over 52 weeks by 51.0% (95% CI 39.1, 63.0) compared with placebo. The relative effect (95% CI) was the same using the fixed effect and random effects models. There was no evidence of heterogeneity in the relative treatment effect of nintedanib across the populations studied ( I 2 = 0%, τ 2 = 0, p = 0.93). Conclusions A meta-analysis of data from four placebo-controlled trials demonstrated that nintedanib approximately halved the rate of decline in FVC over 52 weeks across subjects with different forms of pulmonary fibrosis, with no evidence of heterogeneity in its relative treatment effect across patient populations. Graphical abstract

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Section: Discussionmentioning

confidence: 86%

Meta-Analysis of Effect of Nintedanib on Reducing FVC Decline Across Interstitial Lung Diseases

et al. 2022

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“…In the majority of included studies for this meta-analysis, patients were considered non-responsive or refractory to typical immunosuppression, suggesting a separate role for the targeting of other immune-mediated or inflammatory processes for RTX. Current approval of anti-fibrotic therapy for progressive fibrotic lung disease including CTD-ILD warrants consideration as preferred secondary or tertiary therapies for lung fibrosis over RTX [ 55 , 56 ]. Whether anti-fibrotics are preferred over RTX remains debatable but might be more justified by available controlled studies in progressive ILD over currently uncontrolled and mostly descriptive data for RTX [ 57 ].…”

Section: Discussionmentioning

confidence: 99%

Effect size of rituximab on pulmonary function in the treatment of connective-tissue disease-related interstitial lung disease: a systematic review and meta-analysis

et al. 2022

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Background Rituximab (RTX) has been previously reported as directed treatment in patients with connective-tissue disease-related interstitial lung diseases (CTD-ILD). A systematic assessment of treatment effect size on pulmonary function outcomes and related adverse effects in patients with CTD-ILD has not been previously reported. Methods We performed a systematic review and meta-analysis of published reports from PubMed, Embase, and Cochrane Libraries. Randomized and non-randomized controlled trials, case–control, cohort, and case series (with five or more cases) containing individual pulmonary function data and adverse effects were included. Study endpoints were pre- and post-treatment change in percent predicted forced vital capacity (FVC %) and diffusion capacity for carbon monoxide (DLCO%), along with reported drug-related adverse events. Results Twenty studies totaling 411 patients were identified with 14 included in the meta-analysis of pulmonary function and six in the descriptive review. Random effects meta-analysis of pre- and post-treatment pulmonary function findings demonstrated increases in FVC% (n = 296) (mean difference (MD) 4.57%, [95% CI 2.63–6.51]) and DLCO% (n = 246) (MD 5.0% [95% CI 2.71–7.29]) after RTX treatment. RTX treatment-related adverse effects were reported in 13.6% of the pooled cohort. Conclusions A systematic assessment of post-treatment effect size suggests a potential role for RTX in stabilizing or improving lung function in patients with CTD-ILD, with a modest but not insignificant adverse effect profile.

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“…Another large phase III randomized clinical trial included patients with SSc-ILD as part of a wider progressive fibrosing ILD population ( n = 39/663) [36 ▪▪ ]. The results across the autoimmune subset have been presented [37 ▪▪ ]. Considering the evidence for nintedanib, it can be suggested that it significantly reduces the annual decline in FVC in SSc-ILD or progressive fibrosing ILDs including SSc-ILD.…”

Section: Recent Advances In Clinical Management Of Systemic Sclerosis...mentioning

confidence: 99%

Recent advances in the management of systemic sclerosis-associated interstitial lung disease

Hoffmann‐Vold

Distler

Crestani

et al. 2022

Current Opinion in Pulmonary Medicine

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Purpose of reviewInterstitial lung disease associated with systemic sclerosis (SSc-ILD) is a frequent organ manifestation leading to high morbidity and mortality. In 2020, the European management recommendations for SSc-ILD were published. Despite being comprehensive, several questions could not be answered or no consensus was reached.Recent findingsWe highlight recent advances in the screening and early diagnosis, including surveys emphasizing that still 30–40% of all experts do not order baseline HRCTs in their SSc patients. We discuss recent advances in the assessment of disease progression, risk prediction and monitoring of SSc-ILD including novel insights in the disease course of SSc-ILD, clinical predictive factors for disease progression, the role of increasing extent of ILD on serial HRCT and radiomics, PET/CT and home spirometry as sensitive future tools to monitor SSc-ILD patients. We describe recent advances in the treatment of SSc-ILD, including novel data and trials as well as post hoc analyses of clinical trials on mycophenolate, cyclophosmphamide, tocilizumab, rituximab, riociguat and nintedanib. Lastly, we elucidate on peripheral blood cell gene expression profiling as a novel way to identify patients with a better treatment response to mycophenolate.SummaryIn this review, we highlight recent advances in the management of SSc-ILD.

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Nintedanib in Patients With Autoimmune Disease–Related Progressive Fibrosing Interstitial Lung Diseases: Subgroup Analysis of the INBUILD Trial

Cited by 60 publications

References 34 publications

Meta-Analysis of Effect of Nintedanib on Reducing FVC Decline Across Interstitial Lung Diseases

Meta-Analysis of Effect of Nintedanib on Reducing FVC Decline Across Interstitial Lung Diseases

Effect size of rituximab on pulmonary function in the treatment of connective-tissue disease-related interstitial lung disease: a systematic review and meta-analysis

Recent advances in the management of systemic sclerosis-associated interstitial lung disease

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