Lung function preservation in a phase 3 trial of tocilizumab (TCZ) in systemic sclerosis (SSc)

Denton, Christopher P.; Lin, Celia J F; Goldin, Jonathan G.; Kim, Grace; Kuwana, Masataka; Allanore, Yannick; Batalov, Anastas; Butrimienė, İrena; Carreira, Patrícia; Matucci‐Cerinic, Marco; Distler, Oliver; Kaliterna, Dušanka Martinović; Mihai, Carmen-Marina; Mogensen, Mette; Olesińska, Marzena; Pope, Janet; Riemekasten, Gabriela; Rodriguez-Reyne, Tatiana Sofía; Santos, Maria José; Laar, Jacob M van; Spotswood, Helen; Siegel, Jeffrey; Jahreis, Angelika; Fürst, Daniel E.; Khanna, Dinesh

doi:10.1183/13993003.congress-2019.rct1883

Cited by 4 publications

(7 citation statements)

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“… 31 The anti-interleukin (IL)-6 receptor antibody tocilizumab has been evaluated in patients with SSc and demonstrated preservation of lung function in a phase II study, 32 although a phase III trial did not meet its primary modified Rodnan Skin Score endpoint. 33 The tyrosine kinase inhibitor imatinib is approved for the treatment of chronic myeloid leukaemia and targets the Bcr-Abl/c-Abl, a kinase downstream of transforming growth factor-β (TGF-β) signalling. 34 Imatinib also inhibits the platelet-derived growth factor (PDGF) receptor tyrosine kinase and has been evaluated in small open-label studies in SSc-ILD, 35 36 although no large randomised trials have been conducted and its efficacy is unclear.…”

Section: Interstitial Lung Diseases and The Current Treatment Landscamentioning

confidence: 99%

Mechanisms of progressive fibrosis in connective tissue disease (CTD)-associated interstitial lung diseases (ILDs)

et al. 2020

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Interstitial lung diseases (ILDs), which can arise from a broad spectrum of distinct aetiologies, can manifest as a pulmonary complication of an underlying autoimmune and connective tissue disease (CTD-ILD), such as rheumatoid arthritis-ILD and systemic sclerosis (SSc-ILD). Patients with clinically distinct ILDs, whether CTD-related or not, can exhibit a pattern of common clinical disease behaviour (declining lung function, worsening respiratory symptoms and higher mortality), attributable to progressive fibrosis in the lungs. In recent years, the tyrosine kinase inhibitor nintedanib has demonstrated efficacy and safety in idiopathic pulmonary fibrosis (IPF), SSc-ILD and a broad range of other fibrosing ILDs with a progressive phenotype, including those associated with CTDs. Data from phase II studies also suggest that pirfenidone, which has a different—yet largely unknown—mechanism of action, may also have activity in other fibrosing ILDs with a progressive phenotype, in addition to its known efficacy in IPF. Collectively, these studies add weight to the hypothesis that, irrespective of the original clinical diagnosis of ILD, a progressive fibrosing phenotype may arise from common, underlying pathophysiological mechanisms of fibrosis involving pathways associated with the targets of nintedanib and, potentially, pirfenidone. However, despite the early proof of concept provided by these clinical studies, very little is known about the mechanistic commonalities and differences between ILDs with a progressive phenotype. In this review, we explore the biological and genetic mechanisms that drive fibrosis, and identify the missing evidence needed to provide the rationale for further studies that use the progressive phenotype as a target population.

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Section: Interstitial Lung Diseases and The Current Treatment Landscamentioning

confidence: 99%

Mechanisms of progressive fibrosis in connective tissue disease (CTD)-associated interstitial lung diseases (ILDs)

et al. 2020

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“…Among the five studies evaluating the role of TCZ 19 , 54 – 57 in SSc, three (60%) were RCTs and two (40%) cohort studies. The level of evidence for TCZ in SSc-ILD patients is high as two RCTs were classified as level 1b, one RCT was classified as level 2b, and the other studies were classified as level 2b and 4.…”

Section: Resultsmentioning

confidence: 99%

“…The 12-month follow-up was available in three studies 55 – 57 (60%). In one study, a statistically significant worsening of the predicted FVC compared to baseline was observed and, in another study, a statistically significant drop of the mean predicted FVC >10% compared to controls was observed in three (10%) patients.…”

Section: Resultsmentioning

confidence: 99%

Open questions on the management of targeted therapies for the treatment of systemic sclerosis-interstitial lung disease: results of a EUSTAR survey based on a systemic literature review

Campochiaro

Lazzaroni

Bruni

et al. 2022

Therapeutic Advances in Musculoskeletal

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Background: The results of randomized controlled (RCT) and retrospective studies have expanded the armamentarium of drugs for systemic sclerosis (SSc) – interstitial lung disease (ILD) treatment. The correct positioning of these drugs is not yet clarified. Objectives: Systemic literature review (SLR) on rituximab (RTX), tocilizumab (TCZ), nintedanib and abatacept (ABT) for the treatment of SSc-ILD. The results of the SLR were used to create a dedicated survey. Design: The study was performed as a systematic review. Data sources and methods: the SLR was performed using the following terms: “(systemic sclerosis OR scleroderma) AND (interstitial lung disease OR lung fibrosis OR pulmonary fibrosis) AND (rituximab OR tocilizumab OR abatacept OR nintedanib)”. The results of the SLR were integrated in a survey including 8 domains. These were sent to all EUSTAR members and to the participants of the 2020 Scleroderma World Congress. Results: 41 studies (34 on RTX, 5 on TCZ, 2 on ABT, and 1 on nintedanib) were identified. RCTs supported the use of TCZ and nintedanib, while retrospective studies supported the use of RTX for SSc-ILD. No clear data were obtained about ABT. The survey showed that RTX is the most available option (96%) whereas the most frequent reason for targeted therapy introduction is lung progression while on csDMARDs (86% RTX, 59% TCZ and 63% nintedanib). Combination therapy was the most frequently mentioned therapeutic scheme for nintedanib (75%) and RTX (63%). Physicians’ perception of safety was similar for all drugs, while drug efficacy was the same for RTX and nintedanib, followed by TCZ (4.8 ± 2). The most frequently raised concerns pertained to efficacy, safety and combination regimens. Conclusion: Our SLR supports the use of RTX, TCZ and nintedanib for SSc-ILD patients and underlines the need for more data about upfront combination versus monotherapy. It also highlighted the need to identify predictors supporting drug choice according to both pulmonary and extra-pulmonary manifestations.

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“…Similar results were reported from the RELIEF trial by the German Center for Lung Research, where patients with progressive fibrosing ILD received pirfenidone, demonstrating clinically meaningful effects in this patient cohort as well [26]; however, interpretability of the data were limited by recruiting problems. DENTON et al [27] provided data on the FocuSSed trial, which assessed effects of tocilizumab, an anti-interleukin-6 therapy strategy, in patients with early systemic sclerosis (SSc) and a more inflammatory phenotype. This phase III trial, which missed its primary end-point of change in modified Rodnan skin score, demonstrated meaningful effects in a key secondary end-point, change in FVC predicted.…”

Section: Ilds/dplds Of Known Originmentioning

confidence: 99%

“…D enton et al . [ 27 ] provided data on the FocuSSed trial, which assessed effects of tocilizumab, an anti-interleukin-6 therapy strategy, in patients with early systemic sclerosis (SSc) and a more inflammatory phenotype. This phase III trial, which missed its primary end-point of change in modified Rodnan skin score, demonstrated meaningful effects in a key secondary end-point, change in FVC predicted.…”

Section: Ilds/dplds Of Known Originmentioning

confidence: 99%

ERS International Congress, Madrid, 2019: highlights from the Interstitial Lung Diseases Assembly

et al. 2020

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This article discusses a selection of the scientific presentations in the field of interstitial lung diseases (ILDs) that took place at the 2019 European Respiratory Society International Congress in Madrid, Spain. There were sessions from all four groups within Assembly 12: group 12.01 “Idiopathic interstitial pneumonias”, group 12.02 “ILDs/diffuse parenchymal lung diseases (DPLDs) of known origin”, group 12.03 “Sarcoidosis and other granulomatous ILDs/DPLDs” and group 12.04 “Rare ILDs/DPLDs”. The presented studies brought cutting-edge developments on several aspects of these conditions, including pathogenesis, diagnosis and treatment. As many of the ILDs are individually rare, the sharing of experiences and new data that occur during the Congress are very important for physicians interested in ILDs and ILD patients alike.

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Lung function preservation in a phase 3 trial of tocilizumab (TCZ) in systemic sclerosis (SSc)

Cited by 4 publications

References 0 publications

Mechanisms of progressive fibrosis in connective tissue disease (CTD)-associated interstitial lung diseases (ILDs)

Mechanisms of progressive fibrosis in connective tissue disease (CTD)-associated interstitial lung diseases (ILDs)

Open questions on the management of targeted therapies for the treatment of systemic sclerosis-interstitial lung disease: results of a EUSTAR survey based on a systemic literature review

ERS International Congress, Madrid, 2019: highlights from the Interstitial Lung Diseases Assembly

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