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

Hsu, Vivien; Denton, Christopher P.; Domsic, Robyn T.; Fürst, Daniel E.; Rischmueller, Maureen; Stanislav, Marina; Steen, Virginia D.; Distler, Jörg; Korish, Shimon; Cooper, Alyse; Choi, Suktae; Schäfer, Peter; Horan, Gerald; Hough, Douglas R.

doi:10.3899/jrheum.161040

Cited by 36 publications

(21 citation statements)

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“…In addition, the higher than expected numbers of skin fibrosis regressors18 and stable patients reduced the sensitivity of RISE-SSc to detect a significant change of mRSS. This is consistent with previous trials, in which mRSS improvements were observed in the majority of patients receiving placebo 32 33. Other possible explanations include the very large variation in mRSS scores during the study.…”

Section: Discussionsupporting

confidence: 91%

Riociguat in patients with early diffuse cutaneous systemic sclerosis (RISE-SSc): randomised, double-blind, placebo-controlled multicentre trial

et al. 2020

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ObjectivesRiociguat is approved for pulmonary arterial hypertension and has antiproliferative, anti-inflammatory and antifibrotic effects in animal models of tissue fibrosis. We evaluated the efficacy and safety of riociguat in patients with early diffuse cutaneous systemic sclerosis (dcSSc) at high risk of skin fibrosis progression.MethodsIn this randomised, double-blind, placebo-controlled, phase IIb trial, adults with dcSSc of <18 months' duration and a modified Rodnan skin score (mRSS) 10–22 units received riociguat 0.5 mg to 2.5 mg orally three times daily (n=60) or placebo (n=61). The primary endpoint was change in mRSS from baseline to week 52.ResultsAt week 52, change from baseline in mRSS units was –2.09±5.66 (n=57) with riociguat and –0.77±8.24 (n=52) with placebo (difference of least squares means –2.34 (95% CI –4.99 to 0.30; p=0.08)). In patients with interstitial lung disease, forced vital capacity declined by 2.7% with riociguat and 7.6% with placebo. At week 14, average Raynaud’s condition score had improved ≥50% in 19 (41.3%)/46 patients with riociguat and 13 (26.0%)/50 patients with placebo. Safety assessments showed no new signals with riociguat and no treatment-related deaths.ConclusionsRiociguat did not significantly benefit mRSS versus placebo at the predefined p<0.05. Secondary and exploratory analyses showed potential efficacy signals that should be tested in further trials. Riociguat was well tolerated.

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Section: Discussionsupporting

confidence: 91%

Riociguat in patients with early diffuse cutaneous systemic sclerosis (RISE-SSc): randomised, double-blind, placebo-controlled multicentre trial

et al. 2020

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“…Several other medications (imatinib, bosentan, pomalidomide, abituzumab, tadalafil, abatacept, belimumab, brentuximab, lenabasum, and riociguat) have been examined with varying results and without strong evidence to date to support clinical utility in SSc-ILD [126][127][128][129][130][131][132][133][134][135][136] (►Tables 1 and 2).…”

Section: Rituximabmentioning

confidence: 99%

Systemic Sclerosis Associated Interstitial Lung Disease: A Comprehensive Overview

Mackintosh

Stainer

Barnett

et al. 2019

Semin Respir Crit Care Med

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Interstitial lung disease (ILD) is a common complication of systemic sclerosis (SSc). SSc-ILD adversely impacts quality of life and is currently the leading cause of death in this multisystem disease. Identifying clinically significant SSc-ILD is critically important. Accurate staging and prognostication remain difficult; however, significant advances have been made in the last decade. Evidence supports the need to treat patients with extensive and/or progressive SSc-ILD, while only a subset of patients with limited ILD may require treatment. Research is urgently required to allow improved prediction of patients at risk of ILD progression at an early point in the disease, and ideally prior to its onset, to allow prevention. The last decade has seen the publication of landmark clinical trials for SSc-ILD. More effective strategies with less toxicity are under investigation. For those with refractory or very advanced disease, studies into disease-specific palliative approaches are in their infancy. Lung transplantation as an option for SSc-ILD remains patient- and center-specific, with data to suggest equivalent outcomes to other fibrotic lung diseases, in carefully selected cases. This review aims to provide a comprehensive overview of all key aspects of SSc-ILD.

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“…Pirfenidone has already been evaluated in a small phase II study (LOTUSS) [135] and the SLS III trial comparing MMF combined with pirfenidone treatment and MMF treatment alone is ongoing [136] [https://clinicaltrials.gov/ct2/show/NCT03221257] A large phase III trial investigating the safety and efficacy of nintedanib in SSc-associated lung fibrosis is ongoing [137,138, https://clinicaltrials.gov/ct2/show/NCT02597933]. However, trials of lung fibrosis in SSc are challenging and some studies have failed to recruit enough patients [139] or have had unequivocally negative results [140,141].…”

Section: [H2] Treatment Approaches For Lung Fibrosismentioning

confidence: 99%

Major lung complications of systemic sclerosis

2018

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Systemic sclerosis (SSc) is associated with high mortality owing to internal organ complications, and lung disease is the leading cause of SSc-associated death. The most notable lung complications in SSc are fibrosis and pulmonary arterial hypertension (PAH). A major challenge for the management of lung disease in SSc is detecting those patients with severe pathology and those patients who are likely to benefit from available treatments. In the past few years, strategies for managing lung fibrosis and pulmonary hypertension, including PAH, have greatly progressed. For lung fibrosis, the tools to assess risk of progression and severity of the disease have been refined. Clinical trial results support the use of immunosuppression, including high-intensity regimens with autologous stem cell transplantation. New trials are underway to test other potential therapies including treatments that are approved for use in idiopathic lung fibrosis. For PAH, identifying individuals at high risk of disease development is critical. In addition, individuals who have borderline elevation of pulmonary arterial pressure need to be appropriately managed and followed up. Many approved drugs targeting PAH are now available, and results from large-scale clinical trials provide robust evidence that various treatments for SSc-associated PAH are associated with good long-term outcomes.

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

Cited by 36 publications

References 10 publications

Riociguat in patients with early diffuse cutaneous systemic sclerosis (RISE-SSc): randomised, double-blind, placebo-controlled multicentre trial

Riociguat in patients with early diffuse cutaneous systemic sclerosis (RISE-SSc): randomised, double-blind, placebo-controlled multicentre trial

Systemic Sclerosis Associated Interstitial Lung Disease: A Comprehensive Overview

Major lung complications of systemic sclerosis

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