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Imaging Features of Systemic Sclerosis-Associated Interstitial Lung Disease
Published on: June 16, 2020
The future of treatment in systemic sclerosis: can we design better trials?
1Division of Rheumatology, St Joseph's Health Care, Schulich School of Medicine and Dentistry, University of Western Ontario, London, ON, Canada.
Abstract:
Strides have been made in the treatment of pulmonary arterial hypertension and interstitial lung disease in patients with systemic sclerosis, with successful trials of combination therapies in pulmonary arterial hypertension and of new drugs that slow the decline of lung function in interstitial lung disease. However, many trials in patients with early diffuse cutaneous systemic sclerosis have been negative, including trials of tocilizumab, abatacept, and riociguat, despite improvements in skin scores and other endpoints that approached statistical significance. Trials of macitentan for digital ulcers in these patients have also been disappointing. Trials that do not meet their primary endpoint do not necessarily signify ineffective therapies, as there are many other possible reasons for negative trial results, including features of trial design, insufficient trial duration, or insufficient power to detect differences between groups. In this Series paper, I discuss some of these reasons and what the research community can learn from negative trials to inform future trial design going forward.
Insights
Negative clinical trials for systemic sclerosis treatments, including pulmonary arterial hypertension and interstitial lung disease, may not indicate therapy failure. Reasons for negative results and lessons for future trial design are discussed.
Area of Science:
- Rheumatology
- Pulmonology
- Clinical Trial Design
Background:
- Systemic sclerosis treatment has advanced for pulmonary arterial hypertension and interstitial lung disease.
- However, many clinical trials in early diffuse cutaneous systemic sclerosis have yielded negative results.
- Past trials of tocilizumab, abatacept, riociguat, and macitentan did not meet primary endpoints.
Purpose of the Study:
- To analyze reasons for negative clinical trial outcomes in systemic sclerosis.
- To provide insights from negative trials to improve future study designs.
Main Methods:
- Review of clinical trial outcomes in systemic sclerosis.
- Analysis of potential factors contributing to negative results, such as trial design, duration, and statistical power.
Main Results:
- Negative trial results do not always equate to therapy ineffectiveness.
- Factors like trial design flaws, insufficient duration, or inadequate power can lead to non-significant findings.
- Despite negative primary endpoints, some trials showed trends towards efficacy in specific measures.
Conclusions:
- Negative trial results in systemic sclerosis warrant careful examination beyond simple efficacy assessment.
- Understanding the nuances of trial design and execution is crucial for interpreting outcomes.
- Lessons learned from negative trials can guide more effective future research in systemic sclerosis therapies.
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