Table 2 |.
Fibrosis monitoring in clinical trials: established or proposed end points
| End point status | Technology/measure used | Comments | Proposed use |
|---|---|---|---|
| Lung | |||
| Established | FVC | Provides a reproducible measure of disease severity and is the measure of choice for longitudinal assessment of disease progression | Regulator-preferred end point of choice in phase III trials |
| Established | Six-minute walk distance | Frequently used in trials | High variability; influenced by fitness, cardiovascular disease, pulmonary hypertension and mobility issues; often technically difficult for trial centres to perform |
| Proposed | CT | Image-based analysis of fibrosis progression | Multiple imaging tools are in development, but none has been adequately validated |
| Proposed | Blood biomarkers | Several blood-based markers that track with disease progression and that change with treatment have been identified | None has yet been fully validated |
| Gut | |||
| Proposed | PRO | Recommended for use in clinical trials | Improvement in obstructive symptoms |
| Proposed | Stricture radiology index | Morphological evaluation of stricture | Improvement in stricture morphology |
| Kidney | |||
| Established | Histopathological quantification in kidney biopsy samples | Recommended for use in clinical trials | Assessment of fibrosis progression and/or reversal |
| Established | eGFR slope | Recommended for use in clinical trials as fibrosis correlates well with kidney function; however, large cohorts and long follow-ups might be needed | Assessment of kidney function |
| Skin (SSc) | |||
| Established | Modified Rodnan Skin Score | Frequently used in clinical trials | Assessment of dermal thickness over time and/or in response to therapy |
| Proposed | Ultrasound-based quantification of dermal thickness | Requires further validation | Assessment of dermal thickness over time and/or in response to therapy |
| Liver | |||
| Established | Histological assessment in liver biopsy samples | Standardized histological scoring system | Staging of fibrotic injury, progression or regression of fibrosis |
| Proposed (limited) | Blood biomarkers; imaging biomarkers | FDA workshop in 2023 provided guidance for early-stage clinical trials and for screening for high-risk patients before liver biopsy | |
CT, computed tomography; FVC, forced vital capacity; eGFR, estimated glomerular filtration rate; PRO, patient-reported outcome; SSc, systemic sclerosis.