A sub-study using PET-CT imaging from the ROSETTA trial has found that rosuvastatin, a commonly used statin, does not significantly improve treatment outcomes in patients with pulmonary tuberculosis (TB) when used as an adjunct to standard antibiotic therapy. The study, which involved 24 participants from the Philippines and Vietnam, assessed the impact of rosuvastatin on various imaging metrics, including Total Lesion Glycolysis (TLG) and Total Metabolic Volume (TMV), over an eight-week period.
Lack of Additional Benefit from Rosuvastatin
The research, a sub-study of the larger ROSETTA trial, aimed to determine if rosuvastatin could enhance the effects of standard TB treatment by reducing lung inflammation and improving bacterial clearance. Participants were randomized to receive either rosuvastatin or a placebo in addition to the standard TB drug regimen. PET-CT scans were conducted at baseline and after eight weeks to evaluate changes in lung lesions and metabolic activity.
However, the results indicated no significant difference between the rosuvastatin and control groups in terms of TLG change or any other PET-CT parameters. The median change in TLG was -258.7 in the rosuvastatin group and -141.2 in the control group (P = 0.84). This translates to a median percentage reduction of 65.8% in TLG for rosuvastatin and 64.3% for the control group (P = 0.32).
Impact of Standard TB Treatment
The study did confirm that the intensive phase of TB treatment leads to a reduction in TLG and TMV. The median SUVmax for all participants in the sub-study was 9.3 (Q1 = 5.5, Q3 = 11.4) with no significant change in SUVmax [median reduction of 1.07 (Q1 = −3.8, Q3 = 1.8) p = 0.15], at the 8-week scan. By contrast, median TMV and TLG at week 0 was 167.3 cm3 (IQR 57.9, 323.9) and 544.2 (Q1 = 158.5, Q3 = 1021.7), respectively, with very strong evidence (p < 0.001) of change in both after eight weeks of treatment; median reduction of 69.6 cm3 (Q1 = −191.4, Q3 = −7.4) for TMV and 202.0 (Q1 = −664.4, Q3 = −13.9) for TLG. This represents a 56.1% (IQR 20.7, 88.0) and 64.3% (Q1 = 9.0, Q3 = 88.7) reduction in TMV and TLG, respectively, after eight weeks of tuberculosis treatment.
Correlation with Disease Burden
Researchers also found that baseline TLG was related to other markers of disease burden. In a multiple linear regression model, a positive culture at week eight was associated with increased week eight TLG, by an estimated 438.5 (95% CI 111.1, 765.9, p = 0.012) and a high Xpert Mtb burden at trial entry was associated with increased week eight TLG by an estimated 703.7 (95% CI 376.3, 1031.2, p = 0.0001).
Methodological Considerations
The study used rigorous PET-CT analysis, with scans analyzed by two independent readers to ensure consistency. The two-reader measurements of SUVmax, TMV and TLG showed strong correlation (r > 0.9, p ≤ 0.0001). However, the researchers noted poor agreement between manual and semi-automated analysis methods, highlighting the importance of standardized imaging protocols.
Implications for TB Treatment
While rosuvastatin did not provide additional benefits in this study, the research underscores the value of PET-CT imaging in assessing TB treatment response. The ability to detect changes in volumetric metabolic indices like TMV and TLG offers a more detailed understanding of how the disease is responding to therapy. Further research is needed to explore other potential adjunctive therapies and refine imaging techniques for monitoring TB treatment efficacy.
