Evaluation of tuberculosis treatment response with serial C-reactive protein measurements

Background Novel biomarkers are needed to assess response to antituberculosis therapy in smear-negative patients. Methods To evaluate the utility of CRP in monitoring response to antituberculosis therapy we conducted a post-hoc analysis on a cohort of adults with symptoms of tuberculosis and negative sputum smears in a high tuberculosis and HIV prevalence setting in KwaZulu-Natal, South Africa. Serial changes in CRP, weight, and haemoglobin were evaluated over 8 weeks. Results 421 participants with suspected smear-negative tuberculosis were enrolled and 33 excluded. 295 were treated for tuberculosis (137 confirmed, 158 possible), and 93 did not have tuberculosis. 185 of 215 (86%) participants who agreed to HIV testing were HIV-positive. At week 8, the on-treatment median CRP reduction in the tuberculosis group was 79.5% (IQR 25.4; 91.7), median weight gain 2.3% (IQR −1.0; 5.6), and median haemoglobin increase 7.0% (IQR 0.8; 18.9) (p-value <0.0001 for baseline to week 8 comparison of absolute median values). Only CRP changed significantly at week 2 (median reduction of 75.1% (IQR 46.9; 89.2) in the group with confirmed tuberculosis and 49.0% (IQR −0.4; 80.9) in the possible tuberculosis group. Failure of CRP to reduce to ≤55% of the baseline value at week 2 predicted hospitalization or death in both tuberculosis groups, with 99% negative predictive value. Conclusion Change in CRP may have utility in early evaluation of response to antituberculosis treatment and to identify those at increased risk of adverse outcomes. Key points C-reactive protein (CRP) falls by 80% after eight weeks of antituberculosis treatment. At two weeks sustained CRP elevation is associated with death or hospitalization.