Published: 2 September 2021

Authors: Jan Heyckendorf, Sebastian Marwitz, Maja Reimann, Korkut Avsar, Andrew R. DiNardo, Gunar Günther, Michael Hoelscher, Elmira Ibraim, Barbara Kalsdorf, Stefan H.E. Kaufmann, Irina Kontsevaya, Frank van Leth, Anna M. Mandalakas, Florian P. Maurer, Marius Müller, Dörte Nitschkowski, Ioana D. Olaru, Cristina Popa, Andrea Rachow, Thierry Rolling, Jan Rybniker, Helmut J.F. Salzer, Patricia Sanchez-Carballo, Maren Schuhmann, Dagmar Schaub, Victor Spinu, Isabelle Suárez, Elena Terhalle, Markus Unnewehr, January Weiner, Torsten Goldmann and Christoph Lange

Source: This abstract has been sourced from NZ Respiratory Research Review Issue 199


    Background The World Health Organization recommends standardised treatment durations for patients with tuberculosis (TB). We identified and validated a host-RNA signature as a biomarker for individualised therapy durations for patients with drug-susceptible (DS)- and multidrug-resistant (MDR)-TB.

    Methods Adult patients with pulmonary TB were prospectively enrolled into five independent cohorts in Germany and Romania. Clinical and microbiological data and whole blood for RNA transcriptomic analysis were collected at pre-defined time points throughout therapy. Treatment outcomes were ascertained by TBnet criteria (6-month culture status/1-year follow-up). A whole-blood RNA therapy-end model was developed in a multistep process involving a machine-learning algorithm to identify hypothetical individual end-of-treatment time points.

    Results 50 patients with DS-TB and 30 patients with MDR-TB were recruited in the German identification cohorts (DS-GIC and MDR-GIC, respectively); 28 patients with DS-TB and 32 patients with MDR-TB in the German validation cohorts (DS-GVC and MDR-GVC, respectively); and 52 patients with MDR-TB in the Romanian validation cohort (MDR-RVC). A 22-gene RNA model (TB22) that defined cure-associated end-of-therapy time points was derived from the DS- and MDR-GIC data. The TB22 model was superior to other published signatures to accurately predict clinical outcomes for patients in the DS-GVC (area under the curve 0.94, 95% CI 0.9–0.98) and suggests that cure may be achieved with shorter treatment durations for TB patients in the MDR-GIC (mean reduction 218.0 days, 34.2%; p<0.001), the MDR-GVC (mean reduction 211.0 days, 32.9%; p<0.001) and the MDR-RVC (mean reduction of 161.0 days, 23.4%; p=0.001).

    Conclusion Biomarker-guided management may substantially shorten the duration of therapy for many patients with MDR-TB.

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