Bedaquiline for the treatment of multiresistant tuberculosis in Germany
Tuberculosis (TB) is the infectious disease with the highest number of deaths caused by a bacterial pathogen worldwide. The WHO's annual report currently even shows an increase in TB mortality, which is at least partly due to supply deficits during the corona pandemic. The international goal of eliminating TB has therefore been set back by years. Multidrug-resistant (MDR) TB, which is resistant to the two most important TB drugs isoniazid and rifampicin, is a growing problem, particularly in Eastern Europe. The drugs used to treat MDR-TB are less well tolerated, usually have to be taken for 18 months and lead to treatment failure more frequently than the 6-month standard therapy.
In Germany, 79 - 107 MDR-TB cases per year have been registered in recent years (2015 - 2020, RKI reports). Due to the war in Ukraine, however, the number of MDR-TB cases is expected to increase 2-3-fold(WHO calculator). The MDR-TB pathogens acquired in Ukraine often have additional drug resistance and treatment is often complicated by co-infections, e.g. with HIV. As a result, inpatient treatment, which is usually necessary, is associated with high additional treatment costs. In addition to experience in dealing with complex MDR-TB cases, there is often a lack of structures close to home for outpatient follow-up care and the costs of outpatient MDR-TB therapy also represent a hurdle.
Sirturo® is a drug containing the active ingredient bedaquiline, which was approved in 2014. It is the first newly approved active ingredient since the 1960s that acts specifically against the TB pathogen - mycobacterium tuberculosis. Bedaquiline interferes with mycobacterial energy production at the cellular level and shows very good bactericidal efficacy and tolerability both experimentally and in clinical studies in humans.
In Germany, a benefit assessment was carried out by the Joint Federal Committee (G-BA) in 2019. For adult patients with pulmonary MDR-TB, a considerable additional benefit was identified "if an effective treatment regimen cannot be put together other than with bedaquiline (as part of a suitable combination therapy) due to resistance or intolerance". This area of use corresponds to that of a reserve drug. The current international recommendations of the WHO (2020) for the treatment of MDR-TB envisage the use of bedaquiline in the first instance and not only after other treatment options have been exhausted. The new German S2k guideline on TB treatment in adults agrees with this recommendation and strongly recommends bedaquiline as first-line treatment for MDR-TB.
The purely pharmaceutical costs for MDR-TB therapy in Germany amount to more than 55,000 euros for an 18-month therapy (Diel et al. IJID 2021). Bedaquiline accounts for more than 60% of these costs at just under 35,000 euros. The costs of this new and indispensable drug are not reflected in the DRG system, meaning that inpatient treatment is loss-making for hospitals. In addition, bedaquiline does not meet the criteria for new examination and treatment methods (NUB status 2) in Germany, meaning that hospitals cannot negotiate additional fees. Nevertheless, MDR-TB therapies almost always have to be initiated on an inpatient basis and, due to the poor tolerability of the therapy, inpatient treatment is usually necessary for months. One possible solution could be the separation of medication costs from hospital costs.
The costs of MDR-TB treatment must be covered as a matter of urgency so that the necessary conditions for the complex treatment can be created or maintained and this vulnerable and difficult-to-treat patient group is not disadvantaged. Rapid diagnosis and effective treatment are currently the only ways to stop the spread of resistant TB pathogens.
