Cost and availability of drugs and treatment regimens and availability of drug resistance testing for tuberculosis in Europe

Abstract

AbstractBackgroundAccess to comprehensive diagnostics and novel anti-tuberculosis medicines is crucial to improve tuberculosis control at times of emerging Mycobacterium tuberculosis drug resistance.MethodsWe investigated access to genotypic and phenotypic M tuberculosis drug susceptibility testing (DST), availability of anti-tuberculosis drugs and calculated cost of drugs and treatment regimens at major tuberculosis treatment centers in countries of the World Health Organization (WHO) European region. Results are stratified by middle and high-income countries.ResultsOverall, 43 treatment centers in 43 countries participated in the study. Phenotypic DST was available for WHO group A drugs levofloxacin/moxifloxacin, bedaquiline and linezolid, in 75%/82%, 48%, and 72% of countries, respectively. Overall, 84% and 56% of countries had access to bedaquiline and delamanid, while only 14% had access to rifapentine. Median cost of regimens for drug-susceptible tuberculosis, multidrug-resistant tuberculosis (shorter regimen, including bedaquiline for six months) and pre-extensively drug-resistant tuberculosis (including delamanid) were €44, €764 and €7 094 in middle income countries (n=12), and €280, €29 765, €207 035 in high income countries (n=29).ConclusionTuberculosis control in Europe is limited by widespread lack of DST capacity to new and re-purposed drugs, lack of access to essential medications and high treatment cost for drug-resistant tuberculosis.Research in contextEvidence before this studyAvailability and access to anti-tuberculous treatment are essential for optimal treatment outcomes. Newly developed drugs like bedaquiline have demonstrated an enormous potential to improve outcomes, in particular for the treatment of drug-resistant tuberculosis. However, data on availability and cost of tuberculosis drugs and regimens are scarce. We searched PubMed for original research that reported the cost of anti-tuberculosis drugs and regimens across multiple countries in the WHO European region since Jan 1, 2012. The Pubmed search ((cost[MeSH Major Topic]) AND (tuberculosis[MeSH Major Topic]) AND [(treatment[MeSH Major Topic]) OR (drug[MeSH Major Topic])] AND (“2012/01/01”[Date -Entry] : “3000”[Date - Entry])) did not reveal any comprehensive data on cost of anti-tuberculosis drugs since the introduction of new (bedaquiline, delamanid, pretomanid) and re-purposed drugs in the WHO European region. Recent information on availability of Mycobacterium tuberculosis drug susceptibility testing is limited to a single, laboratory-based survey.Added value of this studyBuilding on a previous study, performed by the Tuberculosis Network European Trialsgroup (TBnet) in 2013, the current study documents a) the concerning lack of diagnostic capacity of drug susceptibility testing for new and repurposed anti-tuberculosis drugs; b) the lack of availability of adequate regimens for the treatment of multidrug-resistant and (pre-) extensively drug-resistant tuberculosis, in particular in middle income countries; and c) the enormous cost of regimens for the treatment of drug-resistant tuberculosis, in particular in high-income countries.Implications of all the available evidenceThe lack of availability of drug-resistance testing in the presence of new and re-purposed drugs bears the high risk of undetected amplification of M tuberculosis drug resistance. In addition, it implies that identification of patients with extensively drug-resistant tuberculosis is currently not possible in many countries in the WHO European region. The cost of drugs and regimens for drug-resistant tuberculosis treatment are very high compared to those for drug-susceptible tuberculosis and highly variable across different countries. Access to adequate treatment regimens for (pre-) extensively drug-resistant tuberculosis is suboptimal.Rapid upscaling of comprehensive M tuberculosis drug resistance testing and provision of novel anti-tuberculosis drugs are urgently required to provide patients affected by drug-resistant tuberculosis with adequate treatment regimens and prevent the emergence of additional drug resistance in M tuberculosis naturally occurring under insufficient treatments.