Availability and costs of medicines for the treatment of tuberculosis in Europe

Abstract

Objectives: To evaluate the access to comprehensive diagnostics and novel antituberculosis medicines in European countries.

Methods: We investigated the access to genotypic and phenotypic Mycobacterium tuberculosis drug susceptibility testing and the availability of antituberculosis drugs and calculated the cost of drugs and treatment regimens at major tuberculosis treatment centres in countries of the WHO European region where rates of drug-resistant tuberculosis are the highest among all WHO regions. Results were stratified by middle-income and high-income countries.

Results: Overall, 43 treatment centres from 43 countries participated in the study. For WHO group A drugs, the frequency of countries with the availability of phenotypic drug susceptibility testing was as follows: (a) 75% (30/40) for levofloxacin, (b) 82% (33/40) for moxifloxacin, (c) 48% (19/40) for bedaquiline, and (d) 72% (29/40) for linezolid. Overall, of the 43 countries, 36 (84%) and 24 (56%) countries had access to bedaquiline and delamanid, respectively, whereas only 6 (14%) countries had access to rifapentine. The treatment of patients with extensively drug-resistant tuberculosis with a regimen including a carbapenem was available only in 17 (40%) of the 43 countries. The median cost of regimens for drug-susceptible tuberculosis, multidrug-resistant/rifampicin-resistant tuberculosis (shorter regimen, including bedaquiline for 6 months), and extensively drug-resistant tuberculosis (including bedaquiline, delamanid, and a carbapenem) were €44 (minimum-maximum, €15-152), €764 (minimum-maximum, €542-15152), and €8709 (minimum-maximum, €7965-11759) in middle-income countries (n = 12) and €280 (minimum-maximum, €78-1084), €29765 (minimum-maximum, €11116-40584), and €217591 (minimum-maximum, €82827-320146) in high-income countries (n = 29), respectively.

Discussion: In countries of the WHO European region, there is a widespread lack of drug susceptibility testing capacity to new and repurposed antituberculosis drugs, lack of access to essential medications in several countries, and a high cost for the treatment of drug-resistant tuberculosis.

Keywords: Antimicrobial resistance; Availability of medicines; Capacity building; Costs; END-TB strategy; MDR-TB; Medicines; Tuberculosis.

Fig. 1.

Availability of phenotypic and genotypic drug susceptibility testing to tuberculosis drugs in countries in the WHO European region^a, in per cent. PAS, para-aminosalicylic acid. ^an = 40 countries; Kosovo, Iceland, and Israel did not provide data on the availability of drug susceptibility testing.

Fig. 2.

Proportion of countries with the availability of antituberculosis drugs in the absence of drug susceptibility testing for those drugs; numbers of countries with available data for amikacin (AM) = 35, moxifloxacin (MFX) = 39, levofloxacin (LFX) = 40, bedaquiline (BDQ) = 35; ethionamide/prothionamide (ETO/PTO) = 32, clofazimine (CFZ) = 32, linezolid (LZD) = 40, delamanid (DLM) = 24, cycloserine/terizidone (CS/TRD) = 39, para-aminosalicylic acid (PAS) = 28, imipenem (IMP) = 23, and meropenem (MPM) = 27. WHO group A medicines are displayed in dark blue, group B medicines in medium blue, and group C medicines in light blue.

Fig. 3.

Box plot of regimen cost for treatment of drug-susceptible TB, MDR/RR-TB, pre-XDR TB, and XDR-TB in middle-income (a) and high-income (b) European countries.^aMDR, multidrug resistant; RR, rifampicin resistant; TB, tuberculosis; XDR, extensively drug resistant. ^an = 41 countries; Malta and Israel (both high-income countries) did not provide data on drug cost. Upper whisker: 75th percentile +1.5 × IQR (or upper value if smaller), lower whisker: 25th percentile − 1.5 × IQR (or smallest value if larger), dots are values exceeding (lower or higher) the whiskers.

Fig. 4.

Density graph of distribution^a of cost for tuberculosis drug regimens in the WHO European region, according to resistance status and World Bank income classification^b (high-income countries in red, middle-income countries in green), in Euros. AM, amikacin; BDQ, bedaquiline; DLM, delamanid; DS-TB, drug-susceptible tuberculosis; FQ, fluoroquinolones; HIC, high-income country; LZD, linezolid; MDR/RR-TB, multidrug-resistant/rifampicin-resistant tuberculosis; MIC, middle-income country; pre-XDR TB, pre-extensively drug-resistant tuberculosis; XDR-TB, extensively drug-resistant tuberculosis. ^a The density graph illustrates the distribution of the cost within a given resistance pattern. The area under the curve is scaled to one. The height in the distribution shows the range of the cost for the majority of countries. The width of the graph shows the range of the costs observed. ^bn = 41 countries, Malta and Israel (both high-income countries) did not provide data on drug cost.