Impact of treatment completion, intolerance and adverse events on health system costs in a randomised trial of 4 months rifampin or 9 months isoniazid for latent TB

Rationale Treatment for latent tuberculosis infection with isoniazid for 9 months (9INH) has poor completion and serious adverse events, while treatment for 4 months with daily rifampin (4RIF) has significantly higher completion and fewer adverse events. Objectives To compare the health system costs of 4RIF and 9INH. Methods In a randomised trial conducted in five Canadian centres, one Brazilian and one Saudi Arabian centre, consenting subjects were randomised to receive 4RIF or 9INH. Health system costs were estimated from healthcare utilisation including scheduled and unscheduled visits, investigations and drugs. All activities for all subjects were evaluated using financial information from 2007 from the Montreal Chest Institute. Costs were expressed in Canadian dollars. Results Total health system cost per patient allocated to 4RIF was $854 compared with $970 for 9INH (p<0.0001). The average cost per patient for the 328 of 420 (78%) who completed 4RIF therapy was $1094 compared with $1625 for the 254 of 427 (60%) completing 9INH (p<0.0001). Costs were modestly increased in patients with minor intolerance and substantially increased if the treating physician stopped treatment because of possible adverse events. Total costs related to management of adverse events with 9INH were $48 142 compared with $25 684 for 4RIF (p=0.008). Using these data, incremental cost-effectiveness analyses showed that 4RIF would be cost saving and prevent more cases within 2 years if efficacy exceeded 74%, and cost saving if efficacy exceeded 65%. Conclusions The 4RIF regimen was significantly cheaper per patient completing treatment because of better completion and fewer adverse events.