Considerations on clinical trials of leprosy treatment: need of novel drug combinations

Abstract

Considering that after 30 years of using multidrug therapy (MDT), leprosy eradication has still not been achieved, leprosy treatment must remain on the drug discovery agenda. Due to the complexities inherent in leprosy disease and the many methodological issues involved in clinical trials, the task of translating the bench findings into clinical practice has been arduous. While the effectiveness of reducing the currently recommended MDT remains controversial, a number of highly bactericidal antibiotics and immune-modulatory drugs have emerged as prospective candidates to improve patient adherence and quality of life, reduce adverse effects and prevent resistance. To replace the standard WHO-MDT, the new combination must be the shortest, simplest and, consequently, most affordable treatment possible.

Bacterial responses to antibiotics and their combinations

“…Combinations of more than two drugs are not uncommon in treatments (Essa et al, 2009;Caminero et al, 2010;Illarramendi et al, 2013). Understanding the principles of interactions between multiple drugs is challenging because quantifying the effects of all possible combinations of n different drugs quickly leads to a combinatorial explosion: for example, for n = 50, there are already nearly 20 000 distinct three-drug combinations.…”