Last week WHO issued key changes to treatment guidelines for multi-drug resistant tuberculosis (MDR-TB) which implement a new priority ranking of available medicines and now include a fully oral regimen as one preferred option for MDR-TB treatment. The new ranking balances effectiveness and harms and prioritizes oral regimens over injection-based regimens.

There is a significant body of evidence showing that older, injection-based MDR medicines (such as kanamycin, amikacin and capreomycin) have poor treatment outcomes and high risk of adverse and severe side effects, raising significant safety and efficacy concerns.

A summary of key concerns with injection-based MDR treatment:

  • Injection-based treatments are painfully administered over many months, leading to unnecessary trauma and harm to patients, especially where other treatment options should be made available.
  • Injection-based regimens have serious side effects, including irreversible hearing loss, kidney failure and psychosis, as well as high levels of toxicity. Other side effects include gastrointestinal events, hypothyroidism, visual disturbances, peripheral neuropathy, skin reactions, swelling or pain at injection sites, anorexia and sleep disturbances, among others.
    • For example, one study found that 55% of injectible users experienced ototoxicity and 40% of discontinued injectible use due to hearing loss.
  • Given the serious side effects from injectible MDR drugs, it is unsurprising that treatment outcomes are often low, with cure rates of only 54% of MDR-TB cases in 2016.

The treatment rankings in the new WHO guidelines:

  • Group A: Medicines to be prioritised: levofloxacin/moxifloxacin, bedaquiline and linezolid
  • Group B: Medicines to be added next: clofazimine, cycloserine/terizidone
  • Group C: Medicines to be included to complete the regimens and when agents from Groups A and B cannot be used: ethambutol, delamanid, pyrazinamide, imipenem-cilastatin, meropenem, amikacin (streptomycin), ethionamide/prothionamide, p-aminosalicylic acid

Kanamycin and capreomycin are no longer recommended, given the high risk of treatment failure, while WHO notes that amikacin has similar safety risks as other injectables (and is only to be used to complete regimens).

Why the new rankings matter

WHO recognition that use of older, harmful and less effective injection-based treatments should be avoided (and that some are not recommended whatsoever) should be commended, and is in line with ensuring a more rights-based approach in the context of MDR treatment regimens. Country adoption of the new guidelines will lead to implementation of more effective treatment regimens which include wide usage of newer drugs such as bedaquiline, linezolid, and delamanid which have fewer adverse effects and have been shown to have significantly better treatment outcomes. As such, the new WHO guidelines are a significant push towards further progressive realization of the rights to health and scientific progress.

The move towards the standard use of newer MDR medicines has already been observed in South Africa where it was recently announced that new TB drugs will be made part of its standard treatment regimen for drug-resistant TB. Efficient and widespread implementation of the new guidelines would be a welcome move away from archaic and outdated approaches to TB and towards an evidence and rights-based approach.