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Inexcusable Excuses: Reluctance to Quickly Improve MDR-TB Treatment

It’s time to stop making excuses and start taking action and implement the new WHO guidance for treating MDR-TB, argue Helena Huerga, Uzma Khan, KJ Seung

This August, the WHO issued new guidance on multi-drug resistant tuberculosis (MDR-TB) with important ramifications for patients.  Among the changes, new and repurposed drugs (e.g., bedaquiline and linezolid) are now recommended for use in all MDR-TB patients.  Other MDR-TB medications, including those administered through daily injections in the buttocks (such as kanamycin, capreomycin) have been completely eliminated. Those that are weaker or toxic (such as ethionamide and PAS) have been demoted.  These are seismic shifts:  the new, more powerful, all-oral regimens could redefine MDR therapy.

The demoted medicines—oral medications and painful daily injections that cause extreme side effects– induce many patients to quit treatment even at the risk of death.  The newer regimens will make treatment more available, less toxic, and less difficult.  Nevertheless, some TB decision makers have reacted to this change with reasons why the new guidelines cannot be quickly implemented, usually citing excuses that fail to stand up to scrutiny.

“It’s Too Expensive…”

It is often argued that the demoted medications are simply cheaper.  Low-and-middle-income countries (LMIC) affected by MDR-TB have not budgeted for the extra expense of the newly prioritized medicines, and the demoted drugs are already in stock in pharmacies.  This cost-based argument runs contrary to cost estimates. In the case of injectable medications, it ignores the additional program costs needed to use them (extra staff time – including on weekends, syringes, sharps boxes and safe needle disposal).  The injectables exemplify another problem with the demoted medications: they cause (or exacerbate) more side effects and complications and are less effective overall; even more resources are required to monitor and manage the side effects.  In reality, the perceived cost benefits of the demoted drug regimens are only realized if patients receive inadequate care and no follow-up.

That said, while price cannot justify holding back on introducing new regimens, the cost of treatment (including drug prices) is too high and must come down so that care can be scaled up as quickly as possible to the millions of untreated people with TB.

“We Don’t Know How…”

A second excuse maintains that many programs lack the technical expertise to use the newly prioritized drugs, suggesting that they were researched inadequately before being brought to market and therefore warrant a cautious rollout.  Yet by now the majority of MDR-TB programs have some experience using them with the most complicated patients. We acknowledge that some questions persist about drugs like bedaquiline and linezolid (including optimal duration and dosing).  However, international bodies like the WHO, CDC, and others, have historically moved forward with new MDR treatments despite uncertainty.  We should remember that unanswered questions persist even today about fluoroquinolones, the revered class of second-line anti-TB drugs.  Despite their recommendation for universal inclusion in MDR-TB regimens, we still do not know which is the most effective and what is the best dose.

We should protect the new drugs…

Finally, some believe the newer therapies should be reserved as drugs of last resort “just in case” treatment fails or in order to avoid resistance.  But, both clinical best practice and medical ethics tell us to always use the most effective treatment, with the highest likelihood of curing the patient, as early as possible: the first chance to cure is the best chance.  The alternative of reserving drugs, and adding new drugs sequentially, can have disastrous consequences.

“Patients Won’t Stay on Treatment…”

Finally, there is a history of viewing injectables—the most notable of the demoted drugs—as a kind of “leash” to healthcare, since the patient is obliged to come to the clinic every day (or remain hospitalized) to receive a shot. Patients who might otherwise drop out of treatment can be retained in care.  This excuse is, at best, disingenuous and, at worst, highly unethical.  Practicing a patient-centered model of TB care where patient needs, respect, and safety are paramount makes a far better motivator to stay with treatment.  Using all-oral regimens with the recently promoted drugs avoids the indignity of painful daily injections, perhaps making patients less likely to quit overall.

Enough excuses, time for action

In the 1990s, the risk of transmitting HIV during TB treatment was reduced by replacing injectable streptomycin with an oral drug with far less evidence of efficacy than we have for bedaquiline or linezolid today, to great success.  Patients receiving injectable medications can lose their hearing, experience permanent kidney damage, and are more likely to die.  These unnecessary consequences are avoidable now if we act quickly. Programs must take up the advice of the WHO and update treatment regimens to take advantage of these new tools and provide the best care possible for their patients.  It is time for action (and new drugs), not excuses.

 

Helena Huerga is a clinician and epidemiologist working with Médecins Sans Frontières (MSF)’s Epicentre.

Uzma Khan is a clinician and public health professional at Interactive Research and Development (IRD).

KJ Seung is a clinician and public health professional at Harvard Medical School and Partners In Health (PIH).

Discussion
  1. Thank you for publishing this valuable information and your strong clinical recommendations. I hope the “sustainable/cost/benefit” excuses do not block this very necessary change in treatment.

    Sincerely

  2. Thank you for this important article/editorial. I read it via PLOS Medicine. I ardently hope that the usual “sustainability/cost-effectiveness” excuse does not get in the way of moving forward.

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