Aggressive therapy for MDR-TB reduces risk of disease recurrence

Aggressive treatment of multidrug-resistant tuberculosis (MDR-TB) significantly reduces the risk of disease recurrence, investigators report in the online edition of Clinical Infectious Diseases. Patients who received intensive therapy for at least 18 months after cure were 60% less likely to have disease recurrence than patients who received less aggressive therapy.

“Robust evidence regarding the optimal management of patients with MDR-TB is scanty,” comment the authors. “Our findings indicate that receipt of aggressive regimens for at least 18 months following sputum conversion may reduce recurrent TB following MDR-TB cure.”

TB that is resistant to the key first-line drugs isoniazid and rifampicin is defined as MDR-TB. Treatment for MDR-TB is long, complex and toxic, limiting its efficacy. Moreover, between 1 and 29% of patients who achieve a cure (sputum conversion) experience a recurrence of disease within two years. The factors associated with an increased risk of disease recurrence are poorly understood.

Investigators from Peru therefore designed a retrospective study involving 402 people who were treated for MDR-TB between 1999 and 2002. These individuals were followed for a median of 41 months.

The researchers especially wanted to see if aggressive therapy was associated with a lower risk of disease recurrence. An aggressive regimen was one that lasted for at 18 or more months post-cure and contained at least five anti-TB drugs, including one fluoroquinolone and one injectable agent.

The median age at the initiation of therapy for MDR-TB was 28 years. Most (61%) of the participants were male. The patients had received a median of three previous TB treatment regimens before starting MDR-TB therapy. A significant minority (44%) had resistance to second-line drugs, 69% were resistant to five or more agents and 7% met the definition for extensively drug-resistant TB (XDR-TB).

Overall, 61% of participants were classified as receiving aggressive therapy. The median duration of treatment surpassed 18 months for those who received aggressive treatment and participants whose therapy did not meet this definition (25 vs 24 months).

A total of 26 cases of recurrent TB were identified. Aggressive treatment reduced the risk of this outcome by 60% (HR = 0.40; 95% CI, 0.17-0.96; p = 0.04).

“Although reducing the number of drugs or the duration of the MDR-TB regimen would certainly be desirable to reduce the burden on patients and programs, any efforts to minimize or shorten MDR-TB therapy must be informed by a better understanding of specific treatment-related factors that may influence recurrent TB after cure,” write the authors. “Use of aggressive regimens for MDR-TB may optimize outcomes and be a suitable background regimen against which future MDR-TB treatment strategies could be compared.”

Patients with diabetes mellitus had a ten-fold increase in the risk of experiencing a disease recurrence (HR = 1.47; 95% CI, 2.17-50.50; p = 0.004). The authors offer several possible reasons for this finding, “including the effects of diabetes on the immune system, evidence that diabetes may alter pharmacokinetics of certain drugs, or an increased risk of adverse events due to overweight or obesity”.

The investigators were unable to say if the cases of disease recurrence represented “true relapse or re-infection”. Nevertheless, they conclude their results “provide a better understanding of the role of MDR-TB regimen’s composition and its association of recurrence after cure. Implementing measures to ensure that aggressive regimens for MDR-TB are implemented widely, early, effectively, and for sufficient duration will likely improve treatment outcomes and reduce the risk of recurrent TB.”