Combination therapy similar to standard therapy regimen in TB patients

Lienhardt C. JAMA. 2011;305:1415-1423.

A four-drug fixed-dose combination regimen in newly diagnosed tuberculosis patients was comparable to a standard therapy regimen of separately administered drugs, according to study results.

Researchers, therefore, recommend fixed-dose combination therapy because of the potential advantages associated with its use. “Fixed-dose combination drugs should be used and delivered, as much as possible, to patients for the treatment of TB, as they allow better adherence to treatment and contribute to prevention of emergence of drug resistance,” Christian Lienhardt, PhD, of WHO, said during a Journal of the American Medical Association media briefing.

In the open-label, randomized controlled trial, Lienhardt and colleagues evaluated the safety and efficacy of a combination four-drug regimen in comparison with a standard therapy regimen (rifampicin, isoniazid, pyrazinamide, and ethambutol administered for 6 months; then four drugs for 2 months and two drugs for 4 months) in 1,585 patients across 11 sites in nine countries. Patients were aged at least 18 years with newly diagnosed smear-positive pulmonary TB. The fixed-dose combination regimen was administered to 798 patients; 787 patients were assigned the same drugs, separately.

Two of three analyses met noninferiority criteria. Results from the per-protocol analysis indicated that 93.9% of patients assigned the fixed-dose combination had a favorable outcome compared with 94.6% of patients assigned the separate-therapy regimen (90% CI, –3 to 1.5).

In addition, 83.3% of patients in the fixed-dose combination group had a favorable outcome compared with 84.8% of patients in the separate-therapy group for the model 1 analysis (90% CI, –4.7 to 1.8); and 89.8% of patients assigned the fixed-dose combination and 91% of patients assigned the separate-therapy regimen had favorable outcomes for the post-hoc model 2 analysis (90% CI, –3.9 to 1.5).

Christian Lienhardt, PhD

“Results of this trial strongly suggest that quality-assured fixed-dose combinations would be equivalent to separate drugs in terms of efficacy and safety,” Lienhardt said. “They allow simpler procurement and prescription to patients, and avoid incorrect dosages. Since multidrug-resistant–TB is a manmade condition, only prevention of further emergence of resistance to TB drugs will be able to limit the spread through proper use and delivery of full treatment with quality-assured drugs.”

Further attention is needed on operational aspects, including stocks of single-drug tablets for patients with severe adverse reactions to drugs, Lienhardt said.

Disclosure: Dr. Lienhardt reports no relevant financial disclosures.

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