Low Weight Gain Among Treated TB Patients Tied to Relapse

ATLANTA, Aug. 3 -- Weight gain of 5% or less among underweight tuberculosis patients after two months of induction treatment was associated with an increased risk of relapse, CDC researchers here reported.

Statistical analysis found that patients who were underweight at diagnosis and who gained no more than 5% of body weight had a relapse rate more than twice that of patients who gained at least 5% of body weight, according to a report in the August issue of the American Journal of Respiratory and Critical Care Medicine.

Of 857 patients in the Tuberculosis Trials Consortium Study 22 who were monitored for two years, 61 (7.1%) relapsed, said Awal Khan, Ph.D., of the CDC, and colleagues.

Compared with not underweight patients the overall relapse risk was high for those who were underweight at diagnosis (19.1 versus 4.8%; P<0.001) or who had a body mass index of less than 18.5 kg/m² (19.5 versus 5.8%; P<0.001). Underweight was defined as 10% or more below ideal body weight at diagnosis.

Among underweight patients, weight gain of 5% or less between diagnosis and completion of two months of induction therapy was moderately associated with an increased relapse risk (18.4% vs. 10.3%; relative risk, 1.79, 95% confidence interval, 0.96-3.32; P=0.06).

However, in a multivariate logistic regression model adjusted for other risk factors, a weight gain of 5% or less was significantly associated with more than twice the risk of relapse (odds ratio, 2.4; P=0.03), the researchers reported.

Median weight at diagnosis was significantly lower in those who relapsed versus those who did not (P=0.047), and median BMI was also lower for relapsed patients compared with cured patients (P<0.0001).

The most notable finding of this study, the researchers said in summarizing their findings, was the lower relapse rate for those who gained more that 5% of their body weight versus those who did not (10.3% versus 18.4%; P=0.06).

This association still held, they said, among underweight patients with a cavity on chest radiograph and a positive sputum culture after two months of treatment. Even among these patients, for those who gained more than 5%, the relapse rate was only 18.5% compared with a 50.5% relapse rate for patients who gained less than 5% (P= 0.02).

Summarizing some of the study's limitations, the researchers mentioned that study patients, who had to receive two months of therapy, were eligible only if they had no severe underlying medical condition, and thus did not reflect the population of all patients, which limited generalizabilty.

Among other limitations, they noted the inability to assess height for all patients, limiting the number of patients for whom BMI could be assessed; also the fact that weight change was assessed over several intervals raised the possibility that statistically significant associations were due to chance.

The high relapse rate among the underweight patients with positive sputum cultures, and x-rays who failed to gain after two months of treatment, suggested that such patients should receive therapy that is either more intensive or longer, Dr. Khan said. Conversely the low relapse rate among patients without these risk factors suggests that they might receive shorter therapy. These questions should be addressed in future randomized controlled trials, he said.

Above all, Dr. Khan said, if the relationship between body weight and outcomes can be reproduced in larger studies, high-risk patients could be easily identified, even in resource-poor settings. In the developing world, for example, resources are limited and chest radiographs and sputum cultures cannot always be obtained, but a simple, inexpensive body-weight marker could have significant benefits.

Additional studies are needed, the researchers added, to better define the underlying mechanism of the weight-relapse association, and to identify interventions that would decrease the risk.

In an accompanying editorial, Wing Wai Yew, M.B., of Grantham Hospital in Hong Kong and Chi Chin Leung, M.B., of the Hong Kong Department of Health emphasized the prognostic significance of early rather than later weight changes on the course of the disease. Such a specific association, they said, suggests that something other than purely nutrition status affects the development of the disease.

Among patients who have lost substantial weight, effective control of the pathogen in the induction phase of treatment is pivotal, and weight gain is likely an independent indicator of clinical response in addition to culture conversion, they said.

As body weight has been well reported to be associated with disease risk and with the response to treatment, "it is surprising that little attention has been paid to such a readily measured and inexpensive marker," they said.

If such a relationship can be reproduced in large TB programs, "this relatively simple finding could be translated into very significant clinical benefits, especially in resource-limited settings," they concluded.