Comparative efficacy and safety of pharmacologic interventions for cachexia: A systematic review and network meta-analysis

Abstract

Background: Recent randomized clinical trials (RCTs) have demonstrated benefits of various pharmacologic interventions for cachexia in improving weight and appetite. However, their comparative efficacy and safety are not available. Therefore, we conduct a systematic review and network-meta-analysis to evaluate the relative efficacy and safety of the pharmacologic interventions for cachexia. Methods: PubMed, EmBase, Cochrane, and ClincalTrials.gov were searched for RCTs until October 2016. Key outcomes were total body weight (TBW) improvementand appetite (APP) score and serious adverse events. Two reviewers independently extracted data and assessed risk of bias of all RCTs. Network meta-analysis was per-formed to estimate relative magnitude of weight gain and appetite score increased at 8 weeks of all interventions, presented as mean difference (MD) or standardized mean difference with 95% confidence interval (CI). To rank the intervention hierarchy in the network meta-analysis, the rankograms, surface under the cumulative ranking (SUCRA) curves, and mean ranks were estimated. Results: 73 RCTs involving 9, 615 patients with 12 therapeutic options were included. Majority is cancer patients (6, 335), while 2, 324 were HIV patients. Compared to placebo, corticosteroids, megace-H-com, megace-H and androgen were significantly associated with MD of TBW of 6.23 (95%CI 1.91, 10.56), 3.73 (95%CI 1.58, 5.88), 2.80 (95%CI 1.46, 4.13) and 1.47 (95%CI 0.31, 2.63) kg, respectively. For appetite improvement, megace-L, megace-H, medroxyprogesterone, androgen, megace-H-com, and ghrelin mimetics had significantly improved standardized APP score, compared to placebo. These score improvements were also reported earlier than 8 weeks in most appetite stimulants (ghrelin, megace-L, megace-H, and medroxyprogesterone). There is no significantly difference in serious ADRs as compared to the placebo. Conclusions: This network meta-analysis suggests that appetite stimulants may offer superior benefits in the treatment of cachexia. Nonetheless, the comparative studies to compare safety and efficacy is warranted to better manage cachexia.