Efficacy and safety of pharmacological cachexia interventions: systematic review and network meta-analysis

Article reference: Saeteaw M, Sanguanboonyaphong P, Yoodee J, et al, Efficacy and safety of pharmacological cachexia interventions: systematic review and network meta-analysis, BMJ Supportive & Palliative Care 2021;11:75-85.

Nathorn (Nui) Chaiyakunapruk,
University of Utah Health
Manit Saeteaw,
Ubon Ratchathani University
Kaitlyn Craft,
University of Utah Health

Cachexia is a syndrome that causes body weight loss in many chronic diseases including HIV and cancer. This syndrome can affect both patient survival and quality of life. Nutritional support is an important method to manage cachexia. However, some patients do not fully respond to treatment and require another effective treatment. Numerous medications have been studied and showed satisfactory results in cachexia. However, limited studies have combined and summarized the risk and benefit of all medications.

Our network meta-analysis (NMA) pooled data of 80 studies (10579 patients) from 4 medical databases from inception to 27th October 2019. We estimated treatment benefit in body weight, appetite, and risk of adverse events. Of all treatments, corticosteroids showed the highest total weight gain of 6.45 kilograms compared to placebo. However, corticosteroids were associated with increased infection risk, outweighing any benefit from body weight gain.  Megestrol acetate showed a dose-response relationship in our study. Only high dose megestrol acetate (at least 400 mg/day) can increase both patient body weight and appetite. Moreover, combining high dose megestrol acetate with another cachexia treatment medication showed increase in total body weight and appetite without significant adverse events. Anamorelin, a novel pharmacologic treatment, can improve both total and lean body weight based on limited study data. Lastly, dronabinol not only failed to improve total body weight, but also decreased body weight in HIV patients, and increased overall adverse events.

In summary, our NMA findings showed that many pharmacologic interventions, especially high dose megestrol acetate and corticosteroid, have efficacy and safety in cachexia treatment. However, pharmacologic intervention alone may not provide the highest treatment benefit. Multimodality therapy combining both pharmacologic intervention and appropriate nutrition support is the most effective way to achieve the best clinical outcome in cachexia treatment.

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