Therapy with GM-CSF fails to improve walking ability for patients with peripheral artery disease


A new study presented at the American Heart Association (AHA) Scientific Sessions in Atlanta and published online in JAMA shows that cell therapy failed to improve walking ability in patients with peripheral arterial disease. Arshed Ali Quyyumi, Emory University School of Medicine, Atlanta, USA, and colleagues studied whether therapy with granulocyte-macrophage colony stimulating factor (GM-CSF), an agent that functions as a white blood cell growth factor, would improve walking performance in patients with symptomatic peripheral artery disease.

“Peripheral artery disease affects more than 8 million individuals in the United States. Although exercise, smoking cessation, antiplatelet therapy, cilostazol, statins, and revascularisation are used to treat peripheral artery disease, men and women with peripheral artery disease have significantly greater functional impairment and faster functional decline than those without peripheral artery disease. Stem and progenitor cell therapy that promotes neoangiogenesis [formation of blood vessels] is an emerging treatment modality in peripheral artery disease,” according to background information in the article. Progenitor cells are involved in vascular repair and regeneration.

The phase II, placebo-controlled GPAD-2 study included 159 patients with intermittent claudication. Participants were randomised to receive four weeks of subcutaneous injections of GM-CSF (leukine), three times a week (n=80), or placebo (n=79). The primary outcome was peak treadmill walking time at three months. Secondary outcomes were peak walking time at six months and changes in circulating progenitor cell levels, ankle brachial index, walking impairment questionnaire and 36-item Short-Form Health Survey scores.

The researchers found that therapy with GM-CSF did not improve treadmill walking time at three months of follow-up. The mean peak walking time at three months increased in the GM-CSF group from 296 (151) seconds to 405 (248) seconds (mean change, 109 seconds) and in the placebo group from 308 (161) seconds to 376 (182) seconds (change of 56 seconds), but this difference was not significant (p=0.08).

At three months, compared with placebo, GM-CSF improved the physical functioning subscore of the SF-36 questionnaire by 11.4 vs. 4.8, with a mean difference in change for GM-CSF vs., placebo of 7.5 (p=0.03). Similarly, the distance score of the walking impairment questionnaire improved by 12.5 vs. 4.8 with GM-CSF compared with placebo (mean difference in change, 7.9, p=0.047). There were no significant differences in the ankle brachial index, claudication onset time, or mental or physical component scores of the SF-36 between the groups.

The authors concluded: “The improvement in a subset of secondary outcomes observed with GM-CSF suggests that GM-CSF may warrant further study in patients with claudication. In addition, further investigation is needed to investigate the variability of responsiveness to GM-CSF and its clinical significance.”