Arginine therapy in sickle cell disease: A systematic review and meta-analysis of clinical outcomes

Vaso-occlusive crises (VOCs) in sickle cell disease involve nitric oxide deficiency, creating a rationale for l-arginine. This meta-analysis evaluates its efficacy on clinical VOC outcomes including pain, opioid use, and hospitalization by synthesizing evidence from RCTS.

The PubMed, Embase, and Cochrane databases were searched for RCTs comparing l-arginine with placebo or standard care in SCD patients. Primary outcomes were pain scores, opioid consumption, time to crisis resolution, and length of hospital stay. Pooled estimates were calculated using random-effects models.

Eight RCTs comprising 830 patients were included. Analysis revealed no statistically significant benefit of arginine on primary outcomes. The evidence, of low certainty, indicated no significant effect on pain scores (SMD -1.55, 95 % CI [-6.72, 3.62]) or opioid consumption (MD -0.78 mg/kg, 95 % CI [-2.80, 1.23]). Similarly, no significant differences were observed for time to crisis resolution (MD -12.64 h, 95 % CI [-25.82, 0.54]) or length of hospital stay (MD -24.83 h, 95 % CI [-71.18, 21.51]). A non-significant 23 % increase in hospital readmission risk was observed (RR 1.23, 95 % CI [0.92, 1.65]). Pharmacodynamic analysis confirmed increased plasma arginine levels but showed no significant change in the arginine-to-ornithine ratio.

In summary, this meta-analysis found that l-arginine showed no statistically significant benefit on any primary clinical outcome in patients with sickle cell disease experiencing VOC. This absence of proven efficacy, coupled with a potential safety signal regarding hospital readmissions, precludes its recommendation for routine clinical use. Consequently, these findings underscore the urgent need for a large, definitive RCT to determine the efficacy and safety of arginine therapy.