Add-On Arginine Betters Pediatric Sickle Cell Anemia Pain

Richard Onalo, FCPaed

Oral arginine may serve as a significantly beneficial adjuvant therapy for children with sickle cell anemia, according to new findings presented at the American Society of Hematology (ASH) 2019 Annual Meeting in Orlando.

New data from a team of Africa-based investigators, involving pediatric patients with sickle anemia from Nigeria, complements previous findings showing the amino acid therapy’s benefit for severe vaso-occlusive pain episodes (VOE) versus placebo.

Led by Richard Onalo, FCPaed, of the Department of Pediatrics at University of Abuja, investigators sought to determine the role of oral arginine in VOE management among children with sickle cell anemia in Sub-Saharan Africa. The opioid-sparing effects of arginine was shown to significantly decrease pain scores in hospitalized children with sickle cell anemia in a phase 2, randomized, placebo-controlled trial conducted in the US earlier this decade.

Onalo and colleagues conducted the double-blind, randomized, controlled trial with 100 mg/kg oral L-arginine, dosed every 8 hours for up to 5 days or 15 doses, in children with sickle cell anemia hospitalized in 1 of 2 Abuja-based facilities. Included children scored at least a 7 of 10 on the Numerical Pain Scale Score (PS).

All patients had received pain management, in both opioids and non-opioid analgesics. Physicians obtained information including patient demographics, clinical characteristics, length of hospital stay, pain scores, time-to-crisis resolution, analgesia medications required, and plasma amino acid levels.

Recruitment included 68 children with sickle cell anemia, aged 5-17 years old. Patients were split to either arginine (n = 35) or placebo (n = 33) therapy. Baseline characteristics, including pain scores, were similar between the treatment arms.

Mean total analgesic medication quantification scale score (MQS) was significantly lower among arginine-treated patients (73; 95% CI, 62-84) than placebo patients (120; 95% CI, 97-143; P <.001). By the fifth day of care, 54% of children treated with arginine had been discharged, versus just 24% of children on placebo.

The worst reported pain score on day 5 were lower in children treated with arginine versus placebo, and the mean rate of pain score decline was greater among treated patients (1.5 vs 1.1 cm/day; P = .009).

Plasma arginine levels increased by nearly 100 percentage points among arginine patients (125% vs 29%) compared to placebo. Treated patients also reported a statistically significant decrease in mean total opioid dose use, a shorter time-to-crisis resolution, and shorter length of hospital stay.

Investigators observed no serious adverse events in treated patients, and 1 death was reported in the placebo group on the second day of admission. More vomiting was reported in the arginine arm versus placebo (20% vs 7%; P = .07).

Just as arginine deficiency plays a role in hospitalizing acute pain among both Nigerian and US children with sickle cell anemia, oral arginine adjuvant therapy has now been shown to benefit both patient populations.

“Plasma arginine levels significantly increased with arginine supplementation, and improved global arginine bioavailability was inversely associated with total analgesia and opioids used in VOE management,” Onalo and colleagues wrote.

The team concluded the oral supplement therapy is a promising add-on to the sickle cell anemia-VOE management regimen.

The study, “Oral Arginine Therapy As a Novel Adjuvant in the Management of Acute Pain in Children with Sickle Cell Anemia in Nigeria: A Randomized Placebo-Controlled TrialClinically Relevant Abstract,” was presented at ASH 2019.