Key clinical point:
Major finding: The median number of pain crises was 3.0 in the L-glutamine group, compared with 4.0 in the placebo group (P = .005).
Study details: A multicenter, randomized, placebo-controlled, double-blind, phase 3 trial including 230 chidren and adults with sickle cell anemia or sickle-beta0-thalassemia and two or more pain crises in the previous year.
Disclosures: Dr. Niihara is the founder and CEO of Emmaus Medical, which sponsored the trial. Other coauthors also reported disclosures related to Emmaus Medical and other companies.
Source: Niihara Y et al. N Engl J Med. 2018 Jul 19;379(3):226-35.
Niihara Y et al. N Engl J Med. 2018 Jul 19;379(3):226-35.
How the findings affect clinical practice
Results of this phase 3 trial were “much awaited” and illustrate the efficacy of L-glutamine in reducing the number of acute vasoocclusive episodes in patients with sickle cell disease.
However, as with any new breakthrough in medicine, there are now compelling questions that need to be answered, Caterina P. Minniti, MD, said in an accompanying editorial.
How to handle cost is one such question. One year of treatment with pharmaceutical-grade L-glutamine carries an estimated cost of $40,515 versus $1,700 for a year of hydroxyurea, but whether the price tag will hinder prescribing of the newer agent has yet to be seen, according to Dr. Minniti.
“This agent certainly has been slow to enter the market because prescribing L-glutamine for patients requires many steps, which may dissuade busy practitioners from actively prescribing it,” she said.
Another question is whether it should be used alongside hydroxyurea, as was done in two-thirds of patients in the present trial. Concomitant use is possible and “most likely advantageous” given that L-glutamine has a different toxicity profile and putatively different mechanism of action from hydroxyurea, Dr. Minniti said.
Who should receive L-glutamine is another important question. Dr. Minniti said that, based on previous trial data, caution may be warranted in giving L-glutamine to patients with significant renal and hepatic dysfunction, but she added that its role could be broad.
“In the absence of specific guidelines, I believe that L-glutamine may be prescribed to persons older than 5 years of age who have any sickle genotype and continue to have episodes of acute disease exacerbations despite appropriate use of hydroxyurea or to those who cannot or do not use hydroxyurea,” she said in the editorial.
Caterina P. Minniti, MD, is with the division of hematology at Montefiore Medical Center at Einstein College of Medicine, New York. These comments are excerpted from her accompanying editorial (). Dr. Minniti reported disclosures related to Global Blood Therapeutics and Bayer, along with a patent pending for a topical sodium nitrite formulation.
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Gene therapy reverses sickle cell phenotype in small study, Esrick EB et al. ASH 2018, Abstract 1023
Sickle cell pain: Opioids appear safe for inpatients, Akinboro OA et al. ASH 2018, Abstract 315
Sickle cell: Daily hydroxyurea safe in African children, Tshilolo L et al. ASH 2018, Abstract 3