L-glutamine reduces complications of SCD

Image by Betty Pace

Results of a phase 3 trial showed that L-glutamine can reduce complications of sickle cell disease (SCD).

SCD patients who received pharmaceutical-grade L-glutamine (with or without hydroxyurea) had a reduction in sickle cell crises, hospitalizations, and acute chest syndrome (ACS) when compared to patients who received placebo (with or without hydroxyurea).

Gastrointestinal events and pain in the chest (noncardiac), back, and extremities were more frequent in L-glutamine recipients than controls.

Yutaka Niihara, MD, of Emmaus Medical, Inc., in Torrance, California, and his colleagues reported these results in NEJM. The research was sponsored by Emmaus Medical.

Dr Niihara noted that L-glutamine (Endari), which was approved by the US Food and Drug Administration last summer, is the first treatment approved to treat SCD in pediatric patients age 5 and older and the first SCD treatment approved for adults in nearly 20 years.

“Our hope in sharing the results [of the phase 3 trial] is to aid in increasing the awareness of sickle cell disease, a life-long hereditary blood disorder which commonly affects those of African descent, as well as those from Central and South America and people of Middle Eastern, Asian, Indian, and Mediterranean descent,” Dr Niihara said.

He and his colleagues enrolled 230 patients on the trial. One hundred and fifty-two were randomized to receive L-glutamine at 0.3 g/kg twice daily (maximum 30 g/day), and 78 were randomized to placebo (maltodextrin) at 0.3 g/kg twice daily for 48 weeks.

Baseline characteristics were similar between the treatment arms. Most patients had sickle cell anemia—89.5% (n=136) in the L-glutamine arm and 91% (n=71) in the placebo arm. Several patients had sickle B⁰ thalassemia—9.2% (n=14) and 9.0% (n=7), respectively. Two patients in the L-glutamine arm had B⁺ thalassemia, but 1 of these patients did not receive L-glutamine.

The median age was 19 (range, 5-57) in the L-glutamine arm and 17 (range, 5-58) in the placebo arm. There were more females than males in both arms—52% (n=79) and 57.7% (n=45), respectively.

Most patients received concomitant hydroxyurea—66.4% (n=101) in the L-glutamine arm and 66.7% (n=52) in the placebo arm.

Efficacy

Patients in the L-glutamine arm had 25% fewer pain crises than patients in the placebo arm. The median number of crises was 3 and 4, respectively (P=0.005).

The median time to a first crisis was 84 days in the L-glutamine arm and 54 days in the placebo arm (P=0.02). The median time to a second crisis was 212 days and 133 days, respectively (P=0.03).

The median number of hospitalizations was 2 in the L-glutamine arm and 3 in the placebo arm, which is a difference of 33% (P=0.005). The median cumulative number of days in the hospital was 6.5 and 11, respectively (P=0.02).

The incidence of ACS was significantly lower in the L-glutamine arm, with 8.6% of patients in that group having at least 1 episode of ACS and 23.1% of the placebo group having at least 1 episode (P=0.003).

Safety

The rate of adverse events (AEs) was 98% in the L-glutamine arm and 100% in the placebo arm. The rate of serious AEs was 78.2% and 87.1%, respectively.

AEs with a higher incidence in the L-glutamine arm (at least 5%) are listed in the table below.

Image by Betty Pace

Results of a phase 3 trial showed that L-glutamine can reduce complications of sickle cell disease (SCD).

SCD patients who received pharmaceutical-grade L-glutamine (with or without hydroxyurea) had a reduction in sickle cell crises, hospitalizations, and acute chest syndrome (ACS) when compared to patients who received placebo (with or without hydroxyurea).

Gastrointestinal events and pain in the chest (noncardiac), back, and extremities were more frequent in L-glutamine recipients than controls.

Yutaka Niihara, MD, of Emmaus Medical, Inc., in Torrance, California, and his colleagues reported these results in NEJM. The research was sponsored by Emmaus Medical.

Dr Niihara noted that L-glutamine (Endari), which was approved by the US Food and Drug Administration last summer, is the first treatment approved to treat SCD in pediatric patients age 5 and older and the first SCD treatment approved for adults in nearly 20 years.

“Our hope in sharing the results [of the phase 3 trial] is to aid in increasing the awareness of sickle cell disease, a life-long hereditary blood disorder which commonly affects those of African descent, as well as those from Central and South America and people of Middle Eastern, Asian, Indian, and Mediterranean descent,” Dr Niihara said.

He and his colleagues enrolled 230 patients on the trial. One hundred and fifty-two were randomized to receive L-glutamine at 0.3 g/kg twice daily (maximum 30 g/day), and 78 were randomized to placebo (maltodextrin) at 0.3 g/kg twice daily for 48 weeks.

Baseline characteristics were similar between the treatment arms. Most patients had sickle cell anemia—89.5% (n=136) in the L-glutamine arm and 91% (n=71) in the placebo arm. Several patients had sickle B⁰ thalassemia—9.2% (n=14) and 9.0% (n=7), respectively. Two patients in the L-glutamine arm had B⁺ thalassemia, but 1 of these patients did not receive L-glutamine.

The median age was 19 (range, 5-57) in the L-glutamine arm and 17 (range, 5-58) in the placebo arm. There were more females than males in both arms—52% (n=79) and 57.7% (n=45), respectively.

Most patients received concomitant hydroxyurea—66.4% (n=101) in the L-glutamine arm and 66.7% (n=52) in the placebo arm.

Efficacy

Patients in the L-glutamine arm had 25% fewer pain crises than patients in the placebo arm. The median number of crises was 3 and 4, respectively (P=0.005).

The median time to a first crisis was 84 days in the L-glutamine arm and 54 days in the placebo arm (P=0.02). The median time to a second crisis was 212 days and 133 days, respectively (P=0.03).

The median number of hospitalizations was 2 in the L-glutamine arm and 3 in the placebo arm, which is a difference of 33% (P=0.005). The median cumulative number of days in the hospital was 6.5 and 11, respectively (P=0.02).

The incidence of ACS was significantly lower in the L-glutamine arm, with 8.6% of patients in that group having at least 1 episode of ACS and 23.1% of the placebo group having at least 1 episode (P=0.003).

Safety

The rate of adverse events (AEs) was 98% in the L-glutamine arm and 100% in the placebo arm. The rate of serious AEs was 78.2% and 87.1%, respectively.

AEs with a higher incidence in the L-glutamine arm (at least 5%) are listed in the table below.

Image by Betty Pace

Results of a phase 3 trial showed that L-glutamine can reduce complications of sickle cell disease (SCD).

SCD patients who received pharmaceutical-grade L-glutamine (with or without hydroxyurea) had a reduction in sickle cell crises, hospitalizations, and acute chest syndrome (ACS) when compared to patients who received placebo (with or without hydroxyurea).

Gastrointestinal events and pain in the chest (noncardiac), back, and extremities were more frequent in L-glutamine recipients than controls.

Yutaka Niihara, MD, of Emmaus Medical, Inc., in Torrance, California, and his colleagues reported these results in NEJM. The research was sponsored by Emmaus Medical.

Dr Niihara noted that L-glutamine (Endari), which was approved by the US Food and Drug Administration last summer, is the first treatment approved to treat SCD in pediatric patients age 5 and older and the first SCD treatment approved for adults in nearly 20 years.

“Our hope in sharing the results [of the phase 3 trial] is to aid in increasing the awareness of sickle cell disease, a life-long hereditary blood disorder which commonly affects those of African descent, as well as those from Central and South America and people of Middle Eastern, Asian, Indian, and Mediterranean descent,” Dr Niihara said.

He and his colleagues enrolled 230 patients on the trial. One hundred and fifty-two were randomized to receive L-glutamine at 0.3 g/kg twice daily (maximum 30 g/day), and 78 were randomized to placebo (maltodextrin) at 0.3 g/kg twice daily for 48 weeks.

Baseline characteristics were similar between the treatment arms. Most patients had sickle cell anemia—89.5% (n=136) in the L-glutamine arm and 91% (n=71) in the placebo arm. Several patients had sickle B⁰ thalassemia—9.2% (n=14) and 9.0% (n=7), respectively. Two patients in the L-glutamine arm had B⁺ thalassemia, but 1 of these patients did not receive L-glutamine.

The median age was 19 (range, 5-57) in the L-glutamine arm and 17 (range, 5-58) in the placebo arm. There were more females than males in both arms—52% (n=79) and 57.7% (n=45), respectively.

Most patients received concomitant hydroxyurea—66.4% (n=101) in the L-glutamine arm and 66.7% (n=52) in the placebo arm.

Efficacy

Patients in the L-glutamine arm had 25% fewer pain crises than patients in the placebo arm. The median number of crises was 3 and 4, respectively (P=0.005).

The median time to a first crisis was 84 days in the L-glutamine arm and 54 days in the placebo arm (P=0.02). The median time to a second crisis was 212 days and 133 days, respectively (P=0.03).

The median number of hospitalizations was 2 in the L-glutamine arm and 3 in the placebo arm, which is a difference of 33% (P=0.005). The median cumulative number of days in the hospital was 6.5 and 11, respectively (P=0.02).

The incidence of ACS was significantly lower in the L-glutamine arm, with 8.6% of patients in that group having at least 1 episode of ACS and 23.1% of the placebo group having at least 1 episode (P=0.003).

Safety

The rate of adverse events (AEs) was 98% in the L-glutamine arm and 100% in the placebo arm. The rate of serious AEs was 78.2% and 87.1%, respectively.

AEs with a higher incidence in the L-glutamine arm (at least 5%) are listed in the table below.