Real-world effectiveness of l-glutamine in Texas Medicaid patients with sickle cell disease Free

Introduction: Sickle cell disease (SCD) is a rare, inherited hemolytic anemia which is characterized by a range of acute and chronic complications, with vaso-occlusive crisis (VOC) as the hallmark of the disease. L-glutamine was approved in July 2017 as the first disease-modifying treatment (DMT) since hydroxyurea to reduce acute SCD complications in patients aged ≥5 years. While its efficacy has been demonstrated in clinical trials, real-world evidence remains limited. The objective of this study is to evaluate the real-world effectiveness of L-glutamine among Texas Medicaid enrollees with SCD.

Method: This retrospective cohort study used Texas Medicaid claims data from July 2017 to August 2023. Patients with SCD were identified using ≥1 inpatient or ≥2 outpatient claims (on separate dates) with an SCD ICD-10-CM diagnosis code. Eligible patients were aged 5–63 years at index date (date of first L-glutamine fill) and had 24 months of continuous Medicaid enrollment (1 year before and after the index date). Patients who received other newly approved SCD DMTs during the study period were excluded. Patients with ≥1 L-glutamine prescription were classified as the user group; all others were non-users. The index date for non-users was a randomly selected date with an SCD diagnosis matched by calendar quarter distribution of the users. Propensity score matching (1:1) was conducted based on baseline demographics (age, sex, metropolitan statistical area [MSA]), and clinical characteristics (VOC frequency, VOC-related inpatient stays, SCD-related outpatient visits, hydroxyurea use, red blood cell transfusions, presence of SCD-related complications, and Charlson Comorbidity Index score). Outcomes during the 1-year follow-up included the number and timing of VOC events, emergency department (ED) visits, inpatient stays, and acute chest syndrome (ACS). Comparisons were made both within (pre- vs. post-L-glutamine) and between groups. Bivariate analyses, multivariate generalized linear models, and logistic regressions were used. Subgroup analyses were conducted among patients with ≥6 months of L-glutamine coverage and matched non-users.

Result: A total of 113 patients (mean age: 21.1±11.6 years) were included in the L-glutamine user group. Within-group comparisons before and after L-glutamine initiation showed no significant differences in the numbers of VOC events (6.4±5.7 vs. 6.2±5.9), ED visits (4.9±8.2 vs. 5.0±8.5), and inpatient stays (0.13±0.7 vs. 0.12±0.6), length of inpatient stay (0.8±4.0 vs. 0.9±5.6), or ACS incidence (30.1%vs. 27.4%). Among 36 patients with ≥6 months of L-glutamine coverage (mean age: 20.4±12.7 years), although not statistically significant, slight improvements were observed in post-index VOC frequency (5.7±5.2 vs.5.5±5.1), number of ED visits (4.7±6.9 vs. 3.7±5.3), and ACS incidence (38.9% vs. 33.3%). After matching, compared to non-users, L-glutamine users were older (mean age: 21.1±11.6 vs. 17.6±11.9 years; p=0.034) and had a higher mean number of baseline VOC episodes (6.4±5.7 vs. 5.5±6.6; p=0.2024), though other baseline characteristics were balanced. During the 1-year follow-up, L-glutamine users experienced more VOC episodes (6.2±5.9 vs. 4.4±5.5; p=0.0037), earlier onset of first and second VOC events (both p<0.0001), and slightly more VOC-related ED visits (5.0±8.5 vs. 4.5±12.3; p=0.0109) than non-users. No significant differences were found in VOC-related inpatient stays or ACS incidents. In adjusted analyses, L-glutamine use remained associated with a higher incidence of VOC episodes (incidence rate ratio [IRR]=1.5; 95% CI: 1.3–1.9; p<0.0001). In the subgroup analysis (n=36, matched non-users' mean age: 16.9±10.4 years), L-glutamine use for 6 months or longer was associated with a higher incidence of VOCs (IRR=1.5, 95% CI=1.0-2.0, p=0.0428) and higher odds of ACS events (Odds ratio [OR]=4.0, 95% CI=1.1-15.0, p=0.0395), after controlling for baseline characteristics.Conclusions: In this real-world effectiveness study, L-glutamine use was not associated with significant improvements in clinical outcomes over one year following treatment initiation. The findings may be influenced by study limitations such as confounding by indication (as L-glutamine users tend to have more severe condition), unmeasured confounding, regression to the mean, and potential delayed treatment effects. Further research with longer follow-up and more robust control of baseline disease severity is warranted.