Comparative Effectiveness of Remestemcel-L-rknd versus Ruxolitinib in Pediatric Patients with Steroid-Refractory Acute Graft-Versus-Host Disease using Simulated Treatment Comparisons
**Background:** Allogeneic hematopoietic stem cell transplantation (allo-HSCT) can be a lifesaving treatment for hematologic malignancies, but acute graft-versus-host-disease (aGVHD) is a potentially deadly adverse effect experienced by up to half of allo-HSCT recipients. Inadequate response to ster...
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| Format: | Article |
| Language: | English |
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Columbia Data Analytics, LLC
2021-02-01
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| Series: | Journal of Health Economics and Outcomes Research |
| Online Access: | https://doi.org/10.36469/jheor.2021.19008 |
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| author | Gabriel Tremblay Dimitrios Tomaras Eric Strati Anna Forsythe |
| author_facet | Gabriel Tremblay Dimitrios Tomaras Eric Strati Anna Forsythe |
| author_sort | Gabriel Tremblay |
| collection | DOAJ |
| description | **Background:** Allogeneic hematopoietic stem cell transplantation (allo-HSCT) can be a lifesaving treatment for hematologic malignancies, but acute graft-versus-host-disease (aGVHD) is a potentially deadly adverse effect experienced by up to half of allo-HSCT recipients. Inadequate response to steroid therapy for aGVHD is associated with poor prognosis and high mortality, including among pediatric patients, who are the focus of this study. Ruxolitinib and remestemcel-L-rknd were evaluated for the treatment of steroid-refractory (SR) aGVHD in two separate single-arm trials. To effectively compare the safety and efficacy of these treatments without a head-to-head trial, a simulated treatment comparison (STC) was conducted.
**Methods:** Regression techniques were used to adjust individual patient-level data from the remestemcel-L-rknd trial to mutually reported baseline characteristics from the ruxolitinib trial. Outcomes of interest included a 28-day overall response rate (ORR), a 28-day ORR in the grade III-IV aGVHD population, and adverse events (AEs).
**Results:** In the full populations, the STC of risk ratios (RRs) found treatment with remestemcel-L-rknd to be associated with a numerical but not statistically significant improvement in the 28-day ORR versus ruxolitinib. In the grade III-IV aGVHD sub-group, the STC showed significantly improved 28-day ORR for remestemcel-L-rknd versus ruxolitinib (_P_=0.04). Remestemcel-L-rknd was also associated with improved safety outcomes (_P_<0.05) in 17 out of 30 AEs, including hematologic events, peripheral edema, muscular weakness, nausea, back pain, and fatigue.
**Conclusion:** Remestemcel-L-rknd was associated with significant improvements in day 28 ORR compared with ruxolitinib in patients with severe (grade III-IV) SR aGVHD. Across all grades of SR aGVHD, remestemcel-L-rknd was associated with fewer all-grade treatment-emergent adverse events (TEAEs) (27/30) available for comparison, including the majority reaching statistical significance. |
| format | Article |
| id | doaj-art-01900f92edd241479260977f04f076b1 |
| institution | Kabale University |
| issn | 2327-2236 |
| language | English |
| publishDate | 2021-02-01 |
| publisher | Columbia Data Analytics, LLC |
| record_format | Article |
| series | Journal of Health Economics and Outcomes Research |
| spelling | doaj-art-01900f92edd241479260977f04f076b12025-02-10T16:13:13ZengColumbia Data Analytics, LLCJournal of Health Economics and Outcomes Research2327-22362021-02-0181Comparative Effectiveness of Remestemcel-L-rknd versus Ruxolitinib in Pediatric Patients with Steroid-Refractory Acute Graft-Versus-Host Disease using Simulated Treatment ComparisonsGabriel TremblayDimitrios TomarasEric StratiAnna Forsythe**Background:** Allogeneic hematopoietic stem cell transplantation (allo-HSCT) can be a lifesaving treatment for hematologic malignancies, but acute graft-versus-host-disease (aGVHD) is a potentially deadly adverse effect experienced by up to half of allo-HSCT recipients. Inadequate response to steroid therapy for aGVHD is associated with poor prognosis and high mortality, including among pediatric patients, who are the focus of this study. Ruxolitinib and remestemcel-L-rknd were evaluated for the treatment of steroid-refractory (SR) aGVHD in two separate single-arm trials. To effectively compare the safety and efficacy of these treatments without a head-to-head trial, a simulated treatment comparison (STC) was conducted. **Methods:** Regression techniques were used to adjust individual patient-level data from the remestemcel-L-rknd trial to mutually reported baseline characteristics from the ruxolitinib trial. Outcomes of interest included a 28-day overall response rate (ORR), a 28-day ORR in the grade III-IV aGVHD population, and adverse events (AEs). **Results:** In the full populations, the STC of risk ratios (RRs) found treatment with remestemcel-L-rknd to be associated with a numerical but not statistically significant improvement in the 28-day ORR versus ruxolitinib. In the grade III-IV aGVHD sub-group, the STC showed significantly improved 28-day ORR for remestemcel-L-rknd versus ruxolitinib (_P_=0.04). Remestemcel-L-rknd was also associated with improved safety outcomes (_P_<0.05) in 17 out of 30 AEs, including hematologic events, peripheral edema, muscular weakness, nausea, back pain, and fatigue. **Conclusion:** Remestemcel-L-rknd was associated with significant improvements in day 28 ORR compared with ruxolitinib in patients with severe (grade III-IV) SR aGVHD. Across all grades of SR aGVHD, remestemcel-L-rknd was associated with fewer all-grade treatment-emergent adverse events (TEAEs) (27/30) available for comparison, including the majority reaching statistical significance.https://doi.org/10.36469/jheor.2021.19008 |
| spellingShingle | Gabriel Tremblay Dimitrios Tomaras Eric Strati Anna Forsythe Comparative Effectiveness of Remestemcel-L-rknd versus Ruxolitinib in Pediatric Patients with Steroid-Refractory Acute Graft-Versus-Host Disease using Simulated Treatment Comparisons Journal of Health Economics and Outcomes Research |
| title | Comparative Effectiveness of Remestemcel-L-rknd versus Ruxolitinib in Pediatric Patients with Steroid-Refractory Acute Graft-Versus-Host Disease using Simulated Treatment Comparisons |
| title_full | Comparative Effectiveness of Remestemcel-L-rknd versus Ruxolitinib in Pediatric Patients with Steroid-Refractory Acute Graft-Versus-Host Disease using Simulated Treatment Comparisons |
| title_fullStr | Comparative Effectiveness of Remestemcel-L-rknd versus Ruxolitinib in Pediatric Patients with Steroid-Refractory Acute Graft-Versus-Host Disease using Simulated Treatment Comparisons |
| title_full_unstemmed | Comparative Effectiveness of Remestemcel-L-rknd versus Ruxolitinib in Pediatric Patients with Steroid-Refractory Acute Graft-Versus-Host Disease using Simulated Treatment Comparisons |
| title_short | Comparative Effectiveness of Remestemcel-L-rknd versus Ruxolitinib in Pediatric Patients with Steroid-Refractory Acute Graft-Versus-Host Disease using Simulated Treatment Comparisons |
| title_sort | comparative effectiveness of remestemcel l rknd versus ruxolitinib in pediatric patients with steroid refractory acute graft versus host disease using simulated treatment comparisons |
| url | https://doi.org/10.36469/jheor.2021.19008 |
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