Crizanlizumab and comparators for adults with sickle cell disease: a systematic review and network meta-analysis
Objectives Treatment options for preventing vaso-occlusive crises (VOC) among patients with sickle cell disease (SCD) are limited, especially if hydroxyurea treatment has failed or is contraindicated. A systematic literature review (SLR) and network meta-analysis (NMA) were conducted to evaluate the...
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BMJ Publishing Group
2020-09-01
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| Series: | BMJ Open |
| Online Access: | https://bmjopen.bmj.com/content/10/9/e034147.full |
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| author | George Joseph Howard Thom Jeroen Jansen Hung-Yuan Cheng Jason Shafrin Lauren Zhao Subhajit Gupta Nirmish Shah |
| author_facet | George Joseph Howard Thom Jeroen Jansen Hung-Yuan Cheng Jason Shafrin Lauren Zhao Subhajit Gupta Nirmish Shah |
| author_sort | George Joseph |
| collection | DOAJ |
| description | Objectives Treatment options for preventing vaso-occlusive crises (VOC) among patients with sickle cell disease (SCD) are limited, especially if hydroxyurea treatment has failed or is contraindicated. A systematic literature review (SLR) and network meta-analysis (NMA) were conducted to evaluate the efficacy and safety of crizanlizumab for older adolescent and adult (≥16 years old) SCD patients.Methods The SLR included randomised controlled trials (RCTs) and uncontrolled studies. Bayesian NMA of VOC, all-cause hospitalisation days and adverse events were conducted.Results The SLR identified 51 studies and 9 RCTs on 14 treatments that met the NMA inclusion criteria. The NMA found that crizanlizumab 5.0 mg/kg was associated with a reduction in VOC (HR 0.55, 95% credible interval (0.43, 0.69); Bayesian probability of superiority >0.99), all-cause hospitalisation days (0.58 (0.50, 0.68); >0.99) and no evidence of difference on adverse events (0.91 (0.59, 1.43) 0.66) or serious adverse events (0.93 (0.47, 1.87); 0.59) compared with placebo. The HR for reduction in VOC for crizanlizumab relative to L-glutamine was (0.67 (0.50, 0.88); >0.99). These results were sensitive to assumptions regarding whether patient age is an effect modifier.Conclusions This NMA provides preliminary evidence comparing the efficacy of crizanlizumab with other treatments for VOC prevention. |
| format | Article |
| id | doaj-art-f6271a44c2c245f38e1ab75c8c0967e9 |
| institution | Kabale University |
| issn | 2044-6055 |
| language | English |
| publishDate | 2020-09-01 |
| publisher | BMJ Publishing Group |
| record_format | Article |
| series | BMJ Open |
| spelling | doaj-art-f6271a44c2c245f38e1ab75c8c0967e92025-01-08T10:45:12ZengBMJ Publishing GroupBMJ Open2044-60552020-09-0110910.1136/bmjopen-2019-034147Crizanlizumab and comparators for adults with sickle cell disease: a systematic review and network meta-analysisGeorge Joseph0Howard Thom1Jeroen Jansen2Hung-Yuan Cheng3Jason Shafrin4Lauren Zhao5Subhajit Gupta6Nirmish Shah7Novartis Pharmaceuticals Corp, East Hanover, New Jersey, USADepartment of Population Health Sciences, Bristol Medical School, Bristol, UKHealth Economics, PRECISIONheor, Los Angeles, California, USAsenior research associate2 FTI Consulting, Los Angeles, California, USAHealth Economics, PRECISIONheor, Los Angeles, California, USANovartis Pharmaceuticals Corp, East Hanover, New Jersey, USADepartment of Medicine, Duke University, Durham, North Carolina, USAObjectives Treatment options for preventing vaso-occlusive crises (VOC) among patients with sickle cell disease (SCD) are limited, especially if hydroxyurea treatment has failed or is contraindicated. A systematic literature review (SLR) and network meta-analysis (NMA) were conducted to evaluate the efficacy and safety of crizanlizumab for older adolescent and adult (≥16 years old) SCD patients.Methods The SLR included randomised controlled trials (RCTs) and uncontrolled studies. Bayesian NMA of VOC, all-cause hospitalisation days and adverse events were conducted.Results The SLR identified 51 studies and 9 RCTs on 14 treatments that met the NMA inclusion criteria. The NMA found that crizanlizumab 5.0 mg/kg was associated with a reduction in VOC (HR 0.55, 95% credible interval (0.43, 0.69); Bayesian probability of superiority >0.99), all-cause hospitalisation days (0.58 (0.50, 0.68); >0.99) and no evidence of difference on adverse events (0.91 (0.59, 1.43) 0.66) or serious adverse events (0.93 (0.47, 1.87); 0.59) compared with placebo. The HR for reduction in VOC for crizanlizumab relative to L-glutamine was (0.67 (0.50, 0.88); >0.99). These results were sensitive to assumptions regarding whether patient age is an effect modifier.Conclusions This NMA provides preliminary evidence comparing the efficacy of crizanlizumab with other treatments for VOC prevention.https://bmjopen.bmj.com/content/10/9/e034147.full |
| spellingShingle | George Joseph Howard Thom Jeroen Jansen Hung-Yuan Cheng Jason Shafrin Lauren Zhao Subhajit Gupta Nirmish Shah Crizanlizumab and comparators for adults with sickle cell disease: a systematic review and network meta-analysis BMJ Open |
| title | Crizanlizumab and comparators for adults with sickle cell disease: a systematic review and network meta-analysis |
| title_full | Crizanlizumab and comparators for adults with sickle cell disease: a systematic review and network meta-analysis |
| title_fullStr | Crizanlizumab and comparators for adults with sickle cell disease: a systematic review and network meta-analysis |
| title_full_unstemmed | Crizanlizumab and comparators for adults with sickle cell disease: a systematic review and network meta-analysis |
| title_short | Crizanlizumab and comparators for adults with sickle cell disease: a systematic review and network meta-analysis |
| title_sort | crizanlizumab and comparators for adults with sickle cell disease a systematic review and network meta analysis |
| url | https://bmjopen.bmj.com/content/10/9/e034147.full |
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