Pharmacotherapeutical strategies in the prevention of acute, vaso-occlusive pain in sickle cell disease: a systematic review

Abstract

Sickle-cell disease (SCD) is characterized by frequent and painful vaso-occlusive crises (VOCs).Various treatments have been evaluated over the years. However, a clear overview is lacking.The objective of this study was to systematically review all pharmacotherapeutical strategies in the prevention of VOCs beyond hydroxyurea. We performed a systematic literature search (MEDLINE, Embase, CENTRAL). Eligible studies were controlled clinical trials evaluating pharmacotherapeutical interventions targeting the reduction of VOCs in patients with SCD.Primary outcomes were the number or duration of SCD-related pain days, VOCs, or hospital admissions for VOCs. Secondary outcomes included time to first VOC or hospital admission for a VOC. A standardized data extraction sheet was used. The methodological quality of studies was assessed using Cochrane's risk-of-bias tool. A total of 36 studies were included in this review, covering 26 different prophylactic interventions. The most promising interventions for reducing the frequency of either VOCs or hospitalizations were the oral antioxidants L-glutamine and v-3 fatty acids and the IV antiadhesive agent crizanlizumab. Twenty-three studies did not show any beneficial effect of the intervention under investigation, and 6 studies were either too small or methodologically inadequate to draw conclusions. Because of the heterogeneity of interventions, no meta-analysis was performed. In conclusion, this review identified 3 promising pharmacotherapeutical strategies in the prevention of VOCs in SCD. Importantly, this study highlights the discrepancy between the significant burden of SCD worldwide and the low number of adequate trials performed. This review was

Mast cell‐neural interactions contribute to pain and itch

“…Vascular occlusion is caused by sickle RBCs obstructing blood flow leading to impaired oxygen supply and nutrients to the organs, vascular dysfunction, ischemia/reperfusion injury, inflammation, and end organ damage. 42,115,128 Ischemia/reperfusion injury stimulates mast cell degranulation. 129 VOC pain is associated with ischemia/reperfusion injury in SCD, and we simulated VOClike pain following hypoxia/reoxygenation in sickle mice.…”

Current and novel therapies for the prevention of vaso-occlusive crisis in sickle cell disease

“…Thus, it is exciting to see that there are several different agents with disparate mechanisms of action under investigation. 4,89 In particular, newer agents that target the underlying adhesion processes contributing to VOCs have the potential to work in conjunction with current therapies to reduce VOCs and associated morbidity. If these newer agents can also have a protective effect on the endothelial cells and blood vessels, they may also prevent long-term organ dysfunction.…”

Crizanlizumab and comparators for adults with sickle cell disease: a systematic review and network meta-analysis

“…22 A PRISMA NMA checklist can be found in online supplemental appendix A. The SLR approach updated and expanded an earlier published SLR by Sins et al 23 by including non-controlled studies and included additional interventions. Inclusion and exclusion criteria for studies are summarised in table 1.…”

“…The search strategies were derived from Sins et al 23 and can be found in online supplemental appendix B along with the complete search protocols in online supplemental appendices C and D. As blood transfusion was not included by Sins et al, 23 we conducted a separate search for blood transfusion from inception of databases to 30 August 2018. For non-transfusion studies, the search date was from 1 January 2017 to 21 June 2018 to bridge the findings of Sins et al 23 Results of searches were managed using Endnote and a Microsoft Excel spreadsheet. Two reviewers screened and selected records independently against inclusion and exclusion criteria using titles and abstracts.…”