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 ω-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 registered at PROSPERO (CRD42015025250).

Figure 1.

PRISMA flow diagram. Flowchart of publications included in this review. Our database searches identified a total of 1,717 unique records for initial abstract screening, of which 141 were selected for full-text screening. Subsequently, 97 studies were excluded for various reasons. Five of the included records involved conference abstracts of studies that were published separately as full papers (duplicates). Six included records involved 3 distinct studies that were all published twice as separate, full-paper publications. A remaining total of 36 unique studies were included in this review, covering 26 different prophylactic interventions.