Dataset Information

Drug repurposing in Raynaud's phenomenon through adverse event signature matching in the World Health Organization pharmacovigilance database.

ABSTRACT:

Aims

Several pharmacological treatments are recommended for Raynaud's phenomenon (RP) secondary to systemic sclerosis, but they only have modest efficacy. A way to efficiently identify new drugs is drug repurposing, which can be based on signature matching. The signature could be derived from chemical structures, pharmacological affinity or adverse event profiles. We propose to use the World Health Organization (WHO) pharmacovigilance database to generate repositioning hypotheses for treatments of RP through adverse event signature matching.

Methods

We first screened all drugs associated with at least 1 case of erythromelalgia, an adverse effect opposite to RP. In parallel, to define the adverse event signature of drugs recommended in secondary RP from the WHO pharmacovigilance database, we selected the 14 most representative adverse drug reactions (ADRs). Lastly, we performed a hierarchical cluster analysis to identify drugs with similar ADR signature to vasodilatory drugs used in RP.

Results

In total, 179 drugs were associated with erythromelalgia; they were related to 860 334 adverse events representative of RP drugs in the WHO pharmacovigilance database. Hierarchical cluster analysis allowed identification of 6 clusters. The most stable cluster contained 7 drugs, among which 5 are recommended in secondary RP, or pertain to the same drug class: epoprostenol, nifedipine, nicardipine, lacidipine and israpidine. The 2 remaining drugs were alemtuzumab and fumaric acid.

Conclusion

Our ADR signature matching approach suggests that alemtuzumab and fumaric acid could be effective treatments of secondary RP. The latter is currently being investigated as a treatment of pulmonary hypertension in systemic sclerosis.

SUBMITTER: Zaza P

PROVIDER: S-EPMC7576623 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundMany different drugs have been suggested for the symptomatic treatment of primary Raynaud's phenomenon. Apart from calcium channel blockers, which are considered the drugs of choice, the evidence of the effects of alternative pharmacological treatments is limited. This is an update of a review first published in 2008.ObjectivesTo assess the effects of various drugs with vasodilator actions on primary Raynaud's phenomenon.Search methodsFor this update the Cochrane Peripheral Vascular Diseases Group Trials Search Co-ordinator searched the Specialised Register (last searched 14 May 2012), CENTRAL (Issue 4, 2012) and clinical trials databases. We contacted one pharmaceutical company and one trial author for additional information. In addition, the reference lists of relevant studies were searched for additional citations. There were no language restrictions.Selection criteriaRandomised controlled trials evaluating the effects of oral formulations of any drug with vasodilator effects on subjective symptoms in primary Raynaud's phenomenon. Treatment with, or comparison with, calcium channel blockers was not assessed in this review.Data collection and analysisTwo members of the review team independently assessed the trials for inclusion and their quality and extracted the data. Data extraction included adverse events. We contacted trial authors for missing data.Main resultsEight studies involving 290 participants were included. Two trials examined the effects of captopril, the rest were single trials on single drugs. All comparisons were with placebo. The methodological quality of most trials was poor.Enalapril was associated with a small increase in the frequency of attacks per week (difference in means 0.8; 95% CI 0.43 to 1.17). The difference between the intervention groups on a subjective improvement score was non-significant. There was a significant effect of buflomedil on the frequency of attacks per week (weighted mean difference (WMD) -8.8; 95% CI -17.55 to -0.09), but there was no evidence of effect on the severity score. The proportion with fewer attacks was significantly higher on moxisylyte than on placebo (relative risk (RR) 4.33; 95% CI 1.36 to 13.81). For captopril, beraprost, dazoxiben and ketanserin there was no evidence of an effect on the frequency, severity or duration of attacks. Beraprost and moxisylyte gave significantly more adverse effects than placebo.Authors' conclusionsPoor methodological quality, small sample sizes and the limited data available resulted in low precision of the statistical results and limited value of the overall results .The overall results show that there is no evidence for an effect of vasodilator drugs on primary Raynaud's phenomenon.