Efficacy of Pharmacological Interventions for Transthyretin Familial Amyloid Polyneuropathy (TTR-FAP): A Systematic Review and Network Meta-Analysis
Muneeb Ahmad Muneer1, Poorvikha S2, Adeeb Ali Mohammad3, Archit Garg4, Arkansh Sharma5, Vinay Suresh6, Vibhor Agrawal6, Varsha Srinivasan3, Ishita Lanjewar7, Kshitij Sonawale7
1Allama Iqbal Medical College, 2St John’s Medical College, 3Madras Medical College, 4Shaheed Hasan Khan Mewati, Government Medical College, 5Government Medical College, 6King George’s Medical University, 7Seth GSMC and KEM hospital
Objective:
To assess and compare the efficacy of disease-modifying pharmacological agents in patients with transthyretin familial amyloid polyneuropathy.
Background:
Transthyretin Familial Amyloid Polyneuropathy (TTR-FAP) is a life-threatening, autosomal dominant disorder causing sensorimotor and autonomic neuropathy due to amyloid fibril deposition. This network meta-analysis aims to identify the most effective pharmacological treatments for managing TTR-FAP.
Design/Methods:
A systematic search in PubMed/MEDLINE, Cochrane, EMBASE, Scopus, and ClinicalTrials.gov identified randomized controlled trials (RCTs) on TTR-FAP interventions up to May 2024. The primary outcomes were the Norfolk Quality of Life-Diabetic Neuropathy (QOL-DN) questionnaire and the Modified Neuropathy Impairment Score +7 (mNIS+7). Pairwise meta-analysis and network meta-analysis were performed using the frequentist approach to obtain both direct and indirect comparisons of each measure in terms of standardized mean difference (SMD).
Results:
The QOL-DN questionnaire was assessed in four studies with a pooled population of 644 and four pairwise comparisons, while the mNIS+7 was assessed in three studies with a pooled population of 455 and three pairwise comparisons. For the QOL-DN questionnaire, Patisiran showed the greatest effect, with an SMD of -1.04 (95% CI: -1.39 to -0.70), followed by Vutrisiran (-0.85, 95% CI: -1.15 to -0.56) and Inotersen (-0.55, 95% CI: -0.90 to -0.20), all statistically significant. Tafamidis had an SMD of -0.24 (95% CI: -0.59 to 0.12), which was not statistically significant. For mNIS+7, Patisiran again demonstrated the strongest impact, with an SMD of -1.71 (95% CI: -2.07 to -1.34). Inotersen showed an SMD of -1.02 (95% CI: -1.39 to -0.65), while Diflunisal had an SMD of -0.42 (95% CI: -0.77 to -0.07), all statistically significant.
Conclusions:
Patisiran and Inotersen demonstrated superior efficacy with significant results, while Vutrisiran and Diflunisal also showed notable outcomes. In contrast, Tafamidis did not yield significant results. Further research is needed to confirm these findings.
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