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Purpose <p>Gabapentin enacarbil (GEn) and pregabalin are considered amongst the first-line drugs for restless legs syndrome (RLS). However, concerns remain about their dose-limiting side effects. This study aimed to elucidate the differences in their benefit-risk profiles through a dose-response model-based network meta-analysis (MBNMA).</p> Methods <p>A systematic review and dose-response MBNMA was conducted to evaluate the effects of GEn and pregabalin on International RLS Study Group Rating Scale (IRLS) scores, rates of responders on investigator-initiated Clinical Global Impression-Improvement (CGI-I) scales, and on prevalence of treatment-emergent adverse effects (TEAE). Dose-response curves (DRC), model-derived median effective and toxic doses (ED<sub>50</sub>, TD<sub>50</sub>) and therapeutic indices (TI = TD<sub>50</sub>/ED<sub>50</sub>) were calculated.</p> Results <p>Fifteen studies involving 2,885 were analyzed. DRCs showed dose-response relationship for IRLS scores only for pregabalin and dose-response relationships for both GEn and pregabalin for CGI-I responder rates, somnolence and dizziness TEAEs. Based on CGI-I responder rates, the model-derived ED<sub>50</sub> for GEn and pregabalin was 93.80&#xa0;mg/d and 123.55&#xa0;mg/d, respectively. The model-derived TD<sub>50</sub> for somnolence and dizziness for GEn and pregabalin were 112.85&#xa0;mg/d and 101.59&#xa0;mg/d, and 106.08&#xa0;mg/d and 104.83&#xa0;mg/d, respectively. At their model-derived ED50 and TD50, there were no significant differences between GEn and pregabalin rankings. The TIs for GEn and pregabalin ranged from 1.08 to 1.20, and 0.84—1.19, respectively.</p> Conclusions <p>GEn and pregabalin have narrow TIs based on model-derived ED<sub>50</sub> and TD<sub>50</sub>.Estimates from this MBNMA could inform future trials for studying optimal dosing that would maximize benefits and minimize risks.</p>

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Benefit-risk comparison of gabapentin enacarbil versus pregabalin for restless legs syndrome: A dose-response model-based network meta-analysis

  • 期刊论文

  • 发表日期：

    2026年2月24日

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  • Imran H. Iftikhar,
  • Saad T. Rao,
  • Essa Albisher,
  • Alex Dworetz,
  • Ahmed S. BaHammam

摘要

Purpose

Gabapentin enacarbil (GEn) and pregabalin are considered amongst the first-line drugs for restless legs syndrome (RLS). However, concerns remain about their dose-limiting side effects. This study aimed to elucidate the differences in their benefit-risk profiles through a dose-response model-based network meta-analysis (MBNMA).

Methods

A systematic review and dose-response MBNMA was conducted to evaluate the effects of GEn and pregabalin on International RLS Study Group Rating Scale (IRLS) scores, rates of responders on investigator-initiated Clinical Global Impression-Improvement (CGI-I) scales, and on prevalence of treatment-emergent adverse effects (TEAE). Dose-response curves (DRC), model-derived median effective and toxic doses (ED50, TD50) and therapeutic indices (TI = TD50/ED50) were calculated.

Results

Fifteen studies involving 2,885 were analyzed. DRCs showed dose-response relationship for IRLS scores only for pregabalin and dose-response relationships for both GEn and pregabalin for CGI-I responder rates, somnolence and dizziness TEAEs. Based on CGI-I responder rates, the model-derived ED50 for GEn and pregabalin was 93.80 mg/d and 123.55 mg/d, respectively. The model-derived TD50 for somnolence and dizziness for GEn and pregabalin were 112.85 mg/d and 101.59 mg/d, and 106.08 mg/d and 104.83 mg/d, respectively. At their model-derived ED50 and TD50, there were no significant differences between GEn and pregabalin rankings. The TIs for GEn and pregabalin ranged from 1.08 to 1.20, and 0.84—1.19, respectively.

Conclusions

GEn and pregabalin have narrow TIs based on model-derived ED50 and TD50.Estimates from this MBNMA could inform future trials for studying optimal dosing that would maximize benefits and minimize risks.