2SPD-010 An adjusted indirect comparison of the efficacy of efgartigimod alfa, ravulizumab, and eculizumab for treating acetylcholine receptor auto-antibody-positive (AChR-Ab+) generalised myasthenia gravis

<h3>Background and Importance</h3> Generalised myasthenia gravis (gMG) is a rare, chronic, neuromuscular autoimmune disease, mediated by pathogenic immunoglobulin auto-antibodies targeting the neuromuscular junction. Approximately 10–15% of patients have refractory gMG, meaning they do not respond despite long-term treatment with corticosteroids and at least two different immunosuppressive therapies. Biologic therapies approved in the European Union as a complementary treatment to standard therapy for AChR-Ab+ refractory gMG patients include eculizumab, ravulizumab and efgartigimod alfa. Comparisons assessing the relative effectiveness of these drugs are lacking. <h3>Aim and Objectives</h3> To assess the relative efficacy of three antibody-based biologic therapies (efgartigimod alfa, ravulizumab, and eculizumab) in this setting. <h3>Material and Methods</h3> An adjusted indirect comparison (AIC) of randomised clinical trials was performed, using Bucher’s method. Outcomes were Myasthenia Gravis-Activities of Daily Living (MG-ADL) reduction of ≥3 points (Δ = 19%), and Quantitative Myasthenia Gravis (QMG) score reduction of ≥5 points (Δ = 24,5%), both assessed at week 26. Equivalence was assessed using the equivalent therapeutic alternatives (ETA) guidelines. The main limitation of the study was the exclusion of the other available biologic drugs for this condition, due to the heterogeneity of the outcomes used in the clinical trials. <h3>Results</h3> Three trials met the inclusion criteria and shared similar baseline characteristics: CHAMPION (efgartigimod alfa vs. placebo), ADAPT (ravulizumab vs. placebo), and REGAIN (eculizumab vs. placebo). AIC showed no statistically significant differences between the therapies regarding MG-ADL score reduction. For QMG score, ravulizumab showed lower efficacy than efgartigimod alfa (RAR −22.7% (IC95% −41.98 to −3.92), p=0.021). Despite no statistical differences for eculizumab, we observed a probably clinically relevant difference regarding QMG, compared to efgartigimod alfa. <h3>Conclusion and Relevance</h3> In conclusion, our results show that eculizumab and efgartigimod alfa present a probable clinic equivalence (ETA category: C), but so are ravulizumab and efgartigimod alfa (ETA category: D) in terms of MG-ADL score reduction. However, there is some inconsistency in the case of ravulizumab as there could be statistically relevant differences versus efgartigimod alfa in terms of QMG. According to ETA guidelines, in cases of inconclusive results such as ours, the absence of equivalence should be assumed. Therefore, more data are needed to position antibody-based biologic therapies. <h3>References and/or Acknowledgements</h3> Alegre EJ, Fénix S, <i>et al</i>. Assessment and positioning of drugs as equivalent therapeutic alternatives. <i>Med Clin</i>. 2014;<b>143</b>(2):85–90. <h3>Conflict of Interest</h3> No conflict of interest