Longitudinal changes in gastrointestinal amyloid deposition before and after patisiran treatment in Hereditary ATTR amyloidosis

Background Whether amyloid deposits regress after RNA interference therapy in hereditary ATTR (ATTRv) amyloidosis remains uncertain.Objective To quantify gastrointestinal amyloid changes before and after patisiran initiation and evaluate gastric and duodenal trajectories.Methods Twenty-six patients underwent serial gastroduodenal biopsies from up to 3 years before through 3 years after patisiran initiation. Digitally quantified submucosal Congo red (CR)-positive and transthyretin (TTR)-immunoreactive area fractions were analyzed using piecewise linear mixed-effects models with a knot at treatment initiation; categorical-year and site-stratified analyses were secondary.Results Among 102 patient-time-point observations, CR positivity increased before patisiran (odds ratio [OR] per year, 1.87; 95% CI, 1.29–2.70) and decreased afterward (OR/year, 0.72; 95% CI, 0.55–0.94), with a significant slope change (OR ratio, 0.38; 95% CI, 0.22–0.66). At year 3, estimated CR positivity was 0.30%, compared with 1.08% at baseline (OR, 0.27; Holm-adjusted p = 0.0287). The TTR slope change was not significant (ratio, 0.56; p = 0.062). Gastric CR positivity showed a pronounced reversal (pretreatment OR/year, 3.71; post-treatment OR/year, 0.48; slope ratio, 0.13; p < 0.001), whereas the duodenal slope did not change significantly.Conclusion Patisiran was associated with regression of CR-positive gastrointestinal amyloid, while TTR-immunostaining and duodenal findings suggested assay- and site-dependent heterogeneity.