Long-Term Efficacy of T3 Analogue Triac in Children and Adults With MCT8 Deficiency: A Real-Life Retrospective Cohort Study
Ferdy S. van Geest, Stefan Groeneweg, Erica L T van den Akker, I. Bacos, Diana Bârcă, Sjoerd A.A. van den Berg, Enrico Bertini, Doris Brunner, Nicola Brunetti‐Pierri, Marco Cappa, Gerarda Cappuccio, Krishna Chatterjee, Alexander Chesover, Peter Christian, Régis Coutant, Dana Craiu, Patricia Crock, Cheyenne Dewey, Alice Dica, Paul Dimitri, Rachana Dubey, Anina Enderli, Jan Fairchild, Jonathan Gallichan, Luigi Garibaldi, Belinda George, Annette Hackenberg, Bianka Heinrich, Tony Huynh, Anna Kłosowska, Amy Lawson‐Yuen, M Linder-Lucht, Greta Lyons, Felipe Monti Lora, Carla Moran, Katalin Eszter Müller, Laura Paone, Praveen George Paul, Michel Polak, Francesco Porta, Christina Reinauer, Yolanda B. de Rijke, Rowen Seckold, tuba seven menevse, Peter Simm, Anna Simon, Marco Spada, Athanasia Stoupa, Lilla Szeifert, Davide Tonduti, Hans van Toor, Serap Turan, Joel A. Vanderniet, Monique de Waart, Ronald van der Wal, Adri van der Walt, Anne‐Marie van Wermeskerken, Jolanta Wierzba, Federica Zibordi, Amnon Zung, Robin P. Peeters, W. Edward Visser
Abstract
CONTEXT: Patients with mutations in thyroid hormone transporter MCT8 have developmental delay and chronic thyrotoxicosis associated with being underweight and having cardiovascular dysfunction. OBJECTIVE: Our previous trial showed improvement of key clinical and biochemical features during 1-year treatment with the T3 analogue Triac, but long-term follow-up data are needed. METHODS: In this real-life retrospective cohort study, we investigated the efficacy of Triac in MCT8-deficient patients in 33 sites. The primary endpoint was change in serum T3 concentrations from baseline to last available measurement. Secondary endpoints were changes in other thyroid parameters, anthropometric parameters, heart rate, and biochemical markers of thyroid hormone action. RESULTS: From October 15, 2014 to January 1, 2021, 67 patients (median baseline age 4.6 years; range, 0.5-66) were treated up to 6 years (median 2.2 years; range, 0.2-6.2). Mean T3 concentrations decreased from 4.58 (SD 1.11) to 1.66 (0.69) nmol/L (mean decrease 2.92 nmol/L; 95% CI, 2.61-3.23; P < 0.0001; target 1.4-2.5 nmol/L). Body-weight-for-age exceeded that of untreated historical controls (mean difference 0.72 SD; 95% CI, 0.36-1.09; P = 0.0002). Heart-rate-for-age decreased (mean difference 0.64 SD; 95% CI, 0.29-0.98; P = 0.0005). SHBG concentrations decreased from 245 (99) to 209 (92) nmol/L (mean decrease 36 nmol/L; 95% CI, 16-57; P = 0.0008). Mean creatinine concentrations increased from 32 (11) to 39 (13) µmol/L (mean increase 7 µmol/L; 95% CI, 6-9; P < 0.0001). Mean creatine kinase concentrations did not significantly change. No drug-related severe adverse events were reported. CONCLUSIONS: Key features were sustainably alleviated in patients with MCT8 deficiency across all ages, highlighting the real-life potential of Triac for MCT8 deficiency.