The Journal of clinical endocrinology and metabolism · 2023
Proof-of-concept and Randomized, Placebo-controlled Trials of an FcRn Inhibitor, Batoclimab, for Thyroid Eye Disease.
Рандомизированное исследованиеМногоцентровое исследованиеСтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Kahaly George J, Dolman Peter J, Wolf Jan, Giers Bert C, Elflein Heike M, Jain Amy P, Srinivasan Ashok, Hadjiiski Lubomir, Jordan David, Bradley Elizabeth A, Stan Marius N, Eckstein Anja, Pitz Susanne, Vorländer Christian, Wester Sara T, Nguyen John, Tucker Nancy, Sales-Sanz Marco, Feldon Steven E, Nelson Christine C, Hardy Isabelle, Abia-Serrano Maravillas, Tedeschi Philip, Janes Jonathan M, Xu Jing, Vue Peter, Macias William L, Douglas Raymond S
Аннотация
CONTEXT: Inhibition of the neonatal fragment crystallizable receptor (FcRn) reduces pathogenic thyrotropin receptor antibodies (TSH-R-Ab) that drive pathology in thyroid eye disease (TED).
OBJECTIVE: We report the first clinical studies of an FcRn inhibitor, batoclimab, in TED.
DESIGN: Proof-of-concept (POC) and randomized, double-blind placebo-controlled trials.
SETTING: Multicenter.
PARTICIPANTS: Patients with moderate-to-severe, active TED.
INTERVENTION: In the POC trial, patients received weekly subcutaneous injections of batoclimab 680 mg for 2 weeks, followed by 340 mg for 4 weeks. In the double-blind trial, patients were randomized 2:2:1:2 to weekly batoclimab (680 mg, 340 mg, 255 mg) or placebo for 12 weeks.
MAIN OUTCOME: Change from baseline in serum anti-TSH-R-Ab and total IgG (POC); 12-week proptosis response (randomized trial).
RESULTS: The randomized trial was terminated because of an unanticipated increase in serum cholesterol; therefore, data from 65 of the planned 77 patients were analyzed. Both trials showed marked decreases in pathogenic anti-TSH-R-Ab and total IgG serum levels (P < .001) with batoclimab. In the randomized trial, there was no statistically significant difference with batoclimab vs placebo in proptosis response at 12 weeks, although significant differences were observed at several earlier timepoints. In addition, orbital muscle volume decreased (P < .03) at 12 weeks, whereas quality of life (appearance subscale) improved (P < .03) at 19 weeks in the 680-mg group. Batoclimab was generally well tolerated, with albumin reductions and increases in lipids that reversed upon discontinuation.
CONCLUSIONS: These results provide insight into the efficacy and safety of batoclimab and support its further investigation as a potential therapy for TED.
OBJECTIVE: We report the first clinical studies of an FcRn inhibitor, batoclimab, in TED.
DESIGN: Proof-of-concept (POC) and randomized, double-blind placebo-controlled trials.
SETTING: Multicenter.
PARTICIPANTS: Patients with moderate-to-severe, active TED.
INTERVENTION: In the POC trial, patients received weekly subcutaneous injections of batoclimab 680 mg for 2 weeks, followed by 340 mg for 4 weeks. In the double-blind trial, patients were randomized 2:2:1:2 to weekly batoclimab (680 mg, 340 mg, 255 mg) or placebo for 12 weeks.
MAIN OUTCOME: Change from baseline in serum anti-TSH-R-Ab and total IgG (POC); 12-week proptosis response (randomized trial).
RESULTS: The randomized trial was terminated because of an unanticipated increase in serum cholesterol; therefore, data from 65 of the planned 77 patients were analyzed. Both trials showed marked decreases in pathogenic anti-TSH-R-Ab and total IgG serum levels (P < .001) with batoclimab. In the randomized trial, there was no statistically significant difference with batoclimab vs placebo in proptosis response at 12 weeks, although significant differences were observed at several earlier timepoints. In addition, orbital muscle volume decreased (P < .03) at 12 weeks, whereas quality of life (appearance subscale) improved (P < .03) at 19 weeks in the 680-mg group. Batoclimab was generally well tolerated, with albumin reductions and increases in lipids that reversed upon discontinuation.
CONCLUSIONS: These results provide insight into the efficacy and safety of batoclimab and support its further investigation as a potential therapy for TED.