BLOG医院ブログ

バセドウ病眼症に対する新薬
「テプロツムマブ」の論文より抜粋

Teprotumumab for Thyroid-Associated Ophthalmopathy

Terry J Smith ¹, George J Kahaly ¹, Daniel G Ezra ¹, James C Fleming ¹, Roger A Dailey ¹, Rosa A Tang ¹, Gerald J Harris ¹, Alessandro Antonelli ¹, Mario Salvi ¹, Robert A Goldberg ¹, James W Gigantelli ¹, Steven M Couch ¹, Erin M Shriver ¹, Brent R Hayek ¹, Eric M Hink ¹, Richard M Woodward ¹, Kathleen Gabriel ¹, Guido Magni ¹, Raymond S Douglas ¹

Abstract

Background: Thyroid-associated ophthalmopathy, a condition commonly associated with Graves’ disease, remains inadequately treated. Current medical therapies, which primarily consist of glucocorticoids, have limited efficacy and present safety concerns. Inhibition of the insulin-like growth factor I receptor (IGF-IR) is a new therapeutic strategy to attenuate the underlying autoimmune pathogenesis of ophthalmopathy.

Methods: We conducted a multicenter, double-masked, randomized, placebo-controlled trial to determine the efficacy and safety of teprotumumab, a human monoclonal antibody inhibitor of IGF-IR, in patients with active, moderate-to-severe ophthalmopathy. A total of 88 patients were randomly assigned to receive placebo or active drug administered intravenously once every 3 weeks for a total of eight infusions. The primary end point was the response in the study eye. This response was defined as a reduction of 2 points or more in the Clinical Activity Score (scores range from 0 to 7, with a score of ≥3 indicating active thyroid-associated ophthalmopathy) and a reduction of 2 mm or more in proptosis at week 24. Secondary end points, measured as continuous variables, included proptosis, the Clinical Activity Score, and results on the Graves’ ophthalmopathy-specific quality-of-life questionnaire. Adverse events were assessed.

Results: In the intention-to-treat population, 29 of 42 patients who received teprotumumab (69%), as compared with 9 of 45 patients who received placebo (20%), had a response at week 24 (P<0.001). Therapeutic effects were rapid; at week 6, a total of 18 of 42 patients in the teprotumumab group (43%) and 2 of 45 patients in the placebo group (4%) had a response (P<0.001). Differences between the groups increased at subsequent time points. The only drug-related adverse event was hyperglycemia in patients with diabetes; this event was controlled by adjusting medication for diabetes.

Conclusions: In patients with active ophthalmopathy, teprotumumab was more effective than placebo in reducing proptosis and the Clinical Activity Score. (Funded by River Vision Development and others; ClinicalTrials.gov number, NCT01868997 .).

薬剤の有効性を評価するために、テプロツムマブを点滴された方と何にも入っていない点滴をされた方で比較しています。両方合わせて合計88人の患者が3週間に1回点滴で計8回治療されました。Clinical activity scoreの2ポイント以上の改善と2mm以上の眼球突出の減少があれば有効であったとされています。

結果は、6週目に、テプロツムマブ群の患者42人中18人（43％）およびプラセボ群の患者45人中2人（4％）に治療効果がありました（P <0.001）。24週の時点では、テプロツムマブを投与された患者42人中29人（69％）が、プラセボを投与された患者45人中9人（20％）と比較して治療効果がありました（P <0.001）。2群間の差異は、時間経過とともに開いています。唯一の薬物関連の有害事象が糖尿病患者の高血糖でしたが、糖尿病の薬を調整することで対応可能でした。

Teprotumumab, an insulin-like growth factor-1 receptor antagonist antibody, in the treatment of active thyroid eye disease: a focus on proptosis

有効率は71.4%と書いてあります

これを読んで、おお！と思った方は多いと思いますが

実はいくつか知っておいていただきたい点があります

まずこれ、活動期のバセドウ病眼症に対して行ったものであるという点

中等度から重症の方に対して有効であったというもの

かなり症状が重い方々にしているという点に注目です

（ひと目でバセドウと分かるような方々です）