Trial of Tocilizumab in Giant-Cell Arteritis @ NEJM

【I will translate NEJM articles from original to Japanese in this series】

巨細胞性動脈炎におけるトシリズマブの試験

BACKGROUND
Giant-cell arteritis commonly relapses when glucocorticoids are tapered, and the prolonged use of glucocorticoids is associated with side effects. The effect of the interleukin-6 receptor alpha inhibitor tocilizumab on the rates of relapse during glucocorticoid tapering was studied in patients with giant-cell arteritis.

背　景

巨細胞性動脈炎は一般に糖質コルチコイドを漸減すると再燃し，糖質コルチコイドの長期使用は副作用を伴う．巨細胞性動脈炎患者において，インターロイキン-6 受容体α阻害薬トシリズマブが糖質コルチコイド漸減中の再燃率に及ぼす影響を検討した．

METHODS
In this 1-year trial, we randomly assigned 251 patients, in a 2:1:1:1 ratio, to receive subcutaneous tocilizumab (at a dose of 162 mg) weekly or every other week, combined with a 26-week prednisone taper, or placebo combined with a prednisone taper over a period of either 26 weeks or 52 weeks. The primary outcome was the rate of sustained glucocorticoid-free remission at week 52 in each tocilizumab group as compared with the rate in the placebo group that underwent the 26-week prednisone taper. The key secondary outcome was the rate of remission in each tocilizumab group as compared with the placebo group that underwent the 52-week prednisone taper. Dosing of prednisone and safety were also assessed.

方　法

1 年間の試験で，患者 251 例を，26 週かけてプレドニゾン（prednisone）を漸減し，トシリズマブ（1 回 162 mg）を毎週皮下投与する群，隔週皮下投与する群，プラセボを投与する群，52 週かけてプレドニゾンを漸減しプラセボを投与する群に，2：1：1：1 の割合で無作為に割り付けた．主要評価項目は，52 週の時点での，26 週かけてプレドニゾンを漸減したプラセボ群と比較した，各トシリズマブ群における糖質コルチコイドなしで寛解を維持していた患者の割合とした．主な副次的評価項目は，52 週かけてプレドニゾンを漸減したプラセボ群と比較した，各トシリズマブ群における寛解を維持していた患者の割合とした．プレドニゾンの投与量と安全性も評価した

RESULTS
Sustained remission at week 52 occurred in 56% of the patients treated with tocilizumab weekly and in 53% of those treated with tocilizumab every other week, as compared with 14% of those in the placebo group that underwent the 26-week prednisone taper and 18% of those in the placebo group that underwent the 52-week prednisone taper (P<0.001 for the comparisons of either active treatment with placebo). The cumulative median prednisone dose over the 52-week period was 1862 mg in each tocilizumab group, as compared with 3296 mg in the placebo group that underwent the 26-week taper (P<0.001 for both comparisons) and 3818 mg in the placebo group that underwent the 52-week taper (P<0.001 for both comparisons). Serious adverse events occurred in 15% of the patients in the group that received tocilizumab weekly, 14% of those in the group that received tocilizumab every other week, 22% of those in the placebo group that underwent the 26-week taper, and 25% of those in the placebo group that underwent the 52-week taper. Anterior ischemic optic neuropathy developed in one patient in the group that received tocilizumab every other week.

結　果

52 週の時点で寛解を維持していた割合は，トシリズマブ毎週投与群 56%，トシリズマブ隔週投与群 53%に対し，26 週かけてプレドニゾンを漸減したプラセボ群では 14%，52 週かけてプレドニゾンを漸減したプラセボ群では 18%であった（いずれの実薬投与もプラセボとの比較で P＜0.001）．52 週間のプレドニゾン累積投与量中央値は各実薬群で 1,862 mg であったのに対し，26 週かけてプレドニゾンを漸減したプラセボ群では 3,296 mg であり（いずれの比較も P＜0.001），52 週かけてプレドニゾンを漸減したプラセボ群では 3,818 mg であった（いずれの比較も P＜0.001）．重篤な有害事象はトシリズマブ毎週投与群で 15%，トシリズマブ隔週投与群で 14%，26 週かけてプレドニゾンを漸減したプラセボ群で 22%，52 週かけてプレドニゾンを漸減したプラセボ群で 25%に発現した．トシリズマブ隔週投与群の 1 例が前部虚血性視神経症を発症した．

CONCLUSIONS
Tocilizumab, received weekly or every other week, combined with a 26-week prednisone taper was superior to either 26-week or 52-week prednisone tapering plus placebo with regard to sustained glucocorticoid-free remission in patients with giant-cell arteritis. Longer follow-up is necessary to determine the durability of remission and safety of tocilizumab. (Funded by F. Hoffmann–La Roche; ClinicalTrials.gov number, NCT01791153.)

結　論

巨細胞性動脈炎患者において，26 週間のプレドニゾン漸減に毎週または隔週のトシリズマブ投与を併用することで，26 週間または 52 週間のプレドニゾン漸減にプラセボを投与した場合と比較して，糖質コルチコイドなしでの寛解維持が優れていた．トシリズマブによる寛解維持の可能性と安全性を明らかにするには，さらに長期の追跡が必要である．（F. Hoffmann–La Roche 社から研究助成を受けた．ClinicalTrials.gov 登録番号 NCT01791153）

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