Kaneshiro Shoichi, Ebina Kosuke, Hirao Makoto, Tsuboi Hideki, Nishikawa Masataka, Nampei Akihide, Nagayama Yoshio, Takahi Koichiro, Noguchi Takaaki, Owaki Hajime, Hashimoto Jun, Yoshikawa Hideki
a Department of Orthopaedic Surgery , Japan Community Healthcare Organization, Osaka Hospital , Osaka , Japan.
b Department of Orthopaedic Surgery , Osaka University Graduate School of Medicine , Osaka , Japan.
Mod Rheumatol. 2017 Jan;27(1):42-49. doi: 10.1080/14397595.2016.1181315. Epub 2016 May 16.
Tocilizumab (TCZ) shows good retention in patients with rheumatoid arthritis (RA), but no previous reports demonstrated hopeful treatment options against inadequate response to TCZ. Tacrolimus (TAC) has proved to show efficacy against inadequate response to tumor necrosis factor alpha inhibitors, yet its add-on effects on TCZ remain unknown.
Twenty patients with RA (17 women, age 58.6 years, disease duration 12.1 years, prior TCZ duration 2.6 years, 18 intravenous [8 mg/kg/month] and 2 subcutaneous [324 mg/month] TCZ treatments, methotrexate 6.1 mg/week [70.0%]) who showed an inadequate response to TCZ (clinical disease activity index [CDAI] ≥ 5.8, 18 secondary non-responders) were additionally treated with TAC (1.1 mg/day), and enrolled in this 24-week, prospective study.
Seventeen patients (85.0%) continued the treatment for 24 weeks. Statistically significant decreases in outcome measures were as follows: disease activity score based on 28 joints with C-reactive protein (DAS28-CRP) from 3.3 at baseline to 2.1 at week 24 (p < 0.001), CDAI from 17.7 to 7.6 (p < 0.001), and serum matrix metalloproteinase-3 levels from 232.8 to 66.2 ng/ml (p < 0.001). About 15 patients (75%) achieved low disease activity or remission (DAS28-CRP ≤2.7 or CDAI ≤10) at week 24.
Adding low-dose TAC to inadequate responders to TCZ may be a promising complementary treatment option.
托珠单抗(TCZ)在类风湿关节炎(RA)患者中显示出良好的药物留存率,但此前尚无报告表明有针对TCZ反应不足的有效治疗方案。他克莫司(TAC)已被证明对肿瘤坏死因子α抑制剂反应不足具有疗效,但其对TCZ的附加作用尚不清楚。
20例对TCZ反应不足(临床疾病活动指数[CDAI]≥5.8,18例为继发无反应者)的RA患者(17例女性,年龄58.6岁,病程12.1年,既往使用TCZ时间2.6年,18例接受静脉注射[8mg/kg/月]和2例接受皮下注射[324mg/月]TCZ治疗,甲氨蝶呤6.1mg/周[70.0%])额外接受TAC(1.1mg/天)治疗,并纳入这项为期24周的前瞻性研究。
17例患者(85.0%)持续治疗24周。结果指标在统计学上有显著下降,如下所示:基于28个关节和C反应蛋白的疾病活动评分(DAS28-CRP)从基线时的3.3降至第24周时的2.1(p<0.001),CDAI从17.7降至7.6(p<0.001),血清基质金属蛋白酶-3水平从232.8降至66.2ng/ml(p<0.001)。约15例患者(75%)在第24周时达到低疾病活动度或缓解(DAS28-CRP≤2.7或CDAI≤10)。
在对TCZ反应不足的患者中添加低剂量TAC可能是一种有前景的辅助治疗选择。