利妥昔单抗治疗寻常型天疱疮的疗效显著优于霉酚酸酯
2021-05-24   阅读:716   来源:新英格兰医学杂志

美国宾夕法尼亚大学Victoria P. Werth团队比较了利妥昔单抗与霉酚酸酯治疗寻常型天疱疮的疗效。2021年5月19日,《新英格兰医学杂志》发表了该成果。

利妥昔单抗和霉酚酸酯可用于治疗寻常型天疱疮,但在临床试验中尚未进行充分比较。

在一项随机对照试验中,研究组招募中度至重度寻常型天疱疮患者,将其按1:1随机分配,除按相同的减量方案口服糖皮质激素外,还分别接受静脉注射利妥昔单抗或口服霉酚酸酯。主要终点为第52周时持续完全缓解,定义为没有新的活动性病变的病变愈合,即天疱疮疾病面积指数(PDAI)活动评分为0(0-250分,评分越高疾病越严重),至少16周不使用糖皮质激素。次要终点为糖皮质激素累积剂量、疾病发作次数、皮肤病生活质量指数(DLQI)评分较基线变化(0-30分,分数越高损伤越严重)。

在接受随机分组的135名患者中,67名接受利妥昔单抗治疗,68名接受霉酚酸酯治疗。主要终点在改良意向治疗人群中进行评估:其中利妥昔单抗组62例,霉酚酸酯组63例。利妥昔单抗组和霉酚酸酯组在基线检查时的PDAI活动中位数分别为22.7和18.3。在第52周,利妥昔单抗组中有25例(40%)患者出现持续完全缓解,显著高于霉酚酸酯组的6例(10%)。

在52周的治疗期间,利妥昔单抗组的平均累积糖皮质激素剂量为3545 mg,显著低于霉酚酸酯组的5140 mg。利妥昔单抗组中有6次疾病发作,显著少于霉酚酸酯组的44次。利妥昔单抗组的DLQI评分平均降低了8.87分,降幅显著大于霉酚酸酯组(降低6.00分)。利妥昔单抗组67例患者中有15例(22%)发生严重不良事件,显著高于霉酚酸酯组,即68例患者中有10例(15%)。

研究结果表明,利妥昔单抗治疗寻常型天疱疮在52周时持续完全缓解方面优于霉酚酸酯。利妥昔单抗与霉酚酸酯相比可显著减少糖皮质激素的使用,但严重不良事件率较高。

附:英文原文

Title: Rituximab versus Mycophenolate Mofetil in Patients with Pemphigus Vulgaris | NEJM

Author: Victoria P. Werth, M.D.,, Pascal Joly, M.D.,, Daniel Mimouni, M.D.,, Emanual Maverakis, M.D.,, Frédéric Caux, M.D.,, Patricia Lehane, Ph.D.,, Liudmila Gearhart, M.D.,, Audrey Kapre, M.S.,, Pooneh Pordeli, Ph.D.,, and Diana M. Chen, M.D.

Issue&Volume: 2021-05-19

Abstract:

Background

Rituximab and mycophenolate mofetil are used to treat pemphigus vulgaris, but they have not been adequately compared in clinical trials.

Methods

In a randomized, controlled trial, we assigned patients with moderate-to-severe pemphigus vulgaris in a 1:1 ratio to receive intravenous rituximab (1000 mg on days 1, 15, 168, and 182) or oral mycophenolate mofetil (2 g per day), in addition to an oral glucocorticoid administered on the same tapering schedule in the two groups. The primary end point was sustained complete remission at week 52, defined as the healing of lesions with no new active lesions, as reflected by a Pemphigus Disease Area Index (PDAI) activity score of 0 (on a scale of 0 to 250, with higher scores indicating greater disease severity), for at least 16 weeks without the use of glucocorticoids. Secondary end points were the cumulative dose of glucocorticoids, the number of disease flares, and the change from baseline in the score on the Dermatology Life Quality Index (DLQI; scores range from 0 to 30, with higher scores indicating greater impairment).

Results

Of the 135 patients who underwent randomization, 67 were assigned to receive rituximab and 68 to receive mycophenolate mofetil. The primary outcome was assessed in the modified intention-to-treat population: 62 patients in the rituximab group and 63 in the mycophenolate mofetil group. The median PDAI activity scores at baseline were 22.7 in the rituximab group and 18.3 in the mycophenolate mofetil group. At week 52, sustained complete remission was observed in 25 patients (40%) in the rituximab group and in 6 (10%) in the mycophenolate mofetil group (difference, 31 percentage points; 95% confidence interval [CI], 15 to 45; P<0.001). The mean cumulative glucocorticoid dose during the 52-week treatment period was 3545 mg in the rituximab group and 5140 mg in the mycophenolate mofetil group (difference, 1595 mg; 95% CI, 2838 to 353; P<0.001). There were 6 disease flares in the rituximab group and 44 in the mycophenolate mofetil group (adjusted rate ratio, 0.12; 95% CI, 0.05 to 0.29; P<0.001). The mean change in DLQI score was 8.87 points and 6.00 points, respectively (difference, 2.87 points; 95% CI, 4.58 to 1.17; P=0.001). Serious adverse events occurred in 15 of 67 patients (22%) in the rituximab group and in 10 of 68 (15%) in the mycophenolate mofetil group.

Conclusions

Rituximab was superior to mycophenolate mofetil in producing sustained complete remission at 52 weeks in patients with pemphigus vulgaris. Rituximab resulted in a greater reduction in glucocorticoid use than mycophenolate mofetil, but more patients in the rituximab group had serious adverse events. Further trials are needed to determine the comparative efficacy and safety of rituximab and mycophenolate mofetil beyond 52 weeks of treatment.

DOI: 10.1056/NEJMoa2028564

 

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