Joly Pascal, Mouquet Hugo, Roujeau Jean-Claude, D'Incan Michel, Gilbert Danièle, Jacquot Serge, Gougeon Marie-Lise, Bedane Christophe, Muller Ralf, Dreno Brigitte, Doutre Marie-Sylvie, Delaporte Emmanuel, Pauwels Christine, Franck Nathalie, Caux Frédéric, Picard Catherine, Tancrede-Bohin Emmanuelle, Bernard Philippe, Tron François, Hertl Michael, Musette Philippe
Rouen University Hospital, Rouen, France.
N Engl J Med. 2007 Aug 9;357(6):545-52. doi: 10.1056/NEJMoa067752.
The combination of multiple cycles of rituximab and intravenous immune globulins has been reported to be effective in patients with severe pemphigus. The aim of this study was to assess the efficacy of a single cycle of rituximab in severe types of pemphigus.
We studied 21 patients with pemphigus whose disease had not responded to an 8-week course of 1.5 mg of prednisone per kilogram of body weight per day (corticosteroid-refractory disease), who had had at least two relapses despite doses of prednisone higher than 20 mg per day (corticosteroid-dependent disease), or who had severe contraindications to corticosteroids. The patients were treated with four weekly infusions of 375 mg of rituximab per square meter of body-surface area. The primary end point was complete remission 3 months after the end of rituximab treatment; complete remission was defined as epithelialization of all skin and mucosal lesions.
Eighteen of 21 patients (86%; 95% confidence interval, 64 to 97%) had a complete remission at 3 months. The disease relapsed in nine patients after a mean of 18.9+/-7.9 months. After a median follow-up of 34 months, 18 patients (86%) were free of disease, including 8 who were not receiving corticosteroids; the mean prednisone dose decreased from 94.0+/-10.2 to 12.0+/-7.5 mg per day (P=0.04) in patients with corticosteroid-refractory disease and from 29.1+/-12.4 to 10.9+/-16.5 mg per day (P=0.007) in patients with corticosteroid-dependent disease. Pyelonephritis developed in one patient 12 months after rituximab treatment, and one patient died of septicemia 18 months after rituximab treatment. These patients had a profound decrease in the number of circulating B lymphocytes but normal serum levels of IgG.
A single cycle of rituximab is an effective treatment for pemphigus. Because of its potentially severe side effects, its use should be limited to the most severe types of the disease. (ClinicalTrials.gov number, NCT00213512 [ClinicalTrials.gov].).
据报道，多次使用利妥昔单抗和静脉注射免疫球蛋白联合治疗对重症天疱疮患者有效。本研究旨在评估单次使用利妥昔单抗治疗重症天疱疮的疗效。
我们研究了21例天疱疮患者，这些患者对每日每千克体重1.5毫克泼尼松为期8周的疗程（皮质类固醇难治性疾病）无反应，尽管泼尼松剂量高于每日20毫克仍至少复发两次（皮质类固醇依赖性疾病），或对皮质类固醇有严重禁忌证。患者接受每周一次共四次静脉输注，剂量为每平方米体表面积375毫克利妥昔单抗。主要终点是利妥昔单抗治疗结束3个月后完全缓解；完全缓解定义为所有皮肤和黏膜病变上皮化。
21例患者中有18例（86%；95%置信区间为64%至97%）在3个月时达到完全缓解。9例患者在平均18.9±7.9个月后疾病复发。中位随访34个月后，18例患者（86%）疾病缓解，其中8例未接受皮质类固醇治疗；皮质类固醇难治性疾病患者的泼尼松平均剂量从每日94.0±10.2毫克降至12.0±7.5毫克（P = 0.04），皮质类固醇依赖性疾病患者的泼尼松平均剂量从每日29.1±12.4毫克降至10.9±16.5毫克（P = 0.007）。1例患者在利妥昔单抗治疗12个月后发生肾盂肾炎，1例患者在利妥昔单抗治疗18个月后死于败血症。这些患者循环B淋巴细胞数量大幅减少，但血清IgG水平正常。
单次使用利妥昔单抗是治疗天疱疮的有效方法。由于其潜在的严重副作用，其使用应限于最严重类型的疾病。（临床试验注册号，NCT00213512 [ClinicalTrials.gov]。）
