From the Perelman School of Medicine, University of Pennsylvania, and the Corporal Michael J. Crescenz Veterans Affairs Medical Center, Philadelphia (V.P.W.); the Department of Dermatology, Rouen University Hospital and INSERM 1234, Normandie Université, Rouen (P.J.), and the Department of Dermatology, Groupe Hospitalier Paris Seine-Saint-Denis, Assistance Publique-Hôpitaux de Paris and INSERM Unité Mixte de Recherche 1125, Bobigny (F.C.) - all in France; the Sackler School of Medicine, Tel Aviv University, Tel Aviv, and Rabin Medical Center, Petah Tikva - both in Israel (D.M.); the Department of Dermatology, University of California, Davis, School of Medicine, Sacramento (E.M.), and Genentech, South San Francisco (A.K., D.M.C.) - both in California; Roche Products, Welwyn Garden City, United Kingdom (P.L.); F. Hoffmann-La Roche, Basel, Switzerland (L.G.); and Roche Products, Mississauga, ON, Canada (P.P.).
N Engl J Med. 2021 Jun 17;384(24):2295-2305. doi: 10.1056/NEJMoa2028564. Epub 2021 May 19.
Rituximab and mycophenolate mofetil are used to treat pemphigus vulgaris, but they have not been adequately compared in clinical trials.
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).
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.
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. (Funded by F. Hoffmann-La Roche; PEMPHIX ClinicalTrials.gov number, NCT02383589.).
利妥昔单抗和吗替麦考酚酯用于治疗寻常型天疱疮，但在临床试验中尚未充分比较。
在一项随机对照试验中，我们将中重度寻常型天疱疮患者按照 1:1 的比例随机分配，接受静脉注射利妥昔单抗（第 1、15、168 和 182 天各 1000mg）或口服吗替麦考酚酯（每天 2g），同时两组患者均接受相同的糖皮质激素递减方案治疗。主要终点是第 52 周时持续完全缓解，定义为 Pemphigus Disease Area Index（PDAI）活动评分达到 0（评分范围为 0 至 250，分数越高表示疾病越严重），且至少 16 周未使用糖皮质激素，且无新的活动性病变。次要终点为糖皮质激素累积剂量、疾病复发次数以及皮肤病生活质量指数（DLQI；评分范围为 0 至 30，分数越高表示损害越大）自基线的变化。
135 例接受随机分组的患者中，67 例接受利妥昔单抗治疗，68 例接受吗替麦考酚酯治疗。在改良意向治疗人群中评估主要结局：利妥昔单抗组 62 例，吗替麦考酚酯组 63 例。利妥昔单抗组和吗替麦考酚酯组患者的基线 PDAI 活动评分中位数分别为 22.7 和 18.3。第 52 周时，利妥昔单抗组 25 例（40%）患者持续完全缓解，吗替麦考酚酯组 6 例（10%）患者持续完全缓解（差异为 31 个百分点；95%置信区间为 15 至 45；P<0.001）。利妥昔单抗组患者在 52 周治疗期间累积使用糖皮质激素的平均剂量为 3545mg，吗替麦考酚酯组为 5140mg（差值为-1595mg；95%置信区间为-2838 至-353；P<0.001）。利妥昔单抗组有 6 例疾病复发，吗替麦考酚酯组有 44 例（调整后的发生率比为 0.12；95%置信区间为 0.05 至 0.29；P<0.001）。DLQI 评分的平均变化分别为-8.87 分和-6.00 分（差值为-2.87 分；95%置信区间为-4.58 至-1.17；P=0.001）。利妥昔单抗组 67 例（22%）和吗替麦考酚酯组 68 例（15%）患者发生严重不良事件。
在 52 周时，与吗替麦考酚酯相比，利妥昔单抗治疗寻常型天疱疮患者的持续完全缓解率更高。与吗替麦考酚酯相比，利妥昔单抗可减少糖皮质激素的使用，但利妥昔单抗组更多患者发生严重不良事件。需要进一步的试验来确定利妥昔单抗和吗替麦考酚酯在 52 周治疗后比较的疗效和安全性。（由 F. Hoffmann-La Roche 资助；PEMPHIX ClinicalTrials.gov 编号，NCT02383589。）
