Center for Neuromuscular Diseases, Unit of Neurology, ASST Spedali Civili and University of Brescia, Brescia, Italy.
Emergency Neurology, IRCCS Mondino Foundation, Pavia, Italy.
Adv Ther. 2019 May;36(5):1177-1189. doi: 10.1007/s12325-019-00926-5. Epub 2019 Mar 16.
Patients with late-onset Pompe disease (LOPD) receiving enzyme replacement therapy (ERT) may develop IgG antibodies against alglucosidase alpha (anti-rhGAA) in the first 3 months of treatment. The exact role of these antibodies in modulating efficacy of ERT in this group of patients is still not fully understood. To assess whether anti rh-GAA antibodies interfere with ERT efficacy, we studied a large Italian cohort of LOPD patients.
We analyzed clinical findings and performed serial measurements of IgG anti rh-GAA antibody titers from 64 LOPD patients treated with ERT. The first examination (T0) was completed on average at 17.56 months after starting ERT, while the follow-up (T1) was collected on average at 38.5 months. Differences in T0-T1 delta of the six-minute walking test (6MWT), MRC sum score (MRC), gait, stairs and chair performance (GSGC) and forced vital capacity (FVC) were considered and then related to the antibody titers.
Almost 22% of the patients never developed antibodies against GAA, while 78.1% had a positive titer (31.2% patients developed a low titer, 43.8% a medium titer and 3.1% a high titer). No statistical significance was found in relating the T0-T1 delta differences and antibody titers, except for MRC sum score values in a subgroup of patients treated < 36 months, in which those with a null antibody titer showed a greater clinical improvement than patients with a positive titer.
Our results confirm that in a large cohort of LOPD patients, anti rh-GAA antibody generation did not significantly affect either clinical outcome or ERT efficacy. However, in the first 36 months of treatment, a possible interference of low-medium antibody titers with the clinical status could be present. Therefore, a careful and regular evaluation of antibody titers, especially in cases with evidence of clinical decline despite ERT, should be performed.
接受酶替代疗法（ERT）的迟发性庞贝病（LOPD）患者在治疗的头 3 个月内可能会产生针对阿尔法葡糖苷酶（抗-rhGAA）的 IgG 抗体。这些抗体在调节该组患者 ERT 疗效中的确切作用尚不完全清楚。为了评估抗 rh-GAA 抗体是否干扰 ERT 疗效，我们研究了一个大型意大利 LOPD 患者队列。
我们分析了 64 名接受 ERT 治疗的 LOPD 患者的临床发现，并对 IgG 抗 rh-GAA 抗体滴度进行了连续测量。第一次检查（T0）在开始 ERT 后平均 17.56 个月完成，而随访（T1）在平均 38.5 个月收集。考虑了 6 分钟步行试验（6MWT）、MRC 总和评分（MRC）、步态、楼梯和椅子表现（GSGC）和用力肺活量（FVC）的 T0-T1 差值的差异，然后将其与抗体滴度相关联。
几乎 22%的患者从未产生过针对 GAA 的抗体，而 78.1%的患者产生了阳性滴度（31.2%的患者产生低滴度，43.8%的患者产生中滴度，3.1%的患者产生高滴度）。除了在治疗<36 个月的患者亚组中 MRC 总和评分值外，未发现 T0-T1 差值差异与抗体滴度相关，在该亚组中，无抗体滴度的患者比有阳性滴度的患者显示出更大的临床改善。
我们的结果证实，在一个大型 LOPD 患者队列中，抗 rh-GAA 抗体的产生并没有显著影响临床结局或 ERT 疗效。然而，在治疗的头 36 个月内，低-中抗体滴度可能会对临床状况产生干扰。因此，应特别在 ERT 治疗后有临床恶化证据的情况下，定期仔细评估抗体滴度。
