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抗CD20疗法的牙科不良反应

Dental Adverse Effects of Anti-CD20 Therapies.

作者信息

Bartak Hélène, Fareh Tasnim, Ben Othman Nouha, Viard Delphine, Cohen Mikael, Rocher Fanny, Ewig Elliot, Drici Milou-Daniel, Lebrun-Frenay Christine

机构信息

Department of Pharmacology and Pharmacovigilance Center of Nice, University Hospital of Nice, Nice, France.

Neurology MS Clinic, UMR2CA-URRIS, University Hospital of Nice, Nice, France.

出版信息

Neurol Ther. 2024 Jun;13(3):917-930. doi: 10.1007/s40120-024-00616-7. Epub 2024 Apr 26.

Abstract

INTRODUCTION

Over the past few years, anti-CD20 therapies like rituximab, ocrelizumab or ofatumumab have seen an increase in interest in the treatment of neurological autoimmune disorders such as multiple sclerosis (MS), neuromyelitis optica spectrum disorders (NMOSD), or resistant forms of generalized myasthenia gravis (MG). They are generally well-tolerated, but recent reports have highlighted severe dental disorders in patients undergoing anti-CD20 therapies. The aim was to describe a series of cases and to compare with the available scientific literature.

METHODS

We reviewed 6 patient cases with dental disorders during anti-CD20 therapy that were reported to the pharmacovigilance center. A disproportionality analysis was also conducted on Vigibase® for each anti-CD20 and each adverse effect described in the cases.

RESULTS

Six cases of dental and gingival conditions in relatively young patients were reported (median age: 40.5 years old [min: 34; max: 79]). Oral conditions were developed in four patients with MS treated with ocrelizumab and in two patients receiving rituximab (one patient with MG and one with NMOSD). The onset of oral conditions ranged from 10 days to 2 years after treatment initiation. Notably, all patients treated with ocrelizumab experienced gingival recession. Various dental pathologies were observed, including tooth loss, dental pain, caries, brittle teeth, dental fractures, dental abscesses, and periodontitis. Analysis of Vigibase® revealed 284 worldwide cases of dental and gingival conditions under ocrelizumab, 386 cases under rituximab, and 80 under ofatumumab. Significant associations were found between these therapies and dental pathologies, particularly tooth abscesses and infections.

CONCLUSION

To our knowledge, this is the first case series reporting dental conditions developed in patients long-term treated with anti-CD20 treatments. This issue, literature data, and Vigilyze® analysis might be considered a safety signal that necessitates being confirmed with more robust data, such as a retrospective study with a control group. Meanwhile, proactive measures are essential like frequent dental checkups and dental hygienic measures to prevent oral health problems associated with anti-CD20 therapies.

摘要

引言

在过去几年中,利妥昔单抗、奥瑞珠单抗或奥法木单抗等抗CD20疗法在治疗诸如多发性硬化症(MS)、视神经脊髓炎谱系障碍(NMOSD)或难治性全身型重症肌无力(MG)等神经自身免疫性疾病方面受到越来越多的关注。它们通常耐受性良好,但最近的报告强调了接受抗CD20治疗的患者出现严重的牙齿疾病。目的是描述一系列病例并与现有科学文献进行比较。

方法

我们回顾了向药物警戒中心报告的6例在抗CD20治疗期间出现牙齿疾病的患者病例。还针对每个抗CD20以及病例中描述的每种不良反应在Vigibase®上进行了不成比例分析。

结果

报告了6例相对年轻患者(中位年龄:40.5岁[最小:34岁;最大:79岁])的牙齿和牙龈疾病。4例接受奥瑞珠单抗治疗的MS患者以及2例接受利妥昔单抗治疗的患者(1例MG患者和1例NMOSD患者)出现了口腔疾病。口腔疾病的发病时间在开始治疗后的10天至2年之间。值得注意的是,所有接受奥瑞珠单抗治疗的患者都出现了牙龈退缩。观察到了各种牙齿病变,包括牙齿脱落、牙痛、龋齿、牙齿脆弱、牙齿骨折、牙脓肿和牙周炎。对Vigibase®的分析显示,全球范围内奥瑞珠单抗治疗下有284例牙齿和牙龈疾病病例,利妥昔单抗治疗下有386例,奥法木单抗治疗下有80例。发现这些疗法与牙齿病变之间存在显著关联,尤其是牙脓肿和感染。

结论

据我们所知,这是首个报告长期接受抗CD20治疗的患者出现牙齿疾病的病例系列。这个问题、文献数据以及Vigilyze®分析可能被视为一个安全信号,需要用更有力的数据(如设立对照组的回顾性研究)来证实。同时,积极的措施至关重要,如频繁的牙齿检查和牙齿卫生措施,以预防与抗CD20治疗相关的口腔健康问题。

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