Thymectomy in myasthenia gravis: “The real world” experience beyond studies

Myasthenia gravis (MG) is an autoimmune disorder caused by specific, most commonly acetylcholine receptor (AChR), antibodies, expressed at the neuromuscular junction. The thymus is affected in most patients with AChR+ MG; approximately 70% of patients have thymic follicular hyperplasia, 10% have thymoma and the remainder have either a normal or atrophic thymus [1]. The thymus gland is not only essential for T cell maturation and removal of selfreactive T cells (central tolerance) but is also believed to be the initial site for triggering humoral immunity in MG. Under physiological circumstances, B cells are almost nonexistent in the thymus. However, in nonthymomatous MG, an initial inflammatory reaction characterized by the release of cytokines, particularly type I interferon and chemokines, leads to several associated immune processes including upregulation of thymic expression of AChR by both thymic epithelial cells and myoid cells; neogenesis; recruitment of immune cells to the thymus; and downregulation of regulatory T cells. This is followed by sensitization of AChRs and organization of B and T cells into germinal centers leading to the production of antiAChR antibodies, thus turning the thymus into a tertiary lymphoid organ [2]. Whilst thymectomy is a standard indication for thymomatous MG, its role in nonthymomatous generalized MG was established in the MGTX trial and its 2year extension which showed the superiority of thymectomy plus prednisone compared to prednisone alone [3, 4]. Although corticosteroid treatment reduces the number and size of germinal centers [5], the superiority of thymectomy + prednisone over prednisone alone in this trial implies that, in addition to germinal centers, thymectomy eliminates molecules and cells that may play a role in disease causation. The results from the MGTX trial provided the basis for the creation of the international consensus guidance statements for early thymectomy in nonthymomatous generalized MG, in subjects aged 18– 50 years. The adoption of these guidance statements will probably improve clinical outcomes and not only minimize the requirement for immunotherapy but also the need for hospitalization for exacerbation of the disease [6]. Despite the positive results in the MGTX trial, several questions regarding the significance of additional factors remained, which preclude study [3, 4] of welldefined inclusion criteria needed in randomized clinical trials. In the retrospective singlecenter study published in this journal, Rath et al. [7] have attempted to address these concerns whilst transferring the issues to utility in a daily clinical setting. They investigated the rate of shortterm and sustained clinical remission after thymectomy in 94 AChR+ MG patients (68% nonthymomatous). In addition, they examined the value of predictors of clinical remission together with changes in serum AChR antibody levels before and after thymectomy. They found that 28% of patients never went into clinical remission; 72% achieved initial remission lasting for at least 12 months, compared to 38%– 72% success reported in previous reports. In contrast to a significantly reduced sustained remission rate seen in the MGTX extension trial, half of the patients with initial remission (32% of the whole cohort) eventually relapsed in the longterm followup of a median of 7 years and up to 28 years. No predictors of both shortterm and sustained clinical remission were detected. In 24 patients who had not received immunosuppressive therapy before thymectomy, a high reduction rate of the AChR antibody titer in percent per day after surgery was associated with a higher chance of achieving initial remission. Even though the report by Rath et al. [7] is from a small, singlecenter and retrospective study, it provides some useful practical information required for counseling and the informed consent process for thymectomy in MG. The following takeaway points could be gathered from this study.