Study Finds Thymectomy Associated with Improved Outcomes in Late-Onset Myasthenia Gravis

A retrospective study conducted at the University of Pisa reports that thymectomy may be associated with higher rates of disease remission in patients with late-onset myasthenia gravis (LOMG) compared to medical therapy alone. The findings, published in the Journal of Neurology, suggest a potential therapeutic role for thymectomy in this subgroup of patients historically underrepresented in clinical trials.

While thymectomy is a recommended treatment for generalized myasthenia gravis (gMG) in patients aged 18 to 50 with acetylcholine receptor antibodies (anti-AChR Ab), its benefit in patients aged 50 and older remains uncertain. Previous randomized trials, including the MGTX study, included relatively few older patients, limiting the generalizability of their findings to this group.

In the present study, 127 patients with non-thymomatous, anti-AChR-positive LOMG were followed at a single center between 1996 and 2024. Of these, 87 underwent thymectomy and 40 received medical therapy alone. After a median follow-up of 36 months, patients who underwent thymectomy had a higher likelihood of achieving pharmacological or complete stable remission. Specifically, adjusted analyses showed a 3.25-fold increase in the probability of remission (HR=3.25; 95% CI 1.31–8.08) compared to the conservative treatment group.

Both groups experienced reductions in symptom severity and corticosteroid use over time, but these changes were more pronounced in the thymectomy group. Improvements in MG-ADL and MGC scores were greatest during the first year after surgery and continued at a slower rate during subsequent follow-up.

Surgical safety was also evaluated. Among the 87 thymectomy patients, the procedure was associated with a low rate of postoperative complications, and no life-threatening events were reported. There were no significant differences in outcomes based on surgical approach (robotic vs. sternotomy).

Histological analysis of thymic tissue showed that 35.6% of patients had thymic hyperplasia, while 51.7% had thymic atrophy. Although patients with hyperplasia demonstrated larger reductions in symptom scores, the overall rates of disease remission did not significantly differ between histology groups.

The study also included a subgroup analysis of 26 patients with very-late-onset MG (VLOMG), defined as disease onset after age 65. Among them, 12 underwent thymectomy and 14 received medical therapy. In this subgroup, thymectomy was associated with an 8.85-fold increased likelihood of achieving remission (HR=8.85; 95% CI 1.05–74.3), though the small sample size limits definitive conclusions.

Additionally, the study compared outcomes between thymectomized early-onset and late-onset MG patients. While early-onset patients more frequently achieved complete stable remission, late-onset patients reached pharmacological remission sooner. No significant differences were observed in total remission rates between the two groups.

The authors acknowledge several limitations, including the retrospective design and potential selection biases. Patients selected for thymectomy were generally younger and had lower disease severity at onset compared to those in the medical therapy group. However, multivariable analysis indicated that these differences did not account for the observed association between thymectomy and remission.

According to the authors, these results indicate that thymectomy may be considered as a treatment option for selected patients with LOMG, including those over the age of 65. They recommend further prospective, randomized studies to evaluate these findings and inform treatment guidelines.