By Michael Rubin, MD
Professor of Clinical Neurology, Weill Cornell Medical College
SYNOPSIS: In this retrospective study of the long-term benefit of thymectomy (median follow-up = 89.5 months), only half of those who had an initial positive response showed a sustained response. There was no clinical factor that predicted a long-term response.
SOURCE: Rath J, Taborsky M, Moser B, et al. Short-term and sustained clinical response following thymectomy in patients with myasthenia gravis. Eur J Neurol 2022;29:2453-2462.
Based on the Thymectomy Trial in Non-Thymomatous Myasthenia Gravis (MG) Study, compared to alternate-day prednisone alone, extended transternal thymectomy plus alternate-day prednisone resulted in lower time-weighted average Quantitative Myasthenia Gravis Score over a three-year period, fewer patients requiring immunosuppression with azathioprine, fewer patients hospitalized for exacerbations, fewer treatment-associated symptoms related to immunosuppressive medications, and lower distress levels related to symptoms.1 Do these benefits last?
A retrospective study of MG patients, treated at the department of neurology of the Medical University of Vienna, Austria, between 1991 and 2019, was undertaken to determine the occurrence of a favorable outcome following thymectomy and to determine the likelihood of deterioration after an initial response. Inclusion criteria encompassed patients who underwent thymectomy at the department of thoracic surgery of the Medical University of Vienna and had sufficient clinical data before thymectomy and follow-up data for at least 18 months following thymectomy, to allow for a one-year clinical response assessment. The primary outcome parameter was the occurrence of a clinical response lasting for at least 12 months, defined as the Myasthenia Gravis Foundation of America postintervention status (MGFA-PIS) categories of complete stable remission, pharmacological remission, or minimal manifestation. Secondary outcome parameters included the rate of clinical response, the MGFA-PIS at last follow-up, the worst MGFA after thymectomy, and immunosuppressive treatment modification during the course of the disease after thymectomy. Statistical analysis comprised the chi-squared test, Student t test, or Mann-Whitney U test as applicable, with P ≤ 0.05 considered statistically significant.
Among 94 patients of median age 33 years, 32% with thymoma-associated MG and 68% without thymoma-associated MG, 72% (68/94) achieved an initial clinical response. During long-term follow-up (median 89.5 months, up to 128 months), only half of those with an initial response sustained their response without relapse. No clinical factor, including disease subtype (thymoma vs. non-thymoma), age at onset, type of surgery, immunosuppressive treatment pre-thymectomy, delay to thymectomy, or histologic thymic hyperplasia, predicted initial response nor whether it would be sustained.
Among patients without immunosuppressive treatment pre-thymectomy (n = 24), a high acetylcholine receptor antibody (AChR-Ab) reduction rate after thymectomy was associated with a higher likelihood of achieving an initial response (P = 0.03). Sustained long-term clinical response in MG patients following thymectomy is significantly lower than the initial response rates would suggest, but decline of AChR-Abs after surgery appears to be a promising prognostic marker.
COMMENTARY
Thymectomies are not all created equal. Among 1,725 thymectomies performed for non-thymomatous MG between 2009-2019 identified in the Society of Thoracic Surgeons General Thoracic Surgery Database, surgical techniques comprised transthoracic (TT), trans-cervical (TC), video-assisted thoracoscopic surgery (VATS), and robotic VATS (RVATS). Compared to TT, TC, VATS, and RVATS had lower odds of perioperative complications, while TC thymectomies had lower odds of complications than VATS or RVATS, socalled minimally invasive procedures. Among thymoma cases (n = 311), TT and VATS/RVATS had similar complication rates. Whether reduced perioperative risk associates with improved MG awaits long-term outcome data.2
REFERENCES
- Wolfe GI, Kaminski HJ, Aban IB, et al. Randomized trial of thymectomy in myasthenia gravis. N Engl J Med 2016;375:511-522.
- Raja SM, Guptill JT, McConnell A, et al. Perioperative outcomes of thymectomy in myasthenia gravis: A thoracic surgery database analysis. Ann Thorac Surg 2022;113:904-910.
