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For Your Patients-Myasthenia Gravis
New Data on Which MG Patients May Benefit Most from Thymectomy



ARTICLE IN BRIEF

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DR. NORMAN LATOV said the new study offers confirmation of what has been suspected — that MG patients “without thymoma are more likely to experience remission followed thymectomy with a reduction in anti-AChR antibody than those with thymoma.”

Researchers offered new analysis of the factors that may predict remissionin in patients with acetylcholine receptor antibody-positive myasthenia gravis who have had a thymectomy.

Patients with myasthenia gravis (MG) who had non-thymomatous pathology and milder disease at the time of thymectomy were more likely to experience remission, according to a review of cases of MG patients who underwent the surgery.

Thymectomy is a standard treatment option for MG, but it hasn't been completely clear which types of MG patients are likely to benefit most from the surgery. The new study from South Korea, which involved a review of medical records of 179 acetylcholine receptor antibody-positive MG patients, does not answer every question, but it does provide some added information for doctors and patients considering whether removing the thymus might lessen disease symptoms or even bring about a complete remission. The new results were published in the July 18 online edition of Muscle and Nerve.

The use of thymectomy to treat MG — an autoimmune disorder of the neuromuscular junction that causes varying weakness of ocular, bulbar, limb, and respiratory muscles — began in the 1930s, but there had long been a debate over just how beneficial the surgery was, if at all, the study authors noted. A firm answer came in 2016 with the publication of a randomized, controlled trial in the New England Journal of Medicine that compared MG patients who received thymectomy plus corticosteroids to patients who were given corticosteroids alone. The study found at the end of three years that those who had surgery had fewer symptoms and didn't have to take as many steroids.

“Some studies have suggested that thymic pathology (thymoma or no thymoma), age at onset, and perioperative disease severity are important prognostic factors, whereas others have not,” the report said. It suggested that the conflicting results may be related to the fact that “previous studies did not consider the status of acetylcholine receptor antibody (AChR-Ab), known to be associated with thymic pathology.”

STUDY DETAILS

To further explore the issue, the researchers from Asan Medical Center and University of Ulsan College of Medicine in Seoul reviewed the medical records of 179 MG patients who underwent thymectomy between February 1994 and March 2016 at the center. Patients without antibody status information in their files were excluded from the analysis as was a patient with thymolipoma.

The average age at disease onset was 41.7 and the average age at thymectomy was 42.5. The average time of disease duration before surgery was 1.1 years. Researchers on average had close to eight years of follow-up information to consider.

Of the 179 patients, 52.5 percent experienced remission (complete stable remission, CSR, or pharmacologic remission) and 10.6 percent achieved CSR. Patients with nonthymomatous pathology were 2.17 times more likely to experience remission than patients with thymomatous pathology. Those with milder disease at the time of surgery were also more likely to have a favorable clinical outcome.

When it came to antibody levels, the researchers found that the level of preoperative AChR-Ab did not affect the remission rate after thymectomy.

They found, however, that “a noticeable difference in the AChR-Ab titer before and after thymectomy was observed in nonthymomatous MG, but not in thymomatous MG. This difference may be due to the different roles of the thymus in the pathogenesis of MG with and without thymoma.”

In a joint email to Neurology Today, two of the coauthors said that the study should not be interpreted as meaning thymomatous MG patients should be discouraged from thymectomy.

“Thymectomy is still recommended to thymomatous patients due to oncologic reasons. Thymectomy should be recommended to nonthymomatous MG patients as well as thymomatous MG patients,” wrote Hyunjin Kim, MD, a clinical fellow in neuromuscular disease and Kwang-Kuk Kim, MD, PhD, professor of neurology at Asan Medical Center and Ulsan College of Medicine.

The study was limited by the fact that it was retrospective, not a randomized, controlled trial. It also involved a mostly homogeneous population at a single medical center in South Korea, so the results may not necessarily be applicable to other groups or settings. The post-surgery remission status was determined based on a chart review of the patients' symptoms and changes in MG medication, according to Myasthenia Gravis Foundation of America post-intervention status. The patients weren't all on the same medication regimen after surgery.

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DR. GIL WOLFE noted that the pattern of improved outcomes after thymectomy in patients with milder disease severity is keeping with findings from other studies that focused on medical therapy. “We hope this type of data gleaned from MGTX (trial) will add to this conversation.”

EXPERT COMMENTARY

Norman Latov, MD, PhD, professor of neurology and neuroscience at Weill Cornell Medicine, said the new study offers confirmation of what has been suspected — that MG patients “without thymoma are more likely to experience remission followed thymectomy with a reduction in anti-AChR antibody than those with thymoma.”

He said the new information will help inform treatment decisions with patients regarding “the likelihood of remission or the need for immunosuppressive therapy depending on whether thymoma is present.”

MG is a variable disease that fluctuates in intensity and can involve different combinations of voluntary muscles. Dr. Latov said doctors can face challenges in diagnosing and treating MG, particularly those “patients with atypical presentations or normal anti-AChR antibody titers” or when their disease does not respond well to therapy.

He said he would like to see future research on thymectomy address the question of whether “patients with thymic hyperplasia respond as well as those with nonthymomatous pathology.”

Gil Wolfe, MD, FAAN, Irvin and Rosemary Smith professor and chairman of the department of neurology at the University at Buffalo Jacobs School of Medicine and Biomedical Sciences, who led the seminal 2016 study on thymectomy for MG, said that the randomized trial helped settle much of the debate around using the treatment approach in non-thymomatous generalized disease.

“Until 2016 there remained some doubt about what you were getting out of thymectomy,” Dr. Wolfe said. While the so-called MGTX trial of 126 patients provided three years of results, an extension study on about half of the original patients will offer an even longer look.

“We analyzed data through month 60 to look at how persistent, how durable, the favorable response to thymectomy is,” he said. “It is quite well established that most myasthenia gravis patients after a prolonged period of focused management do quite well. We wanted to see over how long a period of time you might see benefits from thymectomy that exceeded medical therapy alone.”

Dr. Wolfe said that members of the trial's investigative team are also looking into the question of how thymectomy impacts the ability to come completely off corticosteroids and still maintain a clinical status of minimal manifestations or better. Recent studies that have focused on longer-term outcomes in MG are trying to assess how to manage the disease with either low doses of corticosteroids or other immunosuppressants, and what might be the best strategy and schedule in trying to remove them completely for those patients who are doing well, Dr. Wolfe said.

Dr. Wolfe noted that the pattern of improved outcomes after thymectomy in patients with milder disease severity is keeping with findings from other studies that focused on medical therapy. “We hope this type of data gleaned from MGTX (trial) will add to this conversation,” he said.

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•. Kim H, Lim YM, Lee EJ, et al. Factors predicting remission in thymectomized patients with acetylcholine receptor antibody-positive myasthenia gravis https://onlinelibrary.wiley.com/doi/abs/10.1002/mus.26300. Muscle Nerve 2018; Epub 2018 Jul 18.
    •. Wolfe GI, Kaminski HJ, Aban IB, et al; for the MGTX Study Group. Randomized trial of thymectomy in myasthenia gravis https://www.nejm.org/doi/full/10.1056/nejmoa1602489. N Engl J Med 2016; 375:511–522.