Thymectomy Improves Outcomes in Non-Thymomatous Myasthenia Gravis

By Will Boggs MD

February 06, 2019

NEW YORK (Reuters Health) - Thymectomy plus prednisone improves outcomes in patients with non-thymomatous myasthenia gravis (MG), compared with prednisone alone, according to results from the two-year extension of the MGTX randomized trial.

"Most of us had a hunch that thymectomy was helping this group of MG patients, despite them not having a thymoma to remove," Dr. Gil I. Wolfe from University at Buffalo Jacobs School of Medicine and Biomedical Sciences, Buffalo, New York told Reuters Health. "What was most surprising was the degree that thymectomy reduced hospitalization requirements and how after five years it contributed to such a high proportion of subjects reaching minimal manifestation status for the disease."

The 36-month MGTX randomized controlled study showed that thymectomy in combination with a standardized prednisone protocol was superior to prednisone alone in improving myasthenic weakness and lowering corticosteroid requirements in patients with non-thymomatous myasthenia gravis who were positive for acetylcholine receptor antibodies.

Dr. Wolfe and colleagues now report results of the two-year extension study to assess the durability of the treatment response. Overall, 68 patients entered the extension study, 50 of whom completed the 60-month visit.

As in the main trial, patients in the thymectomy plus prednisone group had significantly greater improvement in Quantitative Myasthenia Gravis scores and significantly lower mean prednisone doses from month 0 to month 60, compared with the prednisone alone group, according to the January 25th Lancet Neurology online report.

The proportion of patients achieving minimal manifestation status at month 60 was significantly higher in the thymectomy plus prednisone group (23/26, 88%) than in the prednisone alone group (14/24, 58%).

From month 0 to month 60, the proportion of patients requiring azathioprine or intravenous immunoglobulin was significantly lower in the thymectomy plus prednisone group than in the prednisone alone group.

Between months 36 and 60, only two patients in each group showed signs of clinical worsening.

"The extension study reinforces the benefit of thymectomy noted in the randomized controlled MGTX, shows continued benefits at five years, and dispels doubts about the procedure's benefits or the longevity of its effects," the researchers conclude.

"I certainly think that thymectomy should be part of the early discussion between the health care provider and the patient," Dr. Wolfe said. "Now I won't argue strongly that if a patient is really doing well on an initial stab at immunotherapy and tolerating it well and really having minimal or perhaps no issues related to myasthenia, that one should do a hard sell to push the patient toward thymectomy. It could be considered, but there are patients who can be managed without it."

"But for those patients who are just not doing as well as one would hope after the initial immunotherapy attempt, I do think it needs to be part of the conversation," he said. "I think the initial trial and the extension study provide a foundation of evidence to support the need for that conversation."

"Based on the cost of some of our immunotherapies for MG and the reduced need for hospitalizations, the one-time ticket price of a thymectomy, even in the U.S. where everything seems to cost more when it comes to health care, can be quite cost-effective," Dr. Wolfe said.

Dr. Sonia Berrih-Aknin from Sorbonne Universite and UPMC Universite Paris 6, who co-authored an editorial related to this report, told Reuters Health by email, "I was surprised by the fact that after five years of thymectomy, the therapeutic effects were even better than after three years, indicating that: 1) the surgery has long-term effect; and 2) an absence of short-term therapeutic effect is not synonymous of no-effect."

"One could think that removing the culprit organ should have short-term and direct effects, but this work clearly shows that the mechanisms are probably complex," she said. "It is possible that autoreactive T cells (and possibly B cells) from the thymus migrate to the periphery and pursue their pathogenicity. Their persistence in the periphery could explain why the effects are long-term."

"The molecular mechanisms that could explain the beneficial effects of thymectomy remain to be known," Dr. Berrih-Aknin said. "That could eventually help to define more precisely the patients who are not susceptible to benefit from surgery."

SOURCE: http://bit.ly/2WHr5us and http://bit.ly/2WE4T4h

Lancet Neurol 2019.

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