International Experts Update, Expand MG Management Guidelines

A panel of 16 international experts has updated and expanded the recommendations for best management of myasthenia gravis (MG), based on the latest evidence in literature.

“Some wealthy countries have established their own guidelines, but most of the world cannot do that,” Gil I. Wolfe, MD, chair of the department of neurology at University at Buffalo’s Jacobs School of Medicine and Biomedical Sciences, and who co-led the panel of experts, said in a university press release.

“The international panel, using the UCLA/RAND Appropriateness Methodology to achieve a formal consensus, hopes to fill that void, providing a treatment/management framework for health care providers, industry, insurers and the patient community,” said Wolfe, also the president of UBMD Neurology.

The guidelines, “International consensus guidance for management of myasthenia gravis: 2020 update,” were published in the journal Neurology.

An initial panel of 15 international MG experts was created by the Myasthenia Gravis Foundation of America in 2013 to address the lack of a uniform, globally accepted standard of care for MG —rarity and variability of which pose a challenge to a “one-size-fits-all” approach.

The panel, already co-chaired by Wolfe at that time, included physicians from the U.S., Canada, the U.K., Germany, Spain, Italy, the Netherlands, Norway, and Japan. Its goal was to develop treatment recommendations for MG, which were published in 2016.

“Results of several new trials of MG treatment have been published since that guidance statement was published, and in 2019, the panel reviewed the previous recommendations for currency and identified new topics that may affect practice,” the researchers wrote.

By that time, an expert from Chile had been added to the panel to represent South America. That had brought the panel’s total to 16 members.

Based on the latest literature evidence, the panel selected a set of recommendations to update. Their specific topics included thymectomy, or the surgical removal of the thymus gland, the use  of several therapies — specifically, Soliris (eculizumab), methotrexate, and rituximab — early immunosuppression in ocular MG, and the management of MG associated with immune checkpoint inhibitor therapies. Of note, rituximab is a cancer therapy used off-label for MG treatment.

To reach a consensus, the experts revised the appropriateness of the selected recommendations using the UCLA/RAND Appropriateness Method. This involved up to three rounds of anonymous e-mail votes.

The final recommendations achieving panel consensus as being appropriate are briefly described below.

Thymectomy

One of the main revisions to the previous recommendations encourages thymectomy in the largest subpopulation of MG patients: those with autoantibodies against acetylcholine receptors (AChRs).

Among this subpopulation, thymectomy should be considered in individuals with generalized MG (gMG), ages 18–50, even if the disease is not associated with tumors of the thymus. It also is highly recommended for gMG patients who fail to respond to or can not tolerate initial immunotherapy.

This type of intervention continues to be unrecommended for patients with other types of autoantibodies.

Soliris

Alexion Pharmaceuticals’ Soliris, an approved immunotherapy for gMG patients with anti-AChR autoantibodies, should be considered in this subpopulation when severe refractory disease is present. It also is recommended after other immunotherapies fail to meet treatment goals.

Recommendations regarding vaccination to protect against meningococcal infections should be followed prior to Soliris treatment, the experts noted, as the therapy is associated with a higher risk of such serious infections.

Further research is needed to determine the optimal duration of Soliris treatment and its effectiveness in other MG subpopulations, as well as in other stages of the disease, the panel said.

Methotrexate

While evidence from appropriately designed studies is missing, oral methotrexate — a non-steroid immunosuppressive therapy — may be considered in gMG patients who are not responding to or tolerating similar treatments whose use is better supported by trial data.

Rituximab

The panel supported the previous recommendation stating that rituximab — an immunosuppressive therapy marketed under the brand names Rituxan and Truxima, among others — should be considered in patients with autoantibodies against muscle-specific kinase (MuSK) and those who fail to respond to initial immunotherapy.

The therapy’s effectiveness in people with anti-AChR autoantibodies not responding to immunotherapy is currently uncertain, and as such, it may be considered in those failing to respond to, or not tolerating, other immunosuppressive therapies.

Ocular MG

People with ocular MG who are not responding to acetylcholinesterase inhibitors should be given immunosuppressive treatments, with corticosteroids (such as prednisone) as the first option.

Early evidence also suggests that low-dose corticosteroids may be a safer effective therapeutic option than high-dose corticosteroids for patients with this disorder type, who often first notice weakness in the muscles that control the movement of their eyes and eyelids.

Certain ocular MG patients with anti-AChR autoantibodies, who are not responding to recommended treatment, also may be offered thymectomy, per the guidelines.

Immune checkpoint inhibitors (ICIs)

MG associated with ICIs — which are most often used in cancer treatment — is generally severe, with a high rate of respiratory crises. Such risk should thereby be discussed with patients who are considered for ICIs initiation.

The physicians agreed that, while such therapies may be used for people with MG, it may be best to avoid ICI combinations and to closely monitor these patients, particularly for problems in lung function, swallowing, chewing, and speech.

Patients developing MG while on ICIs may need early aggressive treatment combining high-dose steroids and strong immunosuppressive therapies, such as plasma exchange and intravenous (into-the-bloodstream) immunoglobulin. The decision to withdraw ICIs is determined by the patient’s cancer status.

In addition to their work on the selected topic areas, the experts updated a list of medications to avoid or use with caution in MG patients. Among them are therapies that were recommended against using in the treatment of COVID-19.

“This updated formal consensus guidance of international MG experts, based on new evidence, provides recommendations to clinicians caring for MG patients worldwide,” the researchers wrote.