Flu Vaccine Safe and Effective for AChR Antibody-positive MG Patients, Study Reports

Patients with myasthenia gravis (MG), who are positive for the acetylcholine receptor (AChR) antibody, respond effectively to influenza vaccination, even if taking immunosuppressants. Also, influenza vaccination is safe, and does not exacerbate MG symptoms in these patients, according to a study.

The study, titled “A prospective, double-blind, randomized, placebo-controlled study on the efficacy and safety of influenza vaccination in myasthenia gravis,” appeared in the journal Vaccine.

People with an autoimmune disease such as MG are usually considered to be at greater risk for infection due to immunosuppressive treatments or their immune system dysfunction. Therefore, an infection may aggravate symptoms.

Data is scarce on the efficacy and safety of vaccination in patients with autoimmune disorders. Although research indicated that influenza vaccination is safe and does not affect AChR antibody levels, patients have expressed concerns that vaccination may trigger an exacerbation of their disease, leading to a significant decline in vaccination rates.

“This is unfortunate, as seasonal vaccination against influenza is highly effective in reducing laboratory-confirmed influenza illness, hospital admissions and risk of death,” the researchers wrote.

Given the effectiveness of the influenza vaccination in elderly patients — the age group with the highest incidence of MG in men — and concerns that immunosuppressive medications may hamper the production of protective antibodies, the team conducted a clinical trial to assess the efficacy and safety of the 2016/2017 seasonal influenza vaccine (Vaxigrip, by Sanofi Pasteur) in patients with AChR MG, with or without immunosuppressants.

The double-blind placebo-controlled study (EudraCT Number: 2016-003138-26) included 47 adults with mild to moderate AChR MG from the Netherlands (median age was 62 years, ranging from 22 to 74 years), and 47 healthy controls — significantly younger (median age of 54 years) and more frequently female — at the start of the flu season in October 2016. The research was conducted at the Leiden University Medical Center.

All enrolled MG patients experienced stable disease over the three months before the study, which permitted the use of immunosuppressants (by 29 patients) and of prednisolone, up to 30 mg daily (by 20 patients). The group on immunosuppressive medications — cyclosporine, azathioprine, or mycophenolic acid — was significantly older and included more women than patients not taking these therapies.

Serum and clinical outcome measures were collected prior to and four weeks after the first flu vaccination in 24 patients (13 men, a median age of 61.5 years, and a mean disease duration of 14.3 years).

At this point, the 23 patients in the placebo group (14 women, a median age of 63 years, and a mean disease duration of 10.7 years) were also vaccinated while unblinded, which means that they knew they were being given this vaccine. Four weeks later, a third blood sample was collected, and assessments were taken of the patients initially on placebo using the MG-specific activities of daily living (MG-ADL) score. Twelve weeks after vaccination, all patients were evaluated using the MG-ADL test.

The trial’s primary goal was to assess the change in the amount of antibodies to the flu vaccine strains. Secondary objectives included the effect of immunosuppressants on humoral immunity — mediated by antibody molecules secreted by plasma cells — changes in levels of antibodies against AChR, and a clinical relevant change in clinical scores. This was assessed with the Quantitative MG (QMG) score of muscle strength and endurance, the MG Composite (MGC) scale, and the MG-ADL scores.

The results revealed that 89.4% of MG patients and 93.6% of controls achieved seroprotection for the H3N2 influenza strain; 95.7% patients and 97.9% controls for the H1N1 strain; and 46.8% patients and 51% controls for the B-strain. Overall, these findings showed no differences between patients and controls. Also, 19 patients (40.4%) and 24 controls (51%) achieved seroprotection for all three strains of the seasonal influenza vaccine.

In addition, taking immunosuppressants, disease duration or undergoing a thymectomy — thymus removal — did not affect a patient’s serological response to influenza vaccination.

The data further showed that vaccination did not affect the total scores of QMG, MGC and MG-ADL in both initially vaccinated and placebo groups. Also, the researchers did not detect changes in antibodies four weeks after vaccination.

At this timepoint, the healthy controls reported significantly more side effects (70%) than both the MG influenza vaccination and placebo groups. Local redness and soreness at the injection site were the most common side effects for MG and healthy controls.

No exacerbation of MG symptoms was found in the originally vaccinated patients. Three of those patients initially on placebo experienced mild exacerbations that did not lead to a change in medication. The team commented that these exacerbations may have been due to “a prejudice among MG patients that vaccination might be harmful, leading to increased reporting of subjective complaints.”

They concluded that “the antibody response to an influenza vaccination in patients with mild to moderate MG is similar as in healthy subjects, and not affected by the use of immunosuppressive medication.”