Recovery after MG flares takes many months, even with newer meds: Study
Clinical trial results not being seen in real world for recent exacerbations
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- Myasthenia gravis flares require many months for recovery, even with newer treatments, a small study found.
- Acceptable recovery typically takes nine months in the real world, contrasting with faster clinical trial results.
- Patients with persistent symptoms needed prolonged treatment with novel therapies like complement or FcRn inhibitors.
Recovery after a myasthenia gravis (MG) exacerbation — a flare up or sudden worsening of disease symptoms — may take many months, even with the newer treatment options now available to MG patients.
That’s according to a small study in Germany that followed 12 people with MG, treated with either standard care or newer medications, for a year after their first flares.
“Acceptable recovery usually takes nine months,” the researchers wrote in detailing the study’s findings.
Clinical trials of newer MG therapies have shown rapid responses to treatment, in some cases as early as three months, the team noted. However, these studies have excluded patients with a recent exacerbation.
The new findings, the scientists say, suggest that strong responses should not be expected “too early in the real-world setting” despite the “repeatedly shown rapid onset of an effect within clinical trials.”
The study, titled “Delayed recovery following myasthenic exacerbation and subsequent endplate-protecting treatment,” was published as a brief communication in the journal Neurological Sciences.
MG occurs when self-reactive antibodies misdirect an immune attack against proteins required for communication between nerves and muscles, leading to symptoms such as muscle weakness and fatigue. Approved treatments for MG help manage symptoms by suppressing the immune system or restoring nerve-muscle communication.
New treatments supposedly show ‘rapid alleviation of symptoms’
Novel treatments, including complement inhibitors and neonatal Fc receptor (FcRn) inhibitors, “have shown rapid alleviation of symptoms,” the researchers wrote.
Complement inhibitors, such as Ultomiris (ravulizumab) and Zilbrysq (zilucoplan), suppress the activity of the complement cascade, a part of the immune system that contributes to the autoimmune attacks in MG. FcR inhibitors, such as Vyvgart (efgartigimod alfa), accelerate the breakdown of antibodies in the blood, including MG-driving antibodies.
“However, [exacerbation] recovery can take up to 12 months following standard-of-care (SOC) treatment,” the researchers wrote.
Now, a team led by scientists at Justus Liebig University described the recovery from a myasthenic exacerbation in 12 MG patients after receiving either standard of care with immunosuppressants — azathioprine, mycophenolate mofetil, or cyclophosphamide — or newer medications.
All participants tested positive for self-reactive antibodies against the acetylcholine receptor protein, the most common type of MG-driving antibody. Each had also undergone a thymectomy, a surgery to remove the thymus gland, within five years of initial symptoms. Abnormalities in the thymus gland are thought to contribute to the production of self-reactive antibodies, including those causing MG.
In all patients, the described myasthenic exacerbation was their first. All were followed for at least one year.
In eight patients, the exacerbation was triggered by reducing or stopping a disease-modifying treatment, and in three, by an infection. The trigger was unknown for the remaining patient. Three people required intensive care, and two required intubation and ventilation to help with breathing.
In terms of well-established rescue therapy, seven patients received plasma exchange, also known as plasmapheresis, while five received intravenous immunoglobulin (IVIG). Plasmapheresis is a procedure that removes disease-causing antibodies from the blood, while IVIG delivers healthy antibodies into the person’s bloodstream to neutralize self-reactive antibodies.
“Two patients received IVIG after plasma exchange due to insufficient clinical improvement,” the team wrote.
Recovery from MG flares in small study seen to take 3-9 months
After hospital discharge, two recovery patterns emerged. Five patients achieved the Patient Acceptable Symptom State (PASS) after three months, and were maintained on standard immunosuppressants alone. PASS is a threshold representing the highest level of symptoms below which a patient considers symptoms are manageable.
The other seven patients had persistent, severe symptoms and required treatment with complement inhibitors and/or FcR inhibitors, combined or not with immunosuppressants. Five people received Ultomiris (followed by Zilbrysq in one person), and two were treated with Vyvgart.
These patients had a higher median body weight (75 vs. 65 kg, or about 165 vs. 143 pounds), and a greater proportion had been previously treated with corticosteroids (57% vs. 20%), powerful anti-inflammatory medications commonly used in MG.
As demonstrated in this study, some patients in the real-world setting take more time to achieve a clinical response. … [In this study,] recovery was substantially prolonged.
Among these seven participants, muscle weakness, as assessed with the Quantitative Myasthenia Gravis (QMG) score, and the disease’s impact on daily life, as measured with the MG Activities of Daily Living (MG-ADL), had returned to pre-exacerbation levels by 12 months.
“However, recovery was substantially prolonged,” the team wrote, with four patients reporting PASS by nine months of treatment. “Only one patient deemed his symptoms acceptable at month six,” the researchers wrote.
While medications such as complement inhibitors and FcRn blockers work, recovery after a myasthenic exacerbation can still be prolonged, the researchers concluded.
“As demonstrated in this study, some patients in the real-world setting take more time to achieve a clinical response,” the team wrote. “This highlights the need for a sufficiently long course of treatment in order to truly assess the full effectiveness of the medication, also of C5 inhibitors and FcRn modulators, especially in patients, who are not only refractory [treatment-resistant] to standard of care therapy, but who also experienced [myasthenic exacerbation].”
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