Study highlights need for care guidelines in seronegative MG
Review of data finds patients may need different diagnostic, treatment strategies
Written by |
- Researchers called for standard diagnosis and treatment guidelines for seronegative myasthenia gravis.
- Seronegative MG often develops earlier than MG with disease-driving antibodies, and many patients don't respond to standard immunosuppressive treatments.
- There's a need for more research, including clinical trials involving people with seronegative MG.
Researchers called for standardized guidelines for diagnosing and treating people with myasthenia gravis (MG) who test negative for typical disease-driving antibodies.
A review study showed that antibody-negative MG tends to manifest earlier than antibody-positive disease, and a substantial portion of antibody-negative patients do not respond adequately to standard immune-suppressing treatments such as corticosteroids.
The scientists also called for future studies to proactively test treatment strategies in antibody-negative patients.
The review study, “Clinical Characteristics and Treatment Management of Seronegative Myasthenia Gravis: A Systematic Review of the Literature,” was published in Muscle & Nerve.
MG is caused by self-reactive antibodies that interfere with the communication between nerve and muscle cells, resulting in MG symptoms including muscle weakness and fatigue.
Types of antibodies
Several types of MG-driving antibodies have been identified, including those that target acetylcholine receptor (AChR), muscle-specific kinase (MuSK), or low-density lipoprotein receptor-related protein 4 (LRP4).
Although antibodies against AChR, MuSK, and/or LRP4 are detectable in most people with MG, some people show all the signs and symptoms of MG, but don’t have any of these antibodies. These cases are referred to as seronegative MG (SNMG).
A team of scientists in Italy conducted a review of scientific literature, aiming to better understand what’s currently known about SNMG. Their goal was to give “a comprehensive overview of SNMG based on published studies, with a focus on diagnostic strategies, clinical characteristics, treatment management, and disease outcomes.”
The review covered 31 previously published studies. These studies included data on more than 700 people with SNMG, though not all types of data were available for all patients.
About two-thirds (67%) of the patients were female, with a mean age at disease onset of 42. The researchers said this is consistent with previous studies suggesting that SNMG usually develops earlier than antibody-positive MG.
Available data showed that slightly more than half (56%) of SNMG patients initially developed ocular MG, a form of the disease in which only muscles around the eyes are affected. Among those whose disease started as ocular MG and had available data, about half (43%) later progressed to generalized MG, a more severe form in which several muscles throughout the body are affected. Again, the researchers said these data align with previous studies showing that SNMG often starts with purely ocular symptoms and then progresses to generalized disease.
Although all the patients were identified as having SNMG, the researchers noted that specific strategies used to diagnose MG varied from study to study. Tests used to look for MG-related antibodies also varied, and fewer than half the patients were tested for antibodies against LRP4.
This variability in diagnostic tests raises the possibility that some of these patients were misclassified or incorrectly diagnosed, the researchers said. There are no solid guidelines for diagnosing MG in the absence of detectable disease-driving antibodies.
“These findings underscore the need for standardized diagnostic algorithms for SNMG,” the team wrote. “Future studies should aim to refine classification by integrating high-sensitivity [tests], supported by prospective validation.”
Among the patients for whom treatment data were available, most were given corticosteroids and other immune-suppressing medications. But even with treatment, fewer than half (39%) of evaluable patients were able to achieve a state of minimal disease manifestations or better (meaning MG symptoms were not causing problems in day-to-day life), and roughly one in four (24%) were classified as being refractory (resistant to treatment).
The scientists noted that studies of MG treatments often only include antibody-positive patients. They called for future studies to proactively include people with SNMG to generate more robust data that can inform how these patients are treated.
Leave a comment
Fill in the required fields to post. Your email address will not be published.