Abstract
The presence of intrathecal IgM synthesis (ITMS) has been associated with an aggressive multiple sclerosis (MS) clinical course. In the present systematic review, we aimed at assessing the prevalence of ITMS among different MS phenotypes. Moreover, we aimed at quantifying the risk of a second relapse in ITMS positive and oligoclonal IgG bands (OCGBs)-positive patients. We selected clinical studies reporting the ITMS prevalence assessed as oligoclonal IgM Bands (OCMBs), lipid-specific OCMBs (LS-OCMBs), and/or as an intrathecal IgM production > 0% (IgMLoc, Reiber formula). The overall prevalence of ITMS was higher in relapsing-remitting (RR) than clinically isolated syndrome (CIS) patients (40.1% versus 23.8%, p < 0.00001), while was in line with that detected in primary progressive MS (PPMS, 26.7%). Almost all patients (98%) with ITMS had also OCGBs. The risk of having a second relapse was higher in OCGBs positive patients (HR = 2.18, p = 0.007) but much higher in ITMS positive patients (HR = 3.62, p = 0.0005). This study revealed that the prevalence of ITMS is higher in RRMS patients. It suggests that the risk of having a second relapse, previously ascribed to OCGBs, may, to a certain extent, be related to the presence of intrathecal IgM.
Highlights
IntroductionAccumulating evidence shows the positive long-term impact of early treatment with high efficacy therapies in multiple sclerosis (MS) patients [1,2]
The prevalence of intrathecal IgM was lower in clinically isolated syndrome (CIS) than in RRMS patients when assessed as LS-oligoclonal IgM Bands (OCMBs) (23.7% versus 38.9%, p < 0.00001), OCMBs (33.0% versus 48.5%, p < 0.00001), and IgMLoc (18.8% versus 31.3%, p < 0.00001)
A plethora of new disease-modifying treatments (DMTs) is available with a wide range of activity and associated risks, and biomarkers that predict future relapse activity are needed to improve the benefit
Summary
Accumulating evidence shows the positive long-term impact of early treatment with high efficacy therapies in multiple sclerosis (MS) patients [1,2]. Such therapies could carry more serious adverse event profiles, underscoring the need for accurate, personalized prognostication in order to identify subjects with more aggressive disease who are most likely to benefit. Clinical characteristics such as sex, age, relapse rate and recovery, the functional system involved at onset, and brain magnetic resonance imaging (MRI) parameters play the most important role [3,4]. The intrathecal synthesis of oligoclonal IgG bands (OCGBs) remains the most consistent laboratory abnormality in MS, present in the cerebrospinal fluid (CSF) of up to 95% of relapsing–remitting
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