Background

Multiple sclerosis (MS) is an acquired, chronic demyelinating disease, affecting more than 2.3 million worldwide.
Tumor necrosis factor alpha (TNFα) is a pro-inflammatory cytokine produced by activated macrophages which in turn activate microglia.
Interleukin-6(IL-6) is a pro-inflammatory, anti-inflammatory myokine secreted by T cells, supporting B cell growth and inhibiting TNFα and regulatory T cells.
Tecfidera® (dimethyl fumarate: DMF) has been FDA-approved for treatment of RRMS since 2013. DMF decreases TNFα and IL-6 synthesis in activated microglia and astrocytes in vitro.

Objectives

A. To obtain TNFα and IL-6 levels in attack-free patients on DMF
B. To check correlations between TNFα, IL-6, EDSS, vitamin D levels, age, duration of disease, or number of MRI lesions

Methods

This was a 6-year retrospective study of patients seen by a single neurologist (WSB) Jan 1, 2014-Oct 31, 2019. Patients were diagnosed based on the 2010 McDonald MS criteria. Those with clinically isolated syndrome were included. Longitudinal data analysis was performed using generalized linear models.

Inclusion criteria:

1. Patients aged 18 or above either with a new or pre-existing diagnosis of MS or CIS

2. Patients with baseline laboratory data (TNFα and IL-6) every 3-4 months afterwards (at least three times), and MRI prior to starting DMF and afterwards (at least twice)

3. Patients who were naïve to MS medications or have been off treatment for at least 1 year prior to starting DMF

Exclusion criteria:

1. Those still on immunomodulatory agents at the time of the initial visit

2. Those non-compliant with either follow up visits, lab tests, MRIs or taking DMF

3. Patients with concurrent infectious or inflammatory/autoimmune conditions

4. Patients who relapsed during the study period

Results

84 patients were started on DMF either as de novo or second-line therapy. After exclusion criteria, 11 were included in the analysis. 10 were female and 1 was male. The average age was 46.9 years; the average age of onset 33.3. The average time from onset till diagnosis was 6.6 years. The average baseline EDSS score was 2.56. The average baseline number of T2-FLAIR lesions was 21.55 and 6.45 for T1 black holes. The median baseline number of T2-FLAIR lesions was 10 and 1 for T1 black holes. The average baseline vitamin D level was 25.84ng/ml.

There was a significant decrease in TNFα levels after initiating DMF in nearly all the cases. The decreasing TNFα levels separated into different groups based on the number of T2 lesions, age, and EDSS.

An insignificant trend towards a decrease in IL-6 levels was observed after initiating DMF in nearly all the cases. The decreasing IL-6 levels separated into different groups based on the number of T2 lesions, and age.

Conclusions

TNFα levels decreased significantly, whereas IL-6 showed only a decreasing trend after initiating DMF.

TNFα may be a promising serum biomarker in monitoring DMF therapy in MS.

Background

Multiple sclerosis (MS) is an acquired, chronic demyelinating disease, affecting more than 2.3 million worldwide.
Tumor necrosis factor alpha (TNFα) is a pro-inflammatory cytokine produced by activated macrophages which in turn activate microglia.
Interleukin-6(IL-6) is a pro-inflammatory, anti-inflammatory myokine secreted by T cells, supporting B cell growth and inhibiting TNFα and regulatory T cells.
Tecfidera® (dimethyl fumarate: DMF) has been FDA-approved for treatment of RRMS since 2013. DMF decreases TNFα and IL-6 synthesis in activated microglia and astrocytes in vitro.

Objectives

A. To obtain TNFα and IL-6 levels in attack-free patients on DMF
B. To check correlations between TNFα, IL-6, EDSS, vitamin D levels, age, duration of disease, or number of MRI lesions

Methods

This was a 6-year retrospective study of patients seen by a single neurologist (WSB) Jan 1, 2014-Oct 31, 2019. Patients were diagnosed based on the 2010 McDonald MS criteria. Those with clinically isolated syndrome were included. Longitudinal data analysis was performed using generalized linear models.

Inclusion criteria:

1. Patients aged 18 or above either with a new or pre-existing diagnosis of MS or CIS

2. Patients with baseline laboratory data (TNFα and IL-6) every 3-4 months afterwards (at least three times), and MRI prior to starting DMF and afterwards (at least twice)

3. Patients who were naïve to MS medications or have been off treatment for at least 1 year prior to starting DMF

Exclusion criteria:

1. Those still on immunomodulatory agents at the time of the initial visit

2. Those non-compliant with either follow up visits, lab tests, MRIs or taking DMF

3. Patients with concurrent infectious or inflammatory/autoimmune conditions

4. Patients who relapsed during the study period

Results

84 patients were started on DMF either as de novo or second-line therapy. After exclusion criteria, 11 were included in the analysis. 10 were female and 1 was male. The average age was 46.9 years; the average age of onset 33.3. The average time from onset till diagnosis was 6.6 years. The average baseline EDSS score was 2.56. The average baseline number of T2-FLAIR lesions was 21.55 and 6.45 for T1 black holes. The median baseline number of T2-FLAIR lesions was 10 and 1 for T1 black holes. The average baseline vitamin D level was 25.84ng/ml.

There was a significant decrease in TNFα levels after initiating DMF in nearly all the cases. The decreasing TNFα levels separated into different groups based on the number of T2 lesions, age, and EDSS.

An insignificant trend towards a decrease in IL-6 levels was observed after initiating DMF in nearly all the cases. The decreasing IL-6 levels separated into different groups based on the number of T2 lesions, and age.

Conclusions

TNFα levels decreased significantly, whereas IL-6 showed only a decreasing trend after initiating DMF.

TNFα may be a promising serum biomarker in monitoring DMF therapy in MS.