Here is my review of new developments in treatment and supportive care for multiple sclerosis (MS). First, I will focus on disease-modifying therapies (DMT). I see DMTs as a base treatment that everyone with MS should be on. The introduction of DMTs over the last 30 years has fueled a tremendous advancement for MS patients. This resulted in a much lower likelihood of developing disability due to MS for the newly diagnosed with MS. Despite the progress, there is still no cure, and the current DMTs are only slowing the MS progression.

The MS itself is highly individual, and different people have MS with various symptoms and degrees of aggression. At the same time, the course of MS disease is heavily influenced by lifestyle. Diet, exercise, level of stress, etc., play a crucial role. All of this makes it hard to find clear trends and order. One has to dive into the pile of data from scientific & medical reports and individual stories.

In the second part of this post, I will try to cover at least the key points beyond DMT, focusing on supportive treatment and care that can complement DMT. This section also covers “alternatives” to make a connection with approaches commonly seen as an alternative to prescription medication. However, I view the alternative supportive treatment for MS as complementary to prescription medication and not their replacement.    

Disease Modifying Therapies (DMTs)

I have divided available DMTs by efficacy as a key that I thought was most relevant and will avoid unnecessary details that can be found elsewhere. The terminology, data, and methodology are adopted from a research paper published in the Journal of Neurology in September 2022. The therapies are further separated into Hight Effiacy (HE) and Moderate Effiacy (ME) categories, as summarized in Table 1 below.     

For relapsing-remitting multiple sclerosis (RRMS), an annual relapse rate (ARR) is used as a measure. The ARR is defined as how often relapses happen in patients on a drug with respect to patients taking a placebo (a fake medication).  For example, an ARR of 0.5 means that, in one year, only 1/2 of RRMS patients taking a drug would have a relapse compared to a group of RRMS patients taking a placebo. In a group of patients taking a drug with ARR of 0.3, only three out of ten would have relapse compared to the placebo group, and so on.  The high efficacy (HE) DMT is often defined as achieving ARR below 0.5. I will set this limit at 0.4 for the median ARR for the sake of simplicity.

High Efficacy DMTs (ARR: 0.25-0.4)

The most appealing high efficacy (HE) DMTs right now seem to be CD20 monoclonal antibodies. The currently available CD20 based DMTs are Ocrevus, Kesimpta, Rituximab and Briumvi. These therapies target a specific subset of B-cells expressing CD20 marker. CD20 B-cells reside mainly in the brain and spinal cord and are believed to be the main cause of demyelination. These DMTs have also shown moderate side effects due to immunosuppression.  

There are some differences between these treatments, though. The most notable difference is that the originally leukemia drug Rituximab (Rituxan) has not been approved for the treatment of MS by the FDA, but it is used for MS treatment as an off-label drug. As a result, there is not much evidence about how comparable this treatment is with the other DMTs.

Cost-Effective Rituxan Drawbacks

A recent study with hundreds of RRMS patients suggests that Rituxan’s efficacy is comparable to Ocrevus, although higher ARR was reported. The relapse rate in this study was nearly twice as high for Rituxan. The difference might be due to the limited number of patients and differences in dosing. Another contributing factor is a higher degree of “humanization” of CD20 antibodies in Ocrevus and other CD20 DMTs.

Rituxan has not been humanized as the other drugs in this category and is more “mouse,” which can lead to allergic reactions of the human immune system. The adverse reaction against Rituxan seems to occur in about 20-30% of cases over time. My guess is that this might be the main reason for the lower efficacy. Nevertheless, the differences are small, and the results keep Rituxan in the HE category. Notably, Rituxan is also off-patent and represents by far the most cost-effective DMT in this category.

All of these drugs, except for Kesimpta, are administered via infusion twice a year. The infusion has to be administered by a nurse in a hospital or an infusion center, which requires at least half a day. Kesimpta can be self-administered into a muscle once a month by an injector pen. The main side effects of these DMTs are a higher risk of various infections due to weakened immunity. The most common are upper respiratory tract infections, reflecting the abundance of infections in the general population.  

Overdoing Immune Damage?

Other highly efficacious DMTs include Lemtrada and Tysabri. These DMTs have different mechanisms of action (MOA) that target a whole range of immune cells, which seems to be associated with more side effects and a higher risk of infection. This includes a risk of progressive multifocal leukoencephalopathy (PML), a serious disease caused by the JC virus (JCV). This risk exists for the CD20 DMTs also, but it seems to be much lower.

With Tysabri, the PML risk goes to 0.7%. Lemtrada’s risk for PML seems to be much lower at about 0.07%. In contrast, only twelve PML cases were confirmed out of 250 000 MS patients on Ocrevus (<0.001%). Tysabri prevents the white blood cells from entering the central nervous system (CNS). The associated infection risk is confined to the CNS as a result. It does not carry the risk for upper respiratory and other infections as the CD20 Bcell antibodies do. However, the PML infection commonly results in death. Lemtrada does not have such a high risk for PML as Tysabri, but it has a wide range of other serious issues, such as increasing chances of cancer, heart problems, etc. My conclusion is that Tysabri and Lemtrada cause wider damage to the immune system in exchange for almost identical efficacy when compared to the more specific CD20 B-cell antibodies.

Here is a brief description:

• Lemtrada: CD52 monoclonal antibody depleting lymphocytes- a whole range of immune cells, including B and T cells.
• Tysabri: A monoclonal antibody binds to α4-integrin of leukocytes, preventing the migration of a range of lymphocytes- white blood cells such as B-cells and T-cells into the central nervous system (CNS) through the brain-blood barrier.

	median ARR	Mechanism of Action (MOA)	Class
Lemtrada	0.28	CD52 white blood cells monoclonal antibody	HE
Kesimpta	0.30	CD20 B-Cells monoclonal antibody	HE
Tysabri	0.31	α4-integrin leukocytes – preventing white blood cells from entering the CNS	HE
Ocrevus	0.33	CD20 B-Cells monoclonal antibody	HE
Mavenclad	0.43	not known- preventing immune cells from getting into the CNS	ME
Zeposia	0.45	not known- preventing immune cells from getting into the CNS	ME
Fingolimod (Gilenya)	0.46	S1P modulator	ME
Dimethyl Fumarate (Tacfidera)	0.5	anti-inflammatory -not known	ME
Glatimer Acetate (Copaxone)	0.62	modulating T-cells attack on myelin	ME
Teriflunomide (Aubagio)	0.66	inhibits dihydro-orotate dehydrogenase -enzyme important in white blood cells production	ME

Moderate Efficacy DMTs (ARR 0.5-0.8)

Moderate efficacy (ME) DMTs are summarized here:

Dimethyl fumarate (Tacfidera)- a twice-a-day tablet reducing inflammation.

Cladribine (Mavenclad)- a pill taken only two weeks a year. Prevents B and T cells from entering the brain and spinal cord.

Fingolimod (Gilenya) – once a day tablet. Stops T and B cells to enter the brain and spinal cord.

Copaxone and generic glatiramer acetate (ARR: 0.62) – under the skin injection every day or three times a week.

Other drugs (ARR > 0.65) – several variations of the above.

Most of these drugs are immunosuppressants that prevent T and/or B cells of the adaptive part of the immune system from causing damage to Myelin. As a result, they bring some risks associated with a weakened immune system. My take on this is that humanized monoclonal antibodies cause the least damage and do only what they are supposed to do with minimal damage. Other drugs can also put an additional burden on the liver or kidney as our body is trying to clean itself.

DMT Strategy

The difficulty with MS is that it works very slowly in the background. There could be a long period of time when the disease is seemingly inactive. Even on average, without treatment, it takes ~10 years before newly diagnosed RRMS patients develop any disability. On top of that, MS diagnosis has improved tremendously. There are more patients with less aggressive MS added into the mix, which further skews any long-term statistics. All of this makes it extremely hard to evaluate the effectiveness of different treatments.

For quite some time, it was believed that it was OK to treat RRMS with lower-efficacy drugs initially. The HE treatment was started once the disease accelerated. However, now that enough clinical data has been obtained, it is clear that the sooner a patient starts the HE DMT, the better outcome can be expected. Not only do HE DMTs lower the frequency of relapses, but also the time until the RRMS phase of the disease transforms into secondary progressive MS. Another endpoint in focus is the development of a degree of disability in patients with progressive type of MS. The data suggests that even the advancement toward higher degrees of disability is significantly slower if the HE treatment is started sooner.

My conclusion is that the sooner the HE DMT treatment is started, the better the chances of avoiding the disability or at least slowing it down significantly. The DMTs can be further complemented by supportive care and treatment of MS described below.

Supportive Care and Treatment of MS

Activemsers.com provides a nice summary of some of the alternative treatments. When I last checked, intermittent fasting wasn’t covered there. Convincing new data now show a profound effect of diet on the immune system and MS, though. I have included a brief summary below. The data hint that diet plays a tremendous role in our immunity and can provide great complementary benefits in supportive care and treatment of MS!

While I am a strong believer that these diet plans can significantly affect the immune system as well as the course of MS in many people, I do not think that diet plans can replace DMT to control MS. There probably are rare cases where people can experience huge improvement of their MS symptoms without DMT.

When deciding whether to take DMT or not, one should consider probability calculus. Sure, there probably are a few cases where a miracle has happened. Are you an outlier, though? Like one in 100 or 1000, who can avoid thoroughly tested DMT? One can find many more stories of people who have been lured down that path and dropped a DMT for whatever reason. A few were lucky, but most did not end well.

The Cause of MS

I believe it is important to keep developing new avenues toward better treatments with minimal side effects. A lot of progress has been made already. The very successful CD20 DMTs are probably targeting the core cause of the MS itself, the malfunctioning B-cells, by depleting them. And yeah, the original culprit is the Eppstein-Barr virus (EBV) that targets B-cells and leaves them malfunctioning sometimes. Still, a mystery remains of why EBV infects about 95% of people while only 0.2% develop MS? Let’s hope a vaccination against EBV is created and MS prevalence decreases as a result. That would confirm the findings of the research above!    

The Alternative’s Attraction

Of course, it would be best if a simple change of everyday habits and diet could solve MS symptoms! Many people also think that medications somehow cause more harm than good and that their primary purpose is to siphon money into pharmaceutical companies. This is a conspiracy theory, though. No doubt, the side effects are real and must be taken seriously. Living with MS is a long-haul journey, and every person on these meds will experience some fallout of side effects. Our immune system is in place for a reason, and tinkering with it inevitably brings risks. However, the treatment side effects can be further minimized by following supportive strategies involving diet, exercise, and supplements.    

Intermittent Fasting

I was surprised by the results of intermittent fasting in mice models with multiple sclerosis. These were quite significant and proved that diet has a profound impact on immunity. I believe that NIH is now sponsoring clinical trials to investigate the effects of intermittent fasting and similar dietary protocol effects in humans with MS (and perhaps other autoimmune diseases). Let’s hope that there will be more developments also in humans like this one and that we will soon have a much better understanding of the relationship between diet and immune response. It is certainly clear already that diet must play a crucial role in supportive care during the treatment of MS.  

Supplements

I believe that supplements that fix possible nutrition deficiencies due to MS or diets are a must in supportive care and treatment. It would be nice to have something that could minimize the higher risk of infection associated with DMTs. When it comes to immunity boosters, there is a danger of interfering with immunosuppressants and boosting the unwanted attack on myelin and worsening MS. However, the demyelination is caused by the adaptive immune system, B-cells and T-cells mostly, as this is what the DMTs work against. I believe there is an open path in bolstering the innate immunity that acts as a first-line defense against infections. I am now testing a liposomal phospholipid-based supplement that is boosting the innate immune system, and it looks very good so far.

More posts on these topics are coming! Stay tuned.

Outlook

I believe that supportive dietary protocols and supplements are great but should be complementary to the medical treatment of MS. The central problem remains, however: we still need a cure. A treatment that would reset the immune system. So that B-cells would no longer malfunction and stop attacking the myelin sheets. That would cure MS and resolve all of the MS-related problems once and for all. I believe that this is achievable with gene editing techniques such as those that Crispr Therapeutics or others are developing. It will probably take a long time before an “immune reset” therapy exists, though. Let’s hope and wish for Godspeed!