This review included 123 trials with a total of 57,682 participants, updated until March 2022.

Population, Intervention, Comparison, Outcome (PICO)
P: Individuals with Multiple Sclerosis (MS) or Clinically Isolated Syndrome (CIS).
I: Immunotherapies, encompassing 25 drugs.
C: Placebo or other active agents.
O: Serious Adverse Events (SAEs).

✅ Certain drugs posed no higher risk compared to placebo condition, including Avonex, Dimethyl Fumarate, and Ocrelizumab. However, evidence quality varied for others. Overall, immunotherapies show no increased risk of serious health events compared to placebos.
✅ Some drugs, however, led to more dropouts due to unwanted effects.
Given the rarity of serious health events in people with MS, studying the issue is challenging, and reported events varied.

🔍 What is PICO and Why We Focus on It?
PICO stands for Population, Intervention, Comparison, and Outcome. It's a structured approach to formulating clinical research questions, ensuring clarity in study design and interpretation. By focusing on PICO, our reviews aim for precision, guiding our investigation into MS therapies and their impacts on specific patient populations and outcomes.

You can find this Review Snapshot in Italian here!

 We updated a network meta-analysis from 2015, finding new surprising evidence about 15 different immunomodulators, immunosuppressants and biological agents in terms of efficacy and safety for the treatment of people with Relapsing-Remitting Multiple Sclerosis (RRMS).

This review included 50 studies with a total of 36,541 participants, updated until August 2022.

Population, Intervention, Comparison, Outcome (PICO)
P: Individuals with RRMS.
I: Immunoglobulins, Fingolimod, Natalizumab, Glatiramer Acetate, Teriflunomide, Ocrelizumab, Pegylated interferon Beta-1a, Alemtuzumab, Daclizumab, Laquinimod, Interferon Beta-1a, Interferon Beta-1b, Mitoxantrone, Azathioprine, Dimethyl Fumarate
C: Placebo.
O: Relapse or Disease Progression.

✅ Some medicines like natalizumab, cladribine, and alemtuzumab are more likely to reduce the number of relapses in people with RMMS over two years compared to other disease-modifying therapies.
✅Natalizumab might also slow down disability progression after two years.
✅Many treatments may cause more people to stop taking them because of side effects when compared to placebo. However, alemtuzumab is associated with fewer discontinuation, and interferon beta‐1b might have a small reduction in serious adverse events.

💡 Limitations:
We don't have enough information to know how well these medicines are efficient or if they are safe for more than two years, clearly a challenge as MS is a long-term condition. Also, some of the studies included were paid for by pharmaceutical, potentially influencing results. 

🔍 What is relapsing-remitting multiple sclerosis (RRMS)?
Relapsing-Remitting Multiple Sclerosis is a form of multiple sclerosis, a condition affecting the nervous system. Typically diagnosed in young and middle-aged adults, RRMS is characterized by fluctuating symptoms. Individuals may experience periods of worsened symptoms (relapses) followed by periods of recovery (remitting).

You can learn more about this review listening to this Cochrane Podcast, available in four languages.
 

This recent systematic review wanted to assess benefits and harms of cannabinoids, including synthetic, or herbal and plant‐derived cannabinoids, for reducing symptoms for adults with MS.

Analysis included 25 trials with a total of 2290 participants, updated until December 2021.

Population, Intervention, Comparison, Outcome (PICO):
P: People with Multiple Sclerosis.
I: Cannabis and synthetic cannabinoids (Dronabinol and Nabilone)
C: Placebo.
O: Serious Adverse Event, Spasticity, Chronic central neuropathic pain, Patient Global Impression of Change.

✅Compared with placebo group, people using cannabinoid-based treatments:

• Perceive a reduction of the severity of spasticity in the short term.
• May experience chronic neuropathic pain reduction, but evidence is limited.
• Are slightly more likely to abandon the treatment.
• Perceive greater improvement in well-being.
• Have no significant effect on Health-Related Quality of Life (HRQoL).
• Experience no substantial difference in serious adverse events.
• May have a potential increase in nervous system and psychiatric disorders.

💡 Limitations:
There is no of high-quality evidence. There is a moderate confidence in the efficacy of cannabinoids for spasticity and well-being in adults with MS, but very limited confidence regarding chronic neuropathic pain. There is also limited evidence on the impact of cannabinoids on serious harmful effects, nervous system or psychiatric disorders, and drug tolerance.

🔍What is spasticity and chronic neuropathic pain in MS patients?
Spasticity in MS  involves increased muscle tone and spasms, while chronic neuropathic pain is persistent nerve-related pain. These common symptoms worsen with disease progression, impacting daily life and well-being. Current medications for spasticity and pain relief are limited in effectiveness or poorly tolerated, leading to a growing interest in cannabinoids for potential relief.

This article is also featured on Cochrane Podcast!

This systematic review evaluated the quality and quantity of available self-management info for People with Multiple Sclerosis (PwMS).

PwMS often lack sufficient information about their condition, including diagnosis, treatment options, and prognosis. Despite guidelines advocating for clear, concise, and high-quality information, several communication gaps persist in MS care, leaving patients without enough support for managing their condition independently.

Analysis included 11 studies with a total of 1387 participants, updated until November 2017.

✅ Some studies aimed to teach about MS or help with decisions, while others focused on sticking to treatment or changing behaviours. The ways they did this varied a lot, and the results were mixed. Some studies found that people learned more about MS after getting information, but it's hard to  assess the overall impact. The effects on making decisions and quality of life were also uncertain, due to variations in approaches and outcome measures across studies.

In this systematic review the authors checked the effectiveness and safety of a treatment called intravenous immunoglobulin (IVIG) in the management of children with some forms of encephalitis (inflammation of the brain).

Analysis included 3 studies with a total of 138 children, updated until September 2016.

✅ All three studies included only children with viral encephalitis.

✅ The other two studies analysed other measurements, such as length of hospital stay and symptoms arising due to nerve damage, and concluded that adding IVIG treatment was more effective than standard care alone when these outcomes were considered.

The evidence's quality is notably low due to the limited number of studies and participants, an issue always relevant when discussing rare diseases' treatments. Other biases are due from lack of transparency regarding funding sources. Consistent outcome measures and long-term follow-ups are crucial for enhancing the reliability of future research.

This systematic review aimed to assess the benefit and harms of palliative care interventions for people with any form of MS, including relapsing‐remitting MS (RRMS), secondary‐progressive MS (SPMS), and primary‐progressive MS (PPMS).

Palliative care interventions play a crucial role in addressing the complex needs of individuals with multiple sclerosis (MS), a condition affecting millions worldwide. 

Analysis included 3 studies with a total of 146 participants, updated until October 2018.

✅ Palliative care interventions were primarily delivered through home visits, and were focused on symptom management and end-of-life planning. However, uncertainty remains regarding their effectiveness compared to usual care, especially concerning long-term health-related quality of life, adverse events, and hospital admission. Notably, the studies did not assess outcomes such as fatigue, cognitive function, or relapse-free survival. No studies assessed the differences between palliative care interventions.

This review examines the effectiveness of memory rehabilitation in enhancing memory functions and overall quality of life for individuals with MS.

Memory problems are common in individuals with multiple sclerosis (MS) and can significantly impact daily life. Memory rehabilitation aims to improve memory skills through various techniques and strategies, such as computerized programs or memory aids like diaries and calendars. 

Analysis included 44 studies with a total of 2714 participants, updated until September 2020.

Analysis included 12 RCTs with a total of 933 participants, updated until October 2017.

Are non-pharmacological therapies effective in managing chronic pain for people with multiple sclerosis (MS)?

Chronic pain is a common issue for individuals with MS, significantly affecting their quality of life. This review evaluates the effectiveness and safety of non-pharmacological interventions for managing chronic pain in MS.

Analysis included 10 RCTs with a total of 565 participants, up to December 2017.

Population, Intervention, Comparison, Outcome (PICO)
P: People with multiple sclerosis (PwMS).
I: Non-pharmacological interventions (e.g., transcranial direct stimulation , psychotherapy, hydrotherapy).
C: Placebo, Sham intervention.
O: Pain relief.

✅ Key Results:
There is very low-level evidence supporting the use of non-pharmacological interventions such as transcutaneous electrical nerve stimulation, transcranial direct stimulation, transcranial random noise stimulation, reflexology, psychotherapy and hydrotherapy for reducing pain intensity in PwMS. Findings suggest that use of non‐pharmacological intervention in combination with pharmacological agents is reasonable, showing improvements in secondary outcomes like fatigue, psychological symptoms, and spasm.

💡 Limitations:
These results were limited by methodological biases within the studies, such as low sample. More robust studies with larger sample sizes are needed to confirm these findings.

🔎 What are placebo and sham interventions?
A placebo is an inactive substance or treatment that has no therapeutic effect, often used in clinical trials as a control to test the efficacy of a new drug or treatment. A sham intervention is a procedure that mimics the actual intervention being studied but lacks its active component, used to control for placebo effects in trials of non-drug treatments, such as surgeries or physical therapies.

This recent network meta-analysis compared the efficacy and safety of several immunomodulators and immunosuppressants for the treatment of people with Progressive Multiple Sclerosis (PMS).

Analysis included 23 studies with a total of 10,167 participants, updated until August 2022.

Population, Intervention, Comparison, Outcome (PICO)
P: Individuals with PPMS.
I: Natalizumab, Ponesimod, Glatiramer Acetate, Teriflunomide, Ocrelizumab, Ofatumumab, Leflunomide, Ozanimod, Pegylated Interferon Beta-1a, Mycophenolate Mofetil, Laquinimod, Interferon Beta-1a, Interferon Beta-1b, Minocycline, Mitoxantrone, Methotrexate, Immunoglobulins, Corticosteroids, Fingolimod, Rituximab, Alemtuzumab, Daclizumab, Cyclophosphamide, Diroximel Fumarate, Cladribine, Azathioprine, Siponimod.
C: Placebo.
O: Relapse, Disability, Adverse Event.

• We are very uncertain about the effects of treatments on relapses and slowing the worsening of disability. There is evidence that rituximab after two years and interferon beta-1b after three years of treatment probably slightly reduce the number of people who experience relapses.
• Slightly more people stop taking interferon beta-1a because of unwanted effects when compared to placebo.
• Longer studies that make comparisons between treatments are needed to assess the benefits and harms of drugs acting on the immune system over time for people with progressive multiple sclerosis. 

💡 Limitations:
There is very limited confidence in the effects of disease-modifying drugs because the evidence was based on relatively low numbers of people experiencing events like relapses and worsening of disability, and because several studies were founded by drug companies and may have influenced the reporting of results.

🔍 What is progressive multiple sclerosis (PMS)?
Over the years, in most people with relapsing‐remitting multiple sclerosis (RRMS), worsening of disability will become continuous, without recovery. This is known as "secondary‐progressive" multiple sclerosis. In about 15% of cases, multiple sclerosis shows a progressive course from the onset, without relapse and recovery. This is called "primary progressive" multiple sclerosis.