Key messages
- Immunotherapies used to treat multiple sclerosis appear not to increase serious health events, compared to sham drugs (placebo).
- Many of these drugs have unwanted effects and, for some of them, more people included in studies dropped out because of side effects compared to sham drugs.
- These results are only partly, or are not, reliable since serious health events are relatively rare in people with multiple sclerosis, meaning that the issue is difficult to study, and serious health events were also not well reported in the studies.
What is the condition?
Multiple sclerosis (MS) affects the brain and the spinal cord. MS affects more women than men. In MS, the immune system attacks the sheath that covers our body's nerves and weakens their function. Some people with severe MS may even not be able to use their arms or legs well for some time, but they usually recover. Disability, for example in walking, can arise in some people who have many attacks over the years.
How is the condition treated?
Several treatments that modulate the immune system are available that can help speed recovery from attacks and improve the course of the disease.
What did we want to find out?
We aimed to investigate the risks of the drugs used to treat MS. We wanted to assess all types of health events that are serious, for example, admissions to hospital, or events that made people stop taking the medication. We also wanted to investigate health events in specific body organs.
What did we do?
We searched for studies that investigated drugs aiming to improve the course of MS, compared with other drugs or sham drugs, in people with recurrent episodes of the disease.
What did we find?
Serious health events were found in about one in nine people receiving a sham drug during one or two years. The following drugs were found not to increase these events: interferon beta-1a (Avonex), dimethyl fumarate, glatiramer acetate, teriflunomide, ocrelizumab, ozanimod, interferon beta-1b, interferon beta-1a (Rebif), natalizumab, fingolimod, and laquinimod. We cannot tell whether the following drugs cause more serious health events than sham because the studies were small or there were few events (for cladribine, siponimod, ofatumumab, and rituximab). We were very unsure about daclizumab, immunoglobulins, diroximel fumarate, peg-interferon beta-1a, alemtuzumab, interferons and azathioprine because the evidence regarding serious health events was of very poor quality.
Unwanted effects causing people to stop taking the medication were found in one in 16 people receiving a sham drug for one or two years. The following drugs may have increased these dropouts: teriflunomide, glatiramer acetate, fingolimod, interferon beta-1a (Rebif), daclizumab and interferon beta-1b. We cannot tell whether ofatumumab causes more dropouts than sham because the studies were small or there were few events. We are very unsure about diroximel fumarate, alemtuzumab, methotrexate, corticosteroids, ozanimod, natalizumab, ocrelizumab, dimethyl fumarate, siponimod, rituximab, cladribine, mitoxantrone, interferons, cyclophosphamide, laquinimod, interferon beta-1a (Avonex), immunoglobulins, peg-interferon beta-1a and azathioprine because the evidence regarding dropouts was of very poor quality.
What are the limitations of the evidence?
Most of the evidence came from studies conducted in ways that may have introduced errors into their results, including the fact that harms were not well reported. Moreover, serious health events and unwanted effects are rare in people with MS and, thus, difficult to study.
How up-to-date is the evidence?
This review is up-to-date until March 2022.
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Authors' conclusions:
We found mostly low and very low-certainty evidence that drugs used to treat MS may not increase SAEs, but may increase withdrawals compared with placebo. The results suggest that there is no important difference in the occurrence of SAEs between first- and second-line drugs and between oral, injectable, or infused drugs, compared with placebo.
Our review, along with other work in the literature, confirms poor-quality reporting of adverse events from RCTs of interventions. At the least, future studies should follow the CONSORT recommendations about reporting harm-related issues. To address adverse effects, future systematic reviews should also include non-randomized studies.