Periodic review of treatment safety and monitoring are necessary as medical centers increasingly use newer disease-modifying therapies earlier in the course of multiple sclerosis.
Newer, more potent disease-modifying therapies (DMTs) increasingly are being used in the early stages of multiple sclerosis (MS), but a medical journal review states that data from randomized control trials (RCTs) are insufficient to determine which medications are safest and most effective for a particular patient, making it critical to periodically re-evaluate and adjust monitoring strategies.
According to the review published in December by Vaccines, most of the monitoring strategies are based on phase 3 clinical trials and subsequent studies, but “[p]ostmarketing studies suggest a wider and more serious range of adverse events that needs to be taken into consideration when planning future monitoring strategies to prevent unnecessary harm to patients.”
Nine years was the longest amount of time that data were collected on any of the newer DMTs; the period is much shorter for others, the review said.
MS affects over 2 million people worldwide and is a major cause of disability among the young.
For the last 20 years, practitioners have relied largely on the escalation approach to treating MS: starting treatment with lower-risk, often less-effective DMTs before switching at the onset of breakthrough disease to newer drugs that tend to be more effective but carry a higher risk, the authors said. However, this approach can miss the opportunity to control inflammation during the first few years of the disease, when the inflammatory process is at its peak. Patients tend to accumulate disabilities from MS largely as a result of incomplete recovery from relapses, while neurodegeneration takes on a more important role in the later stages.
In recent years, specialized MS centers have begun to use the newer, higher-efficacy DMTs as a first-line treatment, the review said. Although their long-term benefit has not been definitively illustrated, preliminary results indicate earlier use of the new DMTs provides better disease control and long-term outcomes, with a lower likelihood of transition from relapsing-remitting MS to secondary-progressive MS.
There are now over a dozen DMTs approved for treatment of MS, in contrast to pre-2010 when there were only 3, the review said. The newer DMTs include oral (teriflunomide, dimethyl fumarate, fingolimod, siponimod, ozanimod, and cladribine) and infusion therapies (natalizumab, alemtuzumab, and ocrelizumab). Older therapies comprised such injectables as interferon beta and glatiramer acetate.
Which DMTs to use for each patient, however, remains a “debatable science,” the authors said. RCT samples are not always representative of the overall population, and monitoring those being studied follows a strict process that doesn’t mimic the real world. Postmarketing studies also indicate a wider and more serious range of adverse events; life-threatening adverse events are rare and might not show up during clinical trials. One medication, daclimzumab, was pulled from the market in 2017 after postmarketing evidence of severe liver damage and immune central nervous system reactions, the investigators noted.
Periodic review of case reports or case series are critical to update DMT safety information and identify which patients might be at higher risk of certain adverse events, the authors said.
Jalkh G, Abi N, Macaron G, Rensel M. Safety of newer disease modifying therapies in multiple sclerosis. Vaccines.Published online December 26, 2020. doi:10.3390/vaccines9010012