Lack of Evidence Supporting Pharmacological Interventions for Cognitive Impairment Caused by Multiple Sclerosis

Although patients with multiple sclerosis (MS) have many pharmacologic treatments available to reduce clinical relapses and brain lesions, and to improve physical symptoms, investigators have found little evidence of efficacy in the treatment of cognitive dysfunction.¹

Cognitive impairment is extremely common among patients with MS, affecting approximately two-thirds of this patient population. The most common areas of concern are speed of information processing, learning, and memory, according to the investigators.¹ These symptoms can not only disrupt the patient’s life but can also disrupt symptom management and medication adherence.¹

In an effort to understand how MS treatments could affect these cognitive impairments, researchers conducted a literature search that identified 87 articles for final review. Agents from multiple therapeutic categories were represented, including disease-modifying therapies (DMTs), symptomatic therapies, and other therapies such as estrogen or methylprednisolone.¹

DMTs can include injectable or oral medications and are designed to prevent relapses and slow the progression of MS. They include interferon b-1a and b-1b, glatiramer acetate, natalizumab, and others.¹ Among studies of DMTs, the investigators found very little good-quality evidence in support of their cognitive efficacy for patients with MS. There was no class I evidence for the drugs, and the majority of studies were class III and IV, whereas class II investigations either showed negligible or no significant treatment effects.¹

Symptomatic therapies can be prescribed to treat specific symptoms of MS, such as mobility or fatigue, and include dalfampridine, cognition-enhancing medications, and stimulants.¹ Unlike the studies on DMTs, most studies of symptomatic therapies examined cognition as primary endpoints. They also generally had stronger effect sizes—in the medium range, compared with the small or negligible range of the DMT studies.¹

The best findings in symptomatic therapies were for dalfampridine, with 1 randomized controlled trial in support of its cognitive efficacy. Despite these results, multiple lower-quality trials showed mixed findings for the drug. Multiple class I and II studies showed no significant treatment effects for cognition using dementia medications.¹ Similarly, other therapies yielded mixed results, leading the study authors to conclude that there is insufficient evidence to support the use of symptomatic therapies to improve cognitive function in patients with MS.¹

Finally, non-DMT and non-symptomatic therapies also had very limited evidence to support their use in patients with cognitive difficulties due to MS. In the literature review, no studies had cognition as the sole primary endpoint, and there was very limited quality evidence to support the cognitive efficacy of the medications examined.¹

With so little positive evidence, the investigators concluded that more quality research is needed in order to explore the cognitive efficacy of available treatment options.

“Given the impact of cognitive dysfunction on individuals with MS, it is prudent to explore the potential for cognitive efficacy of available pharmaceuticals,” said Helen Genova, PhD, in a statement. “Randomized, controlled studies with cognition as the primary outcomes will provide clinicians with the information they need to choose optimal treatments for patients.”²

REFERENCES

• Chen M, Goverover Y, Genova H, and Deluca J. Cognitive Efficacy of Pharmacologic Treatments in Multiple Sclerosis: A Systematic Review. CNS Drugs; May 2, 2020. https://link.springer.com/article/10.1007/s40263-020-00734-4. Accessed June 23, 2020.
• Evidence lacking for drug treatment of multiple sclerosis-related cognitive impairment [news release]. EurekAlert; June 17, 2020. https://www.eurekalert.org/pub_releases/2020-06/kf-elf061720.php. Accessed June 23, 2020.