Le Hua, MD

“We can extract from animal models that, yes, it might have this effect, it might have neuroprotective effects, but we never really know 100%. But, it’s reassuring because the whole story is that we probably need to treat both the peripheral immune components as well as the CNS component.”

Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) forum

, February 27-29, 2020, in West Palm Beach, Florida, Le Hua, MD, director, Multiple Sclerosis Program, Cleveland Clinic Lou Ruvo Center for Brain Health, and colleagues presented data from a subanalysis of the EXPAND study of siponimod in patients with secondary progressive multiple sclerosis (SPMS).

The analysis stratified patients by their ages, under and over the age of 45 years, at baseline. In total, the cohort consisted of 779 patients, of which 473 were ≥45 years old (siponimod, n = 213; placebo, n = 93) and 306 were <45 years old (siponimod, n = 303; placebo, n = 170). Those younger than 45 years experienced a reduced risk of 3-month confirmed disease progression (CDP) by 31.9% compared with placebo (hazard ratio [HR], 0.68; 95% CI, 0.45—1.04; 

= .0734), and 6 month CDP risk by 39.5% (HR, 0.61; 95% CI, 0.38—0.96; 

 = .0339). Those 45 years and older reduced the risk of 3-month and 6-month CDP by 31.5% (HR, 0.69; 95% CI, 0.48—0.97; 

 = .0340) and 33.1% (HR, 0.67; 95% CI, 0.45—1.0; 

The aim of the assessment was to further explore some of the complexities which surface when treating patients with MS as they age, particularly when their chronological and immunological ages can be so different. To find out more about what these data mean and what still needs to be elucidated, 

1. Hua L, Bar-Or A, Lublin FD, Meng X, Su W, Cree BA, Fox R. Analyses Of The Effect Of Baseline Age On The Efficacy And Safety Of Siponimod In Patients With Active SPMS From The Expand Study. Presented at 2020 ACTRIMS Forum. February 27-29, 2020; West Palm Beach, FL. Abstract P029.

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The director of the Multiple Sclerosis Program at Cleveland Clinic’s Lou Ruvo Center for Brain Health detailed what can currently be surmised about siponimod’s effect in treating patients with SPMS.

Le Hua, MD: Siponimod in Secondary Progressive Multiple Sclerosis

“It really does get into the question of, can we dichotomize our patients? We know there is a younger group and an older group, and we really wanted to look at if there was a difference in the drug working on one group or the other?”

 in patients with secondary progressive multiple sclerosis (SPMS) validated the oral, second-generation sphingosine 1-phosphate (S1P) receptor modulator versus placebo. At the 

, February 27-29, 2020, in West Palm Beach, Florida, more data were presented from the assessment, the main findings of which showed siponimod had significantly reduced risk of 3-month and 6-month confirmed disability progression (CDP) by 21% and 26%, respectively.

One of those datasets was presented by Le Hua, MD, director, Multiple Sclerosis Program, Cleveland Clinic Lou Ruvo Center for Brain Health. It evaluated the efficacy and safety of the therapy in patients under and over the age of 45 years at baseline. In total, the cohort consisted of 779 patients, of which 473 were ≥45 years old (siponimod, n = 213; placebo, n = 93) and 306 were <45 years old (siponimod, n = 303; placebo, n = 170).

All told, those younger than 45 years experienced a reduced risk of 3 month CDP by 31.9% compared with placebo (hazard ratio [HR], 0.68; 95% CI, 0.45—1.04; 

 = .0339). Those 45 years and older reduced the risk of 3-month and 6-month CDP by 31.5% (HR,0.69; 95% CI, 0.48—0.97; 

, Hua discussed the findings of this subanalysis of the EXPAND study and what it &shy;&shy;means for the understanding of older and younger groups of patients with MS.

1. Bar-Or A, Cohan SL, Coyle PK, Lublin FD, Meng X, Su W, Cree BA. Analysis of the effects of disease duration on the efficacy and safety of siponimod in patients with active SPMS from the Expand study. Presented at 2020 ACTRIMS Forum. February 27-29, 2020; West Palm Beach, FL. Abstract P030.

2. Hua L, Bar-Or A, Lublin FD, Meng X, Su W, Cree BA, Fox R. Analyses Of The Effect Of Baseline Age On The Efficacy And Safety Of Siponimod In Patients With Active SPMS From The Expand Study. Presented at 2020 ACTRIMS Forum. February 27-29, 2020; West Palm Beach, FL. Abstract P029.

The director of the Multiple Sclerosis Program at Cleveland Clinic’s Lou Ruvo Center for Brain Health discussed the findings of a subanalysis of the EXPAND study of siponimod in patients with secondary progressive multiple sclerosis.

Le Hua, MD: Subanalysis of the EXPAND Study of Siponimod in SPMS

“Our main focus [since the first MS approval] has been that we need to get therapies out there, we need to get stronger therapies—we haven’t really thought of age as a factor to consider.”

In the early 1990s, when the first therapies for multiple sclerosis (MS) treatment became widely available, physicians who were managing these patients had little on their minds outside of addressing the need for more therapies. As time went on, this focus shifted toward a need for higher efficacy therapies, but all the while, patients with MS were getting older.

Now, according to Le Hua, MD, director, Multiple Sclerosis Program, Cleveland Clinic Lou Ruvo Center for Brain Health, the prevalence of MS has altered to an older population. As treatment has improved, patients have begun to live longer with the disease—and are on disease-modifying therapies longer. This, she told 

, has required a parallel shift in thinking about age in MS.

, February 27-29, 2020, in West Palm Beach, Florida, Hua discussed the need to take age into consideration when managing a patient with MS, and how the approach to treating this population changes over time.

The director of the Multiple Sclerosis Program at Cleveland Clinic’s Lou Ruvo Center for Brain Health discussed the need to take age into consideration when managing a patient with MS, and how the thinking about the disease and age has shifted.

Le Hua, MD: Considering Age in Multiple Sclerosis Treatment

“A lot of the studies have shown that the older you get, the less relapses there are, the less MRI changes, the less activity. …[But,] we don’t have a really good idea as to if we should be treating older patients differently if what’s actually underlying the disease is different.”

Multiple sclerosis (MS) is a difficult disease for physicians to treat, even with the relatively vast arsenal of therapeutics available as treatment options. Additionally, a wide variety of factors, including a patient’s age at the time and at diagnosis as well as the duration of the disease, influence the physician’s approach to managing its progression.

, February 27-29, 2020, in West Palm Beach, Florida, a number of conversations around the topic of treatment in this sense sprung up. Currently, the disease-modifying therapies are designed to target the early phase disease course, which is characterized by lesion activity and inflammation, while treatments for progressive disease have required a modified approach.

To find out more about the questions facing MS specialists and the correlation between age, disease duration, and treatment in patients, 

 sat with Le Hua, MD, director, Multiple Sclerosis Program, Cleveland Clinic Lou Ruvo Center for Brain Health. Hua detailed the current thinking about how to address this challenge.

The director of the Multiple Sclerosis Program at Cleveland Clinic’s Lou Ruvo Center for Brain Health detailed the current thinking about the challenges of addressing multiple sclerosis in older patients.

Author | Le Hua, MD

Articles

Le Hua, MD: Siponimod in Secondary Progressive Multiple Sclerosis

Le Hua, MD: Subanalysis of the EXPAND Study of Siponimod in SPMS

Le Hua, MD: Considering Age in Multiple Sclerosis Treatment

Le Hua, MD: Disease Duration and Age in MS