Infusible MS Medications Work Best In Younger Patients

By Bruce Jancin

Infusible disease-modifying therapies for multiple sclerosis (MS) are disproportionately more effective at quelling disease activity than oral drugs in younger patients, an advantage that fades by about age 45 years, Enrique Alvarez, MD, PhD, reported at the annual congress of the European Committee for Treatment and Research in Multiple Sclerosis.

This finding from a single-center retrospective chart review of more than 1,000 patients treated for relapsing-remitting MS has important implications for clinical practice, observed Dr. Alvarez, a neurologist at the Rocky Mountain MS Center at the University of Colorado in Aurora.

“We’re starting to incorporate these findings into practice at our center. I think it’s starting to flip the traditional paradigm of an escalation approach to that of a de-escalation approach to treatment,” he explained.

Dr. Enrique Alvarez
Image credit: Bruce Jancin/MDedge News
The de-escalation strategy, also known as induction therapy or early high-efficacy treatment, posits that higher-efficacy therapies (such as infusible agents) are favorable over drugs at the middle tier of efficacy (such as oral therapies) despite increased safety concerns such as heightened risks of infection and hypogammaglobulinemia. Since MS disease activity is much greater in younger patients, it makes sense to utilize the infusibles early on when there is so much disease activity to prevent. Later in life, when maximum-efficacy therapy is no longer needed because disease activity has diminished and disability is increasing, the risk/benefit ratio shifts and the patient can be switched to a disease-modifying oral agent because of its more attractive safety profile coupled with an age-adjusted efficacy that is now similar to an infusible agent, according to Dr. Alvarez.

“At our center we tend to treat pretty aggressively,” he noted. “Our study data allow us some comfort in saying to patients now, ‘If we can get you to the age of 45, maybe switching to an oral agent might be a very efficacious way to control your disease activity.’ We’re starting to do this switch for our patients who are either having issues of tolerability of infusions, or infection, or hypogammaglobulinemia, things like that.”

Source: Ruggieri, S., Pontecorvo, S., Tortorella, C. et al. Induction treatment strategy in multiple sclerosis: a review of past experiences and future perspectives. Mult Scler Demyelinating Disord 3, 5 (2018) doi:10.1186/s40893-018-0037-7

A retrospective review

Dr. Alvarez presented a retrospective study of 509 patients with relapsing MS who were started on an oral agent – either dimethyl fumarate or fingolimod – and 495 patients who were started on infusible natalizumab or rituximab. The patients were followed for 2 years or until discontinuation of disease-modifying therapy. The investigators lumped the two oral agents together because, in their earlier studies using observational real-world data, they found dimethyl fumarate and fingolimod had similar efficacy (Neurol Clin Pract. 2018 Aug;8[4]:292-301), and that natalizumab was more effective than either of them (Ann Clin Transl Neurol. 2018 Dec 9;6[2]:252-62). Age 45 years was used as a cutoff because other investigators have shown that medications for MS start to lose some of their effectiveness at about that time.

During follow-up, 36% of patients on oral disease-modifying therapy experienced disease activity, defined as clinical relapse or a new T2 or gadolinium-enhancing lesion on MRI. So did 21% of patients on an infusible agent. In both groups, disease activity was more common in patients who were younger, had shorter disease duration, and had a gadolinium-enhancing MRI lesion at baseline.

The key study finding was that in a logistic regression analysis, disease activity during follow-up was 2.67-fold more likely in patients under age 45 years who were on oral as compared with infusible therapy, whereas in those age 45 years or older there was no significant difference in risk depending upon type of therapy. Moreover, the same was true in a propensity-matched analysis controlling for age, gender, disease duration, baseline disease burden, and contrast enhancement on the baseline MRI: patients under age 45 years who were on an oral agent remained 2.12-fold more likely to experience disease activity than those on an infusible agent, while once again, there was no significant efficacy difference between oral and infusible therapies in older patients. The same pattern held when disease activity was tracked by age quartile (see graphic).

Implications for treatment

Dr. Alvarez emphasized that he wasn’t saying that treating patients with relapsing MS who are older than 45 years old is without benefit. Rather, the study shows that the substantially greater treatment efficacy gap favoring infusible over oral disease-modifying drugs in younger patients dwindles with age. Older patients with MS most certainly do benefit from treatment, and this study helps clinicians in understanding how to better use the available drugs, he concluded.

This study was sponsored by the Rocky Mountain MS Center. Dr. Alvarez has received financial support from Biogen, Genzyme, Genentech, Teva, Novartis, and Alkermes. Coauthors disclosed financial support from a number of pharmaceutical companies.

SOURCE: Alvarez E et al. ECTRIMS 2019. Abstract 237.