Growth of MS Treatment Options Presents Challenges, Opportunities for Pharmacists to Get Involved

With the explosion of new disease-modifying treatments (DMTs) for multiple sclerosis (MS) in recent decades, deciding which therapy to start can be challenging. However, experts in a session at the Consortium of Multiple Sclerosis Center 2024 Annual Meeting agreed that early treatment is critical, regardless of the agent selected.

“In my practice, I don’t want someone coming in using a walker…we don’t want to do that, because currently we do not have therapies that can reverse time,” said presenter Scott D. Newsome, DO, MSC, FAAN, FANA, a neurologist with Johns Hopkins Medicine.

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Newsome reminded the audience that the first FDA-approved therapy for MS was only approved in 1993, and there are now more than 20 therapies including a variety of administration options, potencies, and more. Data have established that treating patients within the first 5 years of diagnosis is key, and anti-inflammatory strategies may help minimize axonal injury.

Although there are still significant gaps in knowledge for some patient populations and scenarios in MS care (older age, switching therapies, etc), Newsome said the newer medications do appear to be more effective than previous therapies. However, switching therapies after disability has accrued can be problematic.

“Clearly, we need to do better because people continue to progress independent of relapse activity,” Newsome said. “But these therapies we have work quite well, especially early on.”

In MS, the goals of treatment are to maximize and reserve neurologic function, reduce disease activity, and prevent disability. DMT decisions should also be shared, with a careful understanding of the patient’s priorities. Newsome added that nonpharmacologic treatments are also important, such as smoking cessation, weight management, and encouraging patients to remain active.

Regular monitoring is also important, with research showing that regular touchpoints with clinicians can improve adherence to DMTs, increase patient engagement in their care, and help identify subtherapeutic response to treatment. Maintaining these frequent interactions can be done by many members of the care team.

“It really takes a village to treat 1 person with MS, so leveraging other people within the care team, whether it’s pharmacists, nursing, etc, is important,” Newsome said. “In fact, there’s a few studies that have shown, from a pharmacy perspective, that when pharmacists are calling saying, you know, ‘You’re due for your refill’ or ‘Safety labs have not been done yet,’ the patients relay to the pharmacist, ‘Oh, I actually relapsed recently.’ Things [neurologists] don’t even find out about.”

There are a number of potential treatment strategies to consider when selecting a DMT. One option is to initiate patients on a moderate-efficacy therapy, escalate as needed, then potentially de-escalate later. Early aggressive treatment is another option and is typically done with an infusion-based therapy or once-monthly B-cell depleting agent. Newsome acknowledged that standard injectable and oral DMTs typically have lower efficacy but a lower burden of treatment, whereas higher-efficacy DMTs have greater efficacy and a higher burden of treatment. Weighing these options is crucial for selecting the best option for each individual patient.

Regardless of which DMT is selected, Newsome said a significant body of evidence has shown the importance of initiating this treatment. For instance, one study with real-world evidence of treatment initiation showed that those who were treated within 1 year of MS onset were less likely to have an Expanded Disability Status Scale (EDSS) score of 4 (signifying more severe disease), when compared with patients who initiated treatment later.

Similarly, data from the MSBase cohort study of 1555 individuals with relapsing/remitting MS (RRMS) who began DMT showed that all DMTs lengthened the time-to-secondary progressive multiple sclerosis (SPMS) conversion. Additionally, beginning DMT within 5 years of onset lowered the SPMS conversion risk compared with leaving MS untreated for longer.

Despite these growing body of data for DMTs in MS, questions remain about how to decide which DMT to initiate, according to presenter Gabrielle Macaron, MD, a neurologist with Cleveland Clinic. Although Macaron said more treatment choices are inherently better for patients, it also presents significant challenges for clinicians.

“There are too many choices now, and my point here is that you notice in practice that again, [guidelines] are very important, but they cannot replace the critical judgment that we have to individualize treatment decisions that we’re making when we see patients,” Macaron said.

Like Newsome, Macaron said data support the early use of DMT. Irreversible damage in MS stems from axonal injury in acute focal lesions, and the resulting axonal degeneration of chronically demyelinated neurons. This gives a strong rationale for early use of high-efficacy DMTs in MS, because the disease is most active within the first 5 to 10 years of onset. Furthermore, studies such as the ARISE and TERIS trials have established that DMTs work on inflammation and have stronger efficacy earlier in the disease course.

There are data showing that these newer treatment strategies and DMTs are working, Macaron said. For instance, a study between 2005 and 2020 in Sweden showed that the incidence of SPMS decreased from 2.7 per 100 person-years in 2005 to 0.9 per 100 person-years in 2020. Furthermore, the median age at SPMS conversion has also improved, from 58 years in 2005 to 64 in 2020.

Despite the safety risks and adverse effects of high-efficacy DMTs, Macaron said they may still be the safer approach when considering the risks of MS. Some clinicians have argued for the recognition of “benign MS,” but both Newsome and Macaron said they do not believe this is an accurate designation. Studies have shown that benign MS represents between 12% and 15% of patients, but when cognition, employment, fatigue, mood, and other considerations are accounted for, the population frequency drops to 3%. Additionally, Macaron pointed out that benign MS is a retrospective diagnosis and the ability to predict individual prognosis is limited.

With all of these considerations in mind, Macaron said the key considerations when deciding which DMT to use are baseline characteristics, disease activity, adherence, family planning, comorbidities, patient preference, medium-term visibility (how long can this be used), treatment availability, and biomarkers. Higher baseline disease activity, shorter disease duration, young age at treatment initiation and low disability level are all associated with a better treatment response.

Family planning has long been a concern for patients with MS, but newer therapies offer more options. Macaron urged clinicians to ask patients about family planning from the first appointment because it can significantly impact the treatment plan. The primary goal is to have the disease controlled before pregnancy. Some treatments, such as ofatumumab (Kesimpta; Novartis), can be discontinued when patients become pregnant. Patients taking ocrelizumab (Ocrevus; Genentech) should avoid pregnancy for at least 6 to 12 weeks after the last infusion.

Adherence is another crucial challenge for MS medications, and is influenced by tolerance, adverse effects, availability, and other factors. Studies have shown that younger age, first therapy, oral route of administration, poor cognition, single marital status, lower educational level, and lower understanding of the disease are all associated with lower adherence levels. The main causes of lack of adherence are forgetfulness, intolerance, feeling generally unwell, and depression or frustration with the diagnosis.

Studies have shown a wide range of medication adherence levels in MS, anywhere from 41% to 93%. However, Macaron pointed out one study which has shown higher adherence levels in MS compared with other chronic diseases, such as Parkinson disease, epilepsy, and rheumatoid arthritis. Pharmacists can play a vital role in helping patients remain adherent, through counseling, educating, and identifying patient support programs.

Insurance challenges can also play a role in adherence for many patients and give pharmacists opportunities to get involved. Newsome highlighted one study which found that approximately 36% of DMT switches for patients with MS were related to insurance.

“This also, I think, emphasizes the importance if you’re so lucky to have specialty pharmacists to work with you,” Newsome said. “They’re able to find this information just on routine calls [with patients], as well.”

The speakers concluded that although the rapid growth of DMTs for MS can present challenges for clinicians, it is ultimately a great thing for patients. More therapeutic options enable prescribers to better tailor the treatments to patient needs, thereby improving outcomes.

Reference

Macaron G, Newsome SD, Oh J. The Era of Too Many Choices: Starting and Switching Multiple Sclerosis Disease-Modifying Therapies. Presented at: Consortium of Multiple Sclerosis Centers 2024 Annual Meeting. May 29 to June 1, 2024; Nashville, Tennessee.