Living Well with Multiple Sclerosis

Episode: Disease Modifying Therapies with Dr. Aaron Boster (S6E22)

Date: October 30, 2024
Host: Geoff Allix
Guest: Dr. Aaron Boster, MS neurologist, founder of the Boster Center (Ohio, USA)

Episode Overview

This episode delivers an in-depth tour of Disease Modifying Therapies (DMTs) for multiple sclerosis (MS). Host Geoff Allix welcomes back Dr. Aaron Boster, a renowned MS neurologist, to discuss the entire landscape of DMTs—from the earliest injectable drugs to the very latest oral therapies and monoclonal antibodies. The conversation covers efficacy, safety, administration, patient considerations, and emerging treatments, offering clear, practical insights for people living with MS and those supporting them.

Key Topics and Insights

1. Categories of MS Medications

[01:20] Dr. Boster: Outlines the three medication categories:

• Acute attack management: e.g., steroids.
• Symptom management: e.g., bladder medications.
• Disease Modifying Therapies (DMTs): “Medicines created to change the natural history of the disease to literally modify the course of the disease in our favor... The goal is to preserve neurologic reserve so that 30 years from now, you’re still active in the game.” (01:46)

2. Starting a DMT: Timing and Importance

[02:39] Dr. Boster:

• Early treatment is crucial: “The earlier we start a disease modifying therapy, the better the human does long term. And this is not an opinion. This is very strong science.” (02:39)
• Delayed treatment leads to permanent disability accumulation that can't be recovered.

3. Factors in Choosing a DMT

[04:29] Dr. Boster:

• Weighs efficacy, tolerability, safety, and cost:
  “I want you on the most effective drug that you’re comfortable taking.” (04:32)
• Side effects don’t always correlate with efficacy; risks can be upfront or taper off over time (e.g., Lemtrada).

4. Detailed Guide to Current DMTs

The discussion proceeds alphabetically; for each, Dr. Boster highlights:

• Mechanism of action
• Efficacy, target population, and administration
• Key risks, side effects, and monitoring

Highlights for Major DMTs:

Alemtuzumab (Lemtrada)

• Mechanism: Monoclonal antibody, targets and “murders” adult B and T cells (07:11).
• Efficacy: “One of the most effective drugs currently available.”
• Risks:
  • Major infusion reactions, autoimmunity (41% develop thyroid issues), infection risk (esp. shingles, listeria), rare cancers.
  • “Hands down, probably the most complex drug with the broadest risk profile.” (09:13)
• Administration: 2 infusions a year apart, then regular labs for 4 years (11:10).

Cladribine (Mavenclad)

• Mechanism: “Micro induction therapy,” primarily targets B cells, oral dosing in two cycles over two years, no retreatment unless needed (11:14).
• Efficacy: High efficacy; robust relapse rate reduction and promising progression control.
• Risks: Small increased risk of cancer (~1%), manageable infection risk, requires vaccination prior (13:35).

Fingolimod (Gilenya)

• Mechanism: S1P modulator; traps lymphocytes in lymph nodes, oral daily pill.
• Efficacy: “Quite good at reducing relapse rate,” less impact on disability progression (15:05).
• Risks: First dose can slow heart rate (requires monitoring), infection risk, slight increase in skin cancer.

Mitoxantrone (Novantrone)

• Mechanism: Chemotherapy agent, infrequent use due to risks.
• Risks: “Risk of cancer, which is not small...risk of cardiomyopathy.” (17:13)

Natalizumab (Tysabri)

• Mechanism: Monoclonal antibody tightens blood-brain barrier.“Turns the BBB into the Great Wall of China.” (18:39)
• Efficacy: High efficacy even 20 years post-approval.
• Risks: Main is PML (progressive multifocal leukoencephalopathy), risk based on JC virus status; risk can range from 0.1% to 1%.
• Unique: Some patients feel a “euphoric, energized” effect post-infusion (21:10).

Ofatumumab (Kesimpta)

• Mechanism: B-cell depleter, self-injected at home (convenient for rural patients).
• Efficacy: High efficacy, very good MRI and relapse suppression.
• Risks: Minimal, mostly flu-like symptoms with first doses (23:05).

Ocrelizumab (Ocrevus)

• Mechanism: Infused B-cell depleter every 6 months.
• Efficacy: Doubled effect vs. Rebif in trials; only class I evidence for primary progressive MS (28:13).
• Unique: “Crap gap”—some experience wearing-off before next dose (26:38).

Other DMTs Discussed

• Ozanimod, S1P modulators (Zeposia, Mayzent/Siponimod, Ponvory, etc.): Oral, similar to Gilenya; newer ones avoid first-dose heart monitoring; moderate efficacy, less effect on long-term progression (29:01, 32:34, 44:43).

• Rituximab: Off-label B-cell depleter; effective and less expensive, often used where cost is a barrier (30:28, 31:52).

• Injectable Interferons (Avonex, Betaferon, Rebif, Extavia) & Glatiramer acetate (Copaxone):

  • First-line, earlier low-efficacy therapies (35:00, 37:45).
  • Noted for flu-like symptoms, mild efficacy (30% reduction in relapses or disability progression).
  • Copaxone: Fewer side effects; useful for pregnancy, complex comorbidities.

• Dimethyl fumarate (Tecfidera) & Diroximel fumarate (Vumerity): Oral pills, mid-tier efficacy, similar mechanism and safety; main side effect is GI upset and flushing (40:00, 42:29).

• Teriflunomide (Aubagio): Low efficacy for relapses/MRI, but better for brain volume and disability; used later in disease (45:42).

• Ublituximab (Briumvi): New B-cell depleter, similar to Ocrevus; some tolerate first infusions less well (48:33).

5. Off-label and Supportive Therapies

• Low Dose Naltrexone (LDN):
  • Not a DMT, but anecdotally helpful for some; safe and cheap, but “should not be used instead of proven DMTs.” (50:16)

6. What’s on the Horizon?

• Bruton's Tyrosine Kinase (BTK) Inhibitors:

  • Target B-cell signaling & microglial activation, hope to reduce infection risk vs. B-cell depleters.
  • Multiple candidates in late-stage trials; optimism for results in 3–5 years (54:07).
  • Main concern: elevated liver enzymes.

• Anti-CD40 Ligand Therapies:

  • Block interaction between B- and T-cells, early phase trials, aim to disrupt MS signaling with fewer infections (55:10).

Notable Quotes & Memorable Moments

• On Early DMT Initiation:
  “...the earlier we start, the better chances we’re going to have to control the disease.” — Dr. Boster (03:55)

• On Patient-Centric Care:
  “I want you on the most effective drug that you’re comfortable taking.” — Dr. Boster (04:32)

• Latent Humor on Drug Names:
  “By the way, neither Jeff nor I made up these words.” — Dr. Boster on complex generic names (21:32)

• On Future Therapies:
  “We’re very hopeful... Stay tuned as that dataset evolves.” — Dr. Boster on BTK inhibitors (54:25)

• On Combination Approach:
  “It’s a fool of a doctor who thinks that you only take care of the disease by picking one of these DMTs and taking it. I do, however, feel that DMT is one of the components to a successful treatment plan.” (56:37)

Timestamps for Key Segments

• [01:20] Categories of MS Medications
• [02:39] Why Timing Matters for DMTs
• [04:29] Choosing the Right Therapy
• [06:34+] Deep Dive into DMTs (Alemtuzumab and onward, alphabetically)
• [14:32] DMTs for Relapsing vs. Progressive MS
• [18:39] Natalizumab (Tysabri)
• [26:31] Ocrelizumab (Crap Gap, PPMS evidence)
• [35:00] First-generation Injectables
• [40:08] Dimethyl fumarate(s)
• [45:42] Teriflunomide (Aubagio)
• [48:33] Ublituximab and wrap-up of first-line/high-efficacy DMTs
• [50:16] Low Dose Naltrexone (LDN)
• [52:07] BTK Inhibitors and future therapies
• [55:10] Anti-CD40 Ligand Explorations
• [56:37] Concluding Thoughts

Conclusion

This episode provides a comprehensive, up-to-date look at DMTs for MS. Dr. Boster’s expert, accessible explanations make complex information understandable. The episode is invaluable for newly diagnosed individuals, those considering a therapy change, or anyone seeking to make informed, collaborative decisions with their MS care team.

Final Message:
“I want you on the most effective drug that you’re comfortable taking.”
— Dr. Aaron Boster (56:54)