The Silent Withdrawal

A harmless title? Not at all. Beneath this seemingly simple question lurks – as so often – a complex web of data, risks, immune cells, and a lack of predictive markers. I opened my notebook. The case was on.

🧠 The Crime Scene: MS Stability – A Deceptive Peace?

Colleagues from neurology practices increasingly report: "The patient has been relapse-free for years. MRI clean. Why continue treatment?" A valid question. Many people with MS understandably wish to stop medication after years of stability – especially with side effects or increasing age. But this is precisely where things get dangerous. As Sherlock Holmes says: "Danger often lies where you least expect it."

🔍 The Three Trails: Study Summary

🤖 DISCOMS: The American Lead

• Older patients, stable MS for 5+ years
  
• Compared continuation vs. discontinuation of therapy
  
• After 2 years: 3x more disease activity in the discontinuation group, but no difference in EDSS progression

🥵 DOT-MS: The Dutch Revelation

• Randomized, prematurely stopped after interim analysis
• Platform therapies only
• Therapy group: 0% new activity; discontinuation group: 17.8% (2 relapses, 7 new MRI lesions)
• 10 out of 45 had to restart therapy

⚠️ OFSEP: The Registry Perspective

• Older people with MS (>50 yrs) with high-efficacy therapies
  
• Hazard Ratio for relapse after discontinuation:
  • Overall: 4.1
  • Natalizumab: 7.2
  • CD20 therapies (e.g., Ocrelizumab): 1.1 (not significant)

• Many had SPMS; mean EDSS >4.5
  

🧪 The Motive: Why Stop Treatment?

The reasons for stopping MS therapy are diverse:

• Age, comorbidities, side effects
  
• Treatment-related fatigue
  
• Fear of long-term damage or infections
  

But this harbors a fatal error: Many patients have cardiovascular risk factors (e.g., hypertension, diabetes) – and these are proven to worsen MS progression. "Sometimes the greatest enemy is not the visible one, but what you thought was harmless."

🧙️ What’s Missing? The Crystal Ball – or Reliable Predictors

A key point in our case: We lack reliable markers to predict who can safely discontinue therapy – and who cannot. What  we wish for:

• Biomarkers (e.g., neurofilament light chain)
  
• Better MRI algorithms
  
• Individual risk profiles
  
• Cognitive and functional progression data
  

Until then, the rule remains: when in doubt, stay cautious.

🧔️ Age Does Not Protect Against MS

Many believe that after a certain age “nothing happens anymore.” But beware:

• Primary progressive MS often begins around age 50
• Slow progression can occur without relapses or MRI activity
• And: The immune system ages – but not predictably

"Old cases are often the most dangerous – they disguise themselves as solved."

⚖️ My Verdict as Sherlock MS

Discontinuing MS therapy is not a walk in the park, but a highly complex risk maneuver. What looks like peace may in fact be silent progression.

👉 Without reliable predictors, discontinuation is currently only justifiable in selected individual cases.
👉 The path should be multidisciplinary, personalized, and closely monitored (MRI, biomarkers).
👉 And: patients should be actively and honestly involved in the decision.

Our case is not closed.

We need more data, better tools – and the courage to keep asking questions.

"A good detective never stops asking – especially when everyone else believes the answer is already known."

Sherlock MS