Risks associated with converting to SPMS

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I guess you can read this and there is not alot that you can modify except to stop smoking. There was no significant difference between escalation and early intensive therapy approaches in the risk of transition to progressive phase.

Barzegar M, Najdaghi S, Afshari-Safavi A, Nehzat N, Mirmosayyeb O, Shaygannejad V. Early predictors of conversion to secondary progressive multiple sclerosis. Mult Scler Relat Disord. 2021 Jun 26;54:103115. doi: 10.1016/j.msard.2021.103115.

Background: We conducted this study to estimated the time of conversion from relapsing-remitting MS (RRMS) to SPMS and its early predictor factors.

Methods: In this retrospective study, demographic, clinical, and imaging data from MS patients at diagnosis were extracted. Cox proportional hazards model was used to assess the association between various baseline characteristics and conversion to SPMS. We also assessed the association brtween escalation and early intensive therapy approaches with transition to progressive phase.

Results: Out of 1903 patients with RRMS at baseline, 293 (15.4%) patients progressed to SPMS during follow-up. The estimated number of patients converted to SPMS was 10% at 10-years, 50% at 20-years, and 93% at 30-years. On multivariate Cox regression analysis older age at onset (HR: 1.067, 95%CI: 1.048-1.085, p < 0.001), smoking (HR: 2.120, 95%CI: 1.203-3.736, p = 0.009), higher EDSS at onset (HR: 1.199, 95%CI: 1.109-1.295, p < 0.001), motor dysfunction (HR: 2.470, 95%CI: 1.605-3.800, p < 0.001), cerebellar dysfunction (HR: 3.096, 95%CI: 1.840-5.211, p < 0.001), and presence of lesions in spinal cord (HR: 0.573, 95%CI: 0.297-0.989, p = 0.042) increased the risk of conversion from RRMS to SPMS. No significant difference between escalation and EIT groups in the risk of transition to progressive phase (weighted HR = 1.438; 95% CI: 0.963, 2.147; p = 0.076) was found.

Conclusion: Our data support previous observations that smoking is a modifiable risk factor for secondary progressive MS and confirms that spinal cord involvement, age, and more severe disease at onset are prognostic factors for converting to secondary progressive MS.

“Data on disease-modifying therapy was extracted from the database. DMTs were classified into first-line including interferon beta, glatiramer acetate, dimethyl fumarate, and teriflunomide, or second-line consisting of fingolimod, natalizumab, and rituximab. Second-line drugs have better clinical efficacy but unfavorable safety profile. Two approaches for treatment of a naïve MS patient was used: escalation and early intensive treatment [EIT]. Therapeutic escalation was defined as switching from first-line DMT to a second-line drug including fingolimod, natalizumab, or rituximab because of suboptimal response based on new relapses or MRI activity. EIT was defined as starting treatment with fingolimod, natalizumab, or rituximab for naïve MS patients since poor prognostics factors including more active disease”

Simonsen CS, Flemmen HØ, Broch L, Brunborg C, Berg-Hansen P, Moen SM, Celius EG. Early High Efficacy Treatment in Multiple Sclerosis Is the Best Predictor of Future Disease Activity Over 1 and 2 Years in a Norwegian Population-Based Registry. Front Neurol. 2021 Jun 17;12:693017. 

Background: Moderate and high efficacy disease modifying therapies (DMTs) have a profound effect on disease activity. The current treatment guidelines only recommend high efficacy DMTs for patients with highly active MS. The objective was to examine the impact of initial treatment choice in achieving no evidence of disease activity (NEDA) at year 1 and 2. Methods: Using a real-world population-based registry with limited selection bias from the southeast of Norway, we determined how many patients achieved NEDA on moderate and high efficacy DMTs. Results: 68.0% of patients who started a high efficacy DMT as the first drug achieved NEDA at year 1 and 52.4% at year 2 as compared to 36.0 and 19.4% of patients who started a moderate efficacy DMT as a first drug. The odds ratio (OR) of achieving NEDA on high efficacy drugs compared to moderate efficacy drugs as a first drug at year 1 was 3.9 (95% CI 2.4-6.1, p < 0.001). The OR for high efficacy DMT as the second drug was 2.5 (95% CI 1.7-3.9, p < 0.001), and was not significant for the third drug. Patients with a medium or high risk of disease activity were significantly more likely to achieve NEDA on a high efficacy therapy as a first drug compared to moderate efficacy therapy as a first drug. Conclusions: Achieving NEDA at year 1 and 2 is significantly more likely in patients on high-efficacy disease modifying therapies than on moderate efficacy therapies, and the first choice of treatment is the most important. The immunomodulatory treatment guidelines should be updated to ensure early, high efficacy therapy for the majority of patients diagnosed with MS

Disclaimer: Please note that the opinions expressed here are those of the author and do not reflect the positions of the Barts and The London School of Medicine and Dentistry nor Barts Health NHS Trust or Queen Mary Univeristy of London.

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7 comments

  • > EIT was defined as starting treatment with fingolimod, natalizumab, or rituximab for naïve MS patients since poor prognostics factors including more active disease”

    Two huge and obvious problems with this analysis.

    First, you can’t fairly compare EIT to escalation therapy unless you are testing them in comparable groups of MS patients. If the EIT patients are all people with obviously aggressive disease, while the escalation group includes people with obviously milder disease, that is not a fair comparison.

    Second and even more glaring, fingolimod is not even close to qualifying as a high-efficacy treatment, and based on the Swedish data neither is rituximab. Natalizumab is, but I bet this is the least-common drug in the EIT cohort. This analysis needs to at least drop fingolimod and include alemtuzumab and HSCT to be useful.

  • “presence of lesions in spinal cord (HR: 0.573, 95%CI: 0.297-0.989, p = 0.042)”
    HR<1, is it a higher risk of SPMS or lower? Thank you!

  • Also, how did they go about calculating figures for the impact of “EIT” after 30 years? How many of the “high efficacy” DMTs were available in the early 1990s?

  • As other readers have mentioned. There were only interferons in the 90s so intial damage done by MS before the big guns DMT came online in early 2000s would of defined the course of MS. plus how do you define late onset? I had my first CIS when I was 30. Then full MS at 45. Is this late onset. Also no induction therapy included in the data. Really a poorly executed study. And destroys all the points being drummed by Prof G reversing the triangle, etc. Also why doesnt someone say the reason smoking ( and I suspect high blood pressure) accelerates MS. Both make the blood brain barrier more permeable allowing T cells to cross over into CNS. Smoking by the air bubbles that are caused by inhaling.

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