Multiple sclerosis.pptx sms mc jaipur Rajasthan

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1. Multiple sclerosis: approach to treatment DR SHIKHA AGARWAL SR Neurology SMS hospital , jaipur Moderator: DR B L KUMAWAT SIR SENIOR PROFESSOR AND HEAD OF UNIT SMS HOSPITAL , JAIPUR

2. Outlines Introduction and subtypes Classification of DMT by efficacy and common side effect profiles Existing treatment paradigms and need for effective therapy in early ms Real world evidence from Germany based study Barriers to adoption of early het and potential solutions

3. INTRODUCTION Multiple sclerosis (MS) is a chronic , immune mediated neuroinflammatory and neurodegenerative disease of the central nervous system. It is divided into - Clinically isolated syndrome (CIS) Relapsing remitting MS (RRMS) Primary progressive MS (PPMS) Secondary progressive MS (SPMS)

4. MS disease activity and underlying neuroinflammation activity are indicated by- Clinical relapse MRI Worsening disability Since inflammatory disease activity and irreversible neurodegeneration can occur early in the disease course , even before the first clinical event, early therapeutic intervention is thus the best long term prognosis, compared with delayed or no intervention. Real world evidence is emerging that early intervention with high efficacy therapy (HET )may provide the best opportunity to protect CNS against irreversible injury and control the early inflammatory component of the disease. Until ongoing randomized controlled trials are able to confirm this stance from the clinical perspective, there remains no formal consensus on the best therapeutic approach to MS care. In this study the early use of high efficacy therapy in MS is reviewed along with the obstacles and evidence in todays world to implement the same.

5. CLASSIFICATION OF DMT BY EFFICACY BASIS : ABILITY TO REDUCE ANNUAL RELPASE RATES (ARR ): LOW EFFICACY: reduce ARR by 20- 40% vs placebo MODERATE EFFICACY: reduce ARR by 40-60% vs placebo HIGH EFFICACY: reduce ARR by >65% vs placebo

6. EXISTING TREATMENT PARADIGMS

7. comparing the two major strategies… An escalation strategy is one in which patients initially receive lower-efficacy therapies with well-characterized safety profiles to minimize concerns about side effects . HCPs then switch patients to higher-efficacy therapies following breakthrough disease activity (i.e., new clinical relapses and/or MRI activity) . Initial intervention with lower-efficacy therapies might benefit some patients, such as those with a mild disease course or a preference for lower-risk DMTs . Escalation might also allow some patients flexibility with treatment options , taking into account prognostic measures, risk tolerance, age, and available financial resources . Because lower-efficacy DMTs are thought to be more immunomodulatory than immunosuppressive , they can be particularly useful for patients with comorbidities, s uch as chronic infections, where immunosurveillance is essential.

8. The clinical data suggest that low-efficacy therapies may have value in reducing inflammation, mild relapses, and disability progression in the beginning of the disease; however, their effect on accumulation of disability may not be maintained long-term . Society guidelines have traditionally recommended an escalation approach . Patient care is now evolving, with many MS specialists and other clinicians prioritizing treatment goals of mitigating or halting the underlying inflammatory mechanisms of MS to prevent irreversible disability . This has led to a shift toward an early aggressive or proactive treatment approach , where patients are initiated on HETs (often at diagnosis) to more effectively prevent relapses, reduce potential neuronal injury, slow disability accrual, and ultimately improve optimal patient outcomes .

9. Mechanism of disability in MS : main driver of poor quality of life Because current DMT are limited in their ability to sop PIRA , early and effective intervention may therefore be the optimal strategy to prevent or delay long term irreversible disability.

10. The need for effective therapy in early ms …

11. Patients who received HET on the basis of more active disease actually had a lower long-term risk of conversion to SPMS than those with less active disease on escalation therapy . Even after patients switched from moderate- efficacy therapy to HET, those who initiated early HET showed improved longer-term outcomes compared with those on delayed HET . Younger age is a major factor of immunomodulatory drug efficacy , likely due to higher cerebral reserve, further reinforcing the importance of early treatment. Overall, the available data indicate that patients can achieve maximum therapeutic benefit with early HET therapy, regardless of prognostic factors or disease severity.

12. Comparison of safety b/w low vs high effective therapy The proportion of patients discontinuing treatment due to adverse effects was comparable between those of early HET strategy vs those on escalation strategy. OPERA , ASCKEPIOS and ULTIMATE trials showed safety profile of ocrelizumab, ofatumumab were similar to IFN BETA and teriflunamide . low serum Ig levels can occur with lymphocyte depleting HETs and have been associated with increased infection risk. However, in patients treated with ofatumumab for upto 5 years, mean IgG levels remained stable and IgM Levels decreased but remained above the lower limit of normal.

13. Longer term safety analysis suggest that incidence of adverse events like infusion related reactions, reduce overtime with ongoing HET treatment. Overall, long term data suggest that these therapies should not be excluded solely on the basis of their safety profiles but consideration of individual patient factors is warranted. The lower overall costs from reducing disability with early HET compensate for the initial expense of medications.

14. METHOD A total of 7,85,414 transactions related to MS medication were observed in the period from 2019 to 2022. Medication categories 1,2,3 were assigned to each drug based on the efficacy in the form of ARR. To analyze the shift over time, therapy beginners were grouped based on date of medication purchase into 2020,2021, 2022. differences were calculated on the basis of category of medication received or the drug switched within the same category.

15. RESULTS A total of 29,529 individuals who received a DMT for the first time between 2000 and 2022 were analyzed. For the whole observation period, 75% received category 1, 16.2% category 2 and 13.7% category 3. Over the years cat 1 declined from 75% to 60% Cat 2 increased by 2.2% Cat 3 increased by 12.5% In cat 3 Ocrelizumab first increased by 12% in 2021 and then decreased by 33% in 2022 Natalizumab decreased around 22% Alemtuzumab was used in only 0.2% of the beginners Rituximab use decreased by 5% over the years Ofatumumab used in therapy beginners was increased by 49.9% after market introduction in 2022.

16. The most used high efficacy drugs were ocrelizumab and natalizumab. The use of ocrelizumab increased and then decreased might be because of introduction of ofatumumab in 2022. Ofatumumab provides subcutaneous monthly administration compared to ocrelizumab that has to be given by iv infusion every 6 months.

17. conclusion Real world evidence data are becoming increasingly important in understanding patient care reality and therapy approaches. While most individuals started their treatment according to the treat-to-target approach and remained on their initially prescribed medication category, there has been a steadily increasing shift towards the EHT approach since 2020. These insights demonstrate that, while not officially recommended by the DGN guideline, MS care providers are increasingly adopting the EHT approach. Further studies and insights are needed to further assess the value of initiating a HET approach early on.

18. Barriers and solution to adaption of HET

19. Real-world evidence has revealed clinical benefits, lower disease progression, and favorable long-term outcomes for patients receiving early HET vs escalation therapy or delayed HET [13, 15, 85–87]. In an observational study using data from the MSBase and Swedish MS registries, HET treatment initiated within 2 years of disease onset reduced the risk of disability progression by 66% after 6–10 years compared with HET initiated later in the disease course (hazard ratio 0.34; 95% confidence interval, 0.23, 0.51) [14]. Two similar studies comparing data from Danish, Czech, and Swedish MS registries found that the Swedish high-efficacy induction strategy resulted in reduced risk of disability progression and relapses compared with the Danish and Czech escalation strategies [16, 88]. Further, a systematic review of seven studies revealed that early HET had a 30% reduction in disability worsening at 5 years vs escalation therapy [89].

20. Patients who received HET on the basis of more active disease actually had a lower long-term risk of conversion to SPMS than those with less active disease on escalation therapy [85]. Even after patients switched from moderate- efficacy therapy to HET, those who initiated early HET showed improved longer-term outcomes compared with those on delayed HET [14, 86]. Younger age is a major factor of immunomodulatory drug efficacy [90], likely due to higher cerebral reserve, further reinforcing the importance of early treatment . Overall, the available data indicate that patients can achieve maximum therapeutic benefit with early HET therapy, regardless of prognostic factors or disease severity [10, 91].

21. TREAT- MS and DELIVER-MS Two ongoing, prospective, Randomized control trials directly compare HET vs escalation therapy in terms of disability progression, reapses , neurodegeneration, health related quality of life , burdern of MS, cognition , employment and safety. If these trials demonstrate effectiveness, it may serve as acompelling basis for advocating the integration of EHT approach into treatment guidelines and clinical practice. The question of whether early HET or escalation therapy delivers the best long-term outcomes for patients with MS hinges on conclusive evidence from randomized controlled trials for there to be any consensus among MS neurologists.

22. Thank you!