Why is Prof G so disheartened?

I was at an international multiple sclerosis meeting on the weekend, and we used a virtual board game to teach healthcare professionals (HCPs) about clinical decision-making in relation to DMTs. It was surprising and disheartening to hear many of the attendees fail to include alemtuzumab or AHSCT (autologous haemopoietic stem cell transplant) in their decision-making. Many attendees were surprised when I stated ‘that if I were their patient, I would expect them to include alemtuzumab and AHSCT as potential treatment options’. By the look on their faces, they thought I must be deranged. Don’t they know alemtuzumab is a licensed DMT and that AHSCT is reimbursed for treating MS in many countries? It is clear that the message of how effective alemtuzumab and AHSCT are as DMTs is not getting through to the next generation of MSologists or HCPs. This is a tragedy. Nobody could tell me the results when I asked them what they thought about the 10-year alemtuzumab follow-up data. Here are the headline results:* 60% of subjects are free of disability worsening.* 50% had confirmed improvement in disability.* Annualized brain volume loss consistently below 0.2% (essentially in the normal range for age).* Trial subjects who were randomised to interferon-beta for the first 2-years never catch up; time is brain and spinal cord.These results are clouded by a 40% drop-out rate and hence will be enriched for responders. However, these results still support hitting MS early and hard with an IRT will result in a significant number of pwMS going into long-term remission. I recall doing the exit assessments for many pwMS from the 10-year extension study, and I have never seen so many people with MS living normal lives with no disability in long-term remission but still carrying around the label of having MS. The results of AHSCT are similarly impressive, but AHSCT comes with much greater risks up-front. Wouldn’t it be great to tell some of these pwMS that they are cured? This is why we have tried to define what an MS cure would look like (please see ‘How do I want my MS to be treated?; 08-Oct-2021’) so we can look for it in clinical practice. Knowing what MS can do to people and seeing these results, who wouldn’t want to be treated with, or at least offered the option of being treated with, alemtuzumab or another IRT when diagnosed? I sincerely hope that when the 10-year alemtuzumab follow-up data is published, the wider MS community acknowledges how well these patients have done and that we may have a treatment that could offer patients a cure. Giovannoni et al. Early treatment with alemtuzumab maintains its efficacy on clinical and MRI disease activity outcomes, including slowing of brain volume loss, over 10 years in RRMS patients: CARE-MS II follow-up (TOPAZ Study). ECTRIMS 2021, P722. Introduction: In CARE-MS II (NCT00548405), alemtuzumab (12 mg/day; baseline: 5 days; 12 months later: 3 days) significantly improved clinical/MRI outcomes versus SC IFNB-1a over 2 years (y) in RRMS patients with inadequate response to prior therapy and further minimised disease in a 4-y extension study (NCT00930553). Further follow-up was available in an additional 5-y extension, TOPAZ (NCT02255656).Aims: Evaluate the efficacy and safety of alemtuzumab in CARE-MS II patients over 10 y.Methods: At investigator discretion, patients in TOPAZ can receive additional alemtuzumab as needed for disease activity (≥12 months apart) or other disease-modifying therapy (DMT) at any time.Results: Proportions of patients remaining on study after 10 y were 62% (271/435) among those treated initially with alemtuzumab in the core study and 73% (107/146) among those treated with SC IFNB-1a for 2 y before switching to alemtuzumab in the extensions. In the extension studies, 39% of the alemtuzumab group did not receive further treatment (alemtuzumab or other DMT). Among the alemtuzumab group over the combined core and extension studies, 71% of patients had stable/improved EDSS scores, the mean change in EDSS score was +0.34, 58% of patients were free of 6-month confirmed disability worsening, and 49% achieved 6-month confirmed disability improvement. In Y10, the annualised relapse rate was 0.11, 71% of patients were free of MRI disease activity, 92% were free of new gadolinium-enhancing lesions, and 72% were free of new/enlarging T2 hyperintense lesions. The median annual brain volume loss was ≤0.19% each year over Y3–10. Alemtuzumab had a consistent safety profile over 10 y, with the incidence of overall adverse events (AEs) and infections declining through Y10. Cumulative incidence of thyroid AEs was 44% and immune thrombocytopaenia was 4%. Efficacy and safety in SC IFNB-1a–treated patients from the core study who switched to alemtuzumab in the extension were consistent with those treated with alemtuzumab in both the core and extension.Conclusions: Early treatment efficacy with alemtuzumab on clinical, MRI lesion, and brain volume outcomes was maintained over 10 y in CARE-MS II patients, with 62% remaining on study and 39% receiving no additional courses or other DMTs through Y10. Safety remained consistent and manageable over 10 y, with declining AE incidences over time, including a consistent reduction in autoimmune AE occurrence after Y3.Click here to download the poster.Subscriptions and donationsPaid subscriptions to MS-Selfie are being used to administer the Newsletter and associated MS-Selfie microsite currently in development. At the request of several readers, I have now added the option of making a one-off donation. To keep this initiative open to all readers, I would appreciate it if those who can afford a subscription to subscribe. For active paying subscribers, thank you; your contribution is much appreciated.  Because of the falloff in paying subscribers, I am considering returning to a paywall that will give paying subscribers six months of unlimited access to all newsletters. At the same time, free subscribers will have to wait to access the newsletters later as an email but on the substack site.Donations to MS-SelfieProf G’s backstory and CVProf G’s MS Blog ArchiveConflicts of InterestTwitter / LinkedIn / MediumGeneral Disclaimer: Please note that the opinions expressed here are those of Professor Giovannoni and do not necessarily reflect the positions of Barts and The London School of Medicine and Dentistry nor Barts Health NHS Trust. 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