I have been taken to task out my slipshod use of statistics and suggested about 50% get disease control after two doses and about 50% after three doses so that with three doses about 75% of people get control. Yep I have not referenced anything and you perhaps correctly you said that “You’re floating wild numbers here”….You said “In the CARE-MS I study (treatment-naive patients), about 68.5% required no additional treatment after the first two courses over five years”.
In the interests of balance I will go over the data.
So can have a look at the reported 6 year data.
Coles AJ, Arnold DL, Bass AD, Boster AL, Compston DAS, Fernández Ó, Havrdová EK, Nakamura K, Traboulsee A, Ziemssen T, Jacobs A, Margolin DH, Huang X, Daizadeh N, Chirieac MC, Selmaj KW. Efficacy and safety of alemtuzumab over 6 years: final results of the 4-year CARE-MS extension trial. Ther Adv Neurol Disord. 2021 Apr 23;14:1756286420982134.
In the summary it says “Through year 6, 63% of CARE-MS I and 50% of CARE-MS II alemtuzumab-only patients received neither additional alemtuzumab nor other disease-modifying therapy”….
However, the question is how many people at the start were there at the end?…People drop out for many reasons but one of those reasons is the drug was not working fully and so the demominator is changing with time.
If your trial starts with 1000 ends with 250 people with no disease over the entire period then diseasee is inhibited by 250/1000 = 25% however if only 500 people get to the end there has been a drop-out of 500 people and so 250/500 is 50% so the effect is great but what was the reason why 500 people dropped out some of the reason was because the drug is not working.
In the initial trial
Cohen JA, Coles AJ, Arnold DL, Confavreux C, Fox EJ, Hartung HP, Havrdova E, Selmaj KW, Weiner HL, Fisher E, Brinar VV, Giovannoni G, Stojanovic M, Ertik BI, Lake SL, Margolin DH, Panzara MA, Compston DA; CARE-MS I investigators. Alemtuzumab versus interferon beta 1a as first-line treatment for patients with relapsing-remitting multiple sclerosis: a randomised controlled phase 3 trial. Lancet. 2012;380:1819-28.
It said that that 386 were allocated to people recieved alemtuzumab, 82 relapsed but only 376 people were actually dosed and only 362 people actually finish the study but because the trial outcome is based on “intention to treat” the demonator was set a 376. Number of people with new or enlarging lesions were 176/363 i.e. 48% (~50%) and of a relapse-free was 279 it was 279/376 = 74%. There were 139/360 people that were MRI or clinically disease free so that was 39% (~50%) meaning that 61% were not. But at the end there were 139 active disease free of 376 starters = 37%. Disease activity could be a signal for offering another treatment.
Obviously some of the disease activity was probably in year one so they got another shot as part of the protocol and perhaps this is where my numbers may have come from as we had full access to the CARE-MSI data as well as MS-CARE II. T2 lesions are much more frequent than relapses. But as the companies don’t allow us to keep the data, I can’t go back to check…Sorry. Or was it that we looked at the whole chort of people in the two trials I think about n=811 people
Havrdova E, Arnold DL, Cohen JA, Hartung HP, Fox EJ, Giovannoni G, Schippling S, Selmaj KW, Traboulsee A, Compston DAS, Margolin DH, Thangavelu K, Rodriguez CE, Jody D, Hogan RJ, Xenopoulos P, Panzara MA, Coles AJ; CARE-MS I and CAMMS03409 Investigators. Alemtuzumab CARE-MS I 5-year follow-up: Durable efficacy in the absence of continuous MS therapy. Neurology. 2017;89:1107-1116.
However, in the extension study year 3-5 there are 349 of the 367 finishers and 63/349 got a third treatment straight away = 18.1% at the start. In total 110 recieved the third dose, but only 335 completed the 5 year study. In the original study they reported the annualised relapse rate for year 3, year 4, year 5 and years 3-5 but this did not tell you of the original cohort of 376 how many people were continually free of disease over the 5 year period. So abit of a fudge as they are looking ar data year by year. In the core study it said 88% were free of relapses and for year 5 88% were free of relapses but as they had administered third doses to 110 people meaning clinical or MRI activity. It said there was 77 percent free of MRI activity in the core and 70% in year 5. What happened over the whole period?
So on to the 6 year and final analysis
Coles AJ, Arnold DL, Bass AD, Boster AL, Compston DAS, Fernández Ó, Havrdová EK, Nakamura K, Traboulsee A, Ziemssen T, Jacobs A, Margolin DH, Huang X, Daizadeh N, Chirieac MC, Selmaj KW. Efficacy and safety of alemtuzumab over 6 years: final results of the 4-year CARE-MS extension trial. Ther Adv Neurol Disord. 2021 ;14:1756286420982134.
It is evident n=376 treatment naive started drug at baseline and n=321 completed the analysis So that is 85%
Background: In the 2-year CARE-MS I and II trials, alemtuzumab 12 mg administered on 5 consecutive days at core study baseline and on 3 consecutive days 12 months later significantly improved outcomes versus subcutaneous interferon beta-1a (SC IFNB-1a) in relapsing-remitting multiple sclerosis patients. Here, we present the final 6-year CARE-MS extension trial results (CAMMS03409), and compare outcomes over 6 years in patients randomized to both treatment groups at core study baseline.
Methods: Over a 4-year extension, alemtuzumab patients (alemtuzumab-only) received as-needed additional alemtuzumab (⩾12 months apart) for disease activity after course 2. SC IFNB-1a patients who entered the extension discontinued SC IFNB-1a and received 2 alemtuzumab 12 mg courses (IFN-alemtuzumab), followed by additional, as-needed, alemtuzumab.
Results: Through year 6, 63% of CARE-MS I and 50% of CARE-MS II alemtuzumab-only patients received neither additional alemtuzumab nor other disease-modifying therapy, with lasting suppression of disease activity, improved disability, and slowing of brain volume loss (BVL). In CARE-MS I patients (treatment-naive; less disability; shorter disease duration), disease activity and BVL were significantly reduced in IFN-alemtuzumab patients, similar to alemtuzumab-only patients at year 6. Among CARE-MS II patients (inadequate response to prior treatment; more disability; longer disease duration), alemtuzumab significantly improved clinical and magnetic resonance imaging outcomes, including BVL, in IFN-alemtuzumab patients; however, disability outcomes were less favorable versus alemtuzumab-only patients. Safety profiles, including infections and autoimmunities, following alemtuzumab were similar between treatment groups.
Conclusion: This study demonstrates the high efficacy of alemtuzumab over 6 years, with a similar safety profile between treatment groups.
My Bad?
In Coles et al. 2021 they say “We now show that alemtuzumab-only patients continued to experience disease suppression over 4 more years, with 50% needing no further treatment”. That is what I said isn’t it
It says for the combined CARE-MS 1 and 2 trials that 221 + 192/349 + 387 = 413/736 = 56.1% did not need additional treatment. If we look at the whole original cohort it would be 413/802 = 51.5% from the start of the trial.
In the extension cohort it says 302 of 736 (41.0%) were given a third dose, so 59% didn’t get it and 105 of 736 were given a forth treatment. So 197/302 (65.3%) who got the third dose did not need the forth dose, so abit better than 50% so isn’t that good after three doses it was so n=631 of the starting cohort did not need a forth dose not that far away from 75% protected (85.7%)
Alemtuzumab is a very effective agen,t but sadly the baggage associated with the side-effect profile means that it is seldom used within the the NHS(England) as there is lots of monitoring associated with it. I haven’t looked at the data (Secondary care medicine data) this year but BartsMS was the largest user followed by Cambridge some way behind.
coi Multiple but not considered relevant
Disclaimer; my views
Source: multiple-sclerosis-research.org