Some neuros think this is causing unnecessary alarm
This is great news for the people that go NEDA.
What is the advantage of further treatment cycles?
The best way to look is through analysis of the long-term data.
Tuohy O, Costelloe L, Hill-Cawthorne G, Bjornson I, Harding K, Robertson N, May K, Button T, Azzopardi L, Kousin-Ezewu O, Fahey MT, Jones J, Compston DA, Coles A. Alemtuzumab treatment of multiple sclerosis: long-term safety and efficacy.
J Neurol Neurosurg Psychiatry. 2015; 86:208-15
Giving people two infusions and then switching to a lower cost DMT (but which do you switch too?) means that by the 5 year mark the drug costs (3 x £7,000) will be the same except that you will now be treating people yearly from year 3 onwards and you have exposed people to the risk without allowing them to get full benefit.
Extra infusions appear to be worthwhile while the antibody is still depleting, but if there is disease breakthough and lack of effective depletion of white cells then one has to ask whether there is any neutralizing antibody response that block, or partially inhibit the action of alemtuzumab.
It was mentioned in the phase III trial data published that at the end of cycle on about 30% of people have binding antibodies and this goes up to over 80% after the second infusion. It is said that this does not affect the depletion.
However, such responses must have a consequence, whether this can contribute to infusion reactions which occur in about 90% of people. One must suspect that with each cycle of alemtuzumab the anti-alemtuzumab response is boosted.
Although alemtuzumab is a humanised antibody it is amazing that about 75% of people develop neutralizating anti-alemtuzumab antibodies contrasting to only about 1-9% with other humanised antibodies in MS.
How do I work this figure out?
Ziemssen et al. Immunogenicity of alemtuzumab does not impact safety and efficacy in relapsing remitting multiple sclerosis patients in the CARE-MS I study
Anti-alemtuzumab antibodies were detected in 87.0% of
alemtuzumab-treated patients. Titers increased at Months 1 and 3
of the first course, declining by Month 12, when 29.2% of patients
remained antibody-positive. Among patients with binding antibodies, 93.3% tested positive also for inhibitory anti-alemtuzumab antibodies. Development of both binding and inhibitory antibodieswas further increased after the second course, with titers peaking at Month 13 and declining thereafter. Antibody status did not affect clinical efficacy (6-month SAD or annualized relapse rate), magnetic resonance imaging outcomes (T2-hyperintense lesion volume; T1-hypointense, T2-hyperintense, or gadolinium-enhancing lesion counts), overall incidence of adverse events, or the incidence of infusion-associated reactions. Through 2 courses of treatment, the presence and titer of binding or inhibitory antibodies had no discernible effect on T- or B-lymphocyte depletion or recovery.
Therefore 87% of people in care-MS I made binding antibodies and of those it states that 93.3% have neutralizing antibodies.
Yep neutralizing antibodies also known as inhibitory antibodies
Furthermore, they were there after one month of the first infusion, which is amazing considering alemtuzumab is a T and B cell depleting antibody. We have a fair idea why this happens.
Therefore do people, who don’t respond to alemtuzumab have very active disease that is requiring 4 or 5 infusions or do they have neutralizing antibodies that stops the drug working properly (depletion not as good, or lasts for a shorter period of time=currently argued not to occur at least after two infusions)?
Maybe this aspect should be considered if you have active disease on alemtuzumab but it is evident that most people have them.