Omitted data reveals why Lemtrada's treatment of multiple sclerosis could leave patients susceptible to secondary autoimmune conditions.
Scientists in London say they now know why multiple sclerosis (MS) patients who take Lemtrada (alemtuzumab) have a high risk of developing secondary autoimmune diseases.
The apparent answer was found in data that was omitted when the original 2012 clinical trials were published. The data came to light when researchers from Queen Mary University of London filed a Freedom of Information request with the European Medicines Agency seeking access to the full trials data.
What they found was that the mechanism that helps fight MS — the blocking of memory T and B cells — also creates a situation in which one subset of immature B cells thrives. The proliferation of those cells, called CD19+ cells, can make MS patients more susceptible to secondary autoimmune problems.
“Although blockade of memory T and B cells may limit MS, rapid CD19+ B-cell subset repopulation in the absence of effective T-cell regulation has implications for the safety and efficacy of alemtuzumab,” the authors wrote.
Studies have shown that as many as 50% of patients prescribed alemtuzumab will develop secondary autoimmunities within five to seven years of treatment.
When the clinical trials were first published in 2012, the headline from the published data set was that the drug appeared to reduce annual relapse rates and rates of sustained accumulation of disability by about 70%.
Klaus Schmierer (pictured), PhD, the study’s lead author, said the data he uncovered is key to fully understanding the pros and cons of alemtuzumab.
“We were very surprised to find such important information on B cell dynamics were only partially described and remained unpublished, even though they were observed and analyzed several years ago following the pivotal phase III trials,” Schmierer, of Queen Mary University’s Blizard Institute, said.
Schmierer and colleagues suggest that the secondary autoimmune side effects of alemtuzumab might be avoided if physicians seek ways to limit B-cell reconstitution until a patient’s T cells have rebounded to the point where they are able to effectively carry out their regulatory function again.
However, the authors also caution that therapies designed to target B cells might bring their own side effects, many of which could be serious or fatal, such as cancer and serious infections.
“Therefore, careful consideration is needed before such an approach is undertaken and should be formally tested to ensure patient safety,” the authors conclude.
Aside from this most recent study, alemtuzumab has continued to get positive reviews.
Two studies presented in February at the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) conference in Orlando showed alemtuzumab is highly effective in slowing relapsing remitting MS (RRMS).
One study showed the majority of patients with inadequate responses to previous therapies reported improvements with alemtuzumab. A majority of patients also showed no evidence of disease activity. Another study showed the drug slowed down brain volume loss. MS patients lose brain volume 3-5 faster than the general population.
Schmierer said his analysis ought to help physicians ensure that the right patients get access to alemtuzumab, in the safest possible way.
“This new information will help contribute to the effective management of people with MS, firstly during the decision process about disease modifying treatment, and secondly in people who have been treated with alemtuzumab, to ensure the risks associated with dangerous side effects are minimized,” Schmierer said.
The study, titled “Interpreting Lymphocyte Reconstitution Data from the Pivotal Phase 3 Trials of Alemtuzumab,” was published online June 12 in JAMA Neurology.
A press release regarding the study was made available.