The use of off-label monoclonal antibodies in neurology. #MSBlog #MSResearch
"The following is my teaching course slides from the EAN (European Academy of Neurology) meeting in Berlin. I was asked to talk on the use of off-label monoclonal antibodies (MABs) in in neurology. It was a very difficult talk to present, because outside of rituximab, alemtuzumab and the anti-TNF-alpha MABs, I don't have much personal experience with MABs. I therefore, tried to cover emerging drugs and orphan diseases in which MABs will have a potential effect."
"Interestingly, most of the questions were directed at the use of rituximab in NMO and related disorders. I tried to cover adverse events of MABs in general terms and discovered that therein lies the problem with rituximab. The fact that it is not fully humanised is a problem and results in anti-drug antibodies that cause infusion reactions and prevent the drug from working. Hopefully, ocrelizumab will solve this problem. It is clear already that it is associated with fewer infusion reactions and less anti-drug antibodies. This in itself should make it a safer drug to use in MS. Maybe ocrelizumab will be effective in MSers treated with rituximab off-label who have developed anti-drug antibodies and have a blunted therapeutic response? The CDR (complementarity determining region) that recognises CD20 is not the site that is generating the ADAs, which will make ocrelizumab a viable option post-rituximab. We have a few cases with neurosarcoidosis who have developed ADA to infliximab (partially humanised. Part animal with a human tail) who have subsequently gone onto adalimumab (Totally human including the CDR) and done well. A rituximab to ocrelizumab (humanised. The CDR are of animal origin) switch study will help answer this question."
Labels: Berlin, Drug switching, EAN, MABs, ocrelizumab, Rituximab