I have a patient with RA and active MS that unfortunately failed treatment on combination therapy with Methotrexate, Abatacept and Tecfidera. She had an allergic reaction to Rituximab. We could consider monotherapy with Alemtuzumab for MS, but would not like to decompensate her relatively stable RA.
Dear Tatiana,
If I remember rightly alemtuzumab is Campath-1H. A large trial of Campath-1H in rheumatoid was done by Herman Waldman and John Isaacs maybe around 1996. There was improvement during the relatively brief period of B cell depletion (about 3 months) but no long term benefit. However, as far as I know there was no suggestion of deterioration. Look up Isaacs and Campath on PubMed and I think you will find the papers. John Isaacs is in Newcastle and would be able to advise.
An allergic reaction to rituximab is unusual. In my experience reactions tend to occur with rapid infusion but rarely with careful monitoring. Moreover, we have successfully reintroduced rituximab to patients who have had vernalised rash.
I guess natalizumab might be another option for MS? I am not aware of any use in RA although, because it targets the VCAM-1 ligand alpha 4 integrin one might expect it to be rather good (B cells need the ligand interaction to survive in most environments).
Sorry, 'vernalised' should be generalised. The autocorrect is weird on this software.
I was at Elan for a number of years. The natalizumab (Tysabri) studies in RA were terminated, lack of effect. Also note that the labeling includes patient deaths from progressive multifocal leukoencephalopathy (JC virus). I have no experience with alemtuzumab, but it has been studies in RA. From a review: In the early 1990s a number of protocols allowed the administration of alemtuzumab to patients with refractory RA. Alemtuzumab (CAMPATH-1H) is a depleting, humanized mAb that targets CD52 expressed on the surface of B and T lymphocytes, NK cells and monocytes [1]. Although preliminary evidence of efficacy was obtained, therapy was associated with prolonged lymphopenia, in particular of the CD4+ T-cell compartment [2]. Trials were subsequently curtailed but no excess morbidity or mortality has been documented over 12 years of follow-up [3]. Notably, 6 of 25 surviving patients were in DMARD-free clinical remission at the most recent follow-up [3]. Rheumatology (2012)doi:10.1093/rheumatology/kes038First published online: March 24, 2012.
Further, in the review it notes that lymphopenia can be observed > 10 years after cessation of Rx. It wouldn't be my first choice. The above review is helpful.
I agree that although the prolonged t cytosine after natalizumab did not seem to cause too many problems in the RA trial, it would add to concerns about risks associated with any other treatment that might be needed at a later date. Combinations of biologics have caused significant problems in RA.
What about the recently EMA approved Baricitinib? I am not that familiar with MS, but a quick pubmed search revealed that jak Stat inhibition might be beneficial in MS. At least in animal models which not necessarily translates into human disease.
https://www.ncbi.nlm.nih.gov/pubmed/24323580
Thank you for the great suggestions and all the given references. I am tempted to retry IV Rituximab but using much slower infusion in our own infusion unit instead of using rheumatology community infusion centre and have some antihistamines and steroids ready for use if necessary. If this fails, I might give it a go with Alemtuzumab monotherapy.
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