Mavridis T, Papagiannakis N, Breza M, Vavougios GD, Patas K, Daponte A, Laskaratos A, Archontakis-Barakakis P, Pantazopoulos I, Mitsikostas DDB-Cell Targeted Therapies in Patients with Multiple Sclerosis and Incidence of Headache: A Systematic Review and Meta-Analysis. .J Pers Med. 2022 Sep 8;12(9):1474. doi: 10.3390/jpm12091474.
Background: Multiple Sclerosis treatment with B-cell targeted therapies may be associated with an increased incidence of headache. We aimed to find and compare the association of B-cell targeted therapies with the incidence of headache in patients with Multiple Sclerosis.
Methods: In a systematic based approach, the following databases were searched from inception until the 6th of June 2020: Pubmed/MEDLINE, ClinicalTrials.gov, EU Clinical Trials Register. Only randomized clinical trials (RCTs) enrolling patients with Multiple Sclerosis comparing B-cell targeted therapies (Rituximab, Ocrelizumab, Ofatumumab, Ublituximab or Cladribine) with placebo were selected for the systematic review and further meta-analysis. The primary outcome was an all-cause headache of B-cell targeting therapy in patients with Multiple Sclerosis.
Results: Nine RCTs were included. Compared with placebo, treatment with B-cell targeting therapies revealed a trend in headache risk, but it was not statistically significant (Relative Risk 1.12 [95% Confidence Interval 0.96-1.30]; p = 0.15; I2 = 9.32%). Surprisingly, in a sub-group analysis, Cladribine was statistically significant for an increase in headache risk (RR 1.20 [95% CI 1.006-1.42]; p = 0.042; I2 = 0%; 3 studies with 2107 participants).
Conclusions: Even though a trend is shown, B-cell targeted therapies do not correlate with an increased incidence of headache as an adverse effect. Sub-analyses revealed a significant association between Cladribine alone and an increased incidence of headache. Whereas a purinergic signaling cascade is proposed as a mechanism of action, further research is needed to unravel the underlying pathogenetic mechanism of headache induction and establish headache prevention strategies.
A trend means there is no proven difference and data hacking means you trawl through the information until you find something, by chance do it twenty times and you will find something. Now I have no issue with the suggestion that there is an increased chance of headache, but what is the biology that explains it. But they do not find anything with anti-CD20, but there is a suggestion that there is an effect with cladribine . Is it the dreaded non CD20 T cell that makes the difference or is it a chance finding and even if is real the increased risk of 1.2 is small. I would argue that all MS drugs are B cell depleters why not look at alemtuzumab and the others and indeed the introduction talks about headaches in fingolimod. There should be a hierarchy of effects from the good to the weak inhibitors. In addition there are headaches and there are headaches, as one who generally stays clear of paracetemol and asprin etc. I got the headache from hell with COVID, but I am sure this is chicken-feed to any one who gets migraine. However remember when you get an antibody infusion you expect to get infusion reactions and you are given all sorts of preventative agents like anti-histamines and guess what? Yep often paracetemol, so is it a fair fight? I will let the manufacturers of cladribine explain this one to me.
What is you experience?
There are people out there who have taken both c;asses of agent. I know people some people have had rituximab, ocrelizumab and cladribine.
Disclaimer. This represents the authours view only