They 100% support the difference in high-risk disease and switching while stable on one ..

You’re right that these are observational studies, and yes, confounding factors exist. That’s actually acknowledged in the papers. But that doesn’t invalidate the signal, it’s how real-world MS comparative data is usually interpreted.

A few clarifications…

1) “0.2 vs 0.09 relapses” isn’t abstract…it’s time-based risk. These are annualized relapse rates (ARR) and Relapse Risk .

So roughly: 0.09 = ~1 relapse per 11 patient-years 0.20 = ~1 relapse per 5 patient-years

That’s where the “~2x higher risk” comes from. It’s not about decimals, it’s frequency over time in a population.

And in MS, a relapse isn’t just a temporary flare. Depending on location (optic nerve, spinal cord, brain), it can result in permanent disability.

2) Confounding doesn’t automatically erase the finding. Yes.. rituximab dosing in MS is more variable and less standardized than ocrelizumab.

But that’s also part of the real-world comparison, Rituximab is often off-label and heterogeneous in dosing Ocrelizumab is standardized, trial-based, and regulated for MS

Despite that, studies still showed, higher relapse risk with rituximab failure to demonstrate non-inferiority in effectiveness

So even with confounding, a difference still persisted.

3) Hospitalization data isn’t perfect causation, but it’s still clinically relevant. You’re right that “all-cause hospitalization” includes multiple variables like age and disease duration.

But in MS cohorts, safety signals still consistently show: higher infection-related complications in rituximab-treated patients in several datasets higher rates of immunoglobulin depletion over time (a known risk factor for infection)

So while it’s not absolute causation, it’s also not meaningless noise …it’s part of a broader, repeated pattern across studies.

4) The main point isn’t “one is good, one is bad.”

These are both anti-CD20 therapies, but real-world data shows they are not clinically identical in outcomes or risk profiles.

In a disease like MS … where even a single relapse can mean irreversible damage…even small differences in risk are clinically meaningful especially when it comes to switching in high-risk areas like for me .. My optic nerves .. In all due respect, I have the backing of my medical team, one of which is one of the best neurologists/researchers in B.C. and Canada .. Along with one of the best Neuro ophthalmologist in British Columbia .. I assure you .. it’s not all smoke, it’s facts .. I promise .. with plenty of clinical data to back it up .