#MSBlog: Anti-CD20 or anti-B cell therapies look relatively safe in MS! Let’s keep our fingers crossed.
“In response to a comment regarding the safety of rituximab and ocrelizumab in MS. This poster was presented at ECTRIMS. This is very reassuring in that the anti-CD20 look as if they will be in the upper zone of efficacy and if they prove to be safe they will steal all the limelight.”
Kappos et al. Risk of infections and malignancies after treatment with anti-CD20 monoclonal antibodies: ocrelizumab and rituximab in rheumatoid arthritis and multiple sclerosis. ECTRIMS 2012.
Background: Ocrelizumab (OCR) and rituximab (RTX) are CD20 targeting B cell depleting monoclonal antibodies. Safety data from their use in MS and rheumatoid arthritis (RA) may inform about expected risks in MS studies.
Methods: Data from all available OCR (RA n=2820; MS n=220), RTX studies (RA n=3914; MS n=569) and post-approval data (RTX RA only; exposure n>188 000) were reviewed for rates of infection and serious infection (SI), including progressive multifocal leucoencephalopathy (PML) and incidence of malignancies.
RTX RA: In the long-term safety extension of the Phase 3 studies (n=3194; <=9.5y follow-up), AE and SAE rates for RTX were comparable vs pooled placebo (PBO) arms from those double-blind Phase 3 studies. SI event (SIE) rates for RTX were comparable vs PBO (all-exposure RTX: 3.94/100 patient-treated years (PTY) [95% CI 3.60–4.31] vs 3.79/100 PTY [2.80–5.13]), and stable over time and multiple treatment courses up to 9.5y. Serious opportunistic infections (OIs) were rare (all-exposure RTX 0.06 events/100 PTY; PBO 0.09 events/100 PTY). There was no increased risk of malignancy with RTX (all-exposure RTX 0.99/100 PTY [95% CI 0.79–1.23] vs 1.05/100 PTY [1.01–1.09] for adult RA patients). Risk of PML with RTX was rare with 6 confirmed cases in >188 000 RA pts.
OCR RA: In a pooled safety analysis of the double-blind PBO-controlled phases of all pivotal Phase 3 OCR studies, SIE rates were comparable between low-dose (200mg x2 or 400mg x1) OCR and PBO. High-dose OCR (500mg x2) was associated with higher SIE rates vs PBO, mainly due to Asia/Pacific data where both dose groups had increased SIE rates. OIs were more frequent with OCR vs PBO irrespective of dose (9 vs 1 event). SIE and OI resolved with appropriate therapy. No PML was reported.
RTX RRMS: SIE rates were similar for RTX (2.9%) and PBO (5.7%) in the phase 2 HERMES study; no PML was reported. OCR RRMS: Incidence of infections (serious and non-serious) was similar for both doses of OCR vs PBO (SIEs 0% vs 1.9% during week 0–24, respectively) and did not increase over time with continued OCR; no PML or other OIs were reported.
Conclusions: Incidence of SIEs and OIs with RTX and OCR treatment were generally low. No PML has been reported with OCR. These data inform the anticipated safety of OCR in ongoing phase 3 MS trials where a lower risk of SIEs and/or OIs may be expected owing to disease- (pathophysiology, co-medication, age) and trial design-inherent (dose, region) factors.