Multiple Sclerosis Research Repository

 “Real-world evidence of ocrelizumab-treated relapsing multiple sclerosis cohort shows changes in progression independent of relapse activity mirroring phase 3 trials” by J Ingwersen et al

-”Mean follow-up time was 29 months (range 6 to 51 months). 23.5% developed CDA under ocrelizumab therapy (n = 23). Of those, the majority developed PIRA (87.0% of CDA, n = 20) rather than RAW (13.0% of CDA, n = 3). An exploratory investigation using Cox proportional hazards ratios revealed two possible factors associated with an increased probability of developing PIRA: a shorter disease duration prior to ocrelizumab (p = 0.02) and a lower number of previous DMTs prior to ocrelizumab (p = 0.04). Our data show that in ocrelizumab-treated RRMS patients, the main driver of disability accumulation is PIRA rather than RAW.”

-”Using data from the pivotal phase 3 randomized controlled trials (RCTs) OPERA I and OPERA II, Kappos et al. investigated RAW and PIRA contributions to the disability accumulation of ocrelizumab-treated vs. interferon-treated patients.  They found that (A) PIRA was responsible for most of the disability accumulation rather than RAW irrespective of the treatment arm (later confirmed by the findings of Lublin et al.) and (B) ocrelizumab was superior in preventing PIRA compared to interferon. However, it was less effective in preventing PIRA than RAW.”

-”In both the interferon and ocrelizumab groups, PIRA (rather than RAW) was responsible for 80–90% of the clinical worsening…”

-”our data contributes to the notion that in typical RRMS patients under effective, immune-directed therapy PIRA is the primary driver of disability progression rather than RAW.”