Multiple Sclerosis Research Repository

1.   “Disease Progression in Multiple Sclerosis”: Genentech (2024)

-relapses were not associated with long-term disability worsening or confirmed disability worsening

-data were consistent with 2 simultaneous processes: focal demyelinating lesions and a more diffuse process that contributes to brain and spinal cord atrophy: this is largely independent of relapses or focal lesion formation and may be the most important contributor to long-term MS disability 

-PIRA was seen early in the MS disease course in a cohort study; 66% had at least 1 PIRA event; 31% developed PIRA within the first 5 years of the disease; 34% had all of their CDA episodes qualify for RAW; 26x greater risk of developing severe disability 

2. “Contribution of relapse-associated worsening in overall disability accrual in patients with relapsing-onset multiple sclerosis: A mediation analysis” by Bo Chen et al

-”In relapsing-onset MS, PIRA is the major contributor to the irreversible disability accrual throughout the whole disease course…”

3. “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

-”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…”

4.  “Relapse-Associated and Relapse-Independent Contribution to Overall Expanded Disability Status Scale Progression in Multiple Sclerosis Patients Diagnosed in Different Eras” by Noemi Montobbio, PhdD et al

-”The average contribution of PIRA to overall EDSS progression, already predominant in patients diagnosed in 1980-1996 (78%)…and in 1997-2008 (76%)…was significantly increased….in patients diagnosed in later years (87%…)”

-”However, although clinical relapses are almost completely eliminated by modern high-efficacy DMTs, the underlying disability progression independent of relapse activity is far from being halted or reversed.  Our results showed a progressive shift toward a mostly relapse-independent progression”