Before you read this paper you have to grasp the new concepts of RAW and PIRA. RAW is worsening in disability due to relapses and PIRA is progression independent of relapse activity. Therefore in PPMS, the progressive worsening would largely be a production of PIRA.
a) Composite RAW and b) composite PIRA are the two
non-mutually exclusive components/drivers of overall accumulation of disability
(as measured by composite CDA) in relapsing and progressive forms of MS.
CDA=confirmed disability accumulation; IID, initial increase of disability; MS=multiple sclerosis. PIRA=progression independent of relapse activity. RAW=relapse-associated worsening.
In this study they try and work out what the disability in relapsing and remitting MS is due to. RAW or PIRA or RAW & PIRA
Preprint site Kappos et al study put online and may be published in the Lancet.
Background: Accumulation of disability in multiple sclerosis (MS) may occur as relapse-associated worsening (RAW) or as steady progression independent of relapse activity (PIRA), regarded as a feature of primary and secondary progressive MS. Using two Phase III trials comparing ocrelizumab and interferon (IFN) β-1a in a typical relapsing MS (RMS) population, we investigated the relative contribution of RAW and PIRA to overall confirmed disability accumulation (CDA), assessed baseline prognostic factors of PIRA and RAW, and respective effects of the two treatments.
Methods: CDA, PIRA, and RAW events were assessed in the pooled intent-to-treat population of the OPERA I and II trials. CDA was defined using a composite measure that included a defined increase in Expanded Disability Status Scale, Timed 25-Foot Walk, or 9-Hole Peg Test confirmed after ≥12 or ≥24 weeks. RAW events were defined as a confirmed worsening occurring ≤90 days after onset of a protocol-defined relapse.
Findings: PIRA events were the main contributors to 12/24-week composite CDA after 96 weeks. Of this overall risk, 78·7% to 88·9% corresponded to PIRA while 13·0% to 21·1% was explained by RAW events. Acute baseline lesional MRI activity only predicted RAW, whereas PIRA was predicted by baseline T1 and T2 lesion burden, whole brain and cortical grey matter atrophy, disease duration, male sex, baseline disability, and perceived quality of life. Very few patients experienced both RAW and PIRA. Compared with IFN β-1a, ocrelizumab reduced the risk of composite CDA, composite PIRA, and composite RAW events confirmed at 12/24 weeks.
Interpretation: A considerable proportion of overall accumulation of disability in RMS is not related to overt relapses. This indicates an underlying progressive course in this typical RMS population and challenges the current clinical distinction of relapsing and progressive forms of MS. Ocrelizumab was superior to IFN β-1a in preventing both RAW and PIRA
CoI None relevant but ProfG is a co author of this