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The importance of MS progression independent of relapses

Conference
ECTRIMS 2021
Confirmed disability accumulation (CDA) in MS may occur as Relapse-Associated Worsening (RAW) or Progression Independent of Relapse Activity (PIRA). Three presentations focused on the role and importance of PIRA during a symposium on MS progression. PIRA is present from disease onset, predominates in later-onset MS, and is associated with increased brain atrophy rates in patients with relapsing MS [1–3].

A Spanish study assessed clinical and MRI features of patients who develop PIRA early on after the first attack of MS, or in the absence of recent inflammatory activity [1]. In a cohort of 754 patients with a clinically isolated syndrome (CIS) or early MS that were followed for >20 years, 209 (28%) developed PIRA after a median of 7.2 years. Presenting with PIRA after a CIS is not uncommon and implies an unfavourable, long-term prognosis, concluded Dr Carmen Tur (Vall d'Hebron University Hospital, Spain). Among all patients with PIRA, one third developed early PIRA, i.e. within 5 years after the CIS. Generally, patients with early PIRA were older at the time of CIS, with more spinal cord lesions and fewer relapses over time than late PIRA. Patients with late PIRA, on the other hand, were younger at CIS, with a higher inflammatory burden. “This suggests that late PIRA occurs as a predominantly inflammation-driven process.” Of all patients with PIRA, one third will develop “pure PIRA”, i.e. PIRA in the absence of recent inflammatory activity on MRI. Pure PIRA shares many characteristics with early PIRA. Dr Tur concluded that identifying those CIS patients who are at risk of developing any form of PIRA may have important therapeutical implications.

An Italian group investigated the rate and predictors of RAW and PIRA in paediatric (PO), adult (AO), and late-onset (LO) MS. In a relapsing MS cohort of 5,287 patients assessed within 1 year from onset, CDA events were more frequent in LOMS (61.3%) than in AOMS (45.9%) and POMS (41.0%; P<0.001) after a mean 11.4 years. PIRA accounted for about two-thirds of disability worsening, Dr Angelo Bellinvia (University of Florence, Italy) concluded. “Underlying MS progression is already detectable early in the disease course also in POMS patients and is more prevalent than RAW in AOMS and LOMS patients at the first demyelinating event. This data suggests that MS can be seen as a continuum from the very onset, and that age at onset seems to be one of the main determinants of CDA subtype, with RAW being more prevalent in POMS and PIRA in LOMS.” Early treatment with a disease-modifying therapy (DMT) was effective in preventing any CDA in all age groups and appeared to slow down the transition to the progressive phase. This underscores the importance of prompt initiation of DMTs in MS patients.

A Swiss group found that PIRA is associated with increased brain atrophy rates [3]. In a retrospective, longitudinal study including 516 relapsing-remitting MS patients, 334 were stable, 122 had relapsed, and 46 experienced PIRA. Both focal inflammatory activity and PIRA were associated with increased brain atrophy rates, without significant differences between the 2. The association between PIRA and diffuse neurodegeneration underscores the necessity to better stratify MS patients in clinical practice, as well as to optimise treatment to prevent accumulation of irreversible neuro-axonal loss.

  1. Tur C. Progression independent of relapse activity is present from disease onset: a complete view of the phenomenon in the CIS/early MS cohort of Barcelona. OP155, ECTRIMS 2021 Virtual Congress, 13–15 October.
  2. Bellinvia A. Progression independent of relapse activity in paediatric, adult and late-onset multiple sclerosis patients. OP154, ECTRIMS 2021 Virtual Congress, 13–15 October.
  3. Cagol A. Progression independent of relapse activity is associated with increased brain atrophy rates in patients with relapsing-remitting multiple sclerosis. OP156, ECTRIMS 2021 Virtual Congress, 13–15 October.

 

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