Assessment of changes in fatigue and cognitive functioning in the absence of progression independent of relapse...

Progression Independent of Relapse Activity (PIRA) has become an important new outcome measure in MS clinical studies since it identifies disability accumulation that this not relapse related. Since PIRA focuses on changes in the expanded disability status scale (EDSS), some aspects of MS are not measured.

Patients enrolled in the Comprehensive Longitudinal Investigation of Multiple Sclerosis at the Brigham Multiple Sclerosis Center completed a measure of fatigue (modified fatigue impact scale (MFIS)) and a brief cognitive screening measure (symbol digit modalities test (SDMT)) yearly and had a complete clinical exam including a measurement of the EDSS every six months. The baseline visit for this analysis was the second visit where the participant completed the SDMT. Longitudinal follow-up of the EDSS and relapses was used to identify whether participants experienced PIRA within 1-, 2-, 3-, 4-, and 5-year intervals. The proportion of participants experiencing worsening of MFIS or SDMT among participants with no PIRA was calculated. Further, the corresponding longitudinal change in MFIS and SDMT were compared in participants with PIRA and with no PIRA using a two-sample t-test and linear regression to adjust for age.

479 participants contributed to our analysis. Among participants with no PIRA, there were 8.8% who had decreases in SDMT of at least 8 points after 2 years and 31.1% who had increases in MFIS of at least 4 points. There were limited differences in the change in MFIS or SDMT between the participants with PIRA and with no PIRA at any time interval.

Participants with no PIRA are still experiencing cognitive worsening and fatigue worsening, and the rate of worsening is similar to those with PIRA.