Confirmed Disability Improvement and Its Sustainability Among Progressive Multiple Sclerosis Patients in Clinical Trial Placebo Arms

Background: The Multiple Sclerosis Outcome Assessments Consortium (MSOAC) Placebo Database includes pooled placebo data from 9 clinical trials and can be used to obtain an estimate for a control arm.

Objectives: This study evaluated progressive multiple sclerosis (PMS) patients (pts) with confirmed disability improvement (CDI) and sustainability through 24 months in the MSOAC Placebo Database.

Methods: Pts with PMS (primary progressive MS [PPMS] and secondary progressive MS [SPMS]) in both active and nonactive disease populations were included. Pts aged from 18 to 61 years with baseline Expanded Disability Status Scale (EDSS) scores between 3 and 6.5 were identified. CDI was defined as ≥1.0-point decrease from EDSS baseline score ≤5.0 or ≥0.5-point decrease from EDSS baseline score ≥5.5 at 9 months confirmed at 12 months (cohort I) or at 12 months confirmed at 15 months (cohort II). Endpoints included mean duration of CDI (calculated from confirmation) and percentage of pts who maintained CDI status through 24 months. Analyses were also conducted for PPMS and SPMS to determine if there was a difference.

Results: In total, 883 PMS pts were identified (n=330 PPMS, n=553 SPMS); 6.5% (45/693) and 7.0% (47/673) of eligible PMS pts had CDI in cohorts I and II, respectively.

The majority of PMS pts were females (60–66%); baseline EDSS scores were ≥5.5 for 66.7% of cohort I and 70.2% of cohort II.

Mean (SD) duration of CDI for cohort I was 7.5 (5.1) months and for cohort II was 5.9 (3.8) months. Overall, 3.3% (23/693) (95% CI: 2.1, 4.9) of the eligible PMS pts in cohort I and 3.9% (26/673) (95% CI: 2.5, 5.6) of the eligible PMS pts in cohort II maintained CDI through 24 months. No differences in percentage of patients with a CDI or those who maintained CDI through 24 months were observed between PPMS and SPMS populations.

Conclusions: CDI was observed in ~7% of active and nonactive PMS pts evaluated in clinical trial placebo arms, with ~3–4% maintaining CDI through 24 months. No difference was seen in disability improvement between PPMS and SPMS pts, supporting the similarity of pts with PMS. More transformative therapies are needed to improve disability in pts with PMS, especially in nonactive disease, where there are limited approved treatment options.

Acknowledgements: Study funded by Atara Biotherapeutics. All authors are employees and shareholders of Atara Biotherapeutics. Medical writing assistance was provided by Tricia Brown, MS, MBA, of AMICULUM Ltd, funded by Atara Biotherapeutics.