PracticeUpdate Conference Series - ANZAN 2018

Ocrelizumab Reduces Progression of Disability Independent of Relapse Activity in Relapsing MS

Ocrelizumab has been shown to reduce progression of disability in relapsing multiple sclerosis (MS) significantly vs interferon β -1a, more in patients at higher risk of secondary progressive disease, reports phase I/II OPERA trial.

L udwig Kappos, MD, of University Hospital Basel in Switzerland, explained that ocrelizumab showed superior efficacy vs interferon β-1a in the OPERA 1/2 trials in relapsing MS. Confirmed disability progression based on a com- posite of the Expanded Disability Status Scale (EDSS), timed 25-foot walk, and 9-hole peg test may characterize aspects of disability progression better than the EDSS alone. The composite has demonstrated improved sensitivity for assessing progression in secondary progressive MS. Patients with relapsing MS, including those with relapsing secondary progressive disease in OPERA 1/2, received IV ocrelizumab 600 mg (every 24 weeks) or subcutaneous interferon β-1a 44 μg (3 times weekly) for 96 weeks. Composite confirmed disability progression was defined as disability progression measured by the EDSS score (increase ≥1.0 or 0.5 if baseline >5.5) or ≥20% increase in timed 25-foot walk or ≥20% increase in the 9-hole peg test, confirmed after ≥12/≥24 weeks. Definition 1 of composite confirmed disability progression independent of relapse activity was reference EDSS score/timed 25-foot walk/nine- hole peg test was re-baselined at the first available assessment ≥30 days, after each relapse, without relapse between baseline and initial progression of disability, and within 30 days post initial progression

of disability and 30 days prior to confirmation of initial progression of disability. Definition 2 was a period of no relapse for 30 days post confirmation of initial progression of disability. Subgroup analysis included patients at potentially higher risk of secondary progressive MS based on baseline EDSS score ≥4.0 and pyramidal Kurtzke Functional Systems Score ≥2. In the pooled intent-to-treat cohort (n=1656), risk reduction (ocrelizumab vs interferon β-1a) for 12 to 24-week composite confirmed disability progres- sion was 34% (30.7% vs 21.5%; P < .001) and 31% (22.6% vs 16.1%; P = .002). Risk ratios for the 12–24-week composite con- firmed disability progression independent of relapse activity for definition 1 were 24% (25.4% vs 19.6%; P = .010) and 22% (19.2% vs 14.9%; P = .046). Risk ratios for the 12 to 24-week composite confirmed disability progression independent of relapse activity for definition 2 were 25% (25.4% vs 19.5%; P = .008) and 23% (19.2% vs 14.8%; P = .039). In the subgroup at higher risk of secondary pro- gressive MS, 12 to 24-week risk ratios for composite confirmed disability progression independent of relapse activity (definition 2) were 40% (31.2% vs 19.1%; P = .022) and 36% (26.9% vs 16.6%; P = .064). All composite confirmed disability progression independent of relapse activity components in the intent-to-treat and subgroups followed similar trends.

Dr. Edward J. Fox

PRACTICEUPDATE CONFERENCE SERIES • ANZAN 2018 10