PracticeUpdate Conference Series - ANZAN 2018

The hand with lower baseline time was termed the better hand, and the hand with higher baseline time was termed the worse hand. Average dominant and nondominant hand times were combined and termed both hands. Analyses included time-to-confirmed progression in hand func- tion, defined as ≥15%, ≥20%, or ≥25% increase in 9-hole peg test time from baseline, confirmed at 12 and 24 weeks, and change in 9-hole peg test time from baseline to week 120. Compared with placebo, ocrelizumab reduced the time to 12- and 24-week confirmed progression of ≥15% increase in nine-hole peg test time by: ƒ ƒ 37% (HR 0.627; P = .001) and 39% (HR 0.607; P = .002), respectively, for both hands ƒ ƒ 30% (HR 0.699; P = .011) and 40% (HR 0.599; P < .001), respectively, for the better hand ƒ ƒ 29% (HR 0.705; P = .016) and 28% (HR 0.717; P = .040), respectively, for the worse hand Time to 12- and 24 week confirmed progression of ≥20% increase in nine-hole peg test time was reduced by: ƒ ƒ 44% (HR 0.561; P < .001) and 45% (HR 0.545; P < .001), respectively for both hands ƒ ƒ 28% (HR 0.723; P =.046) and 35% (HR 0.646; P = .014), respectively, for the better hand ƒ ƒ 37% (HR 0.632; P = .005) and 40% (HR 0.599; P = .004), respectively, for the worse hand Ocrelizumab also reduced the time to 12- and 24-week con- firmed progression of a ≥25% increase in nine-hole peg test time by: ƒ ƒ 48% (HR 0.520; P < .001) and 49% (HR 0.507; P < .001), respectively, for both hands ƒ ƒ 30% (HR 0.698; P = .048), and 39% (HR 0.613; P = .015), respectively, for the better hand ƒ ƒ 48% (HR 0.521; P < .001) and 42% (HR 0.578; P = .004), respectively, for the worse hand At week 120, the increase from baseline 9-hole peg test time for both hands and the worse hand was significantly smaller with ocrelizumab than with placebo (P < .001 and P = .041, respectively). For the better hand, the increase was smaller with ocrelizumab (difference not significant). Dr. Fox concluded that ocrelizumab treatment lowered the risk of progression of upper extremity disability as measured by 9-hole peg test time vs placebo in patients with primary progressive MS. “Our assessment of this data set,” he said, “was that a clear ben- efit could be seen with ocrelizumab treatment in maintaining upper extremity function. The reason for the multiple data points was that it was important to look at each arm independently, since multiple sclerosis is often asymmetric.” He continued, “Better and worse arms were identified and followed over the course of the trial, and multiple degrees of worsening were looked at independently to be more certain of the clinical significance of the findings.” He added, “We recommend that ocrelizumab and other agents be evaluated further with these endpoints in mind. Such assess- ments may yield important information about the prevention of disability caused by upper limb impairment.”

Dr. Kappos concluded that ocrelizumab was shown to reduce progression of disability significantly vs interferon β-1a in the OPERA intent-to-treat population of patients with relapsing MS, more in the subgroup at higher risk of secondary progressive disease. The results showed that considerable disability progression in relapsing MS occurs independently of protocol-defined relapses. Edward J. Fox, MD, PhD, of Central Texas Neurology Consultants in Round Rock, Texas, and colleagues set out to evaluate the effect of ocrelizumab on upper limb function in patients with primary progressive multiple sclerosis in the ORATORIO study (Encore). Dr. Fox told Elsevier’s PracticeUpdate , “The post hoc analysis of the ORATORIO trial is an important piece of information for clinicians and for patients with primary progressive multiple scle- rosis because it explores the effects of ocrelizumab on upper extremity function.” He continued, “The substantial relevance of losing arm and hand dexterity as a part of primary progressive multiple sclerosis is well accepted, but rarely has any data been presented on the impact of treatment on this symptom.” Dr. Fox explained that functional impairment of the upper limb is prevalent among patients with primary progressive MS. Such impairment alters quality of life. The nine-hole peg test is a validated quantitative assessment of upper limb function in multiple sclerosis. The test was administered at baseline and every 12 weeks until study end. The team compared average nine-hole peg test times from two trials of dominant and nondominant hands.

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ANZAN 2018 • PRACTICEUPDATE CONFERENCE SERIES 11