No abstract

Background: Ofatumumab, the first fully human anti-CD20 monoclonal antibody, is approved in several countries for relapsing multiple sclerosis (RMS). Objective: To demonstrate the bioequivalence of ofatumumab administered by an autoinjector versus a pre-filled syringe (PFS) and to explore the effect of ofatumumab on B-cell depletion. Methods: APLIOS (NCT03560739) is a 12-week, open-label, parallel-group, phase-2 study in patients with RMS receiving subcutaneous ofatumumab 20 mg every 4 weeks (q4w) (from Week 4, after initial doses on Days 1, 7, and 14). Patients were randomized 10:10:1:1 to autoinjector or PFS in the abdomen, or autoinjector or PFS in the thigh, respectively. Bioequivalence was determined by area under the curve (AUC τ) and maximum plasma concentration ( Cmax) for Weeks 8–12. B-cell depletion and safety/tolerability were assessed. Results: A total of 256 patients contributed to the bioequivalence analyses (autoinjector-abdomen, n = 128; PFS-abdomen, n = 128). Abdominal ofatumumab pharmacokinetic exposure was bioequivalent for autoinjector and PFS (geometric mean AUC τ, 487.7 vs 474.1 h × µg/mL (ratio 1.03); Cmax, 1.409 vs 1.409 µg/mL (ratio 1.00)). B-cell counts (median cells/µL) depleted rapidly in all groups from 214.0 (baseline) to 2.0 (Day 14). Ofatumumab was well tolerated. Conclusion: Ofatumumab 20 mg q4w self-administered subcutaneously via autoinjector is bioequivalent to PFS administration and provides rapid B-cell depletion.

A prospective 3-year randomized study comparing conservative and surgical treatment of spondylotic cervical myelopathy to establish predictive factors for outcome after conservative treatment and surgery. The clinical, electrophysiological and imaging parameters were examined to reveal how they characterized the clinical outcome. Statistically, pair-wise and multiple comparisons of different were used with the independent t-test and on one-way anova models followed by Tukey multiple-range tests. The patients with a good outcome in the conservatively treated group were of older age before treatment, had normal central motor conduction time (CMCT), and possessed a larger transverse area of the spinal cord. The patients with a good outcome in the surgically treated group had a more serious clinical picture (expressed in mJOA score and slower walk). Patients should rather be treated conservatively if they a spinal transverse area larger than 70 mm2, are of older age, and have normal CMCT. Surgery is more suitable for patients with clinically worse status and a lesser transverse area of spinal cord.

The 3-year follow-up study did not show, on the average, that the surgery is superior to conservative treatment for mild and moderate forms of spondylotic cervical myelopathy.

A prospective 3-year randomized study comparing conservative and surgical treatment of spondylotic cervical myelopathy to establish predictive factors for outcome after conservative treatment and surgery. The clinical, electrophysiological and imaging parameters were examined to reveal how they characterized the clinical outcome. The patients with a good outcome in the conservatively treated group were of older age before treatment, had normal central motor conduction time (CMCT), and possessed a larger transverse area of the spinal cord. The patients with a good outcome in the surgically treated group had a more serious clinical picture (expressed in mJOA score and slower walk). Patients should rather be treated conservatively if they have a spinal transverse area larger than 70 mm2, are of older age and have normal CMCT. Surgery is more suitable for patients with clinically worse status and a lesser transverse area of spinal cord.