Long-term Effect of Ofatumumab on Serum Immunoglobulin Levels in Patients with Relapsing Multiple Sclerosis
Amit Bar-Or1, Heinz Wiendl2, Jerome De Seze3, Jorge Correale4, Anne Cross5, Tobias Derfuss6, Krzysztof Selmaj7, Kevin Winthrop8, Paul Giacomini9, Francesco Sacca10, Xixi Hu11, Roseanne Sullivan11, Valentine Jehl12, Ibolya Boer12, Alit Bhatt13, Stephen Hauser14
1Center for Neuroinflammation and Experimental Therapeutics and Department of Neurology, Perelman School of Medicine, University of Pennsylvania, 2University of Muenster, 3University Hospital of Strasbourg, 4Institute for Neurological Research Dr. Raul Carrea, 5Washington University School of Medicine, 6Neurology Clinic and Policlinic and Research Center for Clinical Neuroimmunology and Neuroscience, Departments of Medicine and Biomedicine, University Hospital and University of Basel, 7Center for Neurology, Lodz, 8Public Health and Preventive Medicine, Division of Infectious Diseases, Oregon Health and Sciences University, 9Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, 10NSRO Department, University “Federico II” of Naples, 11Novartis Pharmaceuticals Corporation, 12Novartis Pharma AG, 13Novartis Healthcare Pvt. Ltd., 14UCSF Weill Institute for Neurosciences, University of California, San Francisco
Objective:
Evaluate the effect of ofatumumab on serum immunoglobulin (Ig) levels ≤5 years during the core phase 3 ASCLEPIOS I/II (NCT02792218/NCT02792231) and on-going open-label ALITHIOS (NCT03650114) extension studies.
Background:
Cumulative safety data from core phase 3 clinical trials and ALITHIOS extension study have shown that most patients with relapsing multiple sclerosis treated with ofatumumab ≤ 4 years had serum IgG and IgM levels that remained above lower limit of normal (LLN).
Design/Methods:
Change in IgG/IgM levels from baseline for up to 5 years of ofatumumab treatment was analyzed in the overall (N=1969), continuous (ofatumumab in core+extension; N=1292), and switch (teriflunomide in core, ofatumumab in extension; N=677) groups. Proportion of patients with IgG/IgM levels <LLN and the number of patients with serious infections within 1 month before/after IgG/IgM <LLN were analyzed.
Results:
In the overall group, IgG levels did not drop below LLN in 98% of patients at any assessment from the first dose of ofatumumab for ≤5 years. Mean IgG levels remained stable for ≤5 years (mean % change from baseline to Week 264, −2%). Serious infections were reported in 7.5% of patients with IgG levels <LLN. IgM levels did not drop below LLN at any assessment in 69.4% of patients. Although mean IgM levels decreased, they remained above LLN (mean % change from baseline to Week 264, −49%). 1.7% of patients with IgM levels <LLN had serious infections. Treatment interruptions/discontinuations were reported in 0.2%/0.2% and 10.3%/3.6% patients due to low IgG and IgM, respectively. Sensitivity analyses demonstrated that interruptions/ discontinuations did not affect the overall IgG/IgM pattern.
Conclusions:
With ≤5 years of ofatumumab treatment, the majority of patients did not have Ig levels that dropped below the LLN at any assessment. Overall, the number of serious infections was low in patients with Ig levels that dropped below the LLN.