The combination of EDSS scores above 6 and age over 55 years resulted in higher serious infection rate that was nearly double that seen in the overall population.
New 6-year data from the ACAPELLA study, a real-world analysis of patients with multiple sclerosis (MS) on ocrelizumab (Ocrevus; Genentech), showed a higher rate of severe infection in treated patients aged 55 years and older with an Expanded Disability Status Scale (EDSS) score of 6 points or more. Investigators noted that the clinical significance of these findings may be limited by small sample size.
ACAPELLA, a prospective study, includes patients exempted from the phase 2 and 3 trials because of preexisting conditions, such as a prior history of malignancy, hypogammaglobulinemia, and advanced age and/or disability. Presented at the 2023 Consortium of Multiple Sclerosis Centers (CMSC) Annual Meeting, held May 31 to June 3, in Aurora, Colorado, 419 individuals were enrolled and followed for 1 to 11 cycles. Patients were between 18 to 75 years, with 21% having a baseline EDSS of at least 6 points.
Senior investigator Joshua D. Katz, MD, co-director, Elliot Lewis Center, and colleagues observed an overall infection rate of 49.8 cases per 100 patient years (PY), which was lower than the 76.2 cases per 100 PY observed in the 5-year clinical trial data. The rate of infection was not increased when independently factoring in age over 55 years or EDSS score over 6; however, patients aged 55 years or older with an EDSS of 6 points or more did have a higher rate of serious infections (4.1 cases/100 PY) as compared with the overall population (2.1 cases/100 PY).
Patients with an EDSS score above 6 also resulted in increases rate of urinary tract infections, with 29.2 cases per 100 PY vs 14.8 cases per 100 PY in the total population. Malignancies occurred at a rate of 0.5 cases per 100 PY, similar to that observed in the general MS population. Of the patient population, which comprised of mostly females (74%), fifteen individuals (3.5%) had low baseline immunoglobulin G (IgG) levels, and 12 patients (3%) with normal baseline IgG developed persistent low IgG levels.
In addition to adverse events, ACAPELLA substudies are evaluating the impact of ocrelizumab on IgG levels, CD19 reconstitution, and JC virus antibody titers. A second analysis of the trial, presented at CMSC 2023, continued to assess the safety of the therapy in 395 patients who had baseline IgG levels. Normal IgG was defined as 600-1640 mg/dL, assessed over 10 treatment cycles.
Over the course of treatment, mean IgG declined by 9.7%, and 92.8% of patients had IgG that remained above the lower limit of normal. Among the fifteen individuals who had low IgG values at baseline, the infection rate was increased to 55.3 cases per 100 PY, compared with patients with normal IgG at baseline, who had an infection rate of 48.9%. The study investigators noted that "with additional cycles of ocrelizumab, an increasing but small proportion of patients developed hypogammaglobulinemia."
Ocrelizumab was approved by the FDA to treat adults with relapsing forms of MS and primary progressive MS (PPMS) in 2017, becoming the first agent specifically greenlit for PPMS. The efficacy ocrelizumab for relapsing MS was shown in 2 clinical trials comprising of more than 1600 participants treated for 96 weeks, while its efficacy for PPMS was shown in a large scale study of 732 individuals treated for at least 120 weeks.