Author Of 2 Presentations
P0110 - Modulation of cerebrospinal fluid immunoglobulins by ocrelizumab treatment (ID 1597)
Abstract
Background
Intrathecal production of immunoglobulin (Ig) and the presence of cerebrospinal fluid (CSF)–specific oligoclonal bands (OCBs) are hallmarks of multiple sclerosis (MS) that persist throughout the disease course and treatment.
Objectives
To describe baseline (BL) correlations of CSF IgM and IgG production with CSF biomarkers and to assess the pharmacodynamic effects of ocrelizumab (OCR) treatment on these parameters in patients with relapsing MS (RMS) from the Ocrelizumab Biomarker Outcome Evaluation (OBOE) study (NCT02688985).
Methods
Seventy-nine of 100 total patients with RMS had available BL CSF samples for assessment of IgG OCBs, IgG and IgM (measured at University Medical Center Göttingen), with demographic, MRI and clinical parameters representative of the total RMS population. CSF samples at either 12 (n=22), 24 (n=24) or 52 (n=17) weeks postdose and from a 12-week reference arm (no OCR; n=16) were assessed for longitudinal changes.
Results
Median (interquartile range [IQR]) CSF levels at BL were as follows: IgG index, 0.79 (0.63–1.28); IgM index, 0.19 (0.11–0.33); CD3+ T cell number, 2.52 (0.80–5.61) cells/µL; CXCL13, 9.89 (3.91–31.50) pg/mL; CCL19, 47.95 (31.09–70.86) pg/mL; neurofilament light chain (NfL) 1280.0 (828.1–2968.9) pg/mL. At BL, IgG index and IgM index correlated moderately with levels of B cells (r=0.65, r=0.4 respectively), T cells (r=0.54, r=0.3 respectively) and CXCL13 (r=0.58, r=0.43 respectively), but not CCL19 or NfL. IgG index tended to decrease with OCR treatment and was significantly reduced by 52 weeks (n=17/79; median [IQR] change from BL −9.5% [−20.4% to −0.1%]; p<0.02) compared with stable levels in the reference arm. While IgG OCBs were detected at BL in all patients, IgG OCBs tended to decrease with OCR treatment, with three of 17 patients having no detectable IgG OCBs at 52 weeks. Reductions in IgM index were not observed with OCR treatment.
Conclusions
Baseline CSF levels of B cells, T cells and CXCL13 correlated with IgG index and to a lesser degree IgM index in patients with RMS from the OBOE study. Significant reductions were observed in IgG index with OCR treatment, along with a trend toward reduced OCBs, with three patients showing no detectable OCBs. These data suggest that OCR impacts CSF Ig production, a hallmark of MS not previously thought to be affected by B-cell depletion therapy. These 1-year observations need to be confirmed with longer-term data and correlated with clinical response.
P0880 - Low discontinuation rate and side-effect burden after switching to cladribine tablets: Canadian experience from the adveva® patient support program (ID 1083)
Abstract
Background
Cladribine tablets were approved in Canada in November 2017. All patients prescribed cladribine tablets in Canada are enrolled upon their consent in the adveva patient support program (PSP), which provides drug education, assistance with reimbursement and patient support services.
Objectives
To examine the demographics and treatment history of patients initiating cladribine tablets in Canada, assess the discontinuation rate over the two-year treatment and describe reported adverse events (AEs).
Methods
Analysis of data routinely collected by adveva nurses and all reported AEs from Dec2017 to Jan2020. Patients were included if they consented to enroll in the adveva PSP. They were contacted at enrollment and periodically therafter. Follow-up stopped when treatment was completed/discontinued.
Results
Overall, 1864 patients enrolled in the program; 1373 were female (74.4%) and mean age was 41.54 years (standard deviation [SD]: 10.34). None of the patients were treatment naïve; most (n=1191; 63.9%) had received only one prior disease modifying drug (DMD). The most recent prior DMDs were glatiramer acetate (23.1%), dimethyl fumarate (20.4%), teriflunomide (16.5%), fingolimod (10.9%), and subcutaneous interferon beta-1a (10.4%). Of 1864 enrolled, 1679 (90.1%) had completed pre-treatment evaluation. Of those, 1415 (84.3%) started year-1. Among those, 483 (34.1%) started year-2 and 394 (27.8%) completed it. Mean time to year-2 initiation was 12.75 (SD: 1.27) months. Among all patients who had started year-1 treatment, 38 (2.69%) reported discontinuation. Among those, 26.3% discontinued within <6 months, 52.6% between 6-12 months and 21.1% at ≥12 months. Main reported reasons were: 28.9% unknown, 21.1% AE other than flu-like syndrome and lymphopenia, 18.4% worsening disease, 10.5% patients decision, and 10.5% family planning/pregnant. A total of 843 patients (59.6%) reported at least one AE. Among the total AEs report (n= 3525)the most frequent were fatigue (8.0%), headache (5.4%), nausea (4.7%), and lymphocytopenia (2.5%).
Conclusions
The Canadian adveva program presented a high enrolment rate. Cladribine tablets were associated with a high continuation rate and most patients successfully self-adminstered the drug. Reported adverse events were not severe.