Author Of 4 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.
P0284 - Age-related efficacy of cladribine tablets in patients with relapsing-remitting MS in the CLARITY Extension study (ID 867)
Abstract
Background
In the CLARITY study, treatment with cladribine tablets 10 mg (3.5 mg/kg cumulative dose over 2 years [yr]) demonstrated significance over placebo on clinical and MRI efficacy outcomes in patients (pts) with relapsing-remitting multiple sclerosis. Pts who completed CLARITY were eligible to participate in CLARITY Extension (EXT).
Objectives
This post hoc analysis explored efficacy outcomes at the end of the core part of CLARITY EXT (Week 96) in pts who were ≤30yr vs >30yr at CLARITY enrollment.
Methods
Analyses were performed by age and treatment (CC7.0 [cladribine-cladribine]: cladribine tablets 3.5 mg/kg in CLARITY and CLARITY EXT; CP3.5 [cladribine-placebo]: cladribine tablets 3.5 mg/kg in CLARITY and placebo in CLARITY EXT). Endpoints included relapse, 3- and 6-month (mo) confirmed disability progression (CDP, based on Expanded Disability Status Scale), MRI activity, and no evidence of disease activity (NEDA; no relapse, 3- or 6-mo CDP, and MRI activity) at Week 96 of CLARITY EXT.
Results
Data from 284 pts were included: ≤30yr: CC7.0 N=49, CP3.5 N=23; >30yr: CC7.0 N=137, CP3.5 N=75. Annualized relapse rate (95% confidence interval [CI]) was similar between age groups for pts receiving CC7.0 (≤30yr, 0.08 [0.04; 0.15]; >30yr, 0.08 [0.05; 0.12]) and numerically higher in younger pts receiving CP3.5 (≤30yr, 0.27 [0.16; 0.47]; >30yr, 0.06 [0.03; 0.11]). The probabilities (Kaplan-Meier estimates) of being free of 3-mo CDP for CC7.0 were 0.98 for ≤30yr and 0.86 for >30yr; and for CP3.5 were 0.79 for ≤30yr and 0.88 for >30yr. The probabilities of being free of 6-mo CDP were similar to those of 3-mo CDP. Mean (95% CI) cumulative numbers of T1 gadolinium-enhancing lesions were similar between age groups for pts receiving CC7.0 (≤30yr, 0.02 [0.01; 0.08]; >30yr, 0.02 [0.01; 0.06]) or CP3.5 (≤30yr, 0.54 [0.16; 1.79]; >30yr, 0.27 [0.10; 0.73]). Mean (95% CI) numbers of active T2 lesions were similar between age groups for pts receiving CC7.0 (≤30yr, 1.36 [0.75; 2.45]; >30yr, 1.12 [0.78; 1.61]) and numerically lower in older pts receiving CP3.5 (≤30yr, 2.95 [1.22; 7.10]; >30yr, 1.40 [0.88; 2.22]). The proportion of pts achieving NEDA based on 3-mo CDP was numerically higher in younger pts receiving CC7.0 (≤30yr, 36.7%; >30yr, 28.5%) and older pts receiving CP3.5 (≤30yr, 21.7%; >30yr, 30.7%). NEDA results based on 6-mo CDP were similar to those based on 3-mo CDP.
Conclusions
Cladribine tablets result in similar clinical and MRI outcomes at Week 96 of CLARITY EXT in both older (>30yr) and younger (≤30yr) pts, providing further evidence of efficacy across age groups.
P0577 - Feasibility of thalamic atrophy measurement in clinical routine using artificial intelligence: Results from multi-center study in RRMS patients (ID 1058)
Abstract
Background
The thalamus is a key gray matter structure, and a sensitive marker of neurodegeneration in multiple sclerosis (MS). Previous reports have indicated that thalamic volumetry on clinical-quality T2-FLAIR images alone is fast and reliable, using artificial intelligence (AI).
Objectives
To investigate the feasibility of thalamic atrophy measurement using AI in patients with MS, in a large multi-center, clinical routine study.
Methods
DeepGRAI (Deep Gray Rating via Artificial Intelligence) is a multi-center (31 USA sites), longitudinal, observational, real-word, registry study that will enroll 1,000 relapsing-remitting MS patients. Brain MRI exams previously acquired at baseline and at follow-up on 1.5T or 3T scanners with no prior standardization are used, in order to resemble real-world situation. Thalamic volume measurement is performed at baseline and follow-up on T2-FLAIR by DeepGRAI tool and on 3D T1-weighted image (WI) and 2D T1-WI by using FIRST software.
Results
In this pre-planned interim analysis, 515 RRMS patients were followed for an average of 2.7 years. There were 487 (94.6%) T2-FLAIR, 342 (66.4%) 2D T1-WI and 176 (34.2%) 3D T1-WI longitudinal pair of MRI exams available for analyses. Estimation of thalamic volume by DeepGRAI on T2-FLAIR correlated significantly with FIRST on 3D-T1-WI (r=0.733 and r=0.816, p<0.001) and with FIRST on 2D-T1-WI (r=0.555 and r=0.704, p<0.001) at baseline and at follow-up. The correlation between thalamic volume estimated by FIRST on 3D T1-WI and 2D T1-WI was r=0.642 and r=0.679, p<0.001, respectively. The thalamic volume % change over the follow-up was similar between DeepGRAI (-0.75) and 3D T1-WI (-0.82), but somewhat higher for 2D T1-WI (-0.92). Similar relationship was found between the Expanded Disability Status Scale (EDSS) and thalamic volume by DeepGRAI on T2-FLAIR and by FIRST on 3D T1-WI at baseline (r=-0.214, p=0.01 and r=-0.287, p=0.001) and at follow-up (r=-0.298, p=0.001 and r=-0.291, p=0.001).
Conclusions
DeepGRAI provides feasible thalamic volume measurement on multi-center clinical-quality T2-FLAIR images. The relationship between thalamic atrophy and physical disability is similar using DeepGRAI T2-FLAIR and standard high-resolution research approaches. This indicates potential for real-world thalamic volume monitoring, as well as quantification on legacy datasets without research-quality MRI.
P0897 - Persistence and adherence to ocrelizumab compared with other disease-modifying therapies for multiple sclerosis for up to 18 months in the US (ID 1222)
Abstract
Background
Adherence to disease-modifying therapy (DMT) is critical for achieving therapeutic goals in multiple sclerosis (MS). Real-world evidence on persistence and adherence with ocrelizumab (OCR) is limited.
Objectives
This analysis aimed to examine the persistence and adherence to OCR compared with other MS DMTs.
Methods
This analysis was conducted in the PharMetrics Plus commercial claims database and included patients with MS who initiated a new DMT between April 2017 and September 2018. Patients were required to have health plan enrollment for ≥12 months before and after DMT initiation. Persistence and adherence were measured in patients with ≥12 months and ≥18 months of follow-up. Persistence was defined as no switch to other DMTs and no gap in supply of initiated DMT for ≥60 days. Adherence was assessed using the proportion of days covered (PDC), calculated as the total days of supply of DMT during the postinitiation period divided by either 365 days (12-month analysis) or 548 days (18-month analysis). Multivariable Poisson regression models were used to compare discontinuation of (nonpersistence) and nonadherence (PDC <0.80) with OCR vs oral, injectable, and other intravenous (IV) DMTs.
Results
A total of 4,587 (OCR, 1,319; injectable, 1,051; oral, 1,876; IV, 341) patients were included. At 12 months, patients initiating OCR had the highest mean PDC (93.4%) compared with other groups (injectable, 69%; oral, 74%; IV, 76%) and the highest proportion of patients persistent with therapy (92% vs 57%, 68% and 72%, respectively). Compared with OCR, adjusted relative risks of 12-month discontinuation (95% CI) were 5.5 (4.1–7.5), 3.8 (3.0–4.9) and 3.3 (2.3–4.6) in patients initiating injectable, oral and IV DMTs, respectively, and relative risks of nonadherence were 6.8 (5.0–9.3), 5.1 (3.9–6.6) and 4.9 (3.6–6.8), respectively. Among patients with 18 months of follow-up (n=2,319), 83% of OCR patients demonstrated persistence vs 45%, 59% and 60% of injectable, oral and IV patients, respectively. Trends in discontinuation and nonadherence for the DMT groups over 18 months were consistent with 12-month results in fully adjusted models.
Conclusions
Patients initiating ocrelizumab had superior persistence and adherence at both 12 and 18 months of follow-up compared with other groups of MS DMTs. Long-term persistence and adherence should be monitored as ocrelizumab experience accrues in a real-world setting.