University of Münster

Author Of 2 Presentations

Disease Modifying Therapies – Risk Management Oral Presentation

FC02.01 - Safety of Alemtuzumab Over 9 Years in Patients With Non-MS Autoimmunity

Speakers
Presentation Number
FC02.01
Presentation Topic
Disease Modifying Therapies – Risk Management
Lecture Time
13:00 - 13:12

Abstract

Background

Alemtuzumab is an anti-CD52 monoclonal antibody therapy approved for treating RRMS. Although alemtuzumab is associated with non–MS-related secondary autoimmune events, the role pre-existing non-MS autoimmunity plays in secondary autoimmunity is unclear.

Objectives

To assess the impact of 1) pre-existing non-MS autoimmunity and 2) post-alemtuzumab thyroid autoimmunity on subsequent onset of new autoimmunity up to 9 years after initiating alemtuzumab.

Methods

In clinical trials (NCT00050778, NCT00530348, NCT00548405, NCT00930553, NCT02255656), patients were monitored for autoimmune adverse events (AEs). All patient- and investigator-reported AEs were recorded. An autoimmune event was pre-existing if it occurred prior to initiating alemtuzumab or was in the medical history database.

Results

A total of 1216 patients from the alemtuzumab clinical development program who received alemtuzumab 12 mg were included in the analysis. Ninety-six had pre-existing non-MS autoimmunity. Up to 9 years after alemtuzumab initiation, the percentage of patients with new autoimmune disease was similar in those with (35.4%) versus without (35.3%) pre-existing autoimmunity; similar percentages of patients with versus without pre-existing autoimmunity had ≥2 new autoimmune events (5.2% vs 8.2%, respectively). Most patients with thyroid disorders at baseline did not experience new autoimmunity after alemtuzumab. Treatment-emergent thyroid autoimmunity after alemtuzumab Course 1 was not associated with subsequent nonthyroid autoimmunity after Course 2 (0% of patients with vs 3.0% of patients without thyroid autoimmunity after Course 1). Similarly, thyroid autoimmunity after Course 2 did not predict nonthyroid autoimmunity after Course 3 (1.8% vs 2.0%, respectively). Among 25,292 patients treated with alemtuzumab in the postmarketing setting as of 31 March 2019, additional events (occurring 18–36 months post treatment) included autoimmune hepatitis (10.7 in 10,000) and hemophagocytic lymphohistiocytosis (2.7 in 10,000).

Conclusions

Over 9 years after alemtuzumab initiation, pre-existing non-MS autoimmunity was not associated with subsequent new autoimmune disease. Emergence of thyroid autoimmunity after Courses 1 and 2 does not appear to predict subsequent serious autoimmune disease.

STUDY SUPPORT: Sanofi and Bayer HealthCare Pharmaceuticals.

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Biomarkers and Bioinformatics Oral Presentation

PS09.05 - Value of serum neurofilament light chain levels as a biomarker of suboptimal treatment response in MS clinical practice

Abstract

Background

Serum neurofilament light chain (sNfL) reflects neuro-axonal damage and may qualify as a biomarker of suboptimal response to disease modifying therapy (DMT).

Objectives

To investigate the predictive value of sNfL in clinically isolated syndrome (CIS) and relapsing-remitting (RR) MS patients with established DMT for future MS disease activity in the Swiss MS Cohort Study.

Methods

All patients were on DMT for at least 3 months. sNfL was measured 6 or 12-monthly with the NF-light®assay. The association between sNfL and age was modeled using a generalized additive model for location scale and shape. Z-scores (sNfLz) were derived thereof, reflecting the deviation of a patient sNfL value from the mean value of same age healthy controls (n=8865 samples). We used univariable mixed logistic regression models to investigate the association between sNfLz and the occurrence of clinical events (relapses, EDSS worsening [≥1.5 steps if EDSS 0; ≥1.0 if 1.0-5.5 or ≥0.5 if >5.5] in the following year in all patients, and in those fulfilling NEDA-3 criteria (no relapses, EDSS worsening, contrast enhancing or new/enlarging T2 lesions in brain MRI, based on previous year). We combined sNfLz with clinical and MRI measures of MS disease activity in the previous year (EDA-3) in a multivariable mixed logistic regression model for predicting clinical events in the following year.

Results

sNfL was measured in 1062 patients with 5192 longitudinal samples (median age 39.7 yrs; EDSS 2.0; 4.1% CIS, 95.9% RRMS; median follow-up 5 yrs). sNfLz predicted clinical events in the following year (OR 1.21 [95%CI 1.11-1.36], p<0.001, n=4624). This effect increased in magnitude with increasing sNfLz (sNfLz >1: OR 1.41 [95%CI 1.15-1.73], p=0.001; >1.5: OR 1.80 [95%CI 1.43-2.28], p<0.001; >2: OR 2.33 [95%CI 1.74-3.14], p<0.001). Similar results were found for the prediction of future new/enlarging T2 lesions and brain volume loss. In the multivariable model, new/enlarging T2 lesions (OR 1.88 [95%CI 1.13-3.12], p=0.016) and sNfLz>1.5 (OR 2.18 [95%CI 1.21-3.90], p=0.009) predicted future clinical events (n=853), while previous EDSS worsening, previous relapses and current contrast enhancement did not. In NEDA-3 patients, change of sNfLz (per standard deviation) was associated with a 37% increased risk of clinical events in the subsequent year (OR 1.37 [95%CI 1.04-1.78], p=0.025, n=587).

Conclusions

Our data support the value of sNfL levels, beyond the NEDA3 concept, for treatment monitoring in MS clinical practice.

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Author Of 15 Presentations

Clinical Outcome Measures Poster Presentation

P0024 - Alemtuzumab slowed brain atrophy over 6 years in patients without relapse and MRI disease activity: post hoc analysis of the pooled CARE-MS studies (ID 784)

Abstract

Background

Over 2 years in the CARE-MS trials (NCT00530348; NCT00548405), alemtuzumab (12 mg/day; baseline (BL): 5 days; 12 months later: 3 days) significantly improved clinical and MRI outcomes versus subcutaneous interferon beta-1a (SC IFNB-1a) in relapsing-remitting multiple sclerosis patients. Alemtuzumab efficacy was maintained through a 4-year extension study (NCT00930553), wherein patients could receive additional 3-day courses (≥12 months apart, as needed for disease activity) or receive other disease-modifying therapy per investigator’s discretion.

Objectives

To evaluate post hoc the effects of alemtuzumab on brain atrophy over 6 years in CARE-MS patients without relapses and MRI disease activity.

Methods

Analysis included pooled CARE-MS patients with or without disease activity between BL and Year 1 or BL and Year 2. Absence of disease activity was defined as no BL gadolinium (Gd)-enhancing T1 lesions and no clinical relapses or MRI disease activity (new Gd-enhancing or new/enlarging T2 lesions) from Years 0-1 or Years 0-2 (Definition 1). A second definition had the additional criterion of no relapse within 60 days before BL (Definition 2). Brain atrophy was measured by brain parenchymal fraction (BPF); differences in the median annualized percent change in BPF were assessed using ranked ANCOVA adjusted for region and BL BPF.

Results

Compared with SC IFNB-1a, alemtuzumab reduced median annualized percent change in BPF in patients free of disease activity during Years 0-1 (Definition 1: -0.37% vs -0.61%, P=0.006; Definition 2: -0.36% vs -0.54%, P=0.024) or Years 0-2 (Definition 1: -0.27% vs -0.44%, P=0.014; Definition 2: -0.28% vs -0.41%, P=0.045). Median annualized percent change in BPF was reduced with alemtuzumab versus SC IFNB-1a in patients with disease activity in Years 0-1 (-0.61% vs -0.79%, P=0.005) or Years 0-2 (-0.40% vs -0.56%, P<0.0001). Over 6 years, brain volume loss (BVL) was slower in patients without disease activity who initiated alemtuzumab at core study BL (-1.66%) than in those who received SC IFNB-1a in the core studies and initiated alemtuzumab in the extension (-2.05%).

Conclusions

Brain atrophy was reduced with alemtuzumab compared with SC IFNB-1a in patients without disease activity over 2 years. A slower rate of BVL was maintained through Year 6 in patients without disease activity who received alemtuzumab in the core study compared with SC IFNB-1a, suggesting alemtuzumab may slow neurodegeneration associated with BVL.

STUDY SUPPORT: Sanofi.

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Biomarkers and Bioinformatics Poster Presentation

P0097 - Intrathecal immunoglobulin M synthesis is associated with higher serum neurofilament light chain levels and increased MRI disease activity in MS (ID 1089)

Abstract

Background

Intrathecal IgM synthesis was reported to be associated with higher clinical disease activity and severity. We found an association also with earlier use of high efficacy treatments in relapsing MS (RMS).

Objectives

To explore whether patients with intrathecal IgM synthesis show a) higher serum neurofilament light chain levels (sNfL) as a reflection of neuronal damage, or b) signs of increased disease severity in cerebral MRI, in patients with RMS followed in the Swiss MS Cohort Study.

Methods

487 patients were categorized by presence of oligoclonal IgG bands (OCGB) and intrathecally produced IgG/M:

1) OCGB-/IgG-/IgM- (reference [ref]);

2) OCGB+/IgG-/IgM-;

3) OCGB+/IgG+/IgM- and

4) OCGB+/IgG+/IgM+.

sNfL was measured (at baseline and every 6- or 12 months) with the NF-light® assay. Age-dependent sNfL z-scores (sNfLz) were modelled in 8865 healthy control samples to reflect the deviation of a patient sNfL value compared to mean values observed in same age healthy controls. Yearly T2 lesion number and occurrence of new/enlarging T2 lesions were automatically assessed in cerebral MRIs and checked manually. Contrast enhancing lesions (CEL) were manually quantified. Linear or negative binomial mixed models were used to investigate the associations between the four CSF Ig patterns and longitudinal sNfLz and MRI measures, adjusted for DMT and other covariates.

Results

IgM+ patients had higher sNfLz vs reference (estimate 0.50 [CI 0.12, 0.89], p=0.011), whereas those with only OCGB+ (0.11 [-0.28, 0.50], p=0.582) or with OCGB+/IgG+ (0.20 [-0.16, 0.56], p=0.270) did not (n=2970 observations). This was confirmed when analyzing only untreated patients adjusting for T2 and CEL numbers (1.16 [0.47, 1.86], p<0.01 vs 0.58 [-0.11, 1.27], p=0.1022 vs 0.51 [-0.11, 1.13], p=0.108 vs ref, respectively) (n=234).

IgM+ patients had 2.28-fold more T2 lesions ([1.51, 3.44], p<0.01) vs ref; for patients with only OCGB+ (1.61 [1.07, 2.43], p=0.0237) or OCGB+/IgG+ (1.58 [CI 1.08, 2.32], p=0.0179) (n=1580) this association was weaker.

IgM+ was associated with a 2.47-fold risk for new/enlarging T2 lesions on yearly follow-up MRIs vs ref (2.47 [1.28, 4.78], p<0.01) but not the two other patient groups (1.84 [CI 0.93; 3.65], p=0.0799 and 1.61 [CI 0.87; 2.95], p=0.1280) (n=861).

Conclusions

Intrathecal IgM synthesis was consistently associated with quantitative measures of neuro-axonal injury and disease severity in RMS. Our findings strongly support the clinical utiliy of this biomarker.

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Biomarkers and Bioinformatics Poster Presentation

P0154 - Serum Neurofilament light chain captures and predicts disability progression independent of relapses (PIRA) in multiple sclerosis (ID 809)

Abstract

Background

In relapsing MS, blood NfL has emerged as a promising biomarker of disease activity and worsening. The ability of serum NfL (sNfL) to detect relapse-independent disability progression is less well established.

Objectives

We investigated whether patients followed in the Swiss Multiple Sclerosis Cohort (SMSC) without any relapses during follow-up, had higher sNfL levels when experiencing confirmed disability progression independent of relapses (PIRA) as compared to stable patients. Secondly, we explored whether baseline (BL) sNfL could predict PIRA.

Methods

BL and 6- or 12-monthly follow-up sNfL were measured by Simoa NF-light® assay in 4608 samples from 806 relapse-free MS patients and 8865 serum samples from 4133 healthy controls (median age 45 yrs). Age-dependent sNfL z-scores (sNfLz) were modeled in healthy controls using a generalised additive model for location scale and shape to reflect the deviation of a patient sNfL value from the mean value of same age healthy controls. PIRA was defined as an EDSS increase of ≥1.5 steps if baseline EDSS 0, ≥1.0 if 1.0-5.5, or ≥0.5 if >5.5, confirmed after ≥6 months. We used mixed effects models to investigate the association between PIRA, clinical parameters, disease modifying treatment, and log(sNfL) as dependent variable at each sampling. The predictive value of BL sNfLz was investigated by uni- and multivariable Cox proportional hazards models.

Results

806 (4608 samples) of 1399 patients in the SMSC did not experience relapses during a median follow-up of 4.7 years (57.6%; BL: 715 RRMS, 43 SPMS, 48 PPMS; median age 42 yrs; samples/patient: 5; EDSS 2.0). PIRA occurred in 153/806 (19.0%). In a multivariable model, sNfL was positively associated with age (1.7%/year [95%CI 1.5;2.0], p<0.001) and EDSS at BL (7.6%/step, [5.8;9.6], p<0.001), whereas it was decreased when sampled during monoclonal antibody therapy (-10.8%, [-14.7;-6.6], p<0.001) or oral MS treatments (-10.4%, [-14.1;-6.5%], p<0.001) as compared to untreated timepoints. Importantly, patients experiencing PIRA had 11.6% higher sNfL levels, compared with stable patients (4.5;19.2, p=0.001). The hazard of future PIRA increased by 23.5% (8.3;40.8, p=0.002) per 1 standard deviation higher BL sNfLz. This finding was confirmed after adjusting for age, EDSS score and treatment at BL (27.8%, [11.5;46.5], p<0.001; sNfLz > 2: 2.5-fold risk [95%CI 1.7-3.9], p<0.001 for PIRA event vs. sNfLz < 2).

Conclusions

Our data support the value of sNfL to capture and predict neuro-axonal injury leading to disability progression independent from relapses.

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Biomarkers and Bioinformatics Poster Presentation

P0160 - Serum NfL z-scores derived from a large healthy control group reflect different levels of treatment effect in a real-world setting (ID 916)

Abstract

Background

Serum neurofilament light chain (sNfL) levels reflect neuroaxonal damage and relate to disease activity in MS. sNfL may qualify as well as a biomarker of suboptimal treatment response to disease modifying therapies (DMT). Establishment of age-dependent reference ranges in healthy controls is a prerequisite for developing this biomarker for clinical use.

Objectives

To compare on-treatment sNfL levels with values from a healthy control cohort and to investigate the effect of DMTs on sNfL levels in patients from the Swiss MS Cohort Study.

Methods

sNfL was measured (at baseline and every 6- or 12 months) with the NF-light® assay. Age-dependent sNfL z-scores (sNfLz) were modeled in healthy controls using a generalized additive model for location scale and shape to reflect the deviation of a patient sNfL value from the mean value of same age healthy controls. Linear mixed models were used to investigate the associations between clinical characteristics, DMT and longitudinal sNfLz. Interaction terms and splines were used to model sNfLz and for comparison log(NfL), and their dynamics under treatment.

Results

sNfL was measured in 1368 patients with 7550 longitudinal samples (baseline: median age: 41.9 yrs; 5.4% CIS, 83.2% RRMS, 5.6% SPMS, 5.8% PPMS; median EDSS: 2.0; median follow-up: 4.6 yrs) and 4133 healthy controls with 8865 samples (median age: 44.8 yrs). In the multivariable model, sNfLz increased with EDSS (0.131/step, [95% CI 0.101;0.161]), recent (<120 days) relapse (0.739 [0.643;0.835]) decreased with age (-0.014/year [-0.02;-0.009]), and time on DMT (-0.040/year [-0.054;-0.027]); sNfLz were lower when sampled while on more effective DMT (oral versus platform injectables: -0.229 [-0.344;-0.144]; monoclonal antibodies (mAB) versus platform injectables: -0.349 [-0.475;-0.224]), (p<0.001 for all associations). sNfLz were inversely associated with the hierarchy in efficacy of mAB over orals and orals over platform therapies with regard to slope and extent of decrease (interaction between time under DMT and DMT class: p<0.001). sNfLz, but not log(NfL) showed normalization of sNfL levels by mAB to healthy control levels.

Conclusions

The dynamic change of sNfLz on DMT reflects closely their relative clinical efficacy and is more meaningful than log(sNfL) by excluding age as a confounding factor. Use of sNfLz based on a large normative database as an age-independent sNfL measure improves the accuracy of the sNfL signal and hence their clinical utility.

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Clinical Trials Poster Presentation

P0219 - Ocrelizumab Phase IIIb efficacy from CASTING: 2-year NEDA (MRI re-baselined) subgroup rates in RRMS patients with a suboptimal response to prior DMTs (ID 974)

Speakers
Presentation Number
P0219
Presentation Topic
Clinical Trials

Abstract

Background

Patients with relapsing-remitting multiple sclerosis (RRMS) often experience disease activity despite receiving a disease-modifying therapy (DMT). The Phase IIIb CASTING study (NCT02861014) of ocrelizumab evaluated the efficacy/safety in patients with RRMS who had a prior suboptimal response to one or two DMTs (primary endpoint: 2-year no evidence of disease activity [NEDA] rate).

Objectives

To evaluate CASTING 2-year NEDA outcomes by inclusion criteria, baseline characteristics and prior DMT.

Methods

Patients (Expanded Disability Status Scale [EDSS] score ≤4.0; discontinued prior DMT of ≥6 months’ duration due to suboptimal disease control) received intravenous ocrelizumab 600 mg every 24 weeks for 96 weeks. The primary endpoint of NEDA (with prespecified MRI re-baselining at Week 8) was defined as absence of: protocol-defined relapses, 24-week confirmed disability progression, T1‑weighted contrast-enhancing and new/enlarging T2-weighted lesions over 2 years.

Results

A total of 680 patients were evaluated (female, 64%; mean [SD] baseline EDSS score, 2.1 [1.1]; pretreated with one or two DMTs, including orals and injectables, n=411 [60.4%]/n=269 [39.6%]; enrolled due to activity of: MRI only, n=167 [24.6%]; relapse only, n=238 [35.0%]; MRI and relapse, n=275 [40.4%]). After 2 years, 74.8% (n/N=492/658) of patients had NEDA (with MRI re-baselined at Week 8). The NEDA rate was highest among patients enrolled due to MRI activity alone (80.6%) versus enrollment for relapse (75.1%) or relapse with MRI (70.5%). NEDA rates across disease-related subgroups were highest in the subgroups of baseline EDSS score <2.5 (77.2%), ≤1 relapse prior to enrollment (78.2%) and the event leading to enrollment occurring ≥6 months prior to study entry (75.8%) versus the counterpart subgroups of EDSS score ≥2.5 (70.8%), >1 relapse prior to enrollment (66.3%) and the event leading to enrollment occurring <6 months prior to entry (71.0%). The NEDA rate did not vary by baseline age (≤40 years, 74.7%; >40 years, 75.0%). NEDA rates were higher in patients receiving one prior DMT (77.6%) versus two prior DMTs (70.3%) and remained generally high when stratified by the last prior DMT received before enrollment: interferons, 81.1%; glatiramer acetate, 73.9%; dimethyl fumarate, 73.8%; teriflunomide 69.8%; fingolimod, 68.9%.

Conclusions

The NEDA rate was high overall and across a wide range of disease-related and demographic subgroups, regardless of prior treatment background.

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Clinical Trials Poster Presentation

P0234 - Safety experience with extended exposure to ofatumumab in patients with relapsing multiple sclerosis from Phase 2 and 3 clinical trials (ID 1638)

Abstract

Background

Ofatumumab, a fully human anti-CD20 monoclonal antibody, demonstrated superior efficacy versus teriflunomide in Phase 3 ASCLEPIOS I/II relapsing multiple sclerosis (RMS) trials. Long-term data to assess the safety and benefit-risk profile of ofatumumab 20 mg per month is required.

Objectives

To report the overall safety data of all patients treated with subcutaneous (s.c.) ofatumumab 20 mg for RMS, including patients who continued treatment and those who were newly switched in the ongoing open-label Phase 3b ALITHIOS study.

Methods

The overall safety population was divided into 2 groups 1) Continuous: Patients randomized to ofatumumab in the core Phase 2 APLIOS (12 weeks) or Phase 3 ASCLEPIOS I/II (up to 30 months) trials and continued in ALITHIOS, or completed core study and continued with the safety follow-up, and 2) Newly-switched: Patients randomized to teriflunomide in ASCLEPIOS I/II and switched to ofatumumab in ALITHIOS. All adverse events (AEs), serious AEs (SAEs) and deaths up to and including the safety cut-off of 100 days after last administration of ofatumumab are included in this safety analysis until 30 November 2019.

Results

A total of 1873 patients (continuous: 1230; newly-switched: 643) were exposed to ofatumumab ([median duration] continuous: 21.0 months; newly-switched: 4.4 months) for 2118.6 patient-years (continuous: 1903 patient-years; newly-switched: 215.6 patient-years). 71.4% of patients (continuous: 82%; newly-switched: 51%) experienced at least one AE; most were mild-to-moderate. AEs led to ofatumumab discontinuation in 3.0% of patients. SAEs were observed in 6.2% of patients. Incidence of infections was 38.5% (continuous: 49.3%, newly-switched: 18.0%). Serious infections occurred in 1.8% of patients. Incidence of injection-related reactions (IRRs) was 23.7% (continuous: 24.9%; newly-switched: 21.3%); most IRRs were non-serious, grade 1 or 2 and none led to ofatumumab discontinuation. Hepatitis B reactivation, progressive multifocal leukoencephalopathy or deaths have not been reported. No cases of opportunistic infections have been identified. Incidence of malignancies was 0.3% (with confounding) and no new cases have been reported in either continuous or newly-switched patients as of the data cut-off time.

Conclusions

No new safety signals were identified in this extended analysis. The safety profile of ofatumumab in RMS patients remains consistent with data reported in the core studies, including the ASCLEPIOS I/II trials.

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Clinical Trials Poster Presentation

P0236 - Serum immunoglobulin levels and infection risk in the Phase 3 trials of ofatumumab in relapsing multiple sclerosis (ID 1566)

Abstract

Background

Ofatumumab, a fully human anti-CD20 monoclonal antibody, demonstrated superior efficacy vs teriflunomide with a favorable safety profile in relapsing MS (RMS) patients in the Phase 3 ASCLEPIOS I/II trials. Reductions in serum immunoglobulin (Ig) M and IgG levels are associated with anti-CD20 therapies.

Objectives

To assess the effect of ofatumumab on serum Ig levels and evaluate potential association between a decrease in IgM/IgG levels and risk of infections.

Methods

Patients were randomized to receive subcutaneous ofatumumab 20 mg (initial doses: Days 1, 7, and 14; subsequent doses: every 4 weeks from Week (W) 4 onwards) or oral teriflunomide 14 mg once-daily for up to 30 months (m, mean follow-up duration: 18m). Serum IgM/IgG levels were monitored at baseline (BL), W4, W12, and every 12 weeks thereafter (ofatumumab, n=946; teriflunomide, n=936). Proportion of patients with IgM/IgG levels below the lower limit of normal (<LLN [g/L]: IgM, 0.4; IgG, 7.0), and association of IgM/IgG levels with incidence of infections that occurred up to 1m prior and 1m after any decrease in IgM/IgG levels (<LLN vs ≥LLN) were analyzed. Infections in conjunction with IgM/IgG <LLN and lymphopenia and/or neutropenia on the same visit were also analyzed.

Results

Mean IgM/IgG levels were well within reference ranges over time. Over all post-BL visits, a higher proportion of patients on ofatumumab had IgM<LLN (17.7% vs 6.6%), whilst a lower proportion had IgG<LLN (14.2% vs 22.9%) vs patients on teriflunomide. At W96, a similar trend was observed (IgM<LLN: 11.1% vs 1.9%; IgG<LLN: 2.7% vs 6.0%). Proportion of patients on ofatumumab who experienced ≥1 infection within 1m prior and until 1m after IgM<LLN was 31.1% (52/167; 2 serious) vs 51.5% (400/777) with IgM≥LLN (18 serious). Similarly, 27.6% (37/134) reported infections during a drop in IgG<LLN (3 serious) vs 50.6% (410/810) with IgG≥LLN (21 serious). The most common infection was nasopharyngitis. Overall, 1/11 patients with concurrent IgM<LLN and lymphopenia and/or neutropenia, and 7/20 patients with concurrent IgG<LLN and lymphopenia and/or neutropenia reported infections; none were serious.

Conclusions

Reduction in serum IgM levels was observed over time, but for the majority of patients, Ig levels remained above the lower limit of normal. No decrease in IgG levels was reported within the observation period (mean follow-up: 18m). There was no apparent association between decreased Ig levels and infections in conjunction with lymphopenia and/or neutropenia in ofatumumab-treated RMS patients.

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Clinical Trials Poster Presentation

P0240 - Therapeutic Decisions in MS Care: An International Study comparing Clinical Judgement vs. Information from Artificial Intelligence-Based Models (ID 752)

Abstract

Background

The rapidly evolving therapeutic landscape of multiple sclerosis (MS) can make treatment decisions challenging. Novel tools using artificial intelligence (AI) can provide estimations of MS disease progression, which may aid MS therapeutic decisions. However, whether neurologists are willing to utilize information provided by AI-based models when making therapeutic decisions is unknown.

Objectives

To assess whether neurologists rely on clinical judgment (CJ) or quantitative/ qualitative estimations of disease progression provided by hypothetical AI-based models (assuming these models can reliably identify patients at high vs. low risk of disease progression) in simulated MS case scenarios.

Methods

Overall, 231 neurologists with expertise in MS from 20 countries were randomized to receive qualitative (high/low) or quantitative (85-90% vs. 15-20%) information regarding the likelihood of disease progression. Participants were presented with simulated MS case scenarios, and initially made 7 treatment decisions based on the clinical information using CJ. After randomization, participants made 10 treatment decisions using CJ and estimations of disease progression provided by AI models. We evaluated concordance and discordance of therapeutic decisions based on CJ and AI. The primary outcome was the proportion of “optimal” treatment decisions defined as treatment escalation when there was evidence of disease progression or continuing the same treatment when clinically stable. Mixed models were used to determine the effect of randomization group, case risk level, and CJ/AI. Clinicaltrials.gov #NCT04035720

Results

Of 300 neurologists invited to participate, 231 (77.0%) completed the study. Study participants had a mean age (SD) of 44 (±10) years. Of 2310 responses, 1702 (73.7%) were classified as optimal. Optimal decisions were more common for the high-risk vs. low-risk CJ group (84.5% vs 57.6%; p<0.001). There were no differences in the estimated odds of optimal responses between the quantitative vs. qualitative groups (OR 1.09; 95%CI 0.86, 1.39) after adjustment for pre-intervention responses. The estimated odds of optimal decisions for the high-risk vs low-risk CJ group was 2.96 (95%CI: 2.47, 3.56 ) after adjusting for group, pre-intervention responses, and AI-based estimations. For low-risk CJ cases, additional input by AI-based estimations was associated with a lower likelihood of optimal responses; being worse for high-risk vs. low-risk AI estimations (OR 0.235; 95%CI: 0.16, 0.340) adjusting for covariables.

Conclusions

Neurologists were more likely to make optimal treatment choices for high-risk simulated scenarios. The addition of hypothetical information provided by AI-based models- did not improve treatment decisions for low-risk cases. These results provide a framework for understanding therapeutic decision-making in MS neurologists, who are more reliant on their own CJ over AI-based tools.

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Clinical Trials Poster Presentation

P0241 - Top-line Results of EMPhASIS, a Phase 2 Clinical Trial of Vidofludimus Calcium (IMU-838) in Relapsing-Remitting Multiple Sclerosis (ID 1409)

Speakers
Presentation Number
P0241
Presentation Topic
Clinical Trials

Abstract

Background

Dihydroorotate dehydrogenase (DHODH) inhibition is an established mode of action for disease-modifying treatment of relapsing-remitting multiple sclerosis (RRMS). Vidofludimus calcium (IMU-838) is a selective and potent second-generation DHODH oral immunomodulator being developed for the treatment of several immune-mediated diseases including MS and COVID-19. The inhibition of the DHODH enzyme leads to metabolic stress in stimulated lymphocytes with subsequent reduction of pro-inflammatory cytokines and induction of apoptosis. Due to IMU-838’s pharmacological selectivity and lack of relevant off-target effects on kinases, increased rates of typical antiproliferative effects (neutropenia, alopecia and gastrointestinal disturbances) have not been observed in clinical trials. The serum half-life of approximately 30 hours allows quick on- and off-dosing.

Objectives

To report top­line efficacy, safety, and tolerability of IMU-838 in the relapsing MS EMPhASIS trial (NCT03846219), the first trial of IMU-838 in MS.

Methods

EMPhASIS is a phase 2 multicenter, double-blind, placebo-controlled, randomized, parallel-group trial to assess the efficacy and safety of two once-daily oral doses of IMU-838 (30 and 45 mg/day) in patients with RRMS. Inclusion criteria are age 18-55 years, active RRMS defined by the evidence of clinical and radiological disease activity, and Expanded Disability Status Scale (EDSS) 0-4. The primary endpoint is the cumulative number of combined unique active MRI lesions over 24 weeks. Secondary endpoints include efficacy, safety and tolerability parameters. The study also includes a subsequent optional, open-label treatment period to evaluate long-term safety and tolerability.

Results

210 subjects (65% women) were enrolled in 36 centers across four European countries. The mean age at baseline was 36.8 years (SD 8.8). 198 subjects (94%) completed the 24-week main treatment period, with the last follow-up visit in April 2020. Database lock will be in July 2020 and top-line data will be available shortly thereafter. Primary outcome and several secondary outcomes (including safety data) will be presented.

Conclusions

IMU-838 is an orally available, next-generation selective immunomodulator with a potentially more favorable profile than first-generation DHODH inhibitors. Top-line results of IMU-838 on primary and several secondary endpoints in patients with RRMS in the EMPhASIS trial will be presented.

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Diagnostic Criteria and Differential Diagnosis Poster Presentation

P0263 - Serum neurofilament predicts clinical progression and increases diagnostic accuracy in patients with early multiple sclerosis (ID 1336)

Abstract

Background

Up to date prognostic estimation in newly diagnosed patients is hardly possible while the differentiation between disabling versus more benign courses is of utmost relevance. Reliable blood-based biomarkers that are associated with diagnosis and prognosis of multiple sclerosis (MS) have not been established.

Objectives

Can serum neurofilament light chain measurements serve as a reliable biomarker for diagnostic accuracy and prognosis for multiple sclerosis patients at the time point of diagnosis?

Methods

In a multicenter prospective longitudinal observational cohort, patients with a first diagnosis of multiple sclerosis (MS) or clinically isolated syndrome (CIS) were recruited between August 2010 and November 2015 in 22 centers and assessed yearly with a standardized protocol. Patients were offered standard immunotherapies according to national treatment guidelines. Serum NfL concentrations were measured using an ultrasensitive single-molecule array (Simoa).

Results

A possible association between sNfL levels and clinical diagnosis, relapses, MRI parameters and treatment decisions was tested in 814 patients classified according to current (2017) and older (2010) McDonald criteria at time point of diagnosis and two years after study inclusion sNfL levels correlated with number of T2 and Gd+ lesions and clinical relapses. After reclassification of CIS[2010] patients with existing CSF analysis, according to 2017 criteria, sNfL levels were lower in CIS[2017] than RRMS[2017] patients (9.1 pg/ml, IQR 6.2-13.7 pg/ml, n = 45; 10.8 pg/ml, IQR 7.4-20.1 pg/ml, n = 213; p = 0.036) and increased accuracy of distinction between CIS and RRMS, when including ≥ 90th percentile of sNfL values. Patients receiving disease-modifying treatment (DMT) during the first two years had higher sNfl baseline levels (11.8 pg/ml, 7.5-20.9 pg/ml, n = 727) than patients never receiving DMT (9.5 pg/ml, IQR 6.4-14.1 pg/ml, n = 87, p = 0.002). Longitudinal sNfL levels reflected treatment decisions within the first four years.

Conclusions

sNfL is associated with diagnosis and prognosis of MS patients at the time point of first diagnosis and may be of use for initial treatment stratification.

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Disease Modifying Therapies – Mechanism of Action Poster Presentation

P0382 - Reduction in CUA MRI lesions in the first 6 months of cladribine tablets treatment for highly active relapsing multiple sclerosis: MAGNIFY-MS study (ID 982)

Speakers
Presentation Number
P0382
Presentation Topic
Disease Modifying Therapies – Mechanism of Action

Abstract

Background

The MAGNIFY-MS study (NCT03364036) aims to determine the onset of action of cladribine tablets 3.5 mg/kg over 2 years (CT3.5) in patients with relapsing multiple sclerosis (RMS). Efficacy data from the pivotal trial CLARITY showed that outcomes in CT3.5-treated patients were superior to placebo with regard to number and relative reduction of standardized combined unique active (CUA) lesions over the 96-week trial. Carrying out early and frequent magnetic resonance imaging (MRI) will provide valuable insights into the onset of action of CT3.5.

Objectives

To report on the onset of action of CT3.5 by observing changes in counts of CUA MRI lesions during the first 6 months of the MAGNIFY-MS study.

Methods

MRI scans were performed at screening, baseline, and at months 1, 2, 3 and 6 following CT3.5 treatment on patients with highly active RMS. Differences in CUA lesions between post-baseline periods (period 1, months 1–6, period 2, months 2–6, and period 3, months 3–6) were compared to the baseline period. CUA lesion count was standardized to period length and number of MRIs in a period. A mixed effects linear model was used to account for within pooled centre correlation and adjusted for CUA lesion count during the baseline period, age, and baseline expanded disability status scale (EDSS; >3, ≤3). Type-I-error inflation due to multiple testing was controlled by a gatekeeping procedure.

Results

The full analysis set considered for primary analysis included 270 patients. Reductions in mean CUA count were observed from month 1 onwards compared to baseline; by -1.193 in period 1, -1.500 in period 2 and -1.692 in period 3 (all p<0.0001). In particular, the mean T1 Gd+ lesion counts were decreased from month 2 onwards compared to baseline; by -0.857 at month 2, -1.355 at month 3 and -1.449 at month 6 (all p<0.0001). Sensitivity analysis using negative binomial distribution showed that the treatment effect increased with time measured as lack of CUA in subsequent periods; by 61% in period 1, 77% in period 2, and 87% in period 3 (all p<0.0001). The proportion of patients without any CUA lesions increased in the first 6 months; by 52% in period 1 (p=0.0241), 66% in period 2 (p<0.001), and 81% in period 3 (p<0.001).

Conclusions

MRI was used to assess disease activity in a group of highly active RMS on CT3.5 treatment from one month onwards. Data show an early onset of action on CUA lesions that was significant from month 1 versus baseline, with a treatment effect that increased over the first 6 months.

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Disease Modifying Therapies – Risk Management Poster Presentation

P0393 - Similar clinical outcomes for natalizumab patients switching to every-6-week dosing versus remaining on every-4-week dosing in real-world practice (ID 679)

Speakers
Presentation Number
P0393
Presentation Topic
Disease Modifying Therapies – Risk Management

Abstract

Background

Natalizumab 300 mg every 4 weeks (Q4W) is an effective therapy for relapsing-remitting multiple sclerosis (MS) but is also associated with increased risk of progressive multifocal leukoencephalopathy (PML) in anti–JC virus seropositive patients. Analysis of the TOUCH Prescribing Program safety database showed that natalizumab extended interval dosing (EID; average dosing interval approximately 6 weeks) is associated with lower risk of PML than Q4W dosing. Previous analysis of TYSABRI Observational Program (TOP) data showed no difference in relapse outcomes for patients on Q4W and every-6-week (Q6W) dosing. Comparative disability outcome data in well-matched real-world populations are lacking.

Objectives

Compare relapse and disability outcomes in propensity-score (PS)–matched TOP patients who switched to Q6W dosing with outcomes in patients who remained on Q4W dosing.

Methods

Intentional dosing data collected in TOP as of November 2019 were used to identify patients with ≥1 year of Q4W dosing who remained on Q4W or switched to Q6W dosing. Patients with dosing intervals ≥12 weeks or <3 weeks were excluded. Patients with similar exposures were PS-matched 1:1 with age, sex, Expanded Disability Status Scale score, time from MS onset, exposure duration, and relapse activity as covariates. Between-group comparisons were made for the post-switch follow-up period for Q6W patients and the matching time period for Q4W patients. Adjusted relapse rates (ARRs) were calculated using negative binomial regression with robust standard error estimation. Hazard ratios (HRs) for time to first relapse and 24-week confirmed disability worsening (CDW) were estimated with Kaplan-Meier and Cox methods.

Results

The analysis included 236 matched pairs of Q6W and Q4W patients. Mean (SD) follow-up times for Q6W and Q4W patients were 2.00 (1.30) and 1.89 (1.15) years, respectively. ARRs (0.146 vs 0.139; P=0.796), time to first relapse (HR [95% CI] 1.078 [0.723–1.608]; P=0.711), and time to CDW (HR [95% CI] 0.749 [0.270–2.074]; P=0.578) did not differ significantly for Q6W and Q4W patients.

Conclusions

Relapse and disability outcomes in TOP were similar for PS-matched patients who switched to Q6W or remained on Q4W dosing. These results are consistent with prior matched and unmatched analyses in real-world settings and underscore the need for the ongoing, prospective, randomized efficacy trial of natalizumab Q6W vs Q4W dosing (NOVA, clinicaltrials.gov NCT03689972).

The TOP study was supported by Biogen.

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Prognostic Factors Poster Presentation

P0460 - Factors Associated with Treatment Escalation in MS care: Results from an International Conjoint Study (ID 753)

Abstract

Background

Therapeutic inertia (TI) is a worldwide phenomenon affecting physicians who manage patients with chronic conditions. Previous studies in Multiple Sclerosis (MS) showed TI affects 60 to 90% of neurologists and up to 25% of daily treatment decisions.

Objectives

To determine the most important factors and levels of attributes associated with treatment escalation in an international sample of neurologists with expertise in the management of patients with MS.

Methods

We conducted an international study comprised of 300 neurologists with expertise in MS from 20 countries (Europe: 59.4%, Asia/Australia: 18.3%, America: 22.3%). Participants were presented with 12 pairs of simulated MS patient profiles reflective of case scenarios encountered in clinical practice. Patient profiles included information on age, sex, previous MS history of relapses, MRI findings, desire for pregnancy, and other relevant details. We used disaggregated discrete choice experiments (a conjoint analysis), which is a standard technique used in economic research to estimate the weight of factors and attributes (e.g. categories) affecting physicians’ decisions when considering treatment selection by asking respondents to choose between pairs of options. In our study, participants were asked to select the ideal candidate (Patient A, B or neither) for treatment escalation (from first-line to second-line therapies- eg. Fingolimod, Cladribine, Monoclonal antibodies).

Results

Of 300 neurologists invited to participate, 229 (76.3%) completed the study. The mean age (SD) of study participants was 44 (±10) years. The mean (SD) number of MS patients seen per week by each neurologist was 18 (±16).

The top 3 factors (relative importance) associated with treatment escalation were: previous relapses (20%), EDSS (18%), and MRI activity (13%). Patient demographics and desire for pregnancy had a modest influence (<3%) in treatment escalation.

Participants were 13% less likely to escalate treatment for patients with EDSS >7.0 (compared to EDSS <6.0), whereas symptom severity during most recent relapse and higher number of MRI lesions at 1 year were each associated with 6% higher likelihood of treatment escalation.

We observed differences in the weight of factors associated with treatment escalation between MS specialists and non-specialists and participants practicing in European vs. non-European countries.

Conclusions

This is the first study applying a conjoint design to assess factors associated with treatment escalation and therapeutic inertia in neurologists caring for people living with MS. Our results provide critical information on factors influencing neurologists’ treatment decisions and should be applied to continuing medical education strategies.

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Patient-Reported Outcomes and Quality of Life Poster Presentation

P1038 - Improved or maintained employment status in natalizumab-treated relapsing-remitting multiple sclerosis patients in the TYSABRI Observational Program (ID 676)

Speakers
Presentation Number
P1038
Presentation Topic
Patient-Reported Outcomes and Quality of Life

Abstract

Background

Unemployment rates can be high among patients with multiple sclerosis (MS), and a return to work after unemployment can be difficult, highlighting the importance of treatment in preventing a departure from the workforce due to MS. Natalizumab is a highly effective treatment for patients with relapsing-remitting MS (RRMS) and was associated with positive employment outcomes in real-world studies.

Objectives

To evaluate changes in employment status in RRMS patients treated with natalizumab in the TYSABRI Observational Program (TOP), a large observational study assessing the long-term safety and effectiveness of natalizumab.

Methods

This retrospective analysis included patients aged ≤65 years at TOP enrolment (i.e., baseline [BL]) who were surveyed on their employment status in the year before natalizumab initiation and in the period since treatment initiation (N=2004). Multivariate logistic regression tested the association between BL characteristics and employment outcomes.

Results

At BL, patients had a mean (standard deviation [SD]) Expanded Disability Status Scale (EDSS) score of 3.5 (1.5). At the survey, patients had a mean (SD) of 5.5 (3.3) years of natalizumab treatment. Survey responses indicated that in the year before natalizumab initiation, 1107 patients (55.2%) were working; 814 patients (40.6%) were working full time, 53 (2.6%) were working part time due to MS, 265 (13.2%) were not working due to MS, and 240 (12.0%) and 632 (31.5%) were working part time or not at all, respectively, for other reasons. After natalizumab initiation, 861 patients (43.0%) improved (1.3%) or maintained (41.6%) their employment level, whereas 170 (8.5%) experienced a decline in employment level due to MS and 256 (12.8%) remained unemployed due to MS. Significant predictors of improving/maintaining employment status were younger age (adjusted odds ratio [aOR]: 0.756; P=0.005), lower BL EDSS score (aOR: 0.747; P<0.001), and fewer relapses in the year before natalizumab initiation (aOR: 0.829; P=0.042), but did not include sex, prior therapy use, or RRMS duration.

Conclusions

Of patients who were working prior to natalizumab initiation, 77.0% maintained or improved their employment level with an average follow up of 5.5 years. Overall, favourable outcomes were predicted by younger age and less BL disease activity, supporting the importance of natalizumab initiation early in the disease course to help prevent patients from leaving the workforce due to MS.

The TOP study is funded by Biogen. Biogen funded the analyses and writing support for this abstract. Writing support was provided by Ashfield Healthcare Communications (Middletown, CT, USA).

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Invited Presentations Invited Abstracts

TC18.01 - Immunotherapy to concepts: from very specific targets to immune regulatory network modulation (ID 642)

Speakers
Authors
Presentation Number
TC18.01
Presentation Topic
Invited Presentations

Abstract

Abstract

Multiple sclerosis immunotherapy can be generally classified into four categories:

General and selective immunesuppression,
Immuno modulation,
leucocyte sequestration,
Immune selective depletion

Furthermore one can distinguish ongoing therapies versus so called immune depletion and repopulations therapies (or alternatively called IRTs - immune reconstitution therapies). The talk will cover strategies and examples how especially the peripheral immune system can be manipulated to excerpt beneficial effects within in the central nervous system. Modern approaches to measure those effects are presented, especially in categories of immunomodulation, leucocyte sequestration and immune depletion and repopulation therapies.
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Presenter Of 3 Presentations

Clinical Trials Poster Presentation

P0219 - Ocrelizumab Phase IIIb efficacy from CASTING: 2-year NEDA (MRI re-baselined) subgroup rates in RRMS patients with a suboptimal response to prior DMTs (ID 974)

Speakers
Presentation Number
P0219
Presentation Topic
Clinical Trials

Abstract

Background

Patients with relapsing-remitting multiple sclerosis (RRMS) often experience disease activity despite receiving a disease-modifying therapy (DMT). The Phase IIIb CASTING study (NCT02861014) of ocrelizumab evaluated the efficacy/safety in patients with RRMS who had a prior suboptimal response to one or two DMTs (primary endpoint: 2-year no evidence of disease activity [NEDA] rate).

Objectives

To evaluate CASTING 2-year NEDA outcomes by inclusion criteria, baseline characteristics and prior DMT.

Methods

Patients (Expanded Disability Status Scale [EDSS] score ≤4.0; discontinued prior DMT of ≥6 months’ duration due to suboptimal disease control) received intravenous ocrelizumab 600 mg every 24 weeks for 96 weeks. The primary endpoint of NEDA (with prespecified MRI re-baselining at Week 8) was defined as absence of: protocol-defined relapses, 24-week confirmed disability progression, T1‑weighted contrast-enhancing and new/enlarging T2-weighted lesions over 2 years.

Results

A total of 680 patients were evaluated (female, 64%; mean [SD] baseline EDSS score, 2.1 [1.1]; pretreated with one or two DMTs, including orals and injectables, n=411 [60.4%]/n=269 [39.6%]; enrolled due to activity of: MRI only, n=167 [24.6%]; relapse only, n=238 [35.0%]; MRI and relapse, n=275 [40.4%]). After 2 years, 74.8% (n/N=492/658) of patients had NEDA (with MRI re-baselined at Week 8). The NEDA rate was highest among patients enrolled due to MRI activity alone (80.6%) versus enrollment for relapse (75.1%) or relapse with MRI (70.5%). NEDA rates across disease-related subgroups were highest in the subgroups of baseline EDSS score <2.5 (77.2%), ≤1 relapse prior to enrollment (78.2%) and the event leading to enrollment occurring ≥6 months prior to study entry (75.8%) versus the counterpart subgroups of EDSS score ≥2.5 (70.8%), >1 relapse prior to enrollment (66.3%) and the event leading to enrollment occurring <6 months prior to entry (71.0%). The NEDA rate did not vary by baseline age (≤40 years, 74.7%; >40 years, 75.0%). NEDA rates were higher in patients receiving one prior DMT (77.6%) versus two prior DMTs (70.3%) and remained generally high when stratified by the last prior DMT received before enrollment: interferons, 81.1%; glatiramer acetate, 73.9%; dimethyl fumarate, 73.8%; teriflunomide 69.8%; fingolimod, 68.9%.

Conclusions

The NEDA rate was high overall and across a wide range of disease-related and demographic subgroups, regardless of prior treatment background.

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Clinical Trials Poster Presentation

P0236 - Serum immunoglobulin levels and infection risk in the Phase 3 trials of ofatumumab in relapsing multiple sclerosis (ID 1566)

Abstract

Background

Ofatumumab, a fully human anti-CD20 monoclonal antibody, demonstrated superior efficacy vs teriflunomide with a favorable safety profile in relapsing MS (RMS) patients in the Phase 3 ASCLEPIOS I/II trials. Reductions in serum immunoglobulin (Ig) M and IgG levels are associated with anti-CD20 therapies.

Objectives

To assess the effect of ofatumumab on serum Ig levels and evaluate potential association between a decrease in IgM/IgG levels and risk of infections.

Methods

Patients were randomized to receive subcutaneous ofatumumab 20 mg (initial doses: Days 1, 7, and 14; subsequent doses: every 4 weeks from Week (W) 4 onwards) or oral teriflunomide 14 mg once-daily for up to 30 months (m, mean follow-up duration: 18m). Serum IgM/IgG levels were monitored at baseline (BL), W4, W12, and every 12 weeks thereafter (ofatumumab, n=946; teriflunomide, n=936). Proportion of patients with IgM/IgG levels below the lower limit of normal (<LLN [g/L]: IgM, 0.4; IgG, 7.0), and association of IgM/IgG levels with incidence of infections that occurred up to 1m prior and 1m after any decrease in IgM/IgG levels (<LLN vs ≥LLN) were analyzed. Infections in conjunction with IgM/IgG <LLN and lymphopenia and/or neutropenia on the same visit were also analyzed.

Results

Mean IgM/IgG levels were well within reference ranges over time. Over all post-BL visits, a higher proportion of patients on ofatumumab had IgM<LLN (17.7% vs 6.6%), whilst a lower proportion had IgG<LLN (14.2% vs 22.9%) vs patients on teriflunomide. At W96, a similar trend was observed (IgM<LLN: 11.1% vs 1.9%; IgG<LLN: 2.7% vs 6.0%). Proportion of patients on ofatumumab who experienced ≥1 infection within 1m prior and until 1m after IgM<LLN was 31.1% (52/167; 2 serious) vs 51.5% (400/777) with IgM≥LLN (18 serious). Similarly, 27.6% (37/134) reported infections during a drop in IgG<LLN (3 serious) vs 50.6% (410/810) with IgG≥LLN (21 serious). The most common infection was nasopharyngitis. Overall, 1/11 patients with concurrent IgM<LLN and lymphopenia and/or neutropenia, and 7/20 patients with concurrent IgG<LLN and lymphopenia and/or neutropenia reported infections; none were serious.

Conclusions

Reduction in serum IgM levels was observed over time, but for the majority of patients, Ig levels remained above the lower limit of normal. No decrease in IgG levels was reported within the observation period (mean follow-up: 18m). There was no apparent association between decreased Ig levels and infections in conjunction with lymphopenia and/or neutropenia in ofatumumab-treated RMS patients.

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Invited Presentations Invited Abstracts

TC18.01 - Immunotherapy to concepts: from very specific targets to immune regulatory network modulation (ID 642)

Speakers
Authors
Presentation Number
TC18.01
Presentation Topic
Invited Presentations

Abstract

Abstract

Multiple sclerosis immunotherapy can be generally classified into four categories:

General and selective immunesuppression,
Immuno modulation,
leucocyte sequestration,
Immune selective depletion

Furthermore one can distinguish ongoing therapies versus so called immune depletion and repopulations therapies (or alternatively called IRTs - immune reconstitution therapies). The talk will cover strategies and examples how especially the peripheral immune system can be manipulated to excerpt beneficial effects within in the central nervous system. Modern approaches to measure those effects are presented, especially in categories of immunomodulation, leucocyte sequestration and immune depletion and repopulation therapies.
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Moderator Of 1 Session

Teaching Course Fri, Sep 11, 2020
Session Type
Teaching Course
Date
Fri, Sep 11, 2020

Invited Speaker Of 1 Presentation

Invited Presentations Invited Abstracts

TC18.01 - Immunotherapy to concepts: from very specific targets to immune regulatory network modulation (ID 642)

Speakers
Authors
Presentation Number
TC18.01
Presentation Topic
Invited Presentations

Abstract

Abstract

Multiple sclerosis immunotherapy can be generally classified into four categories:

General and selective immunesuppression,
Immuno modulation,
leucocyte sequestration,
Immune selective depletion

Furthermore one can distinguish ongoing therapies versus so called immune depletion and repopulations therapies (or alternatively called IRTs - immune reconstitution therapies). The talk will cover strategies and examples how especially the peripheral immune system can be manipulated to excerpt beneficial effects within in the central nervous system. Modern approaches to measure those effects are presented, especially in categories of immunomodulation, leucocyte sequestration and immune depletion and repopulation therapies.
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