Providence MS Center

Author Of 7 Presentations

Clinical Outcome Measures Poster Presentation

P0046 - Comparative Effectiveness of Ozanimod Versus Dimethyl Fumarate: Results of a Matching-Adjusted Indirect Comparison (ID 492)

Speakers
Presentation Number
P0046
Presentation Topic
Clinical Outcome Measures

Abstract

Background

Ozanimod is a selective S1P1-5 modulator recently approved in the US for the treatment of relapsing-remitting multiple sclerosis (RRMS). In the absence of head-to-head studies, a matching-adjusted indirect comparison (MAIC) can be used to compare ozanimod with other oral disease-modifying therapies in patients with MS.

Objectives

The objective of this study was to conduct a MAIC of the relative efficacy and safety of ozanimod 1.0 mg with dimethyl fumarate (DMF) 240 mg.

Methods

A systematic literature review was performed to identify clinical studies evaluating the efficacy and safety of ozanimod vs DMF. Individual patient data (IPD) for ozanimod were obtained from the SUNBEAM and RADIANCE Part B trials, and aggregate level data for DMF were obtained from CONFIRM and DEFINE. A MAIC was conducted while adjusting for imbalances between studies by reweighting IPD from ozanimod trials to match the mean baseline characteristics reported in the DMF trials. In the absence of a common comparator between ozanimod and DMF, an unanchored comparison was used. Thus, potential treatment effect modifiers and prognostic factors were included in matching.

Results

After matching, baseline patient characteristics were balanced between ozanimod and DMF patients. Compared with DMF, ozanimod demonstrated improved annualized relapse rate (ARR; rate ratio [RR]: 0.80; 95% CI: 0.67–0.97), proportion of patients relapsed (odds ratio [OR]: 0.66; 95% CI: 0.52–0.83), overall adverse events (AEs; OR: 0.11; 95% CI: 0.08–0.16), serious AEs (OR: 0.27; 95% CI: 0.19–0.39), and discontinuations (OR: 0.11; 95% CI: 0.07–0.17) as well as nonsignificant differences for confirmed disability progression (CDP) at weeks 12 (RR: 0.79; 95% CI: 0.58–1.07) and 24 (RR: 0.89; 95% CI: 0.62–1.26).

Conclusions

After adjustment of baseline patient characteristics, ozanimod demonstrated improved relapse outcomes, lower risks of adverse outcomes, and low discontinuations compared with DMF. There were no significant differences in CDP.

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Clinical Outcome Measures Poster Presentation

P0047 - Comparative Efficacy and Safety of Ozanimod Versus Teriflunomide for Relapsing-Remitting Multiple Sclerosis: a Matching-Adjusted Indirect Comparison (ID 569)

Speakers
Presentation Number
P0047
Presentation Topic
Clinical Outcome Measures

Abstract

Background

Ozanimod is a selective S1P1-5 modulator recently approved in the US for the treatment of relapsing-remitting multiple sclerosis (RRMS). In the absence of head-to-head studies, a matching-adjusted indirect comparison (MAIC) can be used to compare ozanimod with other oral disease-modifying therapies in patients with MS.

Objectives

The objective of this study was to compare the relative efficacy and safety of ozanimod 1.0 mg and teriflunomide (TEF) 14 mg.

Methods

A systematic literature review was performed to identify clinical trials that evaluated the efficacy and safety of ozanimod and TEF. Individual patient data (IPD) for ozanimod were obtained from the SUNBEAM and RADIANCE Part B trials, and aggregate level data for TEF were obtained from 6 clinical trials. Heterogeneity was observed between the ozanimod and TEF trials with respect to Expanded Disability Status Scale score, gadolinium-enhanced lesions, disease duration from symptom onset, prior relapse and DMT use, age, sex, region, and weight. An unanchored (no common comparator) MAIC was conducted while adjusting for imbalances between studies by weighting IPD from the ozanimod trials to match the mean baseline characteristics reported in the TEF trials. The following outcomes of interest were assessed: annualized relapse rate (ARR), proportion of patients relapsed, confirmed disability progression (CDP) sustained for 12 and 24 weeks, overall adverse events (AEs), serious AEs (SAEs), and discontinuations due to AEs.

Results

After matching, baseline patient characteristics were balanced between ozanimod and TEF. Compared with TEF, ozanimod demonstrated improvements in ARR (rate ratio [RR]: 0.73; 95% CI: 0.62–0.84), proportion of patients relapsed (odds ratio [OR]: 0.56; 95% CI: 0.44–0.70), overall AEs (OR: 0.35; 95% CI: 0.29–0.43), SAEs (OR: 0.53; 95% CI: 0.37–0.77), and discontinuations due to AEs (OR: 0.14; 95% CI: 0.09–0.21) and similar CDP at 12 (RR: 0.80; 95% CI: 0.61–1.05) and 24 (RR: 0.80; 95% CI: 0.59–1.08) weeks.

Conclusions

Ozanimod was associated with improved relapse outcomes and lower risks of AEs over 1–2 years of follow-up compared with TEF, with no differences in CDP.

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Clinical Trials Poster Presentation

P0233 - Safety and tolerability of conversion to siponimod in patients with relapsing multiple sclerosis: interim results of the EXCHANGE study (ID 1134)

Speakers
Presentation Number
P0233
Presentation Topic
Clinical Trials

Abstract

Background

In the USA, siponimod is approved in adults for the treatment of relapsing multiple sclerosis (RMS), including active secondary progressive MS (SPMS). Understanding washout requirements when converting from other disease-modifying treatments (DMTs) to siponimod is important in clinical practice and should be assessed prospectively.

Objectives

To report results from an interim analysis of EXCHANGE (NCT03623243), a prospective, 6 month, multicenter, open-label, single-arm study evaluating safety and tolerability of overlapping effects when converting to siponimod from other DMTs.

Methods

Patients aged 18-65 years with advancing RMS, Expanded Disability Status Scale (EDSS) score of >2.0 to 6.5, and on continuous oral/injectable DMTs for ≥3 months at time of consent were included in the analysis. Patients were immediately converted to siponimod, except those previously on teriflunomide who required 11-14 days’ washout (with cholestyramine or activated charcoal). During days 1-6, siponimod was titrated from 0.25 mg to 2 mg. Primary endpoint was incidence of drug-related adverse events (AEs). About 100 patients are being enrolled in a parallel, novel virtual cohort, with telemedicine tools.

Results

112 patients (1 in the virtual arm; 70.5% female) from 42 centers in the USA were enrolled, completed screening and were eligible for safety analysis (33.9% ongoing; 20.5% discontinued; 45.5% completed). At screening, 74.1% (n=83) of patients had relapsing-remitting MS, 21.4% (n=24) had SPMS, 3.6% (n=4) had primary progressive MS and 0.9% (n=1) had a single demyelinating event; 42.0% (n=47) had ≥1 relapse in the prior 12 months. At baseline, median age was 45.5 years, median time since MS diagnosis was 11.2 years and median EDSS score was 3.5. In the safety analysis set, ≥1 drug-related AE was reported in 34.8% of patients (n=39) (95% confidence interval [CI]: 26.2-44.5); 4.5% (n=5) had ≥1 serious AE and 5.4% (n=6) had ≥1 AE leading to drug discontinuation. In the subgroup of patients who had completed or discontinued from the study (n=74), 40.5% (n=30) (95% CI: 29.5-52.6) had ≥1 drug-related AE. Change from baseline in heart rate to 6 hours post first dose and AEs by prior DMT will be presented.

Conclusions

Conversion from oral/injectable DMTs to siponimod without washout had a good safety and tolerability profile with no unexpected findings. Subsequent analyses will include data on conversion to siponimod from infusible (natalizumab/ocrelizumab) DMTs.

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Disease Modifying Therapies – Risk Management Poster Presentation

P0332 - Evaluating the Efficacy and Safety of Transitioning Patients from Natalizumab to Ocrelizumab (OCTAVE) (ID 439)

Speakers
Presentation Number
P0332
Presentation Topic
Disease Modifying Therapies – Risk Management

Abstract

Background

Natalizumab (NTZ) is an effective therapy for patients with relapsing MS (RMS). However, it is associated with a risk of progressive multifocal leukoencephalopathy (PML) in patients infected with John Cunningham virus (JCV). Ocrelizumab (OCR) has demonstrated efficacy, yet its safety in patients previously treated with NTZ is unclear.

Objectives

To present interim data from OCTAVE, a prospective, observational study to evaluate the efficacy and safety of OCR in RMS patients previously treated with NTZ.

Methods

Clinically and radiologically stable RMS patients, aged 18-65 treated with a stable dose of NTZ for ≥ 12 months, were started on OCR 4-6 weeks after last dose of NTZ and followed for 12 months. Relapse assessment, Expanded Disability Status Scale (EDSS), and MRI were performed prior to starting OCR and at months 3, 6, 9 (no MRI), and 12.

Results

Thirty-seven patients, 75.7% female with mean age of 43.8 (± 10.97) and a median of 33.5 [IQR = 63.2] NTZ infusions prior to starting OCR have been enrolled between August 9th, 2017 and February 3rd, 2020. 23 patients have completed the study duration of 12 months. Thirty-one subjects switched to OCR due to potential PML risk. One patient had a clinical relapse reported at month 12 although no MRI correlate. However, EDSS at baseline was 4.0 and at month 12 the score was 5.5. At month 3, one patient had one enhancing lesion, and one patient had 3 enhancing lesions. At months 6 and 12, there were no enhancing or new/enlarging T2 lesions. There were no significant changes in the EDSS, physical MSIS-29, and psychological MSIS-29 from baseline to months 6 and 12, though there was an increasing trend for EDSS. Median EDSS [IQR] was 3.00 [2.0] at baseline and median EDSS [IQR] was 4.00 [2.50] at month 12. Infusion reactions were seen in 40.5% of patients with the first dose (includes both 300mg infusions) and 13.5 % with the second dose (600mg infusion). Eight serious adverse events (SAEs) have been reported with three possibly related to OCR, breast cancer, urinary tract infection, and acute cystitis. No cases of PML have been reported.

Conclusions

The transition from NTZ to OCR resulted in limited disease activity. In 2 patients, MRI activity was present at 3 months, but no MRI changes were seen at months 6 and 12. One patient was reported to have a clinical relapse at month 12; however, there were no MRI changes. The trend in increasing EDSS is concerning.

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Disease Modifying Therapies – Risk Management Poster Presentation

P0407 - The Impact of Ocrelizumab on Immunoglobulin Levels and the Risk of Infection. (ID 476)

Speakers
Presentation Number
P0407
Presentation Topic
Disease Modifying Therapies – Risk Management

Abstract

Background

Ocrelizumab (OCR), an anti-CD20 antibody, was approved in the US in March 2017 for treating relapsing (RMS) and primary progressive MS (PPMS). Infections were more commonly seen in patients receiving OCR in earlier trials. Last year European Medicines Agency updated the OCR prescribing information to include the association between a reduction in immunoglobulins especially IgG and serious infections.

Objectives

To determine if there is a relationship in baseline and follow up immunoglobulins levels and the risk of having an infection

Methods

MS patients in our OCR registry with at least one IgM/IgG value and who received ≥2 doses of OCR were included. IgG/IgM levels were obtained within a month of each infusion. Wilcoxon rank-sum tests and linear models were used to examine the relationships between IgM/IgG and infections.

Results

337 patients were included. 72.4% were female; median age was 53.2 [IQR = 19.8] years with a median disease duration of 13.5 [IQR = 11.8] years. 78% had RMS, 13.4% had SPMS, and 8.6% had PPMS. 27% of patients were treatment naïve. Median time on OCR was 26 [IQR = 8.9] months. 88.7% of patients had more than one IgG and IgM value. Infections were seen in 226 (67.1%) patients. The median age of patients who did and did not have an infection was 53.5 [IQR =20.2] and 53 [IQR = 18.1] respectively. Prior natalizumab use was associated with a higher rate of infection, 46 of 62 (74%). No significant differences were found between IgM levels nor IgG levels for cases of infection (56 [IQR = 53], 792 [IQR = 294.5] mg/dL) and non-infection (52 [IQR = 51], 828.5 [IQR = 310.2]) mg/dL) (

Conclusions

Older patients with longer duration of disease and OCR therapy have been found to have more infections, but we did not observe age as a risk factor for infection in this cohort. Furthermore, neither baseline nor follow up IgM or IgG levels predicted infections in this study. However, the median time on OCR was a little over 2 years which may be too soon to see a difference in the rate of infection and immunoglobulin levels.

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Disease Modifying Therapies – Risk Management Poster Presentation

P0417 - Utilization, safety, and tolerability of ocrelizumab: year 3 data from the Providence Ocrelizumab Registry (ID 475)

Speakers
Presentation Number
P0417
Presentation Topic
Disease Modifying Therapies – Risk Management

Abstract

Background

Ocrelizumab (OCR), a humanized anti-CD20 monoclonal antibody, was approved in the US in 2017 for the treatment of relapsing MS (RMS) and primary progressive MS (PPMS). The Providence OCR Registry (POR) was established to monitor long-term treatment and safety outcomes.

Objectives

To evaluate OCR treatment outcomes including clinical and radiographic changes as well as safety issues using real-world data from a diverse, community-based MS population.

Methods

Adult MS patients who have been prescribed OCR were eligible. Chart reviews at OCR start date and every 6 months thereafter were done by a trained RN. Expanded Disability Status Scale (EDSS) scores were determined by the treating provider on the start date and then yearly. Descriptive statistics and paired t-tests were used.

Results

Of the 355 patients enrolled from March 2017 to March 2020, 71.9% were female; mean (SD) age was 51.8 (12.5) years; 78.3% had RMS, 13.2% had SPMS, and 8.5% had PPMS. Median baseline EDSS [interquartile range (IQR)] was 3.0 [2.0, 4.0], 6.5 [6.0, 7.5], and 6.5 [6.0, 7.0] respectively. The RMS cohort had an annualized relapse rate (ARR) of 0.34 prior to starting OCR. Among all patients who had > 1 dose of OCR (n=332), ARR was 0.09 with 4 patients having 2 relapses and 1 patient having 3 relapses. Median EDSS scores at 12 months were 3.0 [2.0, 5.5] (n=151) for RMS patients, 6.5 [6.5, 7.5] (n=31) for SPMS, and 6.5 [5.6, 7.5] (n=16) for PPMS. Infusion reactions occurred in 32.9% of patients during dose one, becoming less frequent with subsequent doses. Respiratory infections occurred in 40.1% of patients followed by urinary tract infections (UTI) (33.1%). Of 34 patients hospitalized, 11 patients had multiple hospitalizations. 25 hospitalizations were due to infections, 14 (56%) of which were due to UTIs. Sixty-five percent of these patients were 55 years or older. Forty-three (12.0%) patients have stopped OCR with a median time to discontinuation [IQR] of 10.8 [6.1,18.9] months; 24 patients stopped due to side effects, 15 patients stopped due to a relapse or clinical progression, and four patients died one each due to septic shock from pneumonia, urosepsis, suicide, and respiratory distress. There were no significant changes in Beck Depression Inventory (BDI), but 87 patients who had baseline and 12 month Modified Fatigue Inventory (MFIS), had significant improvement at 12 months (mean difference -3.7 (±14.1), (p=0.02).

Conclusions

Our study showed that OCR was effective in controlling relapse and disability worsening and reported similar rates of infusion reactions compared to earlier phase III clinical trials. Although only a small percentage of patients have stopped OCR, infections resulting in hospitalization are a concern, especially in older patients.

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Imaging Poster Presentation

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.

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