Background

Progressive multifocal leukoencephalopathy (PML) is a serious and potentially fatal complication of some multiple sclerosis (MS) disease-modifying therapies, including fingolimod. Precise estimates and risk stratification tools are not available for fingolimod-related PML.

Objectives

To estimate the global risk of PML in MS patients receiving fingolimod, and to investigate the effect of treatment duration and age on the risk of PML.

Methods

The number of PML cases identified from the manufacturer safety database, attributed to fingolimod by expert adjudication (based on criteria published by Berger et al. in 2014) as of 28 February 2020, was compared with the estimated global number of fingolimod-treated patients at risk (overall, by treatment duration, and by assumed age at fingolimod treatment initiation).

Results

It was estimated that approximately 299,600 patients were treated with fingolimod globally as of 28 February 2020, corresponding to >778,900 patient-years (PYs) of exposure. Of the 188 suspected PML cases reported during fingolimod treatment, 37 confirmed cases were clearly attributed to fingolimod through expert adjudication. In 17 cases, PML was attributed to previous natalizumab treatment. The remaining 134 cases either had inadequate information to confirm the diagnosis of PML or were classified as either possible or not PML. The estimated incidence rate was 4.75 (95% confidence interval [CI]: 3.34; 6.55) per 100,000 PYs. The estimated crude incidence was 0.12 (95% CI: 0.09–0.17) per 1,000 patients. The incidence of PML appears to increase with treatment duration and approach a plateau at approximately 0.13 per 1,000 patients during Year 5, after which data were scarce. Incidence of PML appears to increase between 30 and 50 years of age and then stabilize but the exact shape of the relationship with age is uncertain due to wide CIs, underlying assumptions, and other unknown confounding factors. For both treatment duration and age at treatment initiation, the precision of the incidence estimates was low due to the small number of cases.

Conclusions

PML risk associated with fingolimod is low. Although, the estimated risk of fingolimod-associated PML appears to increase with cumulative exposure, the precise pattern of this relationship remains uncertain. There may be an increase in PML risk with increased age at treatment initiation, although the exact pattern of this possible relationship is also uncertain.

Background

We previously reported a relationship between air pollutants and increased risk of pediatric MS (ped-MS). Environmental risk factor research in ped-MS offers the advantage of shorter duration between exposure and disease onset. Ozone, an air pollutant, is a major global health hazard thought to have a role in MS pathoetiology. Identifying gene-environment interactions advances the understanding of biological processes at play in MS susceptibility.

Objectives

We sought to examine the interaction between ozone pollution and DRB1*15 status as the main genetic variant associated with MS susceptibility.

Methods

Cases and controls enrolled in the Environmental and Genetic Risk Factors for Pediatric MS study of the US Network of Pediatric MS Centers were analysed. County-level modeled ozone data were acquired from the CDC’s Environmental Tracking Network air pollution database. Participants were assigned ozone values based on county of residence. Values were categorized into tertiles based on healthy controls. The association between ozone tertiles and having MS were assessed by logistic regression. Interaction between tertiles of ozone level and presence of DRB1*15 alleles on odds of ped-MS was evaluated. Models were adjusted for sex, race, ethnicity, age, second-hand smoke exposure, and mother’s education. Additive interaction was estimated using relative risk due to interaction (RERI) and attributable proportion of disease were calculated.

Results

355 ped-MS cases and 565 controls contributed to the analyses. Ozone levels were associated with MS with an odds ratio (OR) of 2.35 (95%CI 1.57–3.51) and 2.21 (95%CI 1.48–3.32) in the upper two tertiles, respectively, compared with the lowest tertile. DRB1 status was also independently associated with MS (OR 1.99; 95%CI 1.43–2.78). There was a significant additive interaction between ozone and DRB1, with a RERI of 2.74 (95%CI 0.50–4.98) and 2.43 (95%CI 0.36–4.5) in the upper two tertiles, respectively. Approximately 60% of the ped-MS risk in those with HLA-DRB1*15 haplotype and high ozone exposure was attributable to the interaction between these risk factors.

Conclusions

Our data revealed additive interaction between higher exposure to ozone and DRB1 alleles on ped-MS susceptibility. Further evaluation of additional genetic variants that might play a role in ozone-induced ped-MS is underway to provide mechanistic insight.

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.

Background

Multiple sclerosis (MS) and Parkinson’s Disease (PD) patients display marked bioenergetic deficits in the CNS. ³¹Phosphorous magnetic resonance spectroscopy (³¹P-MRS) is a non-invasive, quantitative imaging technique for monitoring bioenergetic metabolites, as well as phospholipid and myelin precursors. CNM-Au8 is a suspension of clean-surfaced, faceted, gold nanocrystals that catalyze NAD and ATP production and reduce oxidative stress, resulting in remyelination and neuroprotection. Two Phase 2 CNS imaging trials, REPAIR-MS and -PD, were initiated to determine the effects of orally delivered CNM-Au8 on ³¹P-MRS brain metabolites. An interim analysis of data from completers of these ongoing trials is presented.

Objectives

The objective of this study is to determine the effect of CNM-Au8 treatment on ³¹P brain bioenergetic metabolites in MS and PD patients.

Methods

7 Tesla ³¹P-MRS was conducted at baseline (BL) and after 12-16 weeks of CNM-Au8 treatment (30 mg/day, p.o.). A full volume coil was used to collect whole brain spectra in ~600 voxels with a spatial resolution of 2 cm³. Automated analyses of the integrated area of each ³¹P peak by voxel was normalized to phosphocreatine area and then averaged across voxels for each patient at BL and end of study (EOS). Linear regression determined r² values for the percentage change from BL for each metabolite versus BL values.

Results

Results for 4 MS and 6 PD completers were analyzed. Percent change from BL at the EOS visit was highly correlated to BL levels for key bioenergetic markers. Patients with nicotinamide adenine dinucleotide (NAD) levels less than the BL mean significantly increased whole-brain NAD levels at the EOS visit, while patients with BL NAD levels greater than the mean normalized levels to the BL mean. Importantly, this relationship was observed for total NAD levels (r² = 0.6384; p = 0.0056), β-ATP (r² = 0.8723; p < 0.0001), and several other ³¹P metabolites, indicating a homeostatic effect of CNM-Au8 on brain bioenergetics. In the 4 MS patients, there were marked correlations for NAD (r² = 0.9241; p = 0.039), β-ATP (r² = 0.968; p=0.016), and several other ³¹P metabolites.

Conclusions

These preliminary results provide the first clinical evidence demonstrating the catalytic effects of CNM-Au8 on key bioenergetic metabolites in MS and PD brains. Full analyses will be conducted once the trials are completed. The brain metabolic homeostasis observed with CNM-Au8 treatment may be neuroprotective, a hypothesis currently being explored in the ongoing VISIONARY-MS study.

Background

Depletion of B cells in patients with relapsing multiple sclerosis (RMS) using anti-CD20 monoclonal antibodies (mAbs) reduces annualized relapse rates and inflammatory lesion activity on magnetic resonance imaging, and delays time to confirmed disability worsening. Anti-CD20 mAbs ocrelizumab and rituximab are administered by intravenous infusion in clinic; ofatumumab is administered subcutaneously with a pre-filled syringe or autoinjector (AI) pen, facilitating self-administration. No outcome data exist relating to transition of patients treated with ocrelizumab or rituximab to ofatumumab.

Objectives

OLIKOS is a 12 month, prospective, single-arm, multicenter phase 3b study that will explore maintained efficacy of ofatumumab in patients with RMS who transition from intravenous anti-CD20 mAb therapy.

Methods

About 100 adults with RMS will be enrolled at 10-20 centers in the USA. Eligible patients will have been previously treated with 2-5 consecutive courses of intravenous ocrelizumab or rituximab (other anti-CD20 mAbs are excluded), with last dose 4-9 months before OLIKOS baseline. Other inclusion criteria are Expanded Disability Status Scale score 5.5 or lower at screening and CD19 B cells depleted to below 1% at baseline. Patients with suboptimal response to anti-CD20 therapy in the previous 6 months (relapse, ≥2 active gadolinium-enhancing [Gd+] lesions, any new/enlarging T2 lesions, clinical worsening), or who discontinued anti-CD20 therapy because of severe infusion-related reactions or recurrent infections, or with progressive disease, will be excluded. All participants will receive subcutaneous ofatumumab 20 mg administered by AI pen on Days 1, 7 and 14, then monthly in Months 1-12. The primary endpoint will be no change or a reduction in Gd+ lesion count at Month 12. Secondary endpoints will be participant retention and changes in immune biomarkers, treatment satisfaction, safety and tolerability at Months 6 and 12. There will be a 6 month interim analysis.

Results

The detailed study design will be presented. OLIKOS will complement the ofatumumab phase 3 program in RMS by generating maintained efficacy, retention and satisfaction data based on monthly subcutaneous drug delivery with the AI pen in patients previously treated with ocrelizumab or rituximab.

Conclusions

OLIKOS will provide important data on the maintained efficacy of ofatumumab in patients with RMS transitioning from intravenous anti-CD20 therapies.

Background

Satralizumab, a humanized, monoclonal recycling antibody that targets the interleukin-6 receptor, reduced patients’ risk of NMOSD relapse in the double-blind (DB) periods of two randomized, phase 3 clinical trials in NMOSD: SAkuraSky (satralizumab in combination with baseline immunosuppressants; NCT02028884), and SAkuraStar (satralizumab monotherapy; NCT02073279).

Objectives

To assess the efficacy of satralizumab over a longer period of treatment, using data from the SAkura studies’ open-label extension (OLE) periods.

Methods

Patients entering SAkuraSky/Star were randomized to receive satralizumab 120mg or placebo at Weeks 0, 2, 4, and Q4W thereafter. After completing the DB period or experiencing a relapse, patients could enter the OLE period (same satralizumab dosing as DB period). The primary endpoint of both studies was time to first protocol-defined relapse (PDR) in the DB period, adjudicated by a Clinical Endpoint Committee (CEC). In this analysis, which includes OLE data (CEC adjudication unavailable), we assessed time to first investigator-reported PDR (any relapse considered by the investigator to meet PDR criteria) in the combined DB+OLE periods, using a pooled population from both studies.

Results

Overall, 179 patients were randomized to treatment (satralizumab n=105; placebo n=74), of whom 166 received ≥1 dose of satralizumab in the combined DB+OLE period. The median (range) satralizumab exposure in the DB period was 96.1 (8–224) weeks, and in the combined DB+OLE was 131.9 (13–276) weeks.

In the combined DB+OLE, patients originally randomized to satralizumab had a 51% lower risk of investigator-reported PDR vs those originally randomized to placebo (HR [95% CI] 0.49 [0.31–0.79]; P=0.002); the risk reduction was more pronounced in AQP4-IgG seropositive patients (66% risk reduction; HR [95% CI] 0.34 [0.19–0.62]; P<0.001). Patients who switched from placebo to satralizumab upon entry into the OLE period were included in the placebo group for this analysis, which likely reduced the observed treatment difference between satralizumab and placebo compared with the DB period.

No patients randomized to satralizumab withdrew from the OLE period due to a relapse, vs four patients who were originally randomized to placebo. The safety profile of satralizumab in the OLE was consistent with the DB period.

Conclusions

Across the DB and OLE periods of the SAkura studies, patients randomized to satralizumab had a significantly reduced risk of relapse vs placebo.

Background

NMOSD is a chronic, auto-immune disease characterized by acute relapses that lead to accumulating disability. Satralizumab, a humanized, monoclonal antibody that inhibits the interleukin-6 receptor, reduced relapse frequency and had a favourable safety profile in two randomized, phase 3 clinical trials: SAkuraSky (satralizumab in combination with baseline immunosuppressants; NCT02028884), and SAkuraStar (satralizumab monotherapy; NCT02073279).

Objectives

To assess the impact of satralizumab on infection risk in patients with NMOSD.

Methods

Infections and serious infections (those meeting serious adverse event [AE] criteria) in the double-blind (DB: satralizumab 120mg Q4W vs placebo) and open-label extension (OLE: satralizumab 120mg Q4W) periods of SAkuraSky and SAkuraStar were evaluated (data cut 7 Jun 2019). Exposure-adjusted rates (events per 100 patient-years [PY] of exposure) were assessed, as the total exposure time in the DB period was longer for satralizumab than placebo.

Results

Overall, 180 patients were included. In the DB period, infection rates [95% CI] were lower with satralizumab vs placebo in SAkuraStar (99.8 [82.4–119.8] vs 162.6 [125.8–206.9] events/100PY); there was no between-group difference in infection rates in SAkuraSky (satralizumab: 132.5 [108.2–160.5]; placebo: 149.6 [120.1–184.1] events/100PY). Serious infection rates were comparable between satralizumab and placebo in both studies (SAkuraSky: 2.6 [0.3–9.2] vs 5.0 [1.0–14.7] events/100PY, respectively; SAkuraStar: 5.2 [1.9–11.3] vs 9.9 [2.7–25.2] events/100PY, respectively). In both studies, the most common infections in both treatment groups were upper respiratory tract infections and urinary tract infections.

In the combined DB/OLE period (all patients receiving ≥1 dose of satralizumab; n=166; median [range] exposure: 184 [4–276] weeks in SAkuraSky; 122 [5–243] weeks in SAkuraStar), infection and serious infection rates were similar to the DB period (SAkuraSky: 134.5 [119.5–150.8] infections/100PY, 4.1 [1.9–7.8] serious infections/100PY; SAkuraStar: 90.6 [78.4–104.0] infections/100PY, 3.6 [1.6–7.2] serious infections/100PY). The rates of infections and serious infections did not increase over time. There were no cases of progressive multifocal leukoencephalopathy in either study.

Conclusions

There was no increased risk of infection or serious infection observed in patients treated with satralizumab vs placebo in the DB and OLE periods of the SAkura studies.

Background

Interleukin-6 (IL-6) is implicated in the immunopathology of neuromyelitis optica spectrum disorder (NMOSD). Satralizumab, a humanized recycling monoclonal antibody that inhibits the IL-6 receptor, demonstrated a reduction in NMOSD relapse risk in two phase 3 studies: SAkuraSky (satralizumab in combination with baseline immunosuppressants; NCT02028884), and SAkuraStar (satralizumab monotherapy; NCT02073279).

Objectives

To evaluate the safety of satralizumab vs placebo in a pooled population of NMOSD patients from the SAkura studies, including the latest data from the open-label extension (OLE) period of the studies.

Methods

SAkuraStar and SAkuraSky are randomized studies comprising a double-blind (DB) period (satralizumab 120mg Q4W vs placebo) followed by an OLE period (satralizumab only). The combined DB and extension period was defined as the overall satralizumab treatment (OST) period (cut-off: 7 Jun 2019). Safety was evaluated in the DB and OST periods and reported as adverse event (AE) rates per 100 patient-years (PY).

Results

The pooled DB population included 178 patients (satralizumab, n=104; placebo, n=74), and 166 patients received satralizumab in the OST. Median duration of safety observation with satralizumab was 96.1 weeks in the DB period and 131.9 weeks in the OST period. Rates of AEs and serious AEs were comparable between satralizumab and placebo groups in the DB period (AEs: 478.49 vs 506.51 events/100PY, respectively; serious AEs: 14.97 vs 17.98 events/100PY, respectively), and were consistent in the OST period. In the DB period, four patients (3.8%) in the satralizumab group and five (6.8%) in the placebo group discontinued treatment due to AEs. Serious infection rates were comparable between the satralizumab and placebo groups in the DB period (4.13 vs 6.99 events/100PY) and remained stable in the OST (3.88 events/100PY). No opportunistic infections were observed in the satralizumab group. The injection-related reaction (IRR) rate was higher with satralizumab vs placebo in the DB period (17.03 vs 8.99 events/100PY); IRRs were mostly mild-to-moderate and did not lead to treatment discontinuation. Laboratory abnormalities were in line with those expected with IL-6 receptor antagonists in the DB and OST period. No deaths or anaphylactic reactions were reported.

Conclusions

In NMOSD patients, satralizumab was well tolerated and showed a favorable safety profile. Results from the OST period were consistent with the DB period.

Background

With implementation of “site of care” policies in recent years, an increasing number of health plans now require patients with multiple sclerosis (MS) to receive their infused therapies at non-hospital outpatient centers. In a quality improvement (QI) initiative, we examined patients’, neurologists’, and infusions centers’ practices, perceptions, and barriers related to off-site infusion care following this shift.

Objectives

Assess (1) therapy adherence, administration, and adverse event (AE) monitoring at off-site infusion centers; (2) communication and care coordination between MS clinics and infusion centers; (3) provider and patient perceptions of infusion care; (4) barriers to optimal infusion care.

Methods

(1) Reviews of electronic medical records (EMRs) of MS patients (n = 100) in 3 large specialty clinics; and (2) surveys administered to providers from MS clinics [n = 15] and infusion centers [n = 33], and patients [n = 18].

Results

EMR reviews indicated that 53% of patients missed at least some of their infusions at off-site centers. The vast majority of patients (75%) identified scheduling as the greatest barrier to therapy adherence, however, only 50% of MS clinic and 5% of infusion center providers considered scheduling a significant barrier to care. Discordances were also observed on how often infusion-related details are being communicated, including frequently/very frequently sharing whether patients received their infusions as prescribed (33% MS clinics vs 74% infusion centers; p=.008) and a numerical difference in whether patients had infusion-related AEs (40% vs 61%; p=.180). In fact, infusion notes were only documented for 29% of infusions and over half of patients had infusion-related AEs. Providers also differed on their perceptions of the following as significant barriers to care: lack of time to communicate (80% MS clinic vs 10% infusion center; p<.001); ineffective procedures for bidirectional communication (73% vs 3%; p<.001); oversights in regular communication and follow-up (67% vs 17%; p=.001); and insufficient sharing of patient information (74% vs 17%; p=<.001).

Conclusions

Our findings reveal opportunities to optimize MS infusion care, including improved scheduling procedures and patient monitoring. In addition, aligning communication and care coordination practices among providers has the potential to enhance the quality of care for MS patients receiving their infusions off-site.

Background

Depletion of B cells in patients with relapsing multiple sclerosis (RMS) using anti-CD20 monoclonal antibodies (mAbs) reduces annualized relapse rates and inflammatory lesion activity on magnetic resonance imaging, and delays time to confirmed disability worsening. Anti-CD20 mAbs ocrelizumab and rituximab are administered by intravenous infusion in clinic; ofatumumab is administered subcutaneously with a pre-filled syringe or autoinjector (AI) pen, facilitating self-administration. No outcome data exist relating to transition of patients treated with ocrelizumab or rituximab to ofatumumab.

Objectives

OLIKOS is a 12 month, prospective, single-arm, multicenter phase 3b study that will explore maintained efficacy of ofatumumab in patients with RMS who transition from intravenous anti-CD20 mAb therapy.

Methods

About 100 adults with RMS will be enrolled at 10-20 centers in the USA. Eligible patients will have been previously treated with 2-5 consecutive courses of intravenous ocrelizumab or rituximab (other anti-CD20 mAbs are excluded), with last dose 4-9 months before OLIKOS baseline. Other inclusion criteria are Expanded Disability Status Scale score 5.5 or lower at screening and CD19 B cells depleted to below 1% at baseline. Patients with suboptimal response to anti-CD20 therapy in the previous 6 months (relapse, ≥2 active gadolinium-enhancing [Gd+] lesions, any new/enlarging T2 lesions, clinical worsening), or who discontinued anti-CD20 therapy because of severe infusion-related reactions or recurrent infections, or with progressive disease, will be excluded. All participants will receive subcutaneous ofatumumab 20 mg administered by AI pen on Days 1, 7 and 14, then monthly in Months 1-12. The primary endpoint will be no change or a reduction in Gd+ lesion count at Month 12. Secondary endpoints will be participant retention and changes in immune biomarkers, treatment satisfaction, safety and tolerability at Months 6 and 12. There will be a 6 month interim analysis.

Results

The detailed study design will be presented. OLIKOS will complement the ofatumumab phase 3 program in RMS by generating maintained efficacy, retention and satisfaction data based on monthly subcutaneous drug delivery with the AI pen in patients previously treated with ocrelizumab or rituximab.

Conclusions

OLIKOS will provide important data on the maintained efficacy of ofatumumab in patients with RMS transitioning from intravenous anti-CD20 therapies.

Background

Satralizumab, a humanized, monoclonal recycling antibody that targets the interleukin-6 receptor, reduced patients’ risk of NMOSD relapse in the double-blind (DB) periods of two randomized, phase 3 clinical trials in NMOSD: SAkuraSky (satralizumab in combination with baseline immunosuppressants; NCT02028884), and SAkuraStar (satralizumab monotherapy; NCT02073279).

Objectives

To assess the efficacy of satralizumab over a longer period of treatment, using data from the SAkura studies’ open-label extension (OLE) periods.

Methods

Patients entering SAkuraSky/Star were randomized to receive satralizumab 120mg or placebo at Weeks 0, 2, 4, and Q4W thereafter. After completing the DB period or experiencing a relapse, patients could enter the OLE period (same satralizumab dosing as DB period). The primary endpoint of both studies was time to first protocol-defined relapse (PDR) in the DB period, adjudicated by a Clinical Endpoint Committee (CEC). In this analysis, which includes OLE data (CEC adjudication unavailable), we assessed time to first investigator-reported PDR (any relapse considered by the investigator to meet PDR criteria) in the combined DB+OLE periods, using a pooled population from both studies.

Results

Overall, 179 patients were randomized to treatment (satralizumab n=105; placebo n=74), of whom 166 received ≥1 dose of satralizumab in the combined DB+OLE period. The median (range) satralizumab exposure in the DB period was 96.1 (8–224) weeks, and in the combined DB+OLE was 131.9 (13–276) weeks.

In the combined DB+OLE, patients originally randomized to satralizumab had a 51% lower risk of investigator-reported PDR vs those originally randomized to placebo (HR [95% CI] 0.49 [0.31–0.79]; P=0.002); the risk reduction was more pronounced in AQP4-IgG seropositive patients (66% risk reduction; HR [95% CI] 0.34 [0.19–0.62]; P<0.001). Patients who switched from placebo to satralizumab upon entry into the OLE period were included in the placebo group for this analysis, which likely reduced the observed treatment difference between satralizumab and placebo compared with the DB period.

No patients randomized to satralizumab withdrew from the OLE period due to a relapse, vs four patients who were originally randomized to placebo. The safety profile of satralizumab in the OLE was consistent with the DB period.

Conclusions

Across the DB and OLE periods of the SAkura studies, patients randomized to satralizumab had a significantly reduced risk of relapse vs placebo.

Background

Interleukin-6 (IL-6) is implicated in the immunopathology of neuromyelitis optica spectrum disorder (NMOSD). Satralizumab, a humanized recycling monoclonal antibody that inhibits the IL-6 receptor, demonstrated a reduction in NMOSD relapse risk in two phase 3 studies: SAkuraSky (satralizumab in combination with baseline immunosuppressants; NCT02028884), and SAkuraStar (satralizumab monotherapy; NCT02073279).

Objectives

To evaluate the safety of satralizumab vs placebo in a pooled population of NMOSD patients from the SAkura studies, including the latest data from the open-label extension (OLE) period of the studies.

Methods

SAkuraStar and SAkuraSky are randomized studies comprising a double-blind (DB) period (satralizumab 120mg Q4W vs placebo) followed by an OLE period (satralizumab only). The combined DB and extension period was defined as the overall satralizumab treatment (OST) period (cut-off: 7 Jun 2019). Safety was evaluated in the DB and OST periods and reported as adverse event (AE) rates per 100 patient-years (PY).

Results

The pooled DB population included 178 patients (satralizumab, n=104; placebo, n=74), and 166 patients received satralizumab in the OST. Median duration of safety observation with satralizumab was 96.1 weeks in the DB period and 131.9 weeks in the OST period. Rates of AEs and serious AEs were comparable between satralizumab and placebo groups in the DB period (AEs: 478.49 vs 506.51 events/100PY, respectively; serious AEs: 14.97 vs 17.98 events/100PY, respectively), and were consistent in the OST period. In the DB period, four patients (3.8%) in the satralizumab group and five (6.8%) in the placebo group discontinued treatment due to AEs. Serious infection rates were comparable between the satralizumab and placebo groups in the DB period (4.13 vs 6.99 events/100PY) and remained stable in the OST (3.88 events/100PY). No opportunistic infections were observed in the satralizumab group. The injection-related reaction (IRR) rate was higher with satralizumab vs placebo in the DB period (17.03 vs 8.99 events/100PY); IRRs were mostly mild-to-moderate and did not lead to treatment discontinuation. Laboratory abnormalities were in line with those expected with IL-6 receptor antagonists in the DB and OST period. No deaths or anaphylactic reactions were reported.

Conclusions

In NMOSD patients, satralizumab was well tolerated and showed a favorable safety profile. Results from the OST period were consistent with the DB period.

Background

With implementation of “site of care” policies in recent years, an increasing number of health plans now require patients with multiple sclerosis (MS) to receive their infused therapies at non-hospital outpatient centers. In a quality improvement (QI) initiative, we examined patients’, neurologists’, and infusions centers’ practices, perceptions, and barriers related to off-site infusion care following this shift.

Objectives

Assess (1) therapy adherence, administration, and adverse event (AE) monitoring at off-site infusion centers; (2) communication and care coordination between MS clinics and infusion centers; (3) provider and patient perceptions of infusion care; (4) barriers to optimal infusion care.

Methods

(1) Reviews of electronic medical records (EMRs) of MS patients (n = 100) in 3 large specialty clinics; and (2) surveys administered to providers from MS clinics [n = 15] and infusion centers [n = 33], and patients [n = 18].

Results

EMR reviews indicated that 53% of patients missed at least some of their infusions at off-site centers. The vast majority of patients (75%) identified scheduling as the greatest barrier to therapy adherence, however, only 50% of MS clinic and 5% of infusion center providers considered scheduling a significant barrier to care. Discordances were also observed on how often infusion-related details are being communicated, including frequently/very frequently sharing whether patients received their infusions as prescribed (33% MS clinics vs 74% infusion centers; p=.008) and a numerical difference in whether patients had infusion-related AEs (40% vs 61%; p=.180). In fact, infusion notes were only documented for 29% of infusions and over half of patients had infusion-related AEs. Providers also differed on their perceptions of the following as significant barriers to care: lack of time to communicate (80% MS clinic vs 10% infusion center; p<.001); ineffective procedures for bidirectional communication (73% vs 3%; p<.001); oversights in regular communication and follow-up (67% vs 17%; p=.001); and insufficient sharing of patient information (74% vs 17%; p=<.001).

Conclusions

Our findings reveal opportunities to optimize MS infusion care, including improved scheduling procedures and patient monitoring. In addition, aligning communication and care coordination practices among providers has the potential to enhance the quality of care for MS patients receiving their infusions off-site.