Background

Antibodies to the aquaporin-4 (AQP4) water channel in neuromyelitis optica spectrum disorder (NMOSD) are reported to trigger the complement cascade, which is implicated in neuronal injury. The terminal complement inhibitor eculizumab is the first treatment approved for use in patients with AQP4 immunoglobulin G-positive NMOSD, based on PREVENT data.

Objectives

To determine whether the beneficial effect of eculizumab in reducing relapse risk in patients with NMOSD is associated with time since diagnosis, relapse history, disability burden or prior immunosuppressant therapy (IST) use, based on data from the phase 3 trial PREVENT (NCT01892345)

Methods

In PREVENT, patients received eculizumab (maintenance dose, 1200 mg/2 weeks) or placebo, with stable-dose concomitant IST (except rituximab and mitoxantrone) permitted. PREVENT was not powered for subgroup analyses; post hoc descriptive analysis was performed on subgroups defined by time since diagnosis, total number of historical relapses, baseline Expanded Disability Status Scale (EDSS) score and prior IST use.

Results

The proportions of patients experiencing an adjudicated relapse were lower with eculizumab than with placebo in all subgroups. Proportions for eculizumab and placebo, respectively, were: 2/31 versus 6/12 for < 1 year since diagnosis and 1/65 versus 14/35 for ≥ 1 year since diagnosis; 1/39 versus 10/24 for 2–4 historical relapses and 2/57 versus 10/23 for ≥ 5 historical relapses; 0/14 versus 3/6 for baseline EDSS scores ≤ 2.0 and 3/82 versus 17/41 for baseline EDSS scores ≥ 2.5 to ≤ 7.0; 0/15 versus 2/5 for no prior IST use (except corticosteroids alone); and 3/81 versus 18/42 for prior IST use. Relapse-risk reductions were consistent and statistically significant in all subgroups.

Conclusions

The data from this post hoc subgroup analysis suggest that eculizumab reduced relapse risk in PREVENT compared with placebo, regardless of time since NMOSD diagnosis, relapse history, disability burden or prior IST use.

Background

In patients with neuromyelitis optica spectrum disorder (NMOSD), relapses may result in cumulative neurological damage and disability. Disease burden may include pain, sensory, cognitive and visual impairment, bowel/bladder dysfunction, weakness or paralysis, and necessitate caregiver support. Prior to 2019, no therapies had received regulatory approval for NMOSD. Thus, off-label immunosuppressive therapies (IST) were commonly used for maintenance therapy. CIRCLES is a prospective, longitudinal, cross-sectional study of disease epidemiology and treatment in North American patients with NMOSD.

Objectives

This study analyzed real-world disease burden in North American patients with NMOSD enrolled in the CIRCLES study from 2013 to 2019.

Methods

Of 629 CIRCLES participants, 523 (83.1%) with anti-aquaporin-4 immunoglobulin G-positive (AQP4-IgG+) NMOSD were assessed for disease burden, including vision loss, paralysis, annual relapse rate (ARR) relative to mobility level, and steroid side effects.

Results

Baseline assessment of disability indicated at least partial (136/523, 26.0%) or complete (55/523, 10.5%) dependence on caregiver support. Among patients on off-label maintenance IST and having ≥60 days of on-study follow-up (n = 469), 136 (29.0%) experienced a total of 209 on-study relapses. The unadjusted ARR (95% confidence interval [CI]) by mobility level was 0.17 (0.14–0.20), 0.21 (0.16–0.27), and 0.24 (0.16–0.34) for independent, partially dependent, and completely dependent patients, respectively. Side effects from steroids were assessed in 429 respondents, of whom, 35 (8.2%) had gastroesophageal reflux disease, 30 (6.9%) had depression/anxiety, and 28 (6.5%) had osteoporosis. Of 77 patients with on-study relapses and vision assessment, 24 (31.2%) had vision loss (unadjusted ARR, 0.18 [CI, 0.13–0.24]; P > 0.05 vs. no relapses). Furthermore, of 129 patients with on-study relapses and paralysis assessment, 68 (52.7%) had partial or complete paralysis (unadjusted ARR, 0.23 [CI, 0.19–0.27]; P = 0.03 vs. no relapses).

Conclusions

NMOSD imposes significant disease burden, including vision loss and paralysis resulting in dependence on caregiver support in over one-third of patients. Despite the use of off-label maintenance ISTs, a substantial proportion of patients with NMOSD continue to experience relapses, disability, and neurological damage. These findings underscore the need for safe, effective, and well-tolerated treatments for preventing relapses.

Background

Neuromyelitis optica spectrum disorder (NMOSD) is a rare, autoimmune condition characterized by unpredictable relapses affecting the optic nerves and spinal cord that can lead to blindness, paralysis, and premature death. Currently, evidence on the real-world economic cost of NMOSD is limited.

Objectives

A retrospective observational matched-cohort analysis was conducted to characterize annual healthcare utilization and expenditure attributed to NMOSD in US clinical practice.

Methods

Data from the IQVIA PharMetrics Plus Healthcare Claims Database were used to identify adults who had evidence of NMOSD (≥1 inpatient diagnosis or ≥2 outpatient diagnoses) between 2013 and 2018 and a comparator group of patients without NMOSD who were matched on age, sex, geographic region, and insurance type. All-cause healthcare utilization and expenditure (2018 US dollars) were calculated for the matched cohorts and annualized to adjust for differential follow-up periods (maximum 6 years), with 95% confidence intervals (CI) calculated via nonparametric bootstrapping. Outcomes were analyzed overall and by care setting, diagnosis, and drug therapy.

Results

The study population included 1,363 patients with NMOSD who were matched 1:1 with comparator patients. The mean age was 45 years (standard deviation: 13 years), and 75% were female. Mean (95% CI) annualized all-cause healthcare expenditure was $60,599 ($52,112-$66,716) among patients with NMOSD versus $8,912 ($7,084-$10,727) among matched comparators. Mean (95% CI) annualized expenditure attributed to NMOSD was $51,687 ($43,820-$58,664), of which 49% was for inpatient care and 51% was for ambulatory services. Hospitalizations with a principal diagnosis of neuromyelitis optica, transverse myelitis, optic neuritis, or other NMOSD-related conditions accounted for 51% of the total attributed expenditure in the inpatient setting. Use of rituximab (33%) and immunoglobulin (6%) accounted for 39% of the attributed expenditure in the outpatient setting. Treatment for acute relapses was the largest, single cost category.

Conclusions

Findings of this large retrospective study indicate that annual healthcare expenditure attributed to NMOSD in US clinical practice is over $50,000 per patient. A considerable component of this expenditure is associated with relapse-related care, especially in the inpatient setting.

Background

Patients with neuromyelitis optica spectrum disorder (NMOSD) can experience repeated relapses and increased neurologic disability, such as pain. However, little is known about the impact of relapses on pain and subsequent pain medication use in patients with NMOSD.

Objectives

A retrospective, observational, cohort analysis was conducted to examine pain medication use in patients with NMOSD.

Methods

Patients with anti-aquaporin-4 immunoglobulin G-positive (AQP4+) NMOSD in the University of Utah Health Care System were identified. Electronic data, including patient-level treatments/therapies, medications, health status, and physician notes, were extracted from the Enterprise Data Warehouse and confirmed via chart review by Neurology and Pharmacotherapy faculty members.

Results

Forty-seven patients with AQP4+ NMOSD were included in the analysis. The average age at diagnosis was 46 years; 75% were female, and 70% were white. At the initial presentation of disease, 25 (53%) patients had optic neuritis, 15 (32%) had transverse myelitis, and 7 (15%) had a mixed or unknown presentation. The mean follow-up time was 4 years (standard deviation 3.64 years). During the follow-up period, 14 of 47 patients experienced 26 provider-documented relapses.

Overall, pain medication was used by 45 (95.7%) of 47 patients with AQP4+ NMOSD. A higher proportion of relapsing patients used pain medication than nonrelapsing patients: opioid analgesics (79% vs 58%), non-narcotic analgesics (93% vs 43%), anticonvulsants (86% vs 46%), and musculoskeletal therapy agents (71% vs 46%). Furthermore, among the relapsing patients with AQP4+ NMOSD, pain medication use increased within 90 days of the relapse when compared with the prerelapse use of pain medications: opioids analgesics (27% vs 12%), non-narcotic analgesics (39% vs 12%), anticonvulsants (35% vs 27%), and musculoskeletal therapy agents (39% vs 23%).

Conclusions

In this study, more patients with AQP4+ NMOSD who experienced relapses used pain medication than nonrelapsing patients. In addition, the increase in pain medication use within 90 days following a relapse suggests that pain is associated with relapse activity in patients with NMOSD. Treatment strategies that reduce relapses should be considered for all patients with NMOSD, not only to reduce traditional measures of neurological disability, but also to reduce the burden of pain and accompanying use of relapse-related pain medication.

Background

Neuromyelitis optica spectrum disorder (NMOSD) is a relapsing disease predominately affecting the optic nerves and spinal cord. Patients with NMOSD may experience visual and neurological deficits that can lead to blindness and paralysis. However, little is reported about the cumulative impact of relapses on visual acuity and recovery.

Objectives

A retrospective, observational cohort analysis was conducted to assess the impact of relapses on visual acuity and neurological disability in patients with anti-aquaporin-4 immunoglobulin G-positive (AQP4+) NMOSD.

Methods

Patients with AQP4+ NMOSD in the University of Utah healthcare system were identified. Electronic data (health status, physician notes, AQP4+ status, NMOSD diagnosis, and other key patient data) were extracted from the Enterprise Data Warehouse and confirmed via medical chart reviews.

Results

The analysis included 47 patients with AQP4+ NMOSD (mean age at diagnosis: 46 years; female: 75%, white: 70%; median [minimum, maximum] follow-up time: 3.6 [0.0, 11.4] years). At enrollment, 25 patients (53%) had optic neuritis, 15 (32%) had transverse myelitis, and 7 (15%) had a mixed or unknown presentation. Of the 47 patients, 14 experienced a total of 26 relapses, and 33 did not relapse.

Baseline visual acuity was assessed in a subset of symptomatic patients. Data were available for 9 relapsing and 23 nonrelapsing patients. At baseline, 28% of patients had bad eyesight (20/150-no light perception). From baseline to last follow-up, the proportion of patients with bad eyesight increased from 21% to 29% in relapsing patients and decreased from 30% to 24% in nonrelapsing patients.

Neurological disability was assessed via the modified Rankin Scale (mRS). Pre-enrollment mean (standard deviation [SD]) mRS values were similar in relapsing (1.50 [1.22]) and nonrelapsing patients (1.42 [1.39]). At the last visit, the mean (SD) mRS value in relapsing patients was 3.43 (1.79), which was 1.49-fold higher than the mean mRS value in nonrelapsing patients.

Conclusions

In this cohort of patients with AQP4+ NMOSD, the proportion of relapsing patients with bad eyesight increased over time, but the proportion of nonrelapsing patients with bad eyesight decreased. Per the mRS, relapsing patients also experienced increased neurological disability when compared with nonrelapsing patients. Treatment strategies that reduce the risk of relapse should be considered to prevent progression of these deficits in patients with NMOSD.

Background

Little is known about the frequency of relapses and relapse-associated healthcare resource utilization (HCRU) among patients with neuromyelitis optica spectrum disorder (NMOSD), a rare, autoimmune condition characterized by unpredictable relapses affecting the optic nerves and spinal cord that can lead to blindness, paralysis, and premature death.

Objectives

A retrospective, observational cohort analysis was conducted to characterize the rate of relapses and relapse-associated HCRU among patients with NMOSD in US clinical practice.

Methods

Data from the IQVIA PharMetrics Plus Healthcare Claims Database were used to identify adults (aged ≥18 years) with evidence of NMOSD (≥1 inpatient diagnosis or ≥2 outpatient diagnoses) between January 2013 and March 2018. Relapses were defined by hospital admissions for NMOSD-related conditions and ambulatory encounters for disease-related treatment. Relapse-associated HCRU was characterized by care setting, relapse duration, reason for admission (inpatient), and drug therapy (outpatient). Relapse rates per patient were annualized to adjust for differential follow-up (maximum 6 years). HCRU was described per relapse.

Results

The study population included 1,363 patients with NMOSD. The mean age was 45 years (standard deviation [SD]: 13 years), 75% of the cohort was female, and many patients had a recent history of drug therapy. The mean follow-up duration was 2.4 years (SD: 1.5 years). Among all patients, the annualized number of relapses was 0.8 (95% confidence interval [CI]: 0.7–0.9), and the annualized relapse duration was 12.8 days (95% CI: 11.2-14.4 days). Among patients with ≥1 relapse (48% of all patients), 28% had a relapse duration of <5 days, 18% had a relapse duration of 5-9 days, 18% had a relapse duration of 10-19 days, and 36% had a relapse duration of ≥20 days. More than one-third of all relapses required inpatient care (1^◦ diagnosis: neuromyelitis optica 66%; optic neuritis 10%; transverse myelitis 20%). The mean hospital length of stay was 14.6 days (95% CI: 13.9-15.2 days). Relapses requiring outpatient care were typically treated with intravenous (IV) methylprednisolone (60%), IV immunoglobulin (36%), and/or plasma exchange (11%).

Conclusions

In this large study of patients with NMOSD in US clinical practice, almost one-half of patients experienced ≥1 relapse during follow-up. Among these patients, most experienced multiple relapses, and relapses requiring extended hospital stays were common.