Network Meta-analysis of Food and Drug Administration-approved Treatment Options for Adults with Aquaporin-4 Immunoglobulin G-positive Neuromyelitis Optica Spectrum Disorder.

INTRODUCTION: Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune disease defined by attacks on the central nervous system that cause irreversible damage. Recent approval of NMOSD therapies warrants investigations of comparative efficacy to inform treatment decisions. METHODS: A network meta-analysis (NMA) of all U.S. Food and Drug Administration-approved therapies (eculizumab, inebilizumab, and satralizumab) for adults with aquaporin-4 immunoglobulin G-positive (AQP4+) NMOSD was conducted via a systematic literature review (SLR) using data from randomized controlled trials (RCTs). Database searches of MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials were executed for the SLR. A fixed-effects proportional hazards Bayesian NMA was used to estimate relative treatment effects based on data extracted from RCTs identified during the SLR (search end date: 11 September 2020). Four unique RCTs (N-MOmentum, PREVENT, SAkuraSky, and SAkuraStar) were identified, and data from 29 publications were extracted for analysis. Network scenarios describing the most comparable patient population groups (such as by treatment settings) were evaluated in our analyses. Relative treatment effects were evaluated based on time-to-first relapse and were expressed as hazard ratios (HRs) with 95% credible intervals (CrIs). RESULTS: In patients treated with a monoclonal antibody only, eculizumab was associated with a lower risk of relapse compared with satralizumab (HR 0.10, 95% CrI 0.01, 0.65) and inebilizumab (HR 0.11, 95% CrI 0.02, 0.68). In patients treated with monoclonal antibody with or without background immunosuppressive therapy (IST), patients treated with eculizumab ± IST were also less likely to relapse than patients treated with satralizumab ± IST (HR 0.24, 95% CrI 0.06, 0.98). CONCLUSION: The NMA results suggest that complement component 5 (C5) inhibition prevents NMOSD relapses more effectively than broader mechanisms of action.

Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune disease characterized by inflammation that damages the brain and spinal cord. Many patients with NMOSD produce antibodies against a protein called aquaporin-4 (AQP4+). In the past two years, three drugs (eculizumab, inebilizumab, and satralizumab) have been approved by the U.S. Food and Drug Administration for the treatment of adults with AQP4+ NMOSD. Comparing the efficacy of these three drugs would help physicians make treatment decisions for their patients. In the absence of clinical trials directly comparing these three drugs, we conducted a Bayesian network meta-analysis in order to allow for simultaneous comparisons of these three drugs and estimate relative treatment effects between any pair of interventions in a connected network. With a Bayesian methodology, it is also possible to estimate the probability of being the best treatment out of all other interventions in a connected network. While all three drugs are safe and shown to prevent relapses in placebo-controlled trials, the results of our analysis suggests that eculizumab was the most efficacious in preventing relapses when compared with inebilizumab or satralizumab. These findings may help to inform physicians and their patients when determining the best treatment option for preventing the occurrence of relapses in adults with AQP4+ NMOSD.

Clinical burden of relapses in aquaporin-4 immunoglobulin G-positive neuromyelitis optica spectrum disorder: A single center cohort analysis.

A retrospective, observational analysis of 47 patients with aquaporin-4 immunoglobulin G-positive neuromyelitis optica spectrum disorder (AQP4-IgG+ NMOSD) enrolled at the University of Utah healthcare system was conducted. Visual acuity, neurological disability, and pain medication use were compared in relapsing versus non-relapsing patients. The median observation period was 3.6 years (range: 0.0-11.4 years); the annual relapse rate was 0.1376 (95% confidence interval: 0.0874, 0.191). Relapsing patients (n = 14) exhibited diminished visual acuity, clinically meaningful worsening of neurological disability, and greater pain medication use than non-relapsing patients (n = 33). Therapies that reduce the risk of relapses should be considered when making treatment decisions.

Neuromyelitis Optica Spectrum Disorder: Clinical Burden and Cost of Relapses and Disease-Related Care in US Clinical Practice.

INTRODUCTION: Neuromyelitis optica spectrum disorder (NMOSD) is a rare autoimmune condition characterized by unpredictable relapses that affect the optic nerves and spinal cord, which can lead to blindness, paralysis, and increased mortality rates. Evidence on the clinical and economic burden of NMOSD in the USA is currently lacking. METHODS: A retrospective, observational cohort study was conducted using data from the IQVIA PharMetrics Plus Healthcare Claims Database between January 1, 2012 and March 31, 2019. Adults (aged 18 years or more) with evidence of NMOSD and a matched group of comparison patients were identified. Outcomes, including NMOSD relapses, healthcare utilization, and healthcare expenditure (reported in 2018 US dollars), were evaluated during the follow-up period (maximum 6 years). Healthcare utilization and expenditure were assessed overall (all-cause) and during NMOSD relapses. RESULTS: The study included 1363 patients with NMOSD; the mean age was 44.9 years, and 75.3% were female. During the follow-up period (median 2.0 years), 47.7% of patients with NMOSD had one or more relapses, corresponding to an annualized relapse rate of 0.8 (95% confidence interval [CI] 0.7-0.9). When analyzing healthcare expenditure per patient, the mean annualized all-cause healthcare expenditure among patients with NMOSD was $60,599 (95% CI $52,112-66,716) compared with $8912 (95% CI $7084-10,727) among comparison patients, representing a difference of $51,687 (95% CI $43,820-58,664) attributable to NMOSD. The mean annualized total expenditure for NMOSD relapses was $10,070 (95% CI $7726-12,660) per patient, with hospital/inpatient care requiring more expenditure than ambulatory/outpatient care. CONCLUSION: Findings of this large, retrospective, observational study indicate that relapses among patients with NMOSD are common in US clinical practice, leading to substantial healthcare utilization and expenditure. Therapies with the highest relapse risk reduction could lead to markedly lower relapse-associated healthcare utilization and clinical burden in patients with NMOSD.

Neuromyelitis optica spectrum disorder (NMOSD) is a severely debilitating neurological disease that affects the nerves in the brain and spinal cord. People who have NMOSD may experience recurrent attacks, or relapses, that can cause blindness and disability. These relapses may lead to hospitalizations, doctor's office visits, and pharmacy costs that are paid by health insurance plans. Overall, the cost of treating relapses in patients with NMOSD is substantial. Our study analyzed healthcare claims data from the USA. During a median follow-up time of 2.0 years, our study showed that 47.7% of patients with NMOSD experienced one or more relapses, resulting in hospital/inpatient admissions and ambulatory/outpatient treatments. In addition, the average healthcare cost among patients with NMOSD was $60,599 per year compared with $8912 per year for patients without NMOSD. This represents a difference of $51,687 per year, which can be attributed to NMOSD. Among patients with three or more relapses during the follow-up period, the average total healthcare cost was more than $83,000 per patient. Therefore, medicines that prevent relapses could lead to fewer relapse-associated hospitalizations and outpatient treatments for patients with NMOSD.