Medical Drug Criteria (MDC)

Policy Num:       M5.001.023
Policy Name:     Soliris® (eculizumab)
Policy ID:          [M5.001.023] [Ac/Mg/M/ P ][0.00.00]

Last Review:       August 22, 2024
Next Review:      August 20, 2025
 

Related Policies: None

Soliris® (eculizumab)

Summary

Soliris is a complement inhibitor indicated for the treatment of patients with paroxysmal nocturnal hemoglobinuria (PNH) to reduce hemolysis, treatment of patients with atypical hemolytic uremic syndrome (aHUS) to inhibit complement-mediated thrombotic microangiopathy treatment of generalized myasthenia gravis (gMG) in adult patients who are anti-acetylcholine receptor (AchR) antibody positive and the treatment of neuromyelitis optica spectrum disorder (NMOSD) in adult patients who are anti-aquaporin-4 (AQP4) antibody positive.

Policy Statements

Coverage is provided in the following conditions:

• Patient is at least 18 years of age (unless otherwise specified); AND

• Prescriber is enrolled in the Soliris Risk Evaluation and Mitigation Strategy (REMS) 
program; AND
 

Universal Criteria  

• Patient must be vaccinated against meningococcal disease at least two weeks prior to initiation of therapy and will continue to be revaccinated according to current medical guidelines for vaccine use (Note: if urgent Soliris therapy is indicated in an unvaccinated patient, administer meningococcal vaccine(s) as soon as possible and provide patients with two weeks of antibacterial drug prophylaxis); AND

• Patient does not have an unresolved, serious systemic infection (e.g., Neisseria meningitidis, etc.); AND

• Will not be used in combination with other immunomodulatory biologic therapies (e.g.., efgartigimod, ravulizumab, pegcetacoplan, satralizumab, inebilizumab, rozanolixizumab, etc.) [Note: a 4-week run-in period is allowed when transitioning from eculizumab to pegcetacoplan]; AND

Paroxysmal Nocturnal Hemoglobinuria (PNH)

• Diagnosis must be confirmed by detection of PNH clones of at least 10% by flow cytometry diagnostic testing; AND

o Demonstrate the presence of at least 2 different glycosylphosphatidylinositol (GPI) protein deficiencies (e.g., CD55, CD59, etc.) within at least 2 different cell lines (e.g., granulocytes, monocytes, erythrocytes); AND

• Patient has laboratory evidence of significant intravascular hemolysis (i.e., LDH ≥1.5 x ULN) with symptomatic disease and at least one other indication for therapy from the following (regardless of transfusion dependence):

o Patient has symptomatic anemia (i.e., hemoglobin < 7 g/dL or hemoglobin < 10 g/dL, in at least two independent measurements in a patient with cardiac symptoms)

o Presence of a thrombotic event related to PNH

o Presence of organ damage secondary to chronic hemolysis (i.e., renal insufficiency, pulmonary insufficiency/hypertension)

o Patient is pregnant and potential benefit outweighs potential fetal risk

o Patient has disabling fatigue

o Patient has abdominal pain (requiring admission or opioid analgesia), dysphagia, or erectile dysfunction; AND

• Documented baseline values for one or more of the following (necessary for renewal): serum lactate dehydrogenase (LDH), hemoglobin level, packed RBC transfusion requirement, and history of thrombotic events; AND

• Patient had an inadequate response, contraindication, or intolerance to a trial of ravulizumab (Ultomiris®)

Atypical Hemolytic Uremic Syndrome (aHUS)

• Patient is at least 2 months of age; AND

• Patient shows signs of thrombotic microangiopathy (TMA) (e.g., changes in mental status, seizures, angina, dyspnea, thrombosis, increasing blood pressure, decreased platelet count, increased serum creatinine, increased LDH, etc.); AND

• Thrombotic Thrombocytopenic Purpura (TTP) has been ruled out by evaluating ADAMTS-13 level (i.e., ADAMTS-13 activity level ≥ 10%); AND

• Shiga toxin E. coli related hemolytic uremic syndrome (STEC-HUS) has been ruled out; AND

• Other causes have been ruled out such as coexisting diseases or conditions (e.g., bone marrow transplantation, solid organ transplantation, malignancy, autoimmune disorder, drug-induced, malignant hypertension, HIV infection, Streptococcus pneumoniae sepsis or known genetic defect in cobalamin C metabolism, etc); AND

• Documented baseline values for one or more of the following (necessary for renewal): serum lactate dehydrogenase (LDH), serum creatinine/eGFR, platelet count, and plasma exchange/infusion requirement; AND

• Patient had an inadequate response, contraindication, or intolerance to a trial of ravulizumab (Ultomiris®)

Generalized Myasthenia Gravis (gMG)

• Patient has Myasthenia Gravis Foundation of America (MGFA) Clinical Classification of Class II to IV disease §; AND

• Patient has a positive serologic test for anti-acetylcholine receptor (AChR) antibodies; AND

• Patient has had a thymectomy (Note: Applicable only to patients with thymomas OR nonthymomatous patients who are 50 years of age or younger); AND

• Physician has assessed objective signs of neurological weakness and fatiguability on a baseline neurological examination [e.g., including, but not limited to, the Quantitative Myasthenia Gravis (QMG) score, etc.]; AND

• Patient has a baseline MG-Activities of Daily Living (MG-ADL) total score of ≥6; AND

o Patient had an inadequate response after a minimum one-year trial of concurrent use with two (2) or more immunosuppressive therapies (e.g., corticosteroids plus an immunosuppressant such as azathioprine, cyclosporine, mycophenolate, etc.); OR

o Patient required chronic treatment with plasmapheresis or plasma exchange (PE) or intravenous immunoglobulin (IVIG) in addition to immunosuppressant therapy

• Patient will avoid or use with caution medications known to worsen or exacerbate symptoms of MG (e.g., certain antibiotics, beta-blockers, botulinum toxins, hydroxychloroquine, etc.); AND

• Patient had an inadequate response, contraindication, or intolerance to a trial of ravulizumab (Ultomiris®)

Neuromyelitis Optica Spectrum Disorder (NMOSD)

• Patient has a confirmed diagnosis based on the following:

o Patient was found to be seropositive for aquaporin-4 (AQP4) IgG antibodies; AND

o Patient has at least one core clinical characteristic § (*Note: some core clinical characteristics require both clinical and typical MRI findings); AND

o Alternative diagnoses have been excluded [e.g., myelin oligodendrocyte glycoprotein (MOG) antibody disease (MOGAD), multiple sclerosis, sarcoidosis, cancer, chronic infection, etc.]; AND

• Patient has a history of at least 2 relapses in the last 12 months OR 3 relapses in the last 24 months, with at least 1 relapse in the last 12 months; AND

• Patient has an Expanded Disability Status Score (EDSS) of ≤ 7.0 (i.e., presence of at least limited ambulation with aid); AND

• Patients who are receiving concurrent corticosteroid therapy are on ≤20 mg per day and those receiving immunosuppressive therapy (e.g. azathioprine, glucocorticoids, mycophenolate, etc.) are on a stable dose regimen; AND

• Patient has not received therapy with rituximab or mitoxantrone in the last 3 months; AND

• Patient has not received intravenous immune globulin (IVIG) in the last 3 weeks; AND

• Patient will not concomitantly receive therapy with any of the following:

o IL-6 inhibitor (e.g., satralizumab)

o Anti-CD20-directed antibody (e.g., rituximab)

o Anti-CD19-directed antibody (e.g., inebilizumab)

Policy Guidelines

Renewal Criteria

Coverage may be renewed based upon the following criteria:

• Patient continues to meet the universal and other indication-specific relevant criteria identified in section III; AND

• Absence of unacceptable toxicity from the drug. Examples of unacceptable toxicity include: serious meningococcal infections (septicemia and/or meningitis), infusion reactions, serious infections, etc.; AND

Paroxysmal Nocturnal Hemoglobinuria (PNH)

• Patient has not developed severe bone marrow failure syndrome (i.e., aplastic anemia or myelodysplastic syndrome) OR experienced a spontaneous disease remission OR received curative allogeneic stem cell transplant; AND

• Disease response indicated by one or more of the following:

o Decrease in serum LDH from pretreatment baseline

o Stabilization/improvement in hemoglobin level from pretreatment baseline

o Decrease in packed RBC transfusion requirement from pretreatment baseline (i.e., reduction of at least 30%)

o Reduction in thromboembolic events

Atypical Hemolytic Uremic Syndrome (aHUS)

• Disease response indicated by one or more of the following:

o Decrease in serum LDH from pretreatment baseline

o Stabilization/improvement in serum creatinine/eGFR from pretreatment baseline

o Increase in platelet count from pretreatment baseline

o Decrease in plasma exchange/infusion requirement from pretreatment baseline

Generalized Myasthenia Gravis (gMG)

• Patient has had an improvement (i.e., reduction) of at least 1-point from baseline in the Myasthenia Gravis-Specific Activities of Daily Living scale (MG-ADL) total score Δ; AND

• Improvement in muscle strength testing with fatigue maneuvers as evidenced on neurologic examination when compared to baseline

[Δ May substitute an improvement of at least 1-point from baseline in the Quantitative Myasthenia Gravis (QMG) total score, if available

Neuromyelitis Optica Spectrum Disorder (NMOSD)

• Disease response as indicated by stabilization and/or improvement of neurologic symptoms as evidenced by one or more of the following:

o Decrease in acute relapses

o Improvement in EDSS

o Reduced hospitalizations

o Reduction/discontinuation in plasma exchange treatments

DOSAGE/ADMINISTRATION

REQUIRED MEDICAL INFORMATION

• Physician has assessed baseline disease severity utilizing an objective measure/tool; AND

Universal Criteria  

• Patient must be vaccinated against meningococcal disease at least two weeks prior to initiation of therapy and will continue to be revaccinated according to current medical guidelines for vaccine use (Note: if urgent Soliris therapy is indicated in an unvaccinated patient, administer meningococcal vaccine(s) as soon as possible and provide patients with two weeks of antibacterial drug prophylaxis); AND

• Patient does not have an unresolved, serious systemic infection (e.g., Neisseria meningitidis, etc.); AND

• Will not be used in combination with other immunomodulatory biologic therapies (e.g.., efgartigimod, ravulizumab, pegcetacoplan, satralizumab, inebilizumab, rozanolixizumab, etc.) [Note: a 4-week run-in period is allowed when transitioning from eculizumab to pegcetacoplan]; AND

• Paroxysmal nocturnal hemoglobinuria (PNH) is a rare disorder in which hematopoietic stem cells and their cellular progeny have lost the ability to anchor certain proteins to the cell surface. Loss of the complement inhibitors, CD55 and CD59, on the surface of red blood cells leads to chronic and/or paroxysmal intravascular hemolysis and a propensity for thrombosis.

Studies that support the treatment statement follow:

●C5i versus supportive care alone – In a phase 3 trial, eculizumab was superior to transfusion therapy/supportive care for hemolytic PNH. While transfusion therapy can alleviate pain and anemia-related symptoms, it can cause transfusion-associated iron overload and alloimmunization, and it does not mitigate the risk for thrombosis, which is common, difficult to predict, and may recur or progress despite antithrombotic therapy [4-8].

•Eculizumab achieved better outcomes than placebo in the TRIUMPH trial, which randomly assigned treatment to 87 patients with severe PNH [9,10]. Eculizumab more effectively achieved red blood cell (RBC) transfusion-independence (TI; 49 versus 0 percent, respectively) and led to clinically meaningful improvement in quality of life (measured with two different assessment instruments). There was no difference in overall survival (OS) between treatment arms during the 26-week trial, and no deaths or serious adverse effects (AEs) were attributed to eculizumab; one thrombotic event was reported in the placebo group.

•Ravulizumab has not been directly compared with placebo in a phase 3 trial, but its safety and efficacy were comparable with eculizumab in other randomized trials [11,12], as discussed below. (See 'C5 inhibitors' below.)

●Ravulizumab versus eculizumab – Both C5is have long track records of efficacy for symptom relief and thrombosis prevention in patients with symptomatic hemolytic PNH. They have comparable efficacy and toxicity, but we favor ravulizumab for its greater convenience and lower overall expense.

Treatment of PNH with a C5i must be continued indefinitely, these agents are expensive, and they do not ameliorate PNH-associated BMF. These agents appear to be safe during pregnancy. Like all complement inhibitors, C5is can increase risk for serious and life-threatening infections. Administration and toxicity of C5is are discussed below. (See 'C5 inhibitors' below.)

The following studies compared ravulizumab and eculizumab for hemolytic PNH:

•In an open-label randomized trial, ravulizumab and eculizumab achieved similar outcomes and safety [11]. The trial randomly assigned 246 patients with lactate dehydrogenase (LDH) ≥1.5 x the upper limit of normal (ULN) to receive ravulizumab or eculizumab for 183 days. The agents achieved similar rates of RBC TI, normalization of serum LDH, and improvement of fatigue (change from baseline in Functional Assessment of Chronic Illness Therapy [FACIT]-Fatigue score).

•In another phase 3 trial, among 195 clinically stable patients with PNH who were previously treated with eculizumab and then randomly assigned to continue eculizumab or switch to ravulizumab, the two agents achieved similar results [12].

The European Medicines Agency (EMA) and the US Food and Drug Administration (FDA) have approved ravulizumab and eculizumab for treatment of PNH. The FDA also approved ravulizumab for treatment of PNH in children ≥1 month and adolescents. The FDA approved crovalimab for treatment of PNH in patients ≥13 years and ≥40 kg. In the United States, these agents are available only through a restricted program under a risk evaluation and mitigation strategy (REMS).

• Complement-mediated HUS is a relatively rare disorder, with an estimated prevalence of 7 per 1 million children in Europe [6]. Most complement-mediated HUS cases are due to gene mutations of complement factors. Antibodies to complement proteins have been implicated in the etiology of 6 to 10 percent of patients with complement-mediated HUS [11]. In addition, patients may have concurrent genetic mutations and antibodies to complement proteins

A study of 308 cases of atypical HUS (Newcastle cohort) reported the presence of CFH antibodies in 13 of 142 screened patients (9.2 percent) [26]. Most of these patients also had homozygous or compound heterozygous deletion of CFHR1 and/or CFHR3 and/or CFHR4 genes, suggesting that this deletion has a pathogenetic role in the development of anti-CFH antibodies [22,24,26,31,32]. Variants in other complement genes (CFH, complement factors I and B, CD46, and C3) also were identified in a minority of patients [26]. These findings suggest that in some patients, multiple "hits" to the complement system may be necessary for the clinical presentation of complement-mediated HUS [26,33].

A study of 186 cases of atypical HUS reported the presence of autoantibodies to factor H of the IgM class in seven cases (3.8 percent), with a higher frequency in patients with atypical HUS following bone marrow transplantation [34]. No association was observed between anti-factor H IgM and homozygous deletions involving CFHR3-CFHR1.

Patients with complement antibodies — The management of patients with Complement factor H (CFH) antibodies is challenging and evolving due to the reported beneficial effects of initial therapy with eculizumab, however limited data are based on small case series [27]. Prior to the introduction of eculizumab, the initial management of patients with CFH antibodies included supportive care with plasmapheresis or plasma exchange, followed by immunosuppressive therapy directed to inhibiting further production of antibodies and preventing relapses.

Role of eculizumab – Eculizumab may be considered during the acute stage, particularly if plasma exchange is not available, if severe neurologic or cardiac illness is present, or if the patient does not respond to intensive plasma exchange.

Alternatively, eculizumab may be considered as a first-line treatment with the possibility of adding corticosteroids and/or mycophenolate mofetil in an attempt to reduce antibody titer. However, the safety efficacy profiles and cost-effectiveness of approaches combining few plasma exchanges and immunosuppressive therapy, or long-term eculizumab therapy, have to be determined.

Support for eculizumab therapy without immunosuppression is based on case reports and a small case series [27,79,80]. In a series of 17 children with CFH antibodies, including seven who had concomitant HUS genetic variants, immunosuppressive therapy was not given, because of concerns over treatment-associated complications [27]. The outcome varied based on management. All patients who received eculizumab recovered kidney function and achieved sustained remission. Two patients treated only with supportive care developed end-stage kidney disease (ESKD). Four of 11 patients treated with plasma exchange recovered kidney function. The authors concluded that, based on these results, their clinical practice is to initiate only eculizumab therapy for treatment of CFH autoantibody-mediated HUS and not include plasma exchange or immunosuppressive therapy.

Eculizumab is discussed in greater detail below. (See 'Complement blockade (eculizumab)' below.)

Kidney transplantation – Although data on the outcome of kidney transplantation is limited in patients with CFH antibodies, one-quarter to one-third of patients have allograft loss due to recurrent disease [75]. The risk of recurrence increases with high antibody titers and if there is a concomitant variant in genes encoding CFH, C3, or CFB. For patients at risk for disease recurrence (antibody titers >1000 AU/mL and/or variants in these specific complement protein), additional preventive measures (eg, eculizumab or plasma therapy) should be provided prior to transplantation. (See 'Transplantation' below.)

Patients with genetic variants

Complement blockade (eculizumab) — Eculizumab is the first-line treatment for patients with severe forms of complement-mediated HUS [81,82].

Eculizumab is a humanized monoclonal antibody that binds to complement protein C5, blocking its cleavage, thereby preventing the production of the terminal complement components C5a and the membrane attack complex C5b-9 [83]. This results in reduction of the terminal-complement activation that occurs in patients with complement-mediated HUS, thereby reducing endothelial damage, thrombosis, and subsequent kidney injury. (See 'Pathogenesis' above.)

Indications and timing — We recommend eculizumab in patients with severe forms of complement-mediated HUS (eg, patients with CFH and complement factor I [CFI] variants). Our strong recommendation, despite the lack of prospective clinical trials and despite the known potential for adverse events (ie, severe infections), is based on observational studies demonstrating a large magnitude of effect in reducing progression to kidney failure and death. These data are discussed below. (See 'Efficacy' below.)

Treatment with eculizumab should be started as soon as possible, ideally within the first 48 hours of admission.

Eculizumab may not be available in all settings, due to prohibitive cost [84-86]. Plasma therapy is often used in such cases. However, even in resource-limited areas, eculizumab should be considered in patients who fail to respond to plasma therapy, have life-threatening disease (seizure, heart failure), and have serious complications of plasma [86]. (See 'Plasma therapy' below.)

While eculizumab is generally not considered a first-line therapy in patients with CFH antibodies, it is a reasonable treatment option for severely affected patients, as discussed above. (See 'Patients with complement antibodies' above.)

Pretreatment evaluation and vaccination — Testing for anti-CFH antibodies is the only urgent complement investigation required since other treatment options are available for patients with HUS due to antibodies to CFH [75]. (See 'Complement antibodies' above and 'Plasma therapy' below.)

Patients should receive vaccinations for Neisseria meningitis, S. pneumoniae, and Haemophilus influenza type b since there is a risk of developing serious infections due to these pathogens while on eculizumab. Meningococcal infection is a particular concern. When possible, vaccination should be performed at least two weeks prior to the initiation of eculizumab therapy. However, this may not be possible in some patients, due to the severity of the initial presentation. For such patients, vaccination should be administered once the patient is stable. 

Patients with severe proteinuria are at risk of lower eculizumab exposure and inadequate complement inhibition, especially if a prolonged dosing interval is used [88].

Of note, the doses for young children were calculated from a pharmacokinetic model derived from adult data because there are no data in children. In some children, the above dosing protocol does not completely blocked complement activation and, in these patients, dosing has been increased. If eculizumab is used in young children, complement activity should be assessed by measuring CH50. (See "Overview and clinical assessment of the complement system", section on 'CH50'.)

The use of functional complement testing has been used to monitor and modify eculizumab therapy [89,90].

Monitoring — During initial treatment, monitoring consists of frequent assessment of kidney function (ie, urinalysis, blood urea nitrogen, creatinine) and hematologic testing (ie, complete blood count with platelet count).

In addition, monitoring of complement activity is required during eculizumab treatment [4,90,91]. CH50 should be <10 percent for a complete suppression. However, CH50 cannot be used for patients with complete CFH deficiency. One report demonstrated that using a global complement functional test (Wieslab) and maintaining a complement activity at <30 percent appears to safely reduce the frequency of eculizumab administration while keeping the disease in remission [91].

Although not widely available, eculizumab blood levels appear to be the optimal way to monitor the treatment. Levels at 100 mg/mL or over 100 mg/mL markedly reduce CH50 activity, while values less than 50 mg/mL do not [3]. However, interpretation of eculizumab levels is difficult since the assays differ from each other and all detect both bound and unbound drug [4]. (See "Overview and clinical assessment of the complement system", section on 'Complement measurement' and "Overview and clinical assessment of the complement system", section on 'CH50'.)

The frequency between dosing can be extended if adequate complement blockage is maintained [91].

Adverse effects — Treatment with eculizumab is associated with life-threatening and fatal meningococcal infections, with a reported annual rate of 0.5 percent. (See "Paroxysmal nocturnal hemoglobinuria: Treatment and prognosis", section on 'Eculizumab'.)

In a report from the Centers for Disease Control and Prevention, 16 cases of meningococcal disease were identified in eculizumab recipients in the United States between 2008 and 2016, including patients who had received at least one dose of meningococcal vaccine [92]. (See "Epidemiology of Neisseria meningitidis infection", section on 'Use of eculizumab'.)

Other reported serious adverse events in patients with complement-mediated HUS treated with eculizumab include hypertension, asymptomatic bacteremia, influenza, peritonitis, and venous sclerosis at the infusion site [93].

Efficacy — Based on the available observational data, eculizumab therapy is associated with dramatic improvements in kidney function and possible improvement in survival among patients with severe forms of complement-mediated HUS, particularly those with CFH and CFI genetic variants [9,93,105-115].

The US Food and Drug Administration granted accelerated approval for the use of eculizumab for the treatment of complement-mediated HUS, based on review of two small prospective studies [116]. In both studies, identification of a complement gene variant was not required, but the studies excluded patients with ADAMTS13 activity <5 percent of normal, those who had evidence of STEC-HUS, and those with prior eculizumab treatment. The following findings were noted in these early studies [93]:

●In the first study of 17 pediatric and adult patients who were refractory to plasma therapy, four of five patients who required dialysis at baseline were able to discontinue dialysis therapy while receiving eculizumab and remained off of dialysis over the two-year follow-up period. For 10 patients, there was an improvement in kidney function with an increase of at least 15 mL/min per 1.73 m² in the estimated glomerular filtration rate (eGFR) that was sustained over the two-year follow-up period. Two patients, including one who discontinued eculizumab therapy, progressed to kidney failure and began dialysis therapy.

Normal platelet counts and lactate dehydrogenase levels, indicating thrombotic microangiopathy event-free status, were observed in 14, 13, and 15 patients at 26 weeks, 1 year, and 2 years of follow-up, respectively. Thirteen patients were found to have complement variants or antibodies to complement factor H. At the end of two years, 11 patients remained on eculizumab therapy.

●The second study involved 20 patients who were maintained on plasma therapy. Administration of eculizumab was associated with a discontinuation of plasma therapy in all patients, normalization of hematologic parameters in 18 of the 20 patients that was maintained at two-year follow-up, and improved kidney function in three patients (increase of eGFR >15 mL/min per 1.73 m²). For the two patients who were on dialysis at baseline, there was no improvement as one remained on dialysis and the other remained on dialysis until undergoing kidney transplantation. In addition, another patient required dialysis during a hospitalization for intestinal hemorrhage and subsequently died. Fourteen patients were found to have complement variants or antibodies to complement factor H. At the end of two years, 18 patients remained on eculizumab therapy.

Subsequent studies continue to demonstrate the benefits of eculizumab in children and adults with atypical HUS [113,115,117,118]. In the largest study, which included 72 patients with atypical HUS treated with eculizumab, kidney function improved dramatically on treatment (ie, eGFR increased by a median of 74 mL/min/m²; proteinuria resolved in nearly all cases, and the proportion of patients requiring dialysis decreased from 38 to 10 percent) [115]. There was only one death in this cohort over a median follow-up of 21 months (mortality rate 1.4 percent). This is considerably lower compared with studies published before eculizumab was available, in which mortality rates were as high as 40 to 50 percent in some studies, depending on the specific genetic variants studied. (See 'Clinical course and outcome' above and 'Genetic variants' above.)

Hematologic normalization and recovery of kidney function has been observed in the overwhelming majority of patients treated with eculizumab during their first episode and subsequent episodes of HUS [113,115,117,118], including those who have undergone kidney transplantation [110]. (See 'Kidney transplantation' below.)

• Generalized Myasthenia Gravis (gMG) 

REFRACTORY DISEASE

Approximately 10 percent of patients with generalized MG are refractory to, or are limited by the specific toxicities of, conventional immunosuppressive and immunomodulatory therapies. Some require unacceptably high doses of glucocorticoids despite concurrent use of first-line steroid-sparing agents. In these refractory patients, treatment is individualized and may include strategies such as maintenance intravenous immune globulin (IVIG), rituximab, eculizumab, and pulsed cyclophosphamide. 

• Neuromyelitis Optica Spectrum Disorder (NMOSD) 

Neuromyelitis optica spectrum disorder (NMOSD) is an inflammatory disorder of the central nervous system characterized by severe, immune-mediated demyelination and axonal damage predominantly targeting optic nerves and the spinal cord.

The rationale for treatment of acute and recurrent attacks in NMOSD is based upon evidence that humoral autoimmunity plays a role in the pathogenesis of NMOSD and is driven by the high attack-related disability, poor prognosis, and overall high risk of mortality in untreated patients. Thus, long-term immunotherapy is indicated for the prevention of attacks as soon as the diagnosis of NMOSD is made.

For patients with NMOSD who are seropositive for aquaporin-4 (AQP4)-immunoglobulin G (IgG) antibodies, we suggest treatment with eculizumab, inebilizumab, satralizumab, ravulizumab, or rituximab, rather than other immunosuppressive agents. However, the optimal drug regimen and treatment duration are yet to be determined.

Eculizumab, inebilizumab, ravulizumab, and satralizumab are approved by the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) for the treatment of AQP4-antibody positive NMOSD. All of these agents are very expensive; many clinicians use rituximab, tocilizumab, or other off-label immunotherapies for patients who meet NMOSD diagnostic criteria with or without AQP4-IgG seropositivity.

 High-quality data support the effectiveness of eculizumab. In the PREVENT randomized controlled trial of 143 patients with NMOSD who were seropositive for AQP4-IgG antibodies, treatment with intravenous eculizumab reduced the risk of relapse; the annualized relapse rates for the eculizumab and placebo groups were 0.02 and 0.35 (absolute risk reduction [ARR] 33 percent, rate ratio 0.04, 95% CI 0.01-0.15) [9]. Most patients in the trial were also taking concomitant immunotherapy (eg, azathioprine, glucocorticoids, mycophenolate mofetil) but not rituximab, which was excluded because its mechanism of action is incompatible with eculizumab. Data from an open-label extension phase of the trial suggested that eculizumab treatment was associated with a sustained reduction of the relapse rate

EXCLUSION CRITERIA

BENEFIT APPLICATION

As stated in the policy.

OTHER CRITERIA

Medicare coverage for outpatient (Part B) drugs is outlined in the Medicare Benefit Policy Manual (Pub. 100-2), Chapter 15, §50 Drugs and Biologicals.

No Medicare National Coverage Determination (NCD) or Local Coverage Determinations (LCDs), and Local Coverage Article (LCAs) was identified for this drug.

References

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