soliris FAQ

Soliris and Empaveli are both treatments for paroxysmal nocturnal hemoglobinuria (PNH). This condition is caused by your immune system (your body’s defense system) attacking your red blood cells. Soliris is also used to treat certain other conditions. Both of these drugs work by reducing activity in part of your immune system called the complement system (a series of proteins). Soliris blocks a protein in the complement system called C5, while Empaveli blocks a different protein called C3. These drugs can cause some similar and some different side effects. For example, both drugs can raise your risk of infections, especially serious meningococcal infections. Soliris and Empaveli both have a boxed warning about this side effect. A boxed warning is the most serious warning from the Food and Drug Administration (FDA) about drug side effects that can be dangerous. Additionally, both drugs come as an injection. Soliris is taken by intravenous (IV) infusion, while Empaveli is taken by subcutaneous infusion. Soliris is typically taken once every 2 weeks, while Empaveli is typically taken twice per week. To learn more about Soliris versus Empaveli, including how the dosages of these drugs compare, talk with your doctor.

Soliris and Ultomiris are both used to treat paroxysmal nocturnal hemoglobinuria (PNH) and atypical hemolytic uremic syndrome (aHUS). These conditions are caused by overactivity in your immune system (your body’s defense system). Soliris is also used to treat certain other conditions. Soliris and Ultomiris both work in the same way. They reduce activity in part of your immune system called the complement system. Both drugs block a protein in the complement system called C5. These drugs can cause similar side effects, including a raised risk of serious meningococcal infections. Both drugs have a boxed warning about this side effect. A boxed warning is the most serious warning from the FDA about drug side effects that can be dangerous. Soliris and Ultomiris are both administered by intravenous (IV) infusion. Soliris is usually given once every 2 weeks, while Ultomiris is a longer-acting drug and is usually given once every 4 to 8 weeks. To find out more about how Soliris compares with Ultomiris, talk with your doctor. Soliris can cause mild or serious side effects. The following lists contain some of the key side effects that may occur while taking Soliris. These lists do not include all possible side effects. For more information about the possible side effects of Soliris, talk with your doctor or pharmacist. They can give you tips on how to manage any side effects that may be concerning or bothersome. Note: The Food and Drug Administration (FDA) tracks side effects of drugs it has approved. If you would like to notify the FDA about a side effect you’ve had with Soliris, you can do so through MedWatch.

Supplemental dosing is required in patients undergoing plasma exchange as it can increase the clearance of eculizumab by approximately 250-fold. An additional 600 mg per each plasma exchange session is recommended to be given within 60 minutes after each plasma exchange session.

There are no head to head clinical trials comparing different therapies for antibody positive NMOSD. Prior to the FDA approved medications for AQP4 antibody positive NMOSD, treatments included rituximab, azathioprine, and mcyophenolate mofetil. Factors that may influence selecting a therapy can include route of administration, FDA approval, frequency of administration (every 2 weeks for eculizumab versus every 6 months for anti-CD20 therapies), healthcare costs (greater than $500,000/year for eculizumab), and potential comparative efficacy. While eculizumab can be given as a first line treatment, given the above factors, we would suggest use of eculizumab in patients who have experienced failure or intolerance with other treatments. While eculizumab was only studied in adult patients with AQP4 antibody positive NMOSD, it has been used in the pediatric population safely for its other indication. Unlike satralizumab and inebilizumab, the other two FDA-approved medications for AQP4 antibody positive NMOSD, eculizumab has also been used in patients older than 65. Though the numbers are limited (15 in PNH, 4 in aHUS, 26 in gMG, and 6 in NMOSD), no age related differences in medication effects were noted. Unlike inebilizumab, which carries a warning for fetal harm, there have not been similar adverse effects noted with eculizumab based on limited case reports and case series.

Headache, nausea, and dizziness were the most common side effects reported in the open label trial of eculizumab in APQ4 antibody positive neuromyelitis optica patients. In the PREVENT trial, upper respiratory tract infections, headache, and nasopharyngitis were the most common side effects. With the exception of upper respiratory tract infections, percentages of patients experiencing these effects were comparable in the eculizumab group and the placebo group. Other side effects such as nausea, diarrhea, urinary tract infection, limb pain, and vomiting were also seen in both groups.

Safety of eculizumab during pregnancy and lactation has not been studied in NMOSD patients and is thus not routinely used in this population. Limited data for other clinical indications of eculizumab have not identified specific adverse developmental outcomes. One study of pregnant patients with paroxysmal nocturnal hemoglobinuria, for example, found that all 69 children met developmental milestones for vision, hearing, locomotion, fine-motor skills, behavior, and physical health. Only one child had slightly delayed speech. Eculizumab in concentration below therapeutic range has been detected in cord blood in patients on treatment for paroxysmal nocturnal hemoglobinuria. One study examining 10 breast milk samples found no detectable eculizumab.

We suggest checking absolute lymphocyte count and immunoglobulin levels for patients on other therapies prior to initiating eculizumab to ensure levels are > 0.5k/µL and in a normal range respectively. Transfusions of IV immunoglobulins can be considered in patients who have hypogammaglobulinemia prior to initiation of eculizumab.

The half-life of eculizumab ranges from 270 to 414 hours. Steady state is achieved 4 weeks after starting eculizumab treatment. Age, race, and renal function do not affect pharmacokinetics of eculizumab.

On June 27, 2019, eculizumab, or Soliris, became the first FDA approved treatment for anti-aquaporin-4 (AQP4) antibody positive neuromyelitis optica spectrum disorder (NMOSD) in adults. Eculizumab had previously been FDA approved for treatment of paroxysmal nocturnal hemoglobinuria (PNH), atypical hemolytic uremic syndrome (aHUS), and anti-acetylcholine receptor antibody positive generalized myasthenia gravis (gMG).

Meningococcal disease in patients receiving eculizumab despite vaccination has been reported, therefore clinicians may consider recommending antimicrobial prophylaxis for the duration of treatment:

Prior to starting: complete blood count with differential, comprehensive metabolic panel. Monitoring labs: complete blood count with differential, comprehensive metabolic panel. Although urinalysis and lactate dehydrogenase (LDH) are monitored for patients with paroxysmal nocturnal hematuria, this is not necessary for AQP4 antibody positive NMOSD. A Mayo Clinic Eculizumab monitoring panel (ECUMP) for C5 function and C5 antigen is available to determine the impact of eculizumab on the complement system but as no specific guidelines are available for its use with AQP4 antibody positive NMO, it is not currently recommended. As leukopenia, lymphopenia, and transaminitis were noted with eculizumab for other indications, we suggest routine monitoring labs as above. A reduction in absolute lymphocyte count less than 0.5k/µL or an elevation of AST or ALT greater than 2 times the upper limit of normal should prompt discontinuation of therapy.

While the PREVENT trial did not pharmacodynamics of eculizumab in APQ4 antibody positive NMOSD patients, pharmacodynamics of eculizumab has been studied in other disease states. An inverse relationship appear to exist between eculizumab concentration and C5 complement blockade. Increased dose of eculizumab has also been shown to correlate with longer period of complement activity suppression. One study in patients with hemolytic anemia found that increasing the dose from 2mg/kg to 4mg/kg to 8mg/kg led to increased drug effect from 2 days, to 7-14 days, to 11-21 days.

Eculizumab is supplied in 300 mg vials (30 mL of a 10 mg/mL solution) and is administered via intravenous infusion over 35 minutes. We suggest administration at an infusion center to allow for patient monitoring given the relative newness of the medication for this indication. Dosing regimen consists of:

Eculizumab was first studied in 14 AQP4 antibody positive neuromyelitis optica patients in an open-label trial. This trial showed positive findings in reducing relapses as well as an improvement in median EDSS scores compared with pretreatment. Because of these results, a subsequent randomized, double-blinded, placebo-controlled phase III time-to-event trial over 4 years, Prevention of Relapses in Neuromyelitis Optica (PREVENT), was performed. The majority of patients in both the eculizumab (78%) and placebo (72%) groups continued on prior immunotherapy including glucocorticoids, azathioprine, and mycophenolate mofetil. A significantly smaller proportion of patients in the eculizumab group experienced an adjudicated relapse compared with the placebo group (3% vs 43%). Change from baseline in disability measures including EDSS, modified Rankin scale, and Hauser Ambulation Index did not significantly differ between the two groups.

Required: Meningococcal vaccines (serogroups ACWY and B) All patients are recommended to receive meningococcal vaccination at least 2 weeks prior to starting eculizumab. Both MenACWY and MenB vaccines are required to cover ACWY and B serogroups. There are two MenACWY vaccine products, Menactra® and Menveo®. These products are interchangeable within the MenACWY series, however Menactra must be separated by 4 weeks from the Pneumococcal conjugate vaccine (Prevnar-13). Therefore, we recommend Menveo for the MenACWY “primary series” at 0 and 8 weeks to prevent the Prevnar13/Menactra interaction. There are two MenB vaccine products available: MenB-4 (Bexsero®) and MenB-FHbp (Trumenba®). Bexsero is a 2-dose series administered at least 1 month apart. Trumenba® is a 3-dose series administered at 0, 1-2, and 6 months. Dose 3 not needed if dose 2 is administered at least 6 months after dose 1. Bexsero and Trumenba are not interchangeable (the same product should be used for all doses in series). Trumenba is not available on formulary at the Cleveland Clinic. Vaccination reduces but does not eliminate the risk of meningococcal infections. A review of eculizumab recipients in the United States from 2008 to 2016 identified 16 cases of meningococcal disease with eleven cases caused by nongroupable Neisseria meningitidis not impacted by vaccination. Fourteen patients had received at least one dose of vaccine. All cases had meningococcemia. Six patients had meningitis. Recommended: Streptococcus pneumoniae and Haemophilus influenzae type b (Hib) In previously unvaccinated patients, consider vaccine administration for other encapsulated organisms. This is due to a theoretical increased risk of infection while on eculizumab. The Advisory Committee on Immunization Practices (ACIP) recommend pneumococcal (for all patients) and Hib (for children 12-59 months) vaccination for patients with complement deficiencies; the only ACIP recommendation specific to eculizumab is meningococcal. We recommend initiation of vaccination series at least 2 weeks prior to the first eculizumab dose to optimize immune response.

Histologic studies in NMO lesions have shown pronounced complement activation, eosinophilic infiltration, and vascular fibrosis that differ from prototypical multiple sclerosis lesions. The pathophysiology of NMOSD is primarily a humoral immune system mediated attack on AQP4. Eculizumab is a humanized monoclonal antibody that inhibits the terminal complement protein C5 to prevent its cleavage into C5a and C5b. The exact mechanism for its efficacy in NMOSD is unknown, but is believed to be related to inhibition of the formation of the membrane attack complex mediated by C5b.

Soliris and ravulizumab (Ultomiris) are used to treat the same conditions. (For more information about the conditions these drugs treat, see the “What is Soliris used for?” section.) Both of these drugs are given by IV infusion by a doctor or other healthcare professional. Soliris is usually given once every 2 weeks, while Ultomiris is typically given every 4 to 8 weeks. Soliris and Ultomiris can cause very similar side effects. Both drugs have a boxed warning for an increased risk of meningococcal infections. (For more information, see the “What should be considered before using Soliris?” section.) For more details on how these drugs compare, talk with your doctor. Whether you have health insurance or not, cost may be a factor when you’re considering Soliris. What you’ll pay for Soliris may depend on several things, such as your treatment plan and the pharmacy you use. If you have questions about how to pay for your prescription, talk with your doctor or pharmacist. A program called OneSource may also be available. You can also check out this article to learn more about saving money on prescriptions. Soliris is used to treat certain autoimmune conditions. With these conditions, your immune system attacks healthy tissues in your body by mistake. Specifically, Soliris is used to treat the following conditions in adults:

Both Soliris and pegcetacoplan (Empaveli) are drugs that can be used to treat paroxysmal nocturnal hemoglobinuria (PNH). Empaveli is only used for PNH, but Soliris also has other uses as well. Soliris is given by intravenous (IV) infusion (an injection into a vein given over a period of time). Empaveli is given as a subcutaneous infusion (injection under the skin given over a period of time). A doctor or other healthcare professional will usually administer Soliris. But after training, you can self-administer Empaveli. Soliris is typically given once every 2 weeks, while you can self-administer Empaveli twice per week. These medications work in a similar way in your body and can cause some similar side effects. For example, both drugs have a boxed warning* for an increased risk of meningococcal infections. But they can also cause some different side effects as well. To find out more about how these drugs compare, talk with your doctor. * A boxed warning is a serious warning from the Food and Drug Administration (FDA). For more information, see the “What should be considered before using Soliris?” section.