INDICATION & IMPORTANT SAFETY INFORMATION FOR SOLIRIS (eculizumab) INDICATION What is SOLIRIS? SOLIRIS is a prescription medicine called a monoclonal antibody. SOLIRIS is used to treat: adults and children with a disease called atypical Hemolytic Uremic Syndrome (ahus) SOLIRIS is not for use in treating people with Shiga toxin E. coli related hemolytic uremic syndrome (STEC-HUS) IMPORTANT SAFETY INFORMATION What is the most important information I should know about SOLIRIS? SOLIRIS is a medicine that affects your immune system. SOLIRIS can lower the ability of your immune system to fight infections. SOLIRIS increases your chance of getting serious and life-threatening meningococcal infections. Meningococcal infections may quickly become life-threatening and cause death if not recognized and treated early. 1. You must receive meningococcal vaccines at least 2 weeks before your first dose of SOLIRIS if you have not already had this vaccine. 2. If your doctor decided that urgent treatment with SOLIRIS is needed, you should receive meningococcal vaccination as soon as possible. 3. If you have not been vaccinated and SOLIRIS therapy must be initiated immediately, you should also receive 2 weeks of antibiotics with your vaccinations. 4. If you had a meningococcal vaccine in the past, you might need additional vaccination before starting SOLIRIS. Your doctor will decide if you need additional meningococcal vaccination. 5. Meningococcal vaccines reduce the risk of meningococcal infection but do not prevent all meningococcal infections. Call your doctor or get emergency medical care right away if you get any of these signs and symptoms of a meningococcal infection: headache with nausea or vomiting, headache and fever, headache with a stiff neck or stiff back, fever, fever and a rash, confusion, muscle aches with flu-like symptoms, eyes sensitive to light. Soliris and You Your Guide To Living With ahus Please see the accompanying full Prescribing Information and Medication Guide for SOLIRIS, including Boxed WARNING regarding serious and life-threatening meningococcal infections. Alexion and Soliris are registered trademarks of Alexion Pharmaceuticals, Inc. 2018, Alexion Pharmaceuticals, Inc. All rights reserved. What is SOLIRIS? SOLIRIS is a prescription medicine called a monoclonal antibody. SOLIRIS is used to treat: adults and children with a disease called atypical Hemolytic Uremic Syndrome (ahus) SOLIRIS is not for use in treating people with Shiga toxin E. coli related hemolytic uremic syndrome (STEC-HUS)
INDICATION & IMPORTANT SAFETY INFORMATION FOR SOLIRIS (eculizumab) INDICATION What is SOLIRIS? SOLIRIS is a prescription medicine called a monoclonal antibody. SOLIRIS is used to treat: adults and children with a disease called atypical Hemolytic Uremic Syndrome (ahus) SOLIRIS is not for use in treating people with Shiga toxin E. coli related hemolytic uremic syndrome (STEC-HUS) Notes IMPORTANT SAFETY INFORMATION What is the most important information I should know about SOLIRIS? SOLIRIS is a medicine that affects your immune system. SOLIRIS can lower the ability of your immune system to fight infections. SOLIRIS increases your chance of getting serious and life-threatening meningococcal infections. Meningococcal infections may quickly become life-threatening and cause death if not recognized and treated early. 1. You must receive a meningococcal vaccine at least 2 weeks before your first dose of SOLIRIS if you have not already had this vaccine. 2. If your doctor decided that urgent treatment with SOLIRIS is needed, you should receive meningococcal vaccination as soon as possible. 3. If you have not been vaccinated and SOLIRIS therapy must be initiated immediately, you should also receive 2 weeks of antibiotics with your vaccinations. 4. If you had a meningococcal vaccine in the past, you might need additional vaccination before starting SOLIRIS. Your doctor will decide if you need additional meningococcal vaccination. 5. Meningococcal vaccines reduce the risk of meningococcal infection but do not prevent all meningococcal infections. Call your doctor or get emergency medical care right away if you get any of these signs and symptoms of a meningococcal infection: headache with nausea or vomiting, headache and fever, headache with a stiff neck or stiff back, fever, fever and a rash, confusion, muscle aches with flu-like symptoms, eyes sensitive to light. 2 Please see the accompanying full Prescribing Information and Medication Guide for SOLIRIS, including Boxed WARNING regarding Please see the accompanying full Prescribing Information and Medication Guide for SOLIRIS, including Boxed WARNING regarding serious and life-threatening meningococcal infections. Please see Indication and Important Safety Information on pages 16 20. serious and life-threatening meningococcal infections. Please see Indication and Important Safety Information on pages 16 20. 27
Atypical Hemolytic Uremic Syndrome (ahus) is a rare and complicated disease, and you may have many questions about it. The information in this brochure can help you learn more about the disease, your life with ahus, and what to expect from treatment with Soliris (eculizumab). You can find the definitions of the underlined words in the Glossary on page 24. QUESTIONS ANSWERED IN THIS BROCHURE: What is ahus? p. 4 What is Soliris? p. 7 What do I need to know before taking Soliris? p. 8 How should I take Soliris? p. 10 What happens if I stop taking Soliris? p. 12 What is the Soliris REMS program? p. 14 Indication and Important Safety Information about Soliris p. 16 Where can I find out more? p. 22 Take an active role in your treatment and work with your doctor to help manage ahus. 3
What is ahus? ahus is a genetic disease. ahus is a disease caused by a genetic mutation in your DNA that affects the complement system. 1,2 This disease can develop at any age and is lifelong. The complement system is part of your immune system and is always on at a low level. 3,4 Common occurrences such as infections, allergies, or pregnancy can increase complement activity. 2,5 10 4
In people without ahus, the complement system functions as intended. Complement activity is increased only when needed and then returns to normal levels. 1,3,6 In people with ahus, changes in certain genes result in a loss of the body s ability to control complement activity. 1,3 Uncontrolled complement activity can result in damage to blood vessels and cause platelets to become overactive. 5,11,12 Overactive platelets can lead to thrombotic microangiopathy (TMA), a condition in which blood clots that block blood flow form within the small blood vessels of the body and cause vital organs to either suddenly fail or lose their ability to function over time. 6,11,12 When I was diagnosed with ahus in the hospital, I had no idea what that meant. I soon learned that this disease is rare and very serious. Patient with ahus Please see the accompanying full Prescribing Information and Medication Guide Please see accompanying full Prescribing for Information SOLIRIS, including and Medication Boxed WARNING Guide regarding for Soliris, serious including and life-threatening Boxed Warning 5 regarding serious meningococcal infection. meningococcal Please see infections. Important Please Safety see Information Indication and on pages Important 18 22. Safety Information on pages 16 20.
In ahus, the risk of TMA complications is lifelong. ahus is a chronic disease that can damage organs, such as the kidneys, and may lead to renal failure. 1 Work with your doctor to manage the complications of ahus. 6
What is Soliris? Soliris (eculizumab) is the first and only drug approved by the FDA to treat patients with ahus. Soliris inhibits uncontrolled complement activity in patients with ahus. 13 The safety and efficacy of Soliris in treating patients with ahus was studied in four clinical trials. 14-17 Many patients taking Soliris had an increase in their platelet counts, indicating that the small clots that had been trapping the platelets are no longer forming Many patients were able to discontinue prolonged plasma exchange or plasma infusion (PE/PI) Soliris reduced, and sometimes eliminated, the need for dialysis treatment in some patients with impaired kidney function The most common side effects in people with ahus treated with Soliris include: headache, diarrhea, high blood pressure (hypertension), common cold (upper respiratory infection), stomach-area (abdominal pain), vomiting, pain or swelling of your nose or throat (nasopharyngitis), low red blood cell count (anemia), cough, swelling of legs or feet (peripheral edema), nausea, urinary tract infections, fever. Tell your doctor about any side effect that bothers you or that does not go away. These are not all the possible side effects of Soliris. For more information, ask your doctor or pharmacist. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. Please see the accompanying full Prescribing Information and Medication Guide for SOLIRIS, including Boxed WARNING regarding serious and life-threatening meningococcal infections. Please see Indication and Important Safety Information on pages 16 20. 7
What do I need to know before taking Soliris? Before receiving your first Soliris (eculizumab) treatment Soliris can lower your immune system s ability to fight infections. Soliris increases your chance of getting serious and life-threatening meningococcal infections. This infection may quickly become life-threatening and can cause death if not recognized and treated early. 18 To help reduce the risk of such infections, you will need meningococcal vaccine(s) before beginning treatment with Soliris. You must receive meningococcal vaccines at least 2 weeks before your first dose of Soliris if you have not already had this vaccine If your doctor decided that urgent treatment with Soliris is needed, you should receive meningococcal vaccination as soon as possible»» In clinical studies, 75/100 patients with ahus were treated with Soliris less than 2 weeks after meningococcal vaccination»» 64 of these 75 patients received antibiotics to prevent meningococcal infection until at least 2 weeks after meningococcal vaccine If you have not been vaccinated and Soliris therapy must be initiated immediately, you should also receive 2 weeks of antibiotics with your vaccinations If you had a meningococcal vaccine in the past, you might need additional vaccination before starting Soliris Your doctor will decide if you need additional meningococcal vaccination Meningococcal vaccines reduce the risk of meningococcal infection but do not prevent all meningococcal infections. 18,19 Soliris may also increase the risk of other types of serious infections. If your child is treated with Soliris, make sure that your child receives vaccinations against Streptococcus pneumoniae and Haemophilus influenzae type b (Hib). Certain people may be at risk of serious infections with gonorrhea. Talk to your doctor about whether you are at risk for gonorrhea infection, about gonorrhea prevention, and regular testing. Certain fungal infections (aspergillus) may also happen if you take Soliris and have a weak immune system or a low white blood cell count. 8 Please see the accompanying full Prescribing Information and Medication Guide for SOLIRIS, including Boxed WARNING regarding serious and life-threatening meningococcal infections. Please see Indication and Important Safety Information on pages 16 20.
Soliris (eculizumab) increases your risk of acquiring serious and life-threatening meningococcal infections. Call your doctor or get emergency medical care right away if you get ANY of these signs and symptoms of a meningococcal infection 18 : headache with nausea or vomiting, headache and fever, headache with a stiff neck or stiff back, fever, fever and a rash, confusion, muscle aches with flu-like symptoms, eyes sensitive to light. Get IMMEDIATE medical attention if you experience any signs or symptoms of a meningococcal infection. 79
How should I take Soliris? Your doctor will discuss with you the appropriate dosing schedule for Soliris (eculizumab). Soliris should be administered at the FDA-recommended dosing schedule or within 2 days of the recommended schedule. 18 If you have an allergic reaction during your Soliris infusion, your doctor may decide to give you Soliris more slowly or to stop your infusion. After each infusion, you should be monitored for 1 hour for allergic reactions. 18 Serious allergic reactions. Serious allergic reactions can happen during your Soliris infusion. Tell your doctor or nurse right away if you get any of these symptoms during your Soliris infusion: Chest pain Trouble breathing or shortness of breath Swelling of your face, tongue, or throat Feel faint or pass out If you have an allergic reaction to Soliris, your doctor may need to infuse Soliris more slowly, or stop Soliris. See How will I receive Soliris? in the Medication Guide. 10
Dosing Considerations 18 Soliris is given through a vein as an intravenous (IV) infusion, usually over 35 minutes in adults and 1-4 hours in pediatric patients. If you are over 18 years of age, you will usually receive an infusion: Every week for 5 weeks Every 2 weeks thereafter If you are under 18 years of age, your doctor will decide the dose and frequency of treatment based on your age and weight. If you are also receiving PE/PI, additional doses of Soliris are required based on the Prescribing Information. If you miss a Soliris infusion, call your doctor right away. Our daughter was diagnosed with ahus and has been on Soliris therapy for almost two years. Her blood counts and her kidney function tests have improved. Parent of a patient taking Soliris Please see the accompanying full Prescribing Information and Medication Guide for SOLIRIS, including Boxed WARNING regarding serious and life-threatening meningococcal infections. Please see Indication and Important Safety Information on pages 16 20. 11
What happens if I stop taking Soliris? It is important that you follow the dosing schedule. You may be at risk for TMA complications if you 18 : Stop treatment Wait more than 2 weeks between doses Receive a lower dose In ahus clinical trials 16-18 : 5 out of 18 patients who discontinued Soliris (eculizumab) developed TMA complications. 4 of the 5 patients were reinitiated with Soliris. Soliris continued to be effective in patients who stayed on treatment through 2 years. Your doctor may discontinue Soliris if you are undergoing treatment for a serious meningococcal infection or due to a side effect. 10 12
Patients who stop using Soliris (eculizumab) are at risk for the return of ahus symptoms. 18 IMPORTANT SAFETY INFORMATION IF YOU STOP TREATMENT If you have ahus, your doctor will need to monitor you closely during and for at least 12 weeks after stopping treatment for signs of worsening ahus symptoms or problems related to abnormal clotting (thrombotic microangiopathy). Symptoms or problems that can happen with abnormal clotting may include: stroke, confusion, seizure, chest pain (angina), difficulty breathing, kidney problems, swellings in arms or legs, a drop in your platelet count. If you experience any of these problems or symptoms, it s important that you seek immediate medical care. Remember to keep your Patient Safety Card with you at all times. Please see the accompanying full Prescribing Information and Medication Guide for SOLIRIS, including Boxed WARNING regarding serious and life-threatening meningococcal infections. Please see Indication and Important Safety Information on pages 16 20. 13
What is the Soliris REMS program? Soliris (eculizumab) is only available through a program called the Soliris Risk Evaluation and Mitigation Strategy (REMS). Before you can receive Soliris, your doctor must: Enroll in the Soliris REMS program Counsel you about the risk of meningococcal infection Give you information about the symptoms of meningococcal infection Give you a Patient Safety Card about your risk of meningococcal infection Make sure that you are vaccinated with a meningococcal vaccine My husband was diagnosed with ahus 6 weeks ago and was vaccinated and started on Soliris therapy. He stopped plasmapheresis when he started Soliris and his doctor said that his kidney function has continued to improve. Spouse of a patient taking Soliris 14
Patient Safety Card 18 Below you will find a Patient Safety Card that contains information about the risk of meningococcal infection. Carry it with you at all times during your treatment and for 3 months after your last Soliris dose. Your risk of meningococcal infection may continue for several weeks after your previous dose of Soliris. It is important to show this card to any doctor or nurse who treats you in order to alert them to your risk of infection. This will help them diagnose and treat a potential meningococcal infection quickly. If you need additional copies of the Patient Safety Card, your doctor or OneSource Case Manager can provide those to you. The Patient Safety Card on this page contains important Safety Information you should know while receiving Soliris therapy. Because Soliris may reduce your natural resistance to infections, it is important to recognize the signs and symptoms of infections, including those of meningitis. This card includes a list of the signs and symptoms of these infections, so you can recognize an infection, including meningitis, and seek IMMEDIATE medical attention. Remember to keep your Patient Safety Card with you during treatment and for 3 months after your last Soliris dose. Patient Safety Card will be affixed here. Please see the accompanying full full Prescribing Information and Medication Guide for for SOLIRIS, Soliris, including Boxed Boxed WARNING Warning regarding serious and meningococcal life-threatening infection. meningococcal Please infections. see Important Please Safety see Indication Information and on Important pages 18 22. Safety Information on pages 16 20. 15
Indication and Important safety information for Soliris Indication and Important Safety Information for Soliris (eculizumab) INDICATION What is SOLIRIS? SOLIRIS is a prescription medicine called a monoclonal antibody. SOLIRIS is used to treat: adults and children with a disease called atypical Hemolytic Uremic Syndrome (ahus) SOLIRIS is not for use in treating people with Shiga toxin E. coli related hemolytic uremic syndrome (STEC-HUS) IMPORTANT SAFETY INFORMATION What is the most important information I should know about SOLIRIS? SOLIRIS is a medicine that affects your immune system. SOLIRIS can lower the ability of your immune system to fight infections. SOLIRIS increases your chance of getting serious and life-threatening meningococcal infections. Meningococcal infections may quickly become life-threatening and cause death if not recognized and treated early. 1. You must receive meningococcal vaccines at least 2 weeks before your first dose of SOLIRIS if you have not already had this vaccine. 2. If your doctor decided that urgent treatment with SOLIRIS is needed, you should receive meningococcal vaccination as soon as possible. 3. If you have not been vaccinated and SOLIRIS therapy must be initiated immediately, you should also receive 2 weeks of antibiotics with your vaccinations. 4. If you had a meningococcal vaccine in the past, you might need additional vaccination before starting SOLIRIS. Your doctor will decide if you need additional meningococcal vaccination. 5. Meningococcal vaccines reduce the risk of meningococcal infection but do not prevent all meningococcal infections. Call your doctor or get emergency medical care right away if you get any of these signs and symptoms of a meningococcal infection: headache with nausea or vomiting, headache and fever, headache with a stiff neck or stiff back, fever, fever and a rash, confusion, muscle aches with flu-like symptoms, eyes sensitive to light. 16 Please see the accompanying full Prescribing Information and Medication Guide for SOLIRIS, including Boxed WARNING regarding serious and life-threatening meningococcal infections. Please see Indication and Important Safety Information on pages 16 20.
Please see accompanying full Prescribing Information and Medication Guide for Soliris, including Boxed Warning regarding serious meningococcal infection. Please see Important Safety Information on pages 18 22. 17
Indication and Important Safety Information for Soliris (eculizumab) (CONTINUED) Your doctor will give you a Patient Safety Card about the risk of meningococcal infection. Carry it with you at all times during treatment and for 3 months after your last SOLIRIS dose. Your risk of meningococcal infection may continue for several weeks after your last dose of SOLIRIS. It is important to show this card to any doctor or nurse who treats you. This will help them diagnose and treat you quickly. SOLIRIS is only available through a program called the SOLIRIS REMS. Before you can receive SOLIRIS, your doctor must: Enroll in the SOLIRIS REMS program Counsel you about the risk of meningococcal infection Give you information about the symptoms of meningococcal infection Give you a Patient Safety Card about your risk of meningococcal infection, as discussed above Make sure that you are vaccinated with a meningococcal vaccine SOLIRIS may also increase the risk of other types of serious infections. If your child is treated with SOLIRIS, make sure that your child receives vaccinations against Streptococcus pneumoniae and Haemophilus influenzae type b (Hib). Certain people may be at risk of serious infections with gonorrhea. Talk to your doctor about whether you are at risk for gonorrhea infection, about gonorrhea prevention, and regular testing. Certain fungal infections (aspergillus) may also happen if you take SOLIRIS and have a weak immune system or a low white blood cell count. Who should not receive SOLIRIS? Do not receive SOLIRIS if you: have a meningococcal infection. have not been vaccinated against meningitis infection unless your doctor decides that urgent treatment with SOLIRIS is needed. See What is the most important information I should know about SOLIRIS? 18 Please see the accompanying full Prescribing Information and Medication Guide for SOLIRIS, including Boxed WARNING regarding serious and life-threatening meningococcal infections. Please see Indication and Important Safety Information on pages 16 20.
Before you receive SOLIRIS, tell your doctor about all of your medical conditions, including if you: have an infection or fever. are pregnant or plan to become pregnant. It is not known if SOLIRIS will harm your unborn baby. are breastfeeding or plan to breastfeed. It is not known if SOLIRIS passes into your breast milk. Tell your doctor about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. SOLIRIS (eculizumab) and other medicines can affect each other causing side effects. It is important that you: have all recommended vaccinations before you start SOLIRIS receive 2 weeks of antibiotics if you immediately start SOLIRIS stay up-to-date with all recommended vaccinations during treatment with SOLIRIS Know the medications you take and the vaccines you receive. Keep a list of them to show your doctor and pharmacist when you get a new medicine. Monitoring Disease After Stopping SOLIRIS If you have ahus, your doctor will need to monitor you closely during treatment and for at least 12 weeks after stopping treatment for signs of worsening ahus symptoms or problems related to abnormal clotting (thrombotic microangiopathy). Symptoms or problems that can happen with abnormal clotting may include: stroke, confusion, seizure, chest pain (angina), difficulty breathing, kidney problems, swellings in arms or legs, a drop in your platelet count. 19
Indication and Important Safety Information for Soliris (eculizumab) (CONTINUED) WHAT ARE THE POSSIBLE SIDE EFFECTS OF SOLIRIS? SOLIRIS can cause serious side effects including: See What is the most important information I should know about SOLIRIS? Serious allergic reactions. Serious allergic reactions can happen during your SOLIRIS infusion. Tell your doctor or nurse right away if you notice any of these symptoms during your SOLIRIS infusion: chest pain; trouble breathing or shortness of breath; swelling of your face, tongue, or throat; feel faint or pass out If you have an allergic reaction to SOLIRIS, your doctor may need to infuse SOLIRIS more slowly, or stop SOLIRIS. See How will I receive SOLIRIS? in the Medication Guide. The most common side effects in people with ahus treated with SOLIRIS include: headache, diarrhea, high blood pressure (hypertension), common cold (upper respiratory infection), stomach-area (abdominal pain), vomiting, pain or swelling of your nose or throat (nasopharyngitis), low red blood cell count (anemia), cough, swelling of legs or feet (peripheral edema), nausea, urinary tract infections, fever. Tell your doctor about any side effect that bothers you or that does not go away. These are not all the possible side effects of SOLIRIS. For more information, ask your doctor or pharmacist. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. Please see the accompanying full Prescribing Information and Medication Guide for SOLIRIS, including Boxed WARNING regarding serious and life-threatening meningococcal infections. 20 Please see Indication and Important Safety Information on pages 16 20.
21
Where can I find out more? Additional resources are available to help answer your questions about ahus and Soliris (eculizumab). The complimentary OneSource program is staffed by Case Managers to offer support to both you and your doctor. Case Managers have clinical knowledge and funding expertise OneSource can help you transition from hospital to home OneSource Case Managers are assigned geographically, so they re familiar with doctors, hospitals, community resources, and funding opportunities close to home Visit https://alexiononesource.com/ or call 1.888.SOLIRIS (1.888.765.4747) to speak one-on-one with a OneSource Case Manager today! You are encouraged to report serious side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch, or call 1.800.FDA.1088 (1.800.332.1088). 22 Please see the accompanying full Prescribing Information and Medication Guide for SOLIRIS, including Boxed WARNING regarding serious and life-threatening meningococcal infections. Please see Indication and Important Safety Information on pages 16 20.
If your doctor determines that Soliris (eculizumab) is the right treatment for you, you may learn more by visiting the Soliris website or speaking with a OneSource Case Manager. Case Managers can be an important source of information and support as you navigate this complicated disease. They are trained to: Work with your healthcare team to answer questions and provide educational materials related to ahus Assist you with insurance coverage and funding options Help with solutions for balancing all aspects of ahus management when faced with major life challenges, such as helping you schedule infusions and finding alternative infusion centers if you are traveling 23
Glossary Allergic reaction: an overreaction of the immune system after a substance is introduced into the body. Atypical hemolytic uremic syndrome (ahus): a disease of the blood that causes low red blood cell and platelet counts, kidney failure, and sometimes damage to other vital organs, such as the heart and brain. Blood clot: blood that has changed from liquid to a gel-like or semisolid clump. Blood vessels: tubular structures that carry blood through the human body. Cells: the smallest structural and functional units of the human body. Complement system: a natural part of the immune system that helps protect the body from foreign substances like bacteria or other infections. The complement system is made up of a group of proteins found in the blood. Dialysis: a treatment for kidney failure. Normally, the kidneys work to filter the blood and remove waste, excess salt, and water. Kidney failure, also called end-stage renal disease, occurs when the kidneys stop working completely. During hemodialysis, a machine takes over the job of the kidneys by filtering the blood outside of the body and then returning the filtered blood back to the body. FDA: Food and Drug Administration, the US federal agency that assures the safety and efficacy of drugs, foods, and other products. Genetic: relating to genes, which are units in cells that are passed down through families. Immune system: a complex group of cells, proteins, and other molecules that work together to identify foreign organisms and other substances, such as bacteria; the main role of the system is to protect the body against these foreign organisms. Infusion: a process during which fluid is introduced into the body through a vein. Meningococcal infections: infections caused by a group of bacteria called Neisseria meningitidis. The most common forms of meningococcal infections include meningitis (infection of the membranes that surround the brain and spinal cord) and meningococcemia (bloodstream infections). Platelets: small, irregular, disc-shaped elements in the blood that assist in blood clotting. REMS (Risk Evaluation and Mitigation Strategy): a program required by the FDA to manage known or potential serious risks associated with a drug product. Thrombotic microangiopathy (TMA): formation of clots in small blood vessels throughout the body; this is an underlying cause of the clinical signs and symptoms of ahus. Vaccine: a preparation that is used to increase the body s natural defense against a disease. 24
References 1. Noris M, Remuzzi G. Atypical hemolytic-uremic syndrome. N Engl J Med. 2009;361(17):1676-1687. 2. Noris M, Caprioli J, Bresin E, et al. Relative role of genetic complement abnormalities in sporadic and familial ahus and their impact on clinical phenotype. Clin J Am Soc Nephrol. 2010;5(10):1844-1859. 3. Holers VM. The spectrum of complement alternative pathway-mediated diseases. Immunol Rev. 2008;223(1):300-316. 4. Zipfel PF, Heinen S, Skerka C. Thrombotic microangiopathies: new insights and new challenges. Curr Opin Nephrol Hypertens. 2010;19(4):372-378. 5. Noris M, Mescia F, Remuzzi G. STEC-HUS, atypical HUS and TTP are all diseases of complement activation. Nat Rev Nephrol. 2012;8(11):622-633. 6. Liszewski MK, Atkinson JP. Too much of a good thing at the site of tissue injury: the instructive example of the complement system predisposing to thrombotic microangiopathy. Hematol Am Soc Hematol Educ Program. 2011;2011(1):9-14. 7. Fang CJ, Richards A, Liszewski MK, Kavanagh D, Atkinson JP. Advances in understanding of pathogenesis of ahus and HELLP. Br J Haematol. 2008;14(3):336-348. 8. Campistol JM, Arias M, Ariceta G, et al. An update for atypical hemolytic uraemic syndrome: diagnosis and treatment. A consensus document. Nefrologia. 2015;35(5):421-447. 9. Fakhouri F, Roumenina L, Provot F, et al. Pregnancy-associated hemolytic uremic syndrome revisited in the era of complement gene mutations. J Am Soc Nephrol. 2010;21(5):859-867. 10. Geerdink LM, Westra D, van Wijk JAE, et al. Atypical hemolytic uremic syndrome in children: complement mutations and clinical characteristics. Pediatr Nephrol. 2012;27(8):1283-1291. 11. Langman C. Systemic multi-organ complications in atypical hemolytic uremic syndrome (ahus): retrospective study in a medical practice setting. Haematologica. 2012:97(s1):195-196. 12. Ruggenenti P, Noris M, Remuzzi G. Thrombotic microangiopathy, hemolytic uremic syndrome, and thrombotic thrombocytopenic purpura. Kidney Int. 2001;60(3):831-846. 13. Zuber J, Fakhouri F, Roumenina LT, Loirat C, Fremeaux-Bacchi V. Use of eculizumab for atypical haemolytic uraemic syndrome and C3 glomerulopathies. Nat Rev Nephrol. 2012;8:643-657. 14. Fakhouri F, Hourmant M, Campistol JM, et al. Terminal complement inhibitor eculizumab in adult patients with atypical hemolytic uremic syndrome: a single-arm, open-label trial. Am J Kid Dis. 2016;68(1):84-93. 15. Greenbaum LA, Fila M, Ardissino G, et al. Eculizumab is a safe and effective treatment in pediatric patients with atypical hemolytic uremic syndrome. Kidney Int. 2016;89(3):701-711. 16. Legendre CM, Licht C, Muus P, et al. Terminal complement inhibitor eculizumab in atypical hemolytic-uremic syndrome. N Engl J Med. 2013;368(23):2169-2181. 17. Licht C, Greenbaum LA, Muus P, et al. Efficacy and safety of eculizumab in atypical hemolytic uremic syndrome from 2-Year extensions of phase 2 studies. Kidney Int. 2015;87(5):1061-1073. 18. Soliris [prescribing information]. Boston, MA: Alexion Pharmaceuticals; 2018. 19. Bouts A, Monnens L, Davin JC, Struijk G, Spanjaard L. Insufficient protection by Neisseria meningitidis vaccination alone during eculizumab therapy. Pediatr Nephrol. 2011;26:1919-1920. Please see the accompanying full Prescribing Information and Medication Guide for SOLIRIS, including Boxed WARNING regarding serious and life-threatening meningococcal infections. Please see Indication and Important Safety Information on pages 16 20. 25
Notes 26