The side effects of treatment and residual ailments of an aHUS onset featured highly by aHUS families in the contribution to the aHUS Patients Research Agenda. The topic is covered by this question for researchers in the Agenda.
Can the side effects of treatment using a complement inhibitor be distinguished from those temporary and permanent ongoing ailments which follow initial onset?
One such side effect rides higher than most i.e. the increased risk of a meningococcal infection.
aHUS is “bloody scary” but so too are meningitis and septicemia.
What is meningococcal infection? Why are those aHUS patients treated with eculizumab more susceptible to it?
Meningococcal infection is the result of the bacteria Neisseria meningitidis. The bacteria are divided into 12 groups distinguished by what the capsule shell that they have is made from. Each type or serotype is given a different letter to identify it , These are A, B, C, E , H, I J, L, W ,Y, and Z. Most infections are caused by types A, B, C, W, X, and Y.
Most of the time the bacteria lives in the body , usually at the back of the nose, without doing any harm. Young people in particular are carriers and close contact can considerably increase invasion of the bacteria particularly in places that have a lot of people in a confined spaces.
The highest incidents are in babies less than 1 year old. Another spike occurs between 15 and 25 years.
JFrom being harmless to being deadly, a lot depends on the individual’s immune system working properly.
The bacteria does take advantage if there is any deficiency in someone’s immune system. This is most striking in those with a deficiency in the innate immune system Complement . It is the Complement System which is the first responder to invasion but if it is overwhelmed by the bacteria the resulting uncontrolled interplay with the coagulation system results in a varied response from mild to severe. Either meningitis or sepsis or both. can happen. Severe clotting can stop blood supply and limbs are lost through lack of blood flow.
aHUS patients treatment is to block the Complement System from working thus creating the environment in which the bacteria can thrive and switch from being harmless to deadly. Thus it is a side effect of the use of eculizumab making aHUS patients 1000 times more susceptible to meningococcal infection.
More at risk but not definite to get it.
For the general population in the USA there may be between 1500 and 5000 incidents of meningococcal infection per year. Eculizumab has been in use for more than 10 years with thousands of aHUS and PNH patients at potential risk and in that time only a handful of aHUS patients globally have onset with an infection.
Those incidents can be explained by :
-early risk management protocols for using eculizumab were not as stringent as in later years, a small number of incidents happened during trials which enormously benefited those yet to receive treatment.
– although vaccination for meningococcal infection is compulsory as a condition of use , not all patients have accessed the vaccination for serotype B. Some patients not so vaccinated have experienced the infection.
-even when vaccinated it is advisable to have prophylactic antibiotics because breakthrough can occur in some vaccinated patients. It can take up to 14 days for a vaccination to take effect. So it is with meningococcal vaccination, it takes time for body’s adaptive immune system to create the specific antibodies needed. This natural response varies between individuals and some may need a booster vaccination very soon after the initial one to be fully protected. All will need a booster vaccination every 3 to 5 years as the antibody protection depletes.
aHUS patients need to be vigilant:
Also the following table from Alexion’s literature about all side effects reported and the likelihood of incidence
Table 1: Adverse Reactions reported in 1,407 patients included in overall eculizumab clinical trials, including patients with PNH, aHUS, and refractory gMG as well as from postmarketing experience
|MedDRA System Organ Class||Very Common
(≥1/100 to <1/10)
(≥1/1,000 to <1/100)
(≥1/10,000 to <1/1,000)
|Infection and infestations||Pneumonia, Upper respiratory tract infection, Nasopharyngitis, Urinary tract infection, Oral Herpes||Meningococcal infectiona, Sepsis, Septic shock, Peritonitis, Lower respiratory tract infection, Fungal infection, Viral infection, Bronchitis, Abscess, Cellulitis, Influenza, Gastrointestinal infection, Cystitis, Infection, Sinusitis, Tooth infection||Aspergillus infectionb, Arthritis bacterialb, Genitourinary tract gonococcal infection, Haemophilus influenzae infection, Impetigo, Gingivitis|
|Neoplasms benign, malignant and unspecified (including cysts and polyps)||Malignant melanoma, Myelodysplastic syndrome|
|Blood and lymphatic system disorders||Leukopenia, Anaemia||Thrombocytopenia, Lymphopenia||Haemolysis*, Abnormal clotting factor, Red blood cell agglutination, Coagulopathy|
|Immune system disorders||Anaphylactic reaction, Hypersensitivity|
|Endocrine disorders||Basedow’s disease|
|Metabolism and nutrition disorders||Decreased appetite|
|Psychiatric disorders||Insomnia||Depression, Anxiety, Mood swings||Abnormal dreams, Sleep disorder|
|Nervous system disorders||Headache||Dizziness, Dysgeusia, Tremor||Paraesthesia||Syncope|
|Eye disorders||Vision blurred||Conjunctival irritation|
|Ear and labyrinth disorders||Tinnitus, Vertigo|
|Vascular disorders||Hypertension||Accelerated hypertension, Hypotension, Hot flush, Vein disorder||Haematoma|
|Respiratory, thoracic and mediastinal disorders||Cough, Oropharyngeal pain||Dyspnoea, Epistaxis, Throat irritation, Nasal congestion, Rhinorrhoea|
|Gastrointestinal disorders||Diarrhoea, Vomiting, Nausea, Abdominal pain||Constipation, Dyspepsia, Abdominal distension||Gastroesophageal reflux disease, Gingival pain|
|Skin and subcutaneous tissue disorders||Rash, Pruritus, Alopecia||Urticaria, Erythema, Petechiae, Hyperhidrosis, Dry skin||Dermatitis, Skin depigmentation|
|Musculoskeletal and connective tissue disorders||Arthralgia, Myalgia, Pain in extremity||Muscle spasms, Bone pain, Back pain, Neck pain, Joint swelling||Trismus|
|Renal and urinary disorders||Renal impairment, Dysuria||Haematuria|
|Reproductive system and breast disorders||Spontaneous penile erection, Menstrual disorder|
|General disorders and administration site conditions||Pyrexia, Chills, Fatigue, Influenza like illness||Oedema, Chest discomfort, Asthenia, Chest pain, Infusion site pain||Extravasation, Infusion site paraesthesia, Feeling hot|
|Investigations||Alanine aminotransferase increased, Aspartate aminotransferase increased, Gamma-glutamyltransferase increased, Haematocrit decreased, Haemoglobin decreased||Coombs test positiveb|
|Injury, poisoning and procedural complication||Infusion related reaction|
Also an in-depth clinical publication by Lewis and Ram about Meningococcal DIsease and the Complement System click here
This article is for information and awareness only and not clinical advice ,which should be sought from those medically qualified to give it.