Tocilizumab – a drug for COVID-19. How does it work, who can apply?

Tocilizumab is an immunosuppressive drug, i.e. it suppresses the activity of the immune system. So far, it has been used primarily in the treatment of rheumatoid arthritis and severe arthritis in children. During the coronavirus pandemic, this drug was also used in the experimental treatment of the disease caused by the SARS-CoV-2 virus. How does tocilizumab work and what are the indications for its use? When should you not use this medication? Can its use cause side effects in a patient? Is tocilizumab effective against the coronavirus?

1. Tocilizumab is the drug most commonly used to treat rheumatoid arthritis
2. During the coronavirus pandemic, it was used experimentally in patients hospitalized for COVID-19
3. Improvement in health was noted within 24-48 hours of drug administration
4. You can find more such stories on the TvoiLokony home page

Tocilizumab – basic information

Tocilizumab to immunosuppressive drugwhich works by suppressing the activity of the immune system. It is used primarily in the treatment of rheumatoid arthritis and juvenile idiopathic arthritis. During the coronavirus pandemic, tocilizumab was used experimentally as a treatment for a disease caused by the SARS-CoV-2 virus.

Tocilizumab is a humanized monoclonal IgG1 antibody. This means that it is a set of antibodies showing the same specificity for a given antigen and possibly showing the same or similar affinity. Tocilizumab is produced by recombinant DNA technology in Chinese Hamster Ovary cells.

As a drug, tocilizumab was developed by the pharmaceutical companies Hoffmann-La Roche and Chugai Pharmaceuticals under the trade name RoActemra.

In 2005, tocilizumab was approved by the Japanese Pharmaceutical and Medical Products Agency. In January 2021, it was recommended by the British NIHS for critically ill patients with COVID-19 at the beginning of treatment in intensive care units.

What drugs are used to treat the coronavirus in Poland? Read: What is COVID-19 treated in Poland? Here are the recommended medications

Tocilizumab – action

The action of tocilizumab primarily affects the functioning of the immune system. This drug binds to interleukin receptors, which is one of the most important and multidirectional cytokines.

Cytokines, in turn, are proteins that influence the growth, proliferation and stimulation of cells involved in the immune response and haemopoietic cells.

Interleukin is produced by a wide variety of cells, including T and B lymphocytes, monocytes, and fibroblasts. It is involved in a variety of physiological processes, such as activation of T lymphocytes, induction of immunoglobulin secretion, induction of acute phase protein production in the liver, and stimulation of hematopoiesis. It also plays an important role in the pathogenesis of diseases including inflammatory diseases, osteoporosis and cancer.

Tocilizumab, on the other hand, binds to and inhibits the activity of both soluble and membrane-bound receptors of interleukin 6 (sIL-6R and mIL-6R).

What are cytokines and how do they work? Check: Cytokines, or the communication system inside our body

Further part below the video.

Tocilizumab – indications

Tocilizumab is a drug that stimulates the activity of the immune system. Indications for use of the drug tocilizumab are:

1. rheumatoid arthritis – in combination with methotrexate in adult patients with insufficient response or intolerance to existing treatment with one or more anti-rheumatic drugs. Tocilizumab can be used as monotherapy when methotrexate is not tolerated well or when further treatment with methotrexate is not indicated;
2. active juvenile systemic idiopathic arthritis – in patients who have had an inadequate response to treatment with NSAIDs and systemic corticosteroids. Tocilizumab can be used in combination with methotrexate or as monotherapy when methotrexate is not well tolerated or further treatment with methotrexate is not recommended;
3. active polyarticular juvenile idiopathic arthritis – in patients aged 2 years or older who have had an inadequate response to current treatment with methotrexate;
4. giant cell arteritis;
5. severe or life-threatening cytokine release syndrome induced by therapy with T cells containing a chimeric antigen receptor;
6. COVID-19 in adults receiving systemic corticosteroids and requiring supplemental oxygen therapy or mechanical ventilation.

What is immunosuppression and when is it used? Check: What is immunosuppression?

Tocilizumab a coronavirus

Tocilizumab has been used experimentally to treat COVID-19 in China, Italy, Iran and Poland.

Initially, 21 Chinese patients were treated with tocilizumab. Their health improved within the first 24-48 hours after drug administration. In contrast, three out of six Italian patients suffering from severe coronavirus pneumonia improved significantly after receiving tocilizumab.

In Poland, the drug tocilizumab was administered to three patients hospitalized in Lublin and their health improved within 24-48 hours from the start of therapy.

In early 2021, the British National Institute for Health Research recommended the use of tocilizumab in critically ill COVID-19 patients. This recommendation was formulated on the basis of the preliminary results of the study, which included 353 patients, among whom the mortality was lower by 24%. versus a control group of 402 patients. On the other hand, intensive therapy of seriously ill patients lasted, on average, 10 days.

How to treat coronavirus at home? Check: What should COVID-19 treatment be like at home? The most important recommendations of the expert

Tocilizumab – contraindications to use

Despite its effectiveness, tocilizumab cannot be used in all patients. Hypersensitivity to this substance is a contraindication to the use of tocilizumab.

The contraindications also include:

1. active, severe infections except COVID-19 – Serious infections, some of them fatal, have been reported in patients receiving immunosuppressants, including tocilizumab;
2. comorbidities – diverticulitis, diabetes, interstitial lung disease;
3. recurring infections with a medical history or chronic infections;
4. tuberculosis.

Can Vitamins and Dietary Supplements Help Treat COVID-19? Check: What vitamins and dietary supplements to take while undergoing COVID-19? Advice from your family doctor

Tocilizumab – precautions

Before and during the use of tocilizumab, follow the precautions recommended by your doctor or pharmacist.

Precautions to keep in mind before and during treatment with the drug:

1. In vitro studies on human hepatocytes have shown that cytokines such as interleukin 6 (IL-6) inhibit the expression of hepatic cytochrome P450 enzymes, resulting in a reduction in the expression of the enzymes CYP1A2, CYP2C9, CYP2C19 and CYP3A4. Additionally, treatment of a patient with a potent cytokine inhibitor may lead to an increase in the activity of cytochrome P450;
2. Serious infections, some of them fatal, have been reported in patients receiving immunosuppressants. Treatment should not be initiated in patients with an active infection. If a patient develops a severe infection while on treatment, tocilizumab should be discontinued until the infection is controlled;
3. caution is recommended when deciding to use tocilizumab in patients with a history of recurrent infections or chronic infections or with comorbidities that may predispose to infections;
4. patients with latent tuberculosis should receive standard antituberculosis treatment prior to starting tocilizumab treatment;
5. Cases of viral reactivation, e.g. with hepatitis B virus, have been reported in patients with RA during biological treatment;
6. Cases of diverticulitis perforation have been reported as a complication of diverticulitis after the use of tocilizumab in patients with RA, therefore special caution should be exercised when using tocilizumab in patients with a history of intestinal ulceration or diverticulitis;
7. caution should be exercised when considering treatment in patients with active liver disease or impaired liver function;
8. in case of clinical indications, additional liver function tests, including bilirubin measurement, should be considered;
9. treatment with tocilizumab in patients with RA, pJIA and sJIA and baseline ALT or AST> 5 x ULN is not recommended;
10. in RA, sJIA and pJIA patients, ALT / AST should be monitored every 4 to 8 weeks for the first 6 months of treatment, and then every 12 weeks thereafter;
11. there is an increased risk of neutropenia in patients previously treated with a TNF inhibitor;
12. in patients with sJIA, pJIA and RA, lipid parameters should be assessed 4-8 weeks after starting tocilizumab treatment;
13. in RA patients there is an increased risk of malignant neoplasms;
14. due to the lack of clinical safety data, live and live vaccines with reduced virulence (attenuated) should not be given during treatment;
15. Patients with RA are at increased risk of cardiovascular disease and should be managed in standard care to manage risk factors.

What medications from the home medicine cabinet can help with Omikron? Check: What to have in the home first aid kit in the event of an Omicron? The doctor lists

Tocilizumab – dosage

Always take tocilizumab exactly as your doctor or pharmacist has told you. First of all, everyone treated with tocilizumab should receive Patient Alert Card. Therapy with this drug should only be carried out by an experienced physician specialized in the treatment of rheumatoid arthritis, polyarticular juvenile idiopathic arthritis, systemic juvenile idiopathic arthritis and cytokine release syndrome.

Tocilizumab is administered to the patient after dilution into a vein by infusion over an hour or so. Before administration, the drug should be stored at a temperature of 2 to 6 degrees C and protected from light.

Tocilizumab is used very often in combination with methotrexate. Tocilizumab can also be used as monotherapy when methotrexate treatment is not tolerated or is inappropriate.

For adults with active rheumatoid arthritis who are treated with tocilizumab monotherapy or combination therapy, treatment is dose 8 mg / kg body weight by infusion every 4 weeks. Patients weighing more than 100 kg should increase the dose, but a dose greater than 800 mg per infusion is not recommended.

Dosing of tocilizumab in children depends on the indication, body weight and age. It is usually given by infusion dose 8 – 12 mg / kg once every 2 or 4 weeks.

Patients over 65 years of age and patients with mild renal impairment do not need to have a modified tocilizumab dose.

For the coronavirus, adults are given a dose of 8 mg / kg body weight. This dose can be repeated after 8 hours if necessary. In people who weigh more than 100 kg, it is not recommended to administer a single dose higher than 800 mg.

Adult patients with giant cell arteritis are given 162 mg once weekly in combination with tapering corticosteroids. After the end of their use, the drug can be used as monotherapy. Monotherapy should not be used to treat acute relapses. Treatment beyond 52 weeks should be guided by disease activity and the patient’s clinical judgment.

How to take medication correctly? Check: How to take medications effectively?

Tocilizumab – side effects

The drug tocilizumab, like any other drug, may cause side effects in patients. It is important to report any suspected adverse reactions after authorization of the medicinal product so that the benefit / risk balance of the medicinal product can be monitored.

The frequency classification of adverse body reactions (ADRs) is based on the following principles: very common (≥1 / 10), common (≥1 / 100 to <1/10), uncommon (≥1 / 1 to <000/1), rare (≥ 100 / 1 to <10 / 000), very rare (<1 / 1), not known (cannot be estimated from the available data).

When treating RA in monotherapy or combination therapy, the following may occur:

1. very often: upper respiratory tract infection, hypercholesterolaemia;
2. often: cellulitis, pneumonia, herpes labialis, shingles, abdominal pain, mouth ulceration, gastritis, rash, itching, hives, headache, dizziness, increased liver transaminases and total bilirubin, weight increased, arterial hypertension, leukopenia, neutropenia, hypofibrinogenemia, peripheral edema, hypersensitivity reactions, conjunctivitis, cough, dyspnoea;
3. Not so often: diverticulitis, stomatitis, gastric ulcer, hypertriglyceridemia, nephrolithiasis, hypothyroidism;
4. rarely: Stevens-Johnson syndrome, anaphylaxis (fatal), drug-induced liver damage, jaundice;
5. very rarely: liver failure, pancytopenia.

When treated with sJIA in monotherapy or in combination therapy, they may occur:

1. very often: upper respiratory tract infection, nasopharyngitis, neutropenia;
2. often: diarrhea, headache, infusion-related reactions (including rash, hives, diarrhea, abdominal discomfort, joint pain, headache), decreased platelet count, increased cholesterol.

When treated with pJIA as monotherapy or combination therapy, it may occur:

1. very often: upper respiratory tract infection, nasopharyngitis, headache;
2. often: nausea, diarrhea, infusion-related reactions (including headache, nausea, hypotension), increased liver transaminases, neutropenia;
3. Not so often: decrease in blood platelets, increase in cholesterol.

When treated with the coronavirus, the following may occur:

1. often: urinary tract infections, hypokalaemia, anxiety, insomnia, hypertension, constipation, diarrhea, nausea, increases in AST and ALT.

Can vitamin D help in a pandemic? Check: Why do you need to take vitamin D during a pandemic?

Tocilizumab – drug interactions

Before starting treatment with tocilizumab, please inform your doctor or pharmacist about all the medicines you are taking or have recently taken. You should also inform what medications the patient plans to take in the near future.

Interactions of tocilizumab with other active substances can cause:

1. intensification of the immunosuppressive effect and increased risk of serious infections in combination with such drugs as: Abatacept, Blinatumomab, Everolimus. Hydroxycarbamide, Ibritumomab, Ifosfamide, Canakinumab, Ruxolitinib, Topotecan, Tofacitinib;
2. increased risk of neutropenia and agranulocytosis in combination with drugs such as: Deferiprone;
3. the possibility of hepatotoxic effects in combination with drugs such as: Brentuximab Vedotin and Clofarabine;
4. low blood levels of these substances and their effects due to interactions — Alprazolam, Dienogest, Lewonorgestrel, Medroksyprogesteron, Simwastatyna;
5. increased risk of serious infections and peripheral neuropathy — Bortezomib and Dinutuxymab beta;
6. risk of steroid withdrawal syndrome: Dexamethasone, Methylprednisolone, Prednisolone, Prednisone;
7. tocilizumab may pose a risk of reducing the effectiveness of the therapy: Amlodypine, Atorwastatin, Bromazepam, Diazepam, Phenytoin, Fluwastatin, Clonazepam, Lacydypine, Lorazepam, Lowastatin, Medazepam, Nitrazepam, Nitrendipine, Oxazepam, Rosuwastatin, Simwastatin, Temazepam, Werapamil.

Which drugs should never be combined with each other? Check: Dangerous interactions

Tocilizumab and pregnancy and breast-feeding

The use of any medications or dietary supplements during pregnancy requires consultation with the attending physician. If you are pregnant or breastfeeding, think you may be pregnant or are planning to have a baby, ask your doctor or pharmacist for advice before taking tocilizumab.

There are currently no conclusive data from clinical trials on the use of tocilizumab in pregnant women. However, animal studies have shown that the use of high doses of tocilizumab by pregnant women increases the risk of miscarriage, embryo-fetal death. Despite this, the potential risk for humans has not been determined. Doctors do not recommend the use of medicinal products with tocilizumab in pregnant women unless clearly necessary.

A decision regarding the use or discontinuation of tocilizumab therapy by nursing women is based on an assessment of the risk to the child and the benefit to the mother when breast-feeding. To date, no studies on the excretion of tocilizumab in human milk have been performed, and no such studies have been performed in animals.

It is worth mentioning that the current non-clinical data available to doctors do not indicate a negative effect of tocilizumab treatment on female fertility. For safety reasons, women of childbearing age undergoing therapy must use effective contraception during treatment and for up to 3 months after discontinuing treatment.

What is worth knowing about proper supplementation during pregnancy? Check: Conscious choices. Diet and supplementation in pregnancy

Tocilizumab – available drugs

Currently, there is only one preparation available on the pharmaceutical market, the active substance of which is tocilizumab. It’s a preparation RoActemra in a concentrate for solution for infusion or solution for injection. This drug is a prescription drug and is only available for restricted use.

How to ensure that you do not catch the coronavirus in public transport? Check: What precautions should be taken in public transport to avoid catching the coronavirus?

Tocilizumab – substitutes

Products with the same international name and in the same form do not have to be substitutes, because the content of the active substance, i.e. the dose of the drug, determines the use of a given drug.

Therefore, before using a substitute for tocilizumab, read the package leaflet or consult your doctor or pharmacist.

The drugs that exhibit similar properties to tocilizumab include:

1. Anakinrê – an immunosuppressive drug, an antagonist of human interleukin-1 receptors), produced by recombinant DNA technology in the E. coli gene expression system. Used in the treatment of RA, periodic fever syndromes and Still’s disease. It is a component of Kineret, which is available in a solution for injection;
2. basiliximab – is a chimeric human-murine monoclonal antibody (IgG1κ) produced by genetic engineering using a mouse myeloma cell line and plasmid-borne mouse genes. This medicine is used to prevent acute transplant rejection following allogeneic kidney transplantation. It is a component of Simulect, which is available as a powder and solvent for solution for injection or infusion;
3. daclizumab – it is an immunosuppressive drug, which is a recombinant humanized IgG antibody directed against the interleukin 2 receptor (IL-2). 90% of the sequences are human, 10% are from mice. Daclizumab is indicated for the treatment of RSM – multiple sclerosis with relapsing forms in adults. It is a component of Zenapax, available as a concentrate for solution for infusion;
4. kanakinumab – is a monoclonal antibody that blocks certain proteins in the body that can affect inflammation and other immune responses. Canakinumab is used to treat some types of intermittent fever syndromes, sometimes called autoinflammatory syndromes. It is part of Ilaris, which is available as a powder to be made up into a solution for injection;
5. sekukinumab – is a recombinant human monoclonal antibody of the IgG / κ class obtained by expression in Chinese hamster ovary cells. This medicine is used to treat plaque psoriasis, psoriatic arthritis, ankylosing spondylitis, axial spondyloarthritis without radiographic changes characteristic of ankylosing spondylitis. It is a component of Cosentyx, available as powder for solutions for injection, solution for injection and solution for injection in a pre-filled syringe;
6. I believe – is a fully human IgG1κ monoclonal antibody. This medicine is used to treat plaque psoriasis, psoriatic arthritis, Crohn’s disease and ulcerative colitis. It is a component of Stelara, available as concentrate for solution for infusion, solution for injection and solution for injection in a pre-filled syringe.

When is it worth asking the pharmacy about drug substitutes? Check: Swap when you can