Dr Bruce Kirkham, MBChB, BA, MD, FRCP, FRACP Consultant Rheumatologist, Guy’s Hospital, London
Original article: 22/10/2004
Next review due: 02/02/2014
Adalimumab (Humira) is a biologic drug that binds to tumour necrosis factor alpha (TNFα). TNFα is a protein called a cytokine, produced mainly by white cells (leukocytes). In RA, TNFα is produced by cells inside the joint and plays an important role in stimulating joint inflammation. When adalimumab binds to TNFα, it neutralises the function of TNFα and reduces joint inflammation and damage. Adalimumab is one of the licensed TNFα-blocker or anti-TNFα drugs (the others are infliximab, etanercept, certolizumab pegol and golimumab).
Humira is a 'monoclonal antibody', which is a protein and therefore cannot be taken by mouth as it would be digested. Adalimumab is given by an injection just under the skin, usually once every two weeks, using a special pre-filled syringe.
Does adalimumab work?
For 12 years up until 2009, more than 20,000 patients received Humira during clinical trials evaluating its effectiveness and safety for the treatment of rheumatoid arthritis (but also psoriatic arthritis, ankylosing spondylitis, Crohn’s disease, psoriasis and juvenile idiopathic arthritis), including patients on continuous therapy for up to 8 years. Humira has been approved in 83 countries and nearly 500,000 people worldwide are currently being treated with Humira.
Four randomised double-blind placebo controlled clinical studies which studied at least six months of treatment were used for the original application to the
DE011 study: adalimumab was used alone (monotherapy)
ARMADA and DE019 studies: adalimumab was used along with Methotrexate.
STAR study: adalimumab was used with several anti-RA drugs including methotrexate, sulphasalazine, hydroxychloroquine, leflunomide, gold and prednisolone, with sometimes more than one of these drugs being used with adalimumab.
The STAR study showed that adalimumab was well-tolerated when used alongside other commonly used anti-RA drugs, even if more than one is being used. The DE019 study showed that the progression of joint damage (measured using x-rays of the hands and feet) is also inhibited in over half the treated patients receiving adalimumab.
Clinical trials use several different measures to investigate responses to treatment. The 1987 ACR (American College of Rheumatology) response measurements showed the percentage of patients who achieved a small response, ACR 20, a good response, ACR 50, and a very good response, ACR 70 (this has since been replaced by the 2010 ACR criteria). The Health Assessment Questionnaire (HAQ) measures the ability of a person to perform eight different important tasks of daily life. Fatigue is measured using a questionnaire called the FACIT-F, which gives an indication of levels of fatigue.
These studies show that when given with methotrexate about two thirds of patients respond. Approximately one half of the patients experience a good improvement (ACR 50). It is clear that methotrexate improves the effectiveness of adalimumab, and this has also been shown with the other anti-TNFα treatments.
Does adalimumab have side-effects?
In the 1380 patients receiving adalimumab in the detailed clinical trials described above common side-effects included injection site reaction, headaches and rashes. Many of these effects were transient and only 0.2% of patients had to stop treatment because of the most common side-effect of localised injection site reaction.
Possibly the most serious side-effect to be considered with TNFα-blocking treatment is that of infection. TNFα plays an important, helpful role in the body fighting infections. Studies of adalimumab have shown, as with other TNFα-blocking drugs, a slight increase in serious infections such as pneumonia, pyelonephritis or joint infections. In particular, TNFα-blocking drugs are associated with re-activation of previously undetected infections with tuberculosis (TB, previously known as consumption). Therefore, before taking adalimumab, or any TNFα blocker, you will be asked about any previous infections, or contact with people with TB, including other family members and a chest x-ray will be performed. Sometimes a skin test will also be performed to assess if any dormant (latent) TB may be present. If there are signs of previous TB which has not been thoroughly treated, you will be asked to take anti-TB treatment before starting adalimumab (or any other TNFα-blocking treatment).
TNFα-blockers have all been reported to exacerbate multiple sclerosis, so you may be asked if you have ever experienced symptoms such as transient loss of vision that could indicate a previous attack of multiple sclerosis.
There seems to be no increased risk of most cancers. However it is unclear, if cancer has previously been treated and cured, how long the interval between cancer treatment and starting anti-TNF treatment should be. A cancer of lymph glands called lymphoma is known to be increased in patients with persistent active RA (as well as psoriasis and Crohn’s disease). The clinical trials of adalimumab have recorded 10 cases of lymphoma. This is higher than would be expected in the normal population, but is in keeping with the rate observed in patients with active RA.
Blocking TNFα with drugs in RA is associated with a slight increase in the levels of auto-antibodies in the blood. These auto-antibodies are usually found in a condition called lupus. One patient out of 2334 RA patients treated with adalimumab developed new onset lupus. The patient improved following discontinuation of therapy.
Blocking TNFα may worsen moderate to severe congestive heart failure. Therefore, adalimumab (and other anti-TNFα therapies) is also not recommended for RA patients with moderate to severe heart failure.
What will happen before taking anti-TNFα drugs?
Before you take anti-TNFα drugs your rheumatologist will recommend whether you should receive one of these medications or whether other treatment would be best for you. Your arthritis activity will be measured on two occasions to check that you qualify for this treatment. You will then be screened to exclude an increased risk of side-effects, in particular for a past history of TB, multiple sclerosis, recurrent infection, leg ulcers and a past history of cancer. You will be asked to have a chest x-ray if a recent one is not available to exclude signs of previous TB (which may sometimes be unknown to anyone, including the patient), and to exclude signs of heart failure.
Blood tests to check blood count, liver function tests and in some cases to exclude hepatitis B and C may be taken.
Adalimumab is given using a pre-filled syringe or pen and is usually delivered to your home. You, or a helper, will be taught how to give the injection. Most people continue take other anti-RA medication with adalimumab.
Adalimumab needs to be kept in the refrigerator but can be taken out for 20 minutes before injecting to reduce the stinging that can sometimes occur with the injection.
If you feel unwell, or have a cold or cough with phlegm it is best to postpone your next dose and discuss what to do with your rheumatologist or nurse specialist. Although there is no hard evidence to support this practice, many rheumatologists use antibiotics for coughs with sputum or tonsillitis if patients are taking TNFα blocker drugs.
Frequently Asked Questions - Adalimumab (Humira)
02/10/03 | Abbott Immunology
These information notes have been prepared for the National Rheumatoid Arthritis Society following your direct request. They represent frequently asked questions about adalimumab, an investigational agent for the treatment of rheumatoid arthritis. Adalimumab received its UK licence in September 2003.
Further information is available on request from: Medical Information, Abbott Laboratories Ltd., Abbott House, Vanwall Road, Vanwall Business Park, Maidenhead, Berkshire. Tel: 01628 774920 / email@example.com.
Q What is rheumatoid arthritis (RA)?
A: Rheumatoid arthritis is a disease of the immune system in which your body's own defence system attacks the tissues of your joints. Other tissues apart from the joints, such as the lungs, the skin and the eyes, may also be affected.
Q What is tumour necrosis factor alpha (TNFa)?
A: TNF- is a protein in your immune system that is believed to be one of the main causes of inflammation in rheumatoid arthritis. Normally, it plays an important role in helping your body fight infections. People with rheumatoid arthritis have too much TNF- in their bodies. This extra TNF- inflames the normal body tissues, especially the joints.
Q What is HUMIRA?
A: HUMIRA is a medicine that is used in people with moderate to severe Rheumatoid Arthritis. People with rheumatoid rrthritis are usually given other medicines for their disease before they are given HUMIRA. HUMIRA is for people with Rheumatoid Arthritis who have not responded well enough to these other medicines.
Q How does HUMIRA work?
A: HUMIRA is a medicine called a TNF blocker, that is a type of protein that blocks the action of a substance your body makes called TNFa. TNFa is made by your body's immune system. People with rheumatoid arthritis have too much of it in their bodies. The extra TNFa in your body can attack normal healthy body tissues and cause inflammation especially in the tissues in your bones, cartilage, and joints. HUMIRA helps reduce the signs and symptoms of rheumatoid arthritis (such as pain and swollen joints) and may help prevent further damage to your bones and joints.
Q Is it currently available?
A HUMIRA received its European licence in September 2003
Q How do I take HUMIRA?
A: Patients give themselves an injection of HUMIRA under the skin once every other week, or more frequently (every week) if your doctor tells them to. The medicine is premixed and premeasured, and comes in a ready-to-use syringe.
Q What can I expect from HUMIRA?
A: Clinical trials on HUMIRA have indicated that many people using HUMIRA experience relief from the signs and symptoms of RA (such as pain, swollen joints and tiredness) as early as 1-2 weeks. Importantly, TNFα blockers may also help prevent damage to your bones and joints. This is important because, once bone and joint damage from rheumatoid arthritis happens, it is permanent. Joint damage also plays a big part in how you will feel in the future. As with all medicines, HUMIRA will work better for some people than for others.
Q What important information do I need to know about side-effects with HUMIRA?
A: Any medicine can have side-effects. Like all medicines that affect your immune system, adalimumab can cause side effects. Many patients experience a reaction where the injection was given. These reactions are usually mild and include redness, rash, swelling, itching or bruising. Usually the rash will go away within a few days. Any pain, redness or swelling around an injection site that doesn't go away within a few days should be brought to the attention of your doctor or nurse. Other side-effects include upper respiratory infections (sinus infections), headache and nausea. There are various more severe infections that may occur, such as tuberculosis (TB) and malignancies (e.g. lymphoma), however your doctor will discuss these with you.
Q Can I take HUMIRA if I am taking other medicines for my rheumatoid arthritis or other conditions?
A: Yes, you can take other medicines prescribed by your doctor while on adalimumab (e.g. steroids, non-steroidal anti-inflammatory drugs such as aspirin or prescription pain relievers, methotrexate or other disease-modifying anti-rheumatic drugs). It is important that you tell your doctor about any other medicines you are taking for other conditions (for example, high blood pressure medicine) before you start taking HUMIRA. You should also tell your doctor about any over-the-counter drugs, herbal medicines and vitamin and mineral supplements you are taking.
Q How do I store HUMIRA?
A: HUMIRA should be stored at 2 C-8 C (in a refrigerator) in the original container until it is used. It should be protected from light and should not be frozen. If you need to take it with you, such as when travelling, store it in a cool carrier with an ice pack and protect it from light.
Q: How do I get more information?
A: You should discuss any further questions you may have with your doctor or nurse.
References available on request
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