o

EUROPEAN MEDICINES AGENCY

SCIENCE MEDICINES HEALTH

EMA/CHMP/420642/2016

EMEA/H/C/000481

EPAR summary for the public

Humira

adalimumab

This is a summary of the European public assessment report (EPAR) for Humira. It explains how the Committee for Medicinal Products for Human Use (CHMP) assessed the medicine to reach its opinion in favour of granting a marketing authorisation and its recommendations on the conditions of use for Humira.

What is Humira?

Humira is a medicine that contains the active substance adalimumab. It is available as a solution for injection in a pre-filled syringe or pre-filled pen, and a vial for use in children only, all containing 40 mg adalimumab.

What is Humira used for?

Humira is used to treat adults with moderate to severe plaque psoriasis (a disease causing red, scaly patches on the skin) who need systemic therapy (a treatment given by mouth or injection). It is also used to treat children from 4 years of age with severe plaque psoriasis for whom creams or ointments and light therapies have not worked well or are not suitable.

Humira is also used to treat the following patients who have not responded adequately to other treatments or cannot use them:

•    adults with moderate to severe active rheumatoid arthritis (a disease causing inflammation of the joints), and severe active and progressive rheumatoid arthritis;

•    adults with active and progressive psoriatic arthritis (a disease causing red, scaly patches on the skin and inflammation of the joints);

•    adults with axial spondyloarthritis (a disease causing inflammation and pain in the joints of the spine), including patients with:

- severe active ankylosing spondylitis;

30 Churchill Place • Canary Wharf • London E14 5EU • United Kingdom Telephone +44 (0)20 3660 6000 Facsimile +44 (0)20 3660 5555 Send a question via our website www.ema.europa.eu/contact

© European Medicines Agency, 2016. Reproduction is authorised provided the source is acknowledged.

- severe axial spondyloarthritis without evidence in the X-ray of ankylosing spondylitis but with objective signs of inflammation;

•    adults and children from 6 years of age with moderately to severely active Crohn's disease (a disease causing inflammation of the gut);

•    adults with moderately to severely active ulcerative colitis (a disease causing inflammation and ulcers in the lining of the gut);

•    patients with active polyarticular juvenile idiopathic arthritis from 2 years of age and active enthesitis-related arthritis from 6 years of age (both are rare diseases causing inflammation in the joints);

•    adults with active moderate to severe hidradenitis suppurativa (acne inversa), a chronic skin disease that causes nodules (lumps), abscesses (collections of pus) and scarring on the skin that can lead to hollow passages known as fistulas;

•    adults with non-infectious uveitis with inflammation of the back of the eye.

The medicine can only be obtained with a prescription.

How is Humira used?

Treatment with Humira must be started and supervised by a doctor who has experience in the treatment of the diseases that Humira is used to treat. Doctors treating uveitis should also take advice from doctors who have experience of using Humira.

Humira is given as an injection under the skin. The dose and frequency of injection depends on the condition to be treated and, when used for a child, the dose is calculated according to the child's weight and height. After the starting dose, Humira is usually given every two weeks, but it may be given every week in certain situations or for hidradenitis suppurativa. After training, patients or their carers may inject Humira if their doctor considers it appropriate. Patients who receive Humira must be given a special alert card that summarises the safety information about the medicine. Patients may be given other medicines during treatment with Humira, such as corticosteroids (other anti-inflammatory medicines).

For information on the doses to be used for each condition and other information on the use of Humira, see the package leaflet.

How does Humira work?

The active substance in Humira, adalimumab, is a monoclonal antibody (a type of protein) that has been designed to recognise and attach to a chemical messenger in the body called tumour necrosis factor (TNF). This messenger is involved in causing inflammation and is found at high levels in patients with the diseases that Humira is used to treat. By attaching to TNF, adalimumab blocks its activity, thereby reducing inflammation and other symptoms of the diseases.

How has Humira been studied?

More than twenty main studies involving over 9,000 patients have looked at the effects of Humira in reducing symptoms of inflammatory conditions. The studies included adult patients for the most part, with children included in studies for Crohn's disease, plaque psoriasis, polyarticular juvenile idiopathic arthritis and enthesitis-related arthritis.

Humira

What benefit has Humira shown during the studies?

Humira, when used as directed, has been shown in clinical trials to be effective at reducing important symptoms of each of the conditions for which it has been recommended.

In rheumatoid arthritis, the greatest reductions in symptoms were seen in the studies examining Humira as an add-on to methotrexate: around two-thirds of the patients adding Humira had at least a 20% reduction in symptoms after six months, compared with a quarter of those adding placebo. Patients adding Humira also had less joint damage and experienced less reduction in physical function after a year. In patients who had not taken methotrexate in the past, the combination of Humira and methotrexate was also more effective than methotrexate alone.

Humira also produced a greater improvement in symptoms than placebo (a dummy treatment) in studies of psoriatic arthritis, ankylosing spondylitis, axial spondyloarthritis without evidence in the X-ray of ankylosing spondylitis but with objective signs of inflammation, and induction and maintenance phases of treatment for Crohn's disease, psoriasis and ulcerative colitis. In studies in adults and children with plaque psoriasis, a higher proportion of patients receiving Humira had improvements in symptoms compared with patients receiving methotrexate.

In polyarticular juvenile idiopathic arthritis, around 40% of patients aged between 4 and 17 years receiving Humira, either alone or in combination with methotrexate, had a flare-up of arthritis, compared with around 69% of those receiving placebo. However, fewer patients receiving Humira with methotrexate developed antibodies against Humira (which can prevent its action), so the results favoured the use of Humira with methotrexate over Humira used alone. The study in younger children (aged 2 to 4 years) showed that the majority of children responded well to Humira treatment and this response was maintained after 24 weeks. For enthesitis-related arthritis, treatment with Humira resulted in a larger decrease in the number of swollen and tender joints compared with placebo.

In hidradenitis suppurativa, 59% of patients receiving Humira in one main study and 42% of patients in another achieved at least a 50% reduction in abscesses and nodules after 12 weeks, without any increase in abscess count or fistulas. The proportions of patients taking placebo who achieved this goal were 28% and 26% respectively.

In uveitis, Humira was found effective in 2 studies. The first study involved patients whose disease was not controlled with high doses of corticosteroids. In this study treatment failed in about 79% of patients receiving placebo compared with about 55% given Humira. Another study involved patients whose uveitis was under control with a corticosteroid but whose disease flared-up when the corticosteroid dose was reduced or stopped. In this second study, treatment failed in about 55% of patients receiving placebo compared with 39% receiving Humira.

More information may be found in the products summary of product characteristics (SmPC), also part of the EPAR.

What is the risk associated with Humira?

The most common side effects with Humira (seen in more than 1 patient in 10) were respiratory tract infections (infections of the lungs and airways), leucopenia (low white blood cell counts), anaemia (low red blood cell counts), increased blood levels of lipids (fats), headache, abdominal pain (stomach ache), nausea (feeling sick) and vomiting, rash, musculoskeletal pain (pain in the muscles and bones), injection-site reactions (including redness) and increased levels of liver enzymes. For the full list of all side effects reported with Humira, see the package leaflet.

Humira

Humira must not be used in patients with active tuberculosis, other severe infections, or moderate to severe heart failure (an inability of the heart to pump enough blood around the body). For the full list of restrictions with Humira, see the package leaflet.

Why has Humira been approved?

The CHMP decided that Humira's benefits are greater than its risks and recommended that it be given marketing authorisation.

What measures are being taken to ensure the safe and effective use of Humira?

The company that markets Humira must provide educational packs for doctors who will prescribe Humira. These packs will include information on the safety of the medicine and an alert card to be given to patients.

Recommendations and precautions to be followed by healthcare professionals and patients for the safe and effective use of Humira have also been included in the summary of product characteristics and the package leaflet.

Other information about Humira

The European Commission granted a marketing authorisation valid throughout the European Union for Humira on 8 September 2003.

The full EPAR for Humira can be found on the Agency's website: ema.europa.eu/Find medicine/Human medicines/European Public Assessment Reports. For more information about treatment with Humira, read the package leaflet (also part of the EPAR) or contact your doctor or pharmacist.

This summary was last updated in 06-2016.

Humira

EMA/CHMP/420642/2016

Page 4/4