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EUROPEAN MEDICINES AGENCY

SCIENCE MEDICINES HEALTH

EMA/383370/2015

EMEA/H/C/000958

EPAR summary for the public

Stelara

ustekinumab

This is a summary of the European public assessment report (EPAR) for Stelara. 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 Stelara.

What is Stelara?

Stelara is a medicine that contains the active substance ustekinumab. It is available as a solution for injection in vials or prefilled syringes. Each vial or syringe contains either 45 or 90 mg ustekinumab.

What is Stelara used for?

Stelara is used to treat patients with:

•    moderate to severe plaque psoriasis (a disease causing red, scaly patches on the skin). It is used in adults and children above the age of 12 years who have not responded to or cannot use other systemic (whole-body) treatments for psoriasis, such as ciclosporin, methotrexate or PUVA (psoralen ultraviolet A). PUVA is a type of treatment where the patient receives a medicine containing a compound called a 'psoralen' before being exposed to ultraviolet light.

•    active psoriatic arthritis (inflammation of the joints associated with psoriasis) in adults, when the condition has not responded well enough to other treatments called disease-modifying antirheumatic drugs (DMARDs). Stelara may be used alone or combined with methotrexate (a DMARD).

The medicine can only be obtained with a prescription.

How is Stelara used?

Stelara should only be given under the supervision of a doctor who has experience in diagnosing and treating plaque psoriasis or psoriatic arthritis.

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It is given as an injection under the skin. For adults the usual dose is 45 mg, the dose in children depends on the bodyweight. The first injection is followed by a further injection four weeks later, and then an injection every three months (12 weeks). The doctor should consider stopping treatment if there is no response after 7 months (28 weeks). Patients weighing over 100 kg should be given Stelara in 90-mg doses for psoriasis, and this should also be considered for psoriatic arthritis.

Patients or their caregivers may inject Stelara once they have been trained, if their doctor thinks that this is appropriate.

How does Stelara work?

The active substance in Stelara, ustekinumab, is a monoclonal antibody. A monoclonal antibody is an antibody (a type of protein) that has been designed to recognise and attach to a specific structure (called an antigen) in the body. Ustekinumab has been designed to attach to two cytokines (messenger molecules) in the immune system called interleukin 12 and interleukin 23. These cytokines are involved in the inflammation and other processes that cause psoriasis and psoriatic arthritis. By blocking their activity, ustekinumab reduces the activity of the immune system and the symptoms of the disease.

How has Stelara been studied?

In the treatment of moderate to severe plaque psoriasis, Stelara has been compared with placebo (a dummy treatment) in two main studies involving a total of 1,996 adults with the condition. Over half of the patients had failed one or more other treatments for psoriasis or could not receive them. Both studies looked at two doses of Stelara (45 and 90 mg). The main measure of effectiveness was the number of patients who 'responded' to treatment after 12 weeks, meaning that symptom scores improved by 75% or more. The company subsequently provided the longer-term results of the studies (after 5 years of treatment), and the results of a study comparing Stelara with etanercept (another medicine for psoriasis).

An additional study also looked at 110 children with moderate to severe plaque psoriasis aged between 12 and 18 years. The children either received placebo or Stelara and the main measure of effectiveness was the number of patients who responded to treatment after 12 weeks as shown by an improvement in symptom scores.

In the treatment of active psoriatic arthritis Stelara in doses of 45 or 90 mg was compared with placebo in two main studies involving a total of 927 adults with the condition who had failed to get an adequate response with previous treatments, including DMARDs. One study involved 615 patients whose previous treatment had not involved a DMARD that targets a molecule called tumour necrosis factor (so-called 'anti-TNF therapy', which is usually reserved for treatment of the most severe cases). The other study involved 312 patients, some of whom were previously treated with anti-TNF therapy.

In both studies the main measure of effectiveness was the number of patients who responded to treatment after 24 weeks as shown by an improvement in symptom scores.

What benefit has Stelara shown during the studies?

Stelara was more effective than placebo at improving the symptoms of plaque psoriasis. Looking at the results of the two main studies in adults taken together, around 69% of the patients receiving Stelara responded to treatment after 12 weeks, compared with around 3% of the patients receiving placebo. There was no difference in response rates between the two doses of Stelara in patients weighing below

Stelara

100 kg. Patients weighing over 100 kg had a better response to the 90 mg dose. The longer-term results showed that with continuous treatment, the response to Stelara is maintained over 5 years.

The comparative study has shown that Stelara is more effective than etanercept after 12 weeks of treatment.

The study in children showed that around 69% of children (25 out of 36) who received Stelara responded, compared with 5% of patients receiving placebo (2 out of 37).

Studies in adults with psoriatic arthritis also showed that Stelara was more effective than placebo. In the first study, around 42% of those given Stelara 45 mg and 50% of those given 90 mg responded, compared with around 23% of those given placebo. In the second study, around 44% of those given either dose of Stelara responded, compared with around 20% of those given placebo. There was some evidence that patients weighing more than 100 kg responded better to the 90 mg dose. Stelara was of benefit regardless of whether patients were also taking methotrexate,

What is the risk associated with Stelara?

The most common side effects with Stelara (seen in more than 5% of patients during clinical trials) are upper respiratory tract infection (colds), headache and nasopharyngitis (inflammation of the nose and throat). Most were considered to be mild and did not require treatment to be stopped. The most serious side effect that has been reported with Stelara is serious hypersensitivity (allergic reaction).

For the full list of all side effects reported with Stelara, see the package leaflet.

Stelara must not be used in patients who have an active infection that the doctor considers important. For the full list of restrictions please see the package leaflet.

Why has Stelara been approved?

The CHMP considered that studies had shown that Stelara was effective in the treatment of adults and children over 12 years of age with moderate to severe plaque psoriasis. However, patients in some studies showed unexpected increases in problems affecting the heart and blood vessels and psychiatric problems such as depression which might be related to Stelara. Therefore, the CHMP decided to restrict the use of the medicine in moderate to severe plaque psoriasis to patients aged 12 years and above in whom other treatments had failed or who could not receive them. For adults with psoriatic arthritis who have not responded well to DMARDs the CHMP noted the limited treatments available and considered that Stelara would be of benefit in these patients. The Committee decided that Stelara'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 Stelara?

A risk-management plan has been developed to ensure that Stelara is used as safely as possible.

Based on this plan, safety information has been included in the summary of product characteristics and the package leaflet for Stelara, including the appropriate precautions to be followed by healthcare professionals and patients.

The company that makes Stelara will also provide educational material for healthcare providers and patients. These will focus on the safety of Stelara, particularly the risks of developing tuberculosis, other infections and cancers. The patient material will also include details of how Stelara should be injected.

Stelara

Other information about Stelara

The European Commission granted a marketing authorisation valid throughout the European Union for Stelara on 16 January 2009.

The full EPAR for Stelara 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 Stelara, read the package leaflet (also part of the EPAR) or contact your doctor or pharmacist.

This summary was last updated in 06-2015.

Stelara

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