AbbVie presents first study assessing the role of predefined doses of methotrexate when used in combination with HUMIRA® (adalimumab) for RA

AbbVie (NYSE:ABBV) today announced the results from the CONCERTO trial, the first randomized, controlled trial assessing different predefined doses of methotrexate (MTX) in combination with HUMIRA® (adalimumab) for the treatment of moderate to severe rheumatoid arthritis (RA). CONCERTO shows that at week 26 of treatment, a statistically significant increasing trend was observed in the proportion of patients achieving low disease activity with an increasing dose of MTX when used with open-label HUMIRA®. Results were presented at the European League Against Rheumatism (EULAR) 2013 Congress in Madrid, Spain.

The primary objective of CONCERTO was to determine a dose-response pattern of MTX in combination with HUMIRA® in MTX and biologic-naive patients with active moderate to severe RA for less than 1 year. Patients were randomized into four treatment arms, receiving 40 mg of open-label HUMIRA® every other week in combination with weekly oral MTX at 2.5 mg, 5 mg, 10 mg or 20 mg. For all four treatment groups, the primary endpoint was the achievement, at week 26, of low disease activity, defined by a Disease Activity Score 28 (DAS28) of <3.2. Percentages of patients achieving low disease activity were as follows:

• 43 percent (n=98) of patients in the 2.5 mg per week MTX group;
• 44 percent (n=100) of patients in the 5 mg per week MTX group;
• 57 percent (n=99) of patients in the 10mg per week MTX group; and
• 60 percent (n=98) of patients in the 20 mg per week MTX group (P<0.005 for the trend).

“In general, anti-tumor necrosis factor biologic medications, or anti-TNFs, need methotrexate to achieve better clinical and radiological outcomes versus these medications alone,” said Gerd R. Burmester, M.D., Professor of Medicine, Department of Rheumatology and Clinical Immunology, Charité-University Medicine Berlin, Berlin, Germany. “The CONCERTO trial describes the extent to which the methotrexate dose affects clinical responses when implementing the combination therapy of adalimumab and methotrexate.”

DAS28 measurement is a composite index that includes variables such as tender and swollen joint counts, a patient’s visual analog scale for disease activity and C-reactive protein (CRP) as a measure of inflammation. CONCERTO was double-blind for the MTX dose and open-label for the use of HUMIRA®.

“Combination therapy of an anti-TNF and methotrexate is a standard of care in rheumatoid arthritis,” said John R. Medich, Ph.D., divisional vice president, Immunology Clinical Development, Global Pharmaceutical Research and Development, AbbVie. “With CONCERTO, AbbVie is trying to better understand the methotrexate-dose related trends in combination with HUMIRA®, which is a critical piece of information for physicians and patients. This is part of our continued commitment to exploring ways HUMIRA® can help improve the care for this patient population.

The clinical response rates in this trial were similar to the results from a previous HUMIRA® study in patients with early moderate to severe RA (the PREMIER trial). Safety was assessed in terms of adverse events (AEs) for all patients who received at least one dose of study drug. AEs were consistent with the known profile of HUMIRA® and were generally consistent between arms, occurring most frequently in the HUMIRA® plus MTX 20 mg arm.

About CONCERTO

CONCERTO was a 26-week, parallel-arm trial in MTX and biologic-naive patients with active RA for less than 1 year (n=395). The trial was double-blind for the MTX dose and open-label for the use of HUMIRA®. Patients were randomized into four treatment arms, receiving 40 mg of open-label HUMIRA® every other week in combination with weekly oral MTX at 2.5 mg (n=98), 5 mg (n=100), 10 mg (n=99) or 20 mg (n=98). Patients in the 20 mg MTX arm began with 10 mg and escalated by 2.5 mg every other week to 20 mg. The primary endpoint was the achievement of low disease activity at week 26, as assessed by DAS28 [CRP] <3.2. Secondary endpoints included clinical response defined by ACR 20/50/70, DAS28 remission (DAS28 [CRP] <2.6), change in modified Total Sharp Scores (mTSS), and change in Health Assessment Questionnaire Disability Index (HAQ-DI).

About HUMIRA® (adalimumab)

Uses

From the United States (U.S.) Prescribing Information (PI): HUMIRA® (adalimumab) is a prescription medicine used alone, with MTX, or with certain other medicines to reduce the signs and symptoms of moderate to severe RA in adults. It may prevent further damage to bones and joints and may help with the ability to perform daily activities.

From the European Union (E.U.) Summary of Product Characteristics (SmPC): HUMIRA® in combination with MTX, is indicated for the treatment of moderate to severe, active RA in adult patients when the response to disease-modifying anti-rheumatic drugs, including MTX has been inadequate and for the treatment of severe, active and progressive RA in adults not previously treated with MTX. HUMIRA® can be given as monotherapy in case of intolerance to MTX or when continued treatment with MTX is inappropriate. HUMIRA® has been shown to reduce the rate of progression of joint damage, as measured by X-ray, and to improve physical function, when given in combination with MTX.

Important Safety Information

HUMIRA® is a TNF blocker medicine that affects the immune system and can lower the ability to fight infections. Serious infections have happened in people taking HUMIRA®. These serious infections include tuberculosis (TB) and infections caused by viruses, fungi, or bacteria that have spread throughout the body. Some people have died from these infections.

People should be tested for TB before HUMIRA® use and monitored for signs and symptoms of TB during therapy. People at risk of TB may be treated with medicine for TB. Treatment with HUMIRA® should not be started in a person with an active infection, unless approved by a doctor. HUMIRA® should be stopped if a person develops a serious infection. People should tell their doctor if they live in or have been to a region where certain fungal infections are common, have had TB, hepatitis B, are prone to infections, or have symptoms such as fever, fatigue, cough, or sores. People over 65 years of age may be more susceptible to infections while taking HUMIRA®.

For people taking TNF blockers, including HUMIRA®, the chance of getting lymphoma or other cancers may increase. Some people have developed a rare type of cancer called hepatosplenic T-cell lymphoma. This type of cancer often results in death. If using TNF blockers including HUMIRA®, the chance of getting two types of skin cancer (basal cell and squamous cell) may increase. These types are generally not life threatening if treated.

Other possible serious side effects with HUMIRA® include hepatitis B infection in carriers of the virus, allergic reactions, nervous system problems, blood problems, certain immune reactions, including a lupus-like syndrome, liver problems, and new or worsening heart failure or psoriasis. The use of HUMIRA® with anakinra or abatacept is not recommended. People using HUMIRA® should not receive live vaccines. Common side effects of HUMIRA® include injection site reactions (redness, rash, swelling, itching, or bruising), upper respiratory infections (including sinus infections), headaches, rash, and nausea.

HUMIRA® is given by injection under the skin.

In the E.U. SmPC, HUMIRA® is contraindicated in people who are allergic to adalimumab or any other ingredients of HUMIRA®, those who have a severe infection including active TB, or those who have moderate to severe heart failure.

The benefits and risks of HUMIRA® should be carefully considered before starting therapy.

This is not a complete list of the Important Safety Information for HUMIRA®. For additional Important Safety Information, please click here for the U.S. Full Prescribing Information and Medication Guide.

Globally, prescribing information varies; refer to the individual country product label for complete information.