Abbott Laboratories announced that the European Medicines Evaluation Agency (EMEA) has granted a positive opinion on Humira (adalimumab), previously known as D2E7, for the treatment of adult rheumatoid arthritis (RA).
Humira will become the first human monoclonal antibody approved in Europe for RA, and the first tumor necrosis factor alpha (TNF-a) antagonist approved with an indication for use with methotrexate or as monotherapy. Humira is indicated for the treatment of moderate to severe active RA in adult patients when the response to disease modifying anti-rheumatic drugs (DMARDs), including methotrexate, has been inadequate. To ensure maximum efficacy, Humira is given in combination with methotrexate. Humira can be given as monotherapy in case of intolerance to methotrexate or when continued treatment with methotrexate is inappropriate.
Humira resembles antibodies normally found in the body. It works by blocking TNF-a, a protein that plays a central role in the inflammatory responses of autoimmune diseases such as RA.
"RA is a progressive disease that can be very debilitating for patients. Having Humira offers patients a new treatment option that has demonstrated strong clinical results in placebo-controlled trials and provides convenient dosing and administration," said Paul Emery, M.D., ARC Professor of Rheumatology, Leeds University and Leeds University Teaching Hospitals Trust, United Kingdom.
The European Commission is expected to issue an authorization for the marketing of Humira in European Union (E.U.) countries in approximately 90 days. Abbott filed for E.U. approval in April 2002. The positive opinion was granted through the EMEA's Committee for Proprietary Medicinal Products (CPMP).
Abbott will ship Humira to pharmacies in Germany and the United Kingdom within two weeks of receipt of the marketing authorization. Availability in other E.U. countries will occur in subsequent months as each country adopts pricing and reimbursement policies. In recent months, the drug has been made available in Europe through patient named basis programs or study protocols.
"The availability of Humira is extremely important for the many RA patients who may not be seeing adequate results from their current medications. We're pleased the proposed indication provides physicians with the opportunity to prescribe Humira with methotrexate or as monotherapy, depending upon the need of the individual patient," said Guillermo Herrera, senior vice president, international operations, Abbott Laboratories.
"Abbott is confident it can supply the growing global patient demand for Humira, and looks forward to bringing this important drug to market in Europe," Herrera said.
Humira received approval from the U.S. Food and Drug Administration on December 31, 2002, and since then in six additional countries.
More than five million people worldwide suffer from RA, a chronic autoimmune disease that causes pain, swelling and stiffness in the joints of hands, feet and wrists, and often leads to the destruction of joints. Unlike osteoarthritis, the most common form of arthritis, RA is an autoimmune disease where joints are inflamed, resulting in eventual destruction of the joint's interior and the surrounding bone. The long-term prognosis for patients with RA is poor, and as a result, many patients face increased disability and premature death.
The EMEA positive opinion for Humira was based on data obtained in four controlled clinical trials. In all, 23 trials have been conducted with Humira, involving more than 2,400 RA patients worldwide. The drug's effectiveness was evaluated by measuring patients' improvement in RA signs and symptoms response scores. Safety also was assessed in these trials, which included one of the largest prospective safety trials of a TNF antagonist. Some patients in trials have been taking Humira for more than five years.
In one of these trials, some patients on 40 mg every other week treatment experienced an improvement in RA signs and symptoms as early as one week (22 per cent, 14/63 patients). These studies used a leading measure, the American College of Rheumatology (ACR) scores, as evidence of patient response. After three years of treatment, 45 per cent of patients (24/53) achieved an ACR 50 score and 25 per cent (13/53) achieved an ACR 70 score.
The recommended dose of Humira is 40 mg every other week by subcutaneous injection (a shot beneath the skin). Abbott will offer Humira in specially designed pre-filled syringes so patients don't have to mix and measure the medicine, or leave their homes for treatment. The pre-filled syringe features handles and a plunger head designed for use by patients whose hands have been affected by their RA disease.
Common adverse events (>1/100 and <1/10) at least possibly causally related to Humira included headache, dizziness, respiratory tract and uninary tract infection, nausea, diarrhea, sore throat, herpes simplex, abdominal pain, rash, pruritis and anemia. Injection site pain was reported by >1/10 patients.
Patients must be monitored closely for infections, including tuberculosis (TB), before, during and after treatment with Humira. Treatment should not be initiated in patients with active infections until infections are controlled. Patients who develop new infections while using Humira should be monitored closely. Humira should not be used by patients with active TB or other severe infections such as sepsis and opportunistic infections. Humira should be discontinued if a patient develops a new serious infection until infections are controlled. Physicians should exercise caution when considering use of Humira in patients with a history of recurring infection or with underlying conditions that may predispose patients to infections.
TNF-antagonists, including Humira, have been associated in rare cases with exacerbation of clinical symptoms and/or radiographic evidence of demyelinating disease. Prescribers should exercise caution in considering the use of Humira in patients with pre-existing or recent-onset central nervous system demyelinating disorders.
Humira should be used with caution in patients with mild heart failure, and is contraindicated in patients with moderate or severe heart failure. Humira must be discontinued in patients who develop new or worsening symptoms of congestive heart failure.