Patients with rheumatoid arthritis, whose joint damage is inhibited through a combination therapy of Adalimumab ( Humira ) and Methotrexate early in the course of their disease are less likely to experience further damage two years later.

The PREMIER study found that patients with early rheumatoid arthritis ( less than three years of disease duration ) who were treated for six months with a combination of Adalimumab and Methotrexate experienced significantly less radiographic progression ( joint damage ) compared to patients who took Methotrexate alone.

In addition, PREMIER results also indicate that approximately one in two patients achieved clinical remission ( defined as DAS28 < 2.6 ).
The Disease Activity Score ( DAS ) measures disease activity responses in rheumatoid arthritis by assessing tender and swollen joint count, general health status and an inflammatory marker.

One of the PREMIER study's co-primary endpoints was inhibition of radiographic progression, as measured by the change in Total Sharp Score ( TSS ).
TSS assesses bone erosion and joint-space narrowing on X-rays.

Seventy-six percent of patients treated with combination therapy showed no signs of disease progression at six months and 74 percent of these patients continued to show no progression after two years.
In comparison, only 51 percent of patients taking only Methotrexate showed no signs of disease progression at six months and of those patients 61 percent continued to show no signs of progression at two years.

" The PREMIER data are encouraging because they suggest that early and aggressive treatment may slow or inhibit patients' joint damage," said Ferdinand Breedveld, at the University of Leiden, ( Netherlands ) and study investigator. " It's estimated that 70 percent of people with rheumatoid arthritis experience joint destruction within the first two years. These findings point to the critical need to inhibit disease progression within the first six months of treatment."

The second of the study's co-primary endpoints was ACR 50. This measure, which is used by the American College of Rheumatology, indicates 50 percent or greater improvement in tender and swollen joint count and other relevant clinical measures.

At two years, 59 percent of the patients on combination therapy achieved ACR 50.
PREMIER is the first rheumatoid arthritis study to meet ACR 50 as a primary endpoint.

PREMIER, a two-year, double-blind, controlled study, compared the effectiveness of Adalimumab, Methotrexate and the combination of the two drugs in treating early rheumatoid arthritis.
A total of 799 patients were separated into three groups.
Each group received either the combination therapy of 40 mg Adalimumab every other week with Methotrexate, Adalimumab alone or Methotrexate alone.

More than 5 million people worldwide suffer from rheumatoid arthritis, a chronic autoimmune disease that causes pain, swelling and stiffness in the joints of the hands, feet and wrists, and often leads to the destruction of joints. Unlike osteoarthritis, the most common form of arthritis, rheumatoid arthritis is an autoimmune disease where joints are inflamed, resulting in eventual destruction of the joints' interior and the surrounding bone.

Common adverse events ( >1/100 and less than or equal to 1/10 ) at least possibly causally related to Adalimumab include headache, dizziness, respiratory tract and urinary 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, before, during and after treatment with Adalimumab. Treatment should not be initiated in patients with active infections until infections are controlled. Patients who develop new infections while using Adalimumab should be monitored closely. Adalimumab should not be used by patients with active tuberculosis or other severe infections such as sepsis and opportunistic infections. Adalimumab should be discontinued if a patient develops a new serious infection until infections are controlled.
Physicians should exercise caution when considering use of Adalimumab in patients with a history of recurring infection or with underlying conditions that may predispose patients to infections.

Tumor necrosis factor ( 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.

Physicians should exercise caution when using Humira in patients who have heart failure and monitor them carefully. In clinical studies with another TNF antagonist, a higher rate of serious congestive heart failure ( CHF ) related adverse events, including worsening CHF and new onset CHF, have been reported. Cases of worsening CHF have also been reported in patients receiving Humira.

Humira is the only fully human monoclonal antibody approved by the EMEA and FDA for reducing the signs and symptoms, inhibiting the progression of structural damage, and improving physical function in adults with moderately to severely active rheumatoid arthritis who have had insufficient response to one or more DMARDs.

Source: EULAR 2005, Annual Congress of the European League Against Rheumatism


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