European Commission approved Humira ( Adalimumab ) as a treatment for psoriatic arthritis and as first-line treatment of severe rheumatoid arthritis ( RA ) in Europe.

The approval for psoriatic arthritis marks the second indication for Humira, while the early rheumatoid arthritis approval establishes Humira as a first-line treatment for severe, active and progressive RA in adults not previously treated with Methotrexate.

Humira was previously approved for the treatment of moderate to severe, active rheumatoid arthritis in adult patients when the response to disease-modifying antirheumatic drugs including Methotrexate has been inadequate.

Humira in psoriatic arthritis

Psoriatic arthritis combines the symptoms of arthritis, including joint inflammation, which leads to pain and possible damage, with the symptoms of psoriasis, such as dry, scaly skin. Psoriasis affects nearly 3 percent of the world's population and it is estimated that as many as 10-30 percent of psoriasis sufferers may develop psoriatic arthritis.

Abbott previously released clinical trial data from the Adalimumab Effectiveness in Psoriatic Arthritis Trial ( ADEPT ) showing Adalimumab's ability to treat both the joint and skin symptoms associated with psoriatic arthritis.

Patients' arthritic symptoms exhibited a response to Adalimumab, with nearly 60 percent of patients achieving ACR 20 at week 12, one of the study's primary endpoints, and with a sustained response through week 24.

The study's second primary endpoint examined the change in modified Total Sharp Score ( mTSS ), a measurement used to assess changes in bone erosion and joint-space narrowing in X-rays, at week 24.
Patients treated with Adalimumab had significantly less change in mTSS than patients treated with placebo at week 24.
Approximately three times as many patients receiving placebo had worsening in their scores ( increase in mTSS >0.5 units ) than patients treated with Adalimumab ( 28.9 percent vs. 9 percent, respectively ) at week 24.

Data from the open-label extension showed that the inhibition of disease progression in patients taking Adalimumab at week 24 was maintained through week 48 .

In addition, in this clinical study, among the 69 patients in the trial who had greater than 3 percent body surface involvement who were treated with Adalimumab, 42 percent achieved a PASI 90 response at 24 weeks, which reflects at least 90 percent improvement in psoriasis symptoms assessed by the Psoriasis Area and Severity Index ( PASI ).

Humira as a first-line treatment for severe early rheumatoid arthritis

The PREMIER clinical trial, on which the approval was based, also demonstrated that the combination therapy of Adalimumab and Methotrexate successfully inhibited radiographic progression ( joint damage ) in patients with recently diagnosed, severe rheumatoid arthritis ( less than three years disease duration ).

One of the study's co-primary endpoints was ACR 50.
At 52 weeks, approximately 62 percent of the patients on combination therapy achieved ACR 50, compared to 46 percent in the group receiving only methotrexate. PREMIER is the first RA study to achieve ACR 50 as a primary endpoint.

PREMIER's second primary endpoint, inhibition of radiographic progression, was measured by the change in mTSS. The Adalimumab-Methotrexate combination achieved significantly more favorable results than Methotrexate alone in inhibiting radiographic disease progression.
After one year, the mean change from baseline in mTSS score for the combination arm was 1.3 as compared to 5.7 in the methotrexate alone arm.
After two years, the mean change from baseline in mTSS score for patients in the combination arm was 1.9, while patients in the Methotrexate-only group experienced five times the radiographic progression, with mean clinically significant change from baseline in mTSS scores of 10.4.

In addition, approximately two times more patients in the combination therapy group were without radiographic disease progression versus Methotrexate alone ( 61 percent vs. 34 percent ) at the end of year two. No radiographic progression was defined as <0.5 units change from baseline in mTSS.

PREMIER data also showed that nearly one in two ( 49 percent ) of the early RA patients receiving combination therapy achieved clinical remission at two years, as defined by DAS28 < 2.6, compared to 25 percent of patients taking Methotrexate alone.

Additionally, one-year data showed approximately 43 percent of patients receiving combination therapy in PREMIER achieved a measure of clinical remission at 52 weeks as defined by DAS28 < 2.6, compared to 21 percent on Methotrexate alone.

The recommended dose of HUMIRA for psoriatic arthritis and the usual dose in rheumatoid arthritis is 40 mg every-other-week by subcutaneous injection.

Source: Abbott, 2005


XagenaMedicine2005