Third TNF-blocker targets psoriatic arthritis.
Adalimumab, a fully human, anti-TNF monoclonal antibody, significantly improved joint and skin manifestations, inhibited structural changes on radiographs, lessened disability due to joint damage, and improved quality of life in patients with moderately to severely active psoriatic arthritis, according to the findings of a multicenter study.
Adalimumab and infliximab have been approved by the Food and Drug Administration for the treatment of psoriatic arthritis (PsA), but not for the dermatologic treatment of psoriasis in the absence of joint involvement. A third TNF inhibitor, etanercept, is approved for both PsA and the severe psoriasis plaque.
In the study that served as the basis for the FDA approval of adalimumab for PsA, patients were stratified according to methotrexate use (yes or no) and degree of psoriatic involvement, and then randomized in a 1:1 ratio by site to receive either drug or placebo. Of the 315 patients randomized to receive treatment, 162 were assigned to the placebo group and 153 were assigned to self-injected adalimumab 40 mg every other week. All patients who completed the 24-week protocol were eligible for long-term treatment in an open-label extension study.
The trial, which was conducted at 50 sites in the United States, Canada, and Europe, showed that patients treated with adalimumab achieved significantly higher American College of Rheumatology (ACR) response rates than those treated with placebo at all time points.
"At week 12, the ACR 20 response rate was 58% for the adalimumab treatment group and 14% for the placebo-treated group," study leader Philip J. Mease, M.D., of the Swedish Medical Center in Seattle, and his colleagues reported (Arthritis Rheum. 2005;52:3279-89).
"At week 24, the ACR20 response rates were 57% and 15%, respectively. At 12 and 24 weeks, the ACR50 response rates were significantly higher in the adalimumab arm than in the placebo arm, and a significant difference in ACR 70 responses was also evident," they said, adding that ACR responses developed rapidly, "with statistically significant between-group differences in the ACR20 and ACR50 responses observed at week 2"; 27% vs. 6% achieving ACR20 and 11% vs. 0% achieving ACR50. At week 4, 7% vs. 1% achieved ACR70.
Across the board, response rates did not differ between patients taking adalimumab in combination with methotrexate and those taking the TNF inhibitor alone.
The mean change in the modified total Sharp score in patients who had both baseline and week 24 radiographs was -0.2 for those on adalimumab, significantly lower than the score of 1.0 with placebo injections, "implying that protection against progressive structural damage was achieved," Dr. Mease said.
At week 24, PASI [psoriasis area and severity index] showed a 75% improvement in 16% of patients treated with adalimumab, compared with 3% of those who received placebo, a significant difference.
Similarly, the physician's global assessment of psoriasis resulted in ratings of the lesions as "clear" or "almost clear" in 67% of the 70 adalimumab-treated patients evaluated, compared with 10% of the 70 placebo-treated patients evaluated for psoriasis, also a significant difference.
"It appears that the response was a little faster in the skin with adalimumab, as has also been seen with infliximab, than with other biologics. When it comes to joint symptoms and important aspects such as quality of life, physical function, and inhibition of progressive joint damage, the three anti-TNF drugs are similar; but if you have a patient with really severe skin disease, there may be a slight advantage to using either infliximab or adalimumab," Dr. Mease said.
The ink had hardly dried on this study when, in October, the FDA approved adalimumab for the treatment of PsA. "With etanercept, the PsA indication came ahead of the psoriasis indication, and the same is going to be true of adalimumab; that indication will likely follow once the pure psoriasis trials are fully considered by the FDA," Dr. Mease said.
The cost of etanercept and adalimumab, when used for RA or PsA in the standard dose of 50 mg per week and 40 mg every other week, respectively, is similar, he said.
Adalimumab was generally well tolerated during the 24-week trial. Common side effects "were similar to those seen in clinical trials involving patients with RA or were thought to be related to underlying disease," according to the authors. Serious adverse events were experienced by 12 patients, including 7 in the placebo group and 5 in the adalimumab group. In the latter, events included nasal septum disorder, toe arthrodesis, aggravation of convulsions, viral meningitis (attributed to West Nile virus), and renal calculus; most of these were considered unrelated to the study medication.
The authors stress that longer-term follow-up from the open-label extension study is needed to confirm the results. The study was supported by Abbott Laboratories.
Dr. Mease has received consulting fees or honoraria of less than $10,000/year from Abbott.
BY BRUCE K. DIXON
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|Title Annotation:||Rheumatology; tumor necrosis factor inhibitor|
|Author:||Dixon, Bruce K.|
|Publication:||Internal Medicine News|
|Date:||Dec 15, 2005|
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