VIENNA, Austria-New results presented at the Annual European Congress of Rheumatology of the European League Against Rheumatism (EULAR) in Vienna suggest that alefacept, a memory T-cell suppressor currently approved for psoriasis, is also effective for the treatment for psoriatic arthritis (PsA). The drug gives rheumatologists and dermatologists another treatment option that complements the use of tumor necrosis factor α (TNF-α) inhibitors.
"Clearly, if a patient is not responding to an anti-TNF therapy, then it is appropriate to try one of these drugs," says study author Philip J. Mease, MD, of the department of internal medicine at the Swedish Medical Center and Rheumatology Associates in Seattle, Washington, who spoke with CIAOMed on the role of T-cell directed therapies in the treatment of PsA. "It gives us a larger array of choices to work with."
Of the 185 patients enrolled in the study, 123 were randomized to receive alefacept, and 62 to placebo, and randomization was stratified based on psoriasis severity. All patients had active PsA (>e;3 swollen joints and >e;3 tender joints) despite treatment with methotrexate (MTX) for >e;3 months. Alefacept 15 mg was administered intramuscularly once weekly for 12 weeks, followed by a 12-week observation period, and all patients continued to receive their stable dose of MTX throughout the 24-week study period. Patients were also allowed stable doses of corticosteroids and nonsteroidal anti-inflammatory drugs (NSAIDs).
At week 24, 54% of alefacept-treated patients achieved ACR20, compared with 23% of patients who received placebo, and ACR50 and ACR70 responses were achieved by 17% and 7% of alefacept-treated patients, respectively.1 Significant improvements in psoriasis were also noted, with 53% of alefacept-treated patients achieving a PASI50 (psoriasis area severity index) response compared with 17% of those receiving placebo.
The study "shows you that this drug, even with 3 months' administration, has a sustained response as there is continued improvement over the subsequent 3 months in the absence of drug," Dafna Gladman, MD, FRCPC, one of the authors of the study and senior scientist in the division of Outcomes and Population Health at the Toronto Western Research Institute in Ontario, Canada, tells CIAOMed. "The mechanism is not clear," she adds, "except that maybe you are getting rid of memory cells to the point at which it allows you to maintain the response for that long."
"I emphasize that these are patients who were only treated for the initial 12 weeks," Dr. Gladman says, indicating that extended treatment regimens may generate better results. "Dermatologists tend not to do continuous treatment," she points out, adding that "they tend to treat, clear, and then they stop."
"That's what they did in the psoriasis studies, so that's what we did in the psoriatic arthritis studies," Dr. Gladman says. However, the results suggest that "the idea of stopping therapy at 12 weeks does not make sense whatsoever."
Since 85% of PsA patients display psoriasis before arthritic symptoms, Dr. Mease points out that it's important to know that alefacept can also effectively treat joint involvement. "Now with the new data, we know that if a patient is being treated for psoriasis, that this drug will also effectively treat his psoriatic arthritis," he adds.
Although there were no significant safety concerns associated with alefacept in this study, potential long-term issues may be raised by depletion of CD4 T cells. "You have to make sure you have a minimum CD4 count before you give this drug, because otherwise you will get into trouble," indicates Dr. Gladman. Mean CD4+ T-cell counts remained above 500 cells/mm3 throughout the study,2 however, and only several patients had to stop alefacept because of T-cell lymphopenia. "All of these patients were able to continue after their cell counts went back up," she says, adding that "the goal of the therapy is to deplete CD4 cells, but not to wipe them out."
Dr. Mease discussed with CIAOMed some of the reasons underlying the extraordinary recent progress in treatment of psoriasis and PsA. "There's been an explosion of interest since we've seen such highly effective results with the biologic agents. It has led to the recruitment of a significant number of clinician investigators that are interested in a better understanding of the disease state, a better understanding of the basic pathophysiology behind psoriasis and psoriatic arthritis, and improved methods of measuring change in clinical trials. There is also interest in determining which are the most appropriate patients for use of these agents and, especially in this regard, possibly treating the disease earlier in order to prevent damage from occurring."
References:
- Mease P, Gladman D, Keystone E. Efficacy of alefacept in combination with methotrexate in the treatment of psoriatic arthritis. Presented at: Annual European Congress of Rheumatology of EULAR; June 8-11, 2005; Vienna, Austria. Abstract FRI0224.
- Gladman D, Mease P, Keystone E. Safety of alefacept in combination with methotrexate in the treatment of psoriatic arthritis. Presented at: Annual European .