BOSTON -- The phosphodiesterase 4 (PDE4) inhibitor apremilast (Otezla) provided clinically meaningful and sustained improvements in psoriatic arthritis in a phase III study presented here.
Among patients receiving 20 mg of apremilast twice daily for 2 years, 20% improvements on the criteria of the American College of Rheumatology (ACR20) were seen in 64.8%, and among those given 30 mg twice daily, 57.3% had ACR20 responses, according to , of the Rheumatology and Immunotherapy Center in Franklin, Wisc.
Action Points
- Note that these studies were published abstracts and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.
And the more stringent ACR50 and ACR70 responses were seen in 40% and 27.9% of patients on the lower dose and in 37.3% and 18.9% of those on the higher dose, Wells reported in a late-breaking poster session at the
"The drug was given as monotherapy, and the results at 2 years were not much different than what you see with methotrexate plus a biologic," he told 乌鸦传媒.
PDE4 has intracellular effects that help modulate the immune responses that lead to the skin and joint manifestations of psoriatic arthritis.
In a study known as PALACE 4, 527 patients who had not previously received disease-modifying anti-rheumatic drugs or biologics were treated for up to 2 years.
All patients had disease duration of at least 3 months and three or more swollen and tender joints.
Concomitant treatment with low dose steroids and nonsteroidal anti-inflammatory drugs was permitted.
Participants' mean age was 50, and most were men. Duration of psoriatic arthritis was slightly over 3 years.
Mean baseline disease activity scores were about 4.5, and mean psoriasis area and severity index (PASI) scores were about 7.
The first year of the trial was a double-blind, placebo-controlled phase, although patients on placebo who had not achieved an ACR20 response at week 24 were re-randomized to one of the active treatment groups.
At the end of that phase, ACR20 responses were observed in 53.4% of the 20 mg group and in 58.7% of the 30 mg group, while ACR50s were seen in 27.1% and 31.9% and ACR70s in 13.7% and 18.1%.
Benefits also were seen on a variety of other endpoints. By the end of year two, the Health Assessment Questionnaire Disability Index had decreased by 0.37 points in the 20 mg group and by 0.40 points in the 30 mg group.
A total of 46.9% of patients in the 20 mg group had 75% improvements on their PASI scores, as did 38.9% of those in the 30 mg group. Dactylitis also had completely resolved in 82.5% and 84%, respectively.
During the first year of the study, serious adverse events were reported in 7.1% and 3.6% of the lower dose and higher dose groups, respectively. During the second year, the rates were 5.6% and 5%.
The most common adverse events were diarrhea and nausea. During the first year, 9.5% of patients in the 20 mg group had diarrhea, as did 11.1% of those in the 30 mg group. By the end of the second year, however, the numbers had fallen to 3.4% and 2%.
No cases of tuberculosis were reported, and no new safety signals emerged during the second year of the trial, which is expected to continue for another 3 years.
Disclosures
The study was sponsored by Celgene, and the authors disclosed financial relationships with the company.