GLASGOW -- Treatment with the oral phosphodiesterase 4 inhibitor apremilast (Otezla) led to improvements in enthesitis and dactylitis among patients with psoriatic arthritis, a pooled analysis of three trials showed.
Among patients in the PALACE 1, 2, and 3 studies, a Maastricht Ankylosing Spondylitis Enthesitis Score (MASES) of zero was achieved at weeks 52 and 104 by 37.7% and 48.7% of patients receiving 30 mg of apremilast twice per day, according to Christopher J. Edwards, MD, of the University of Southampton in England.
In addition, a dactylitis score of zero was seen in 67.5% and 77.5% of patients at weeks 52 and 104, he reported at the British Society for Rheumatology annual meeting.
"Enthesitis and dactylitis are hallmark features of psoriatic arthritis. Traditionally, nonsteroidals and classical disease modifying anti-rheumatic drugs have been used, but were not always effective for these symptoms," he said.
In the three PALACE studies, 1,500 patients were randomized to receive 20 mg or 30 mg apremilast twice per day or placebo for the first 16 weeks, and a 4-year open-label extension phase is ongoing.
Patients' average age was around 50, about half were women, and body mass index averaged 30 kg/m2.
They were allowed to have previous disease-modifying anti-rheumatic drug (DMARD) therapy, and about 75% had used these drugs. Around 25% had previously been given a biologic therapy.
They had very active disease, Edwards noted, with a mean Disease Activity Score in 28 joints of 4.7, at least three tender and swollen joints, and an average duration of psoriasis of 17 years. Half had psoriasis body surface area involvement of greater than 3%.
More than half of patients continued on methotrexate, with mean dosages of 15 mg/week. They could also continue on other DMARDs and low-dose corticosteroids.
This pooled analysis included the 915 patients with enthesitis and the 610 with dactylitis at baseline, and focused on the 30 mg twice daily licensed dose.
Baseline scores on MASES were 4.4 to 4.8 (range 0-13) and the mean dactylitis counts were 3.2 to 3.4.
At week 24, the mean changes in MASES were -1.3 for the 30-mg apremilast group compared with -0.9 for placebo (P=0.0194), for a mean percent change of -23.6% versus -7% (P<0.05).
At that time point, a MASES of zero was seen in 27.5% and 22.5% of the 30-mg and placebo groups, respectively.
Mean change in dactylitis count at week 24 was -1.8 in the 30-mg group compared with -1.3 in the placebo group (P=0.0097), for mean percent changes of -48.6% and -38.2%. A dactylitis score of zero was seen in 46.2% and 39%, respectively.
Improvements continued with long-term treatment, Edwards noted. By 52 weeks, the mean change in MASES in the 30-mg group was -2, for a mean percent change of -43.5%. By 104 weeks, the mean change was -2.6, for a mean percent change of -57.5%.
Mean change in dactylitis count at 52 weeks was -2.5, for a percent change of -67.9%, and change at 104 weeks was -2.9, for a mean percent change of -80%.
"The safety data have been pretty good so far for apremilast, with more widespread use in the U.S. than in the U.K.," Edwards said. Some patients have gastrointestinal disturbances, particularly in the first couple of weeks, and 1-2% of patients in the study program have discontinued early because of this and some weight loss, which appears to be unrelated to the diarrhea and may relate to a central mechanism. That remains unclear, he noted.
"Laboratory abnormalities were infrequent, and there have been no particularly scary signs with regard to cardiac problems, malignancies, or opportunistic infections," he said.
The overall attrition rate has been gradual as would be expected, at around 20% in the long-term extension phase.
Edwards disclosed relevant relationships with Celgene, Pfizer, Roche, and Samsung.
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