Published: Jun 13, 2013 | Updated: Jun 14, 2013
By Nancy Walsh, Staff Writer, MedPage Today
Reviewed by Robert Jasmer, MD; Associate Clinical Professor of Medicine, University of California, San Francisco and Dorothy Caputo, MA, BSN, RN, Nurse Planner
MADRID — A year of treatment with apremilast, which targets inflammatory mediators, led to significant long-term reduction in disease activity among patients with psoriatic arthritis, a researcher reported here.
At week 52 in a trial known as PALACE 1, 63% of patients receiving 20 mg of the new oral agent twice daily had experienced a 20% reduction in symptoms according to the criteria of the American College of Rheumatology, as had 54.6% of those receiving 30 mg of the drug, according to Arthur Kavanaugh, MD, of the University of California San Diego, and colleagues.
In addition, improvements of 50% were seen in 24.8% and 24.6% of the two dosage groups, respectively, while improvements of 70% were seen in 15.4% and 13.8%, Kavanaugh reported at the annual meeting of the European League Against Rheumatism.
Apremilast is a phosphodiesterase 4 inhibitor that breaks down cyclic AMP. “Cyclic AMP tends to be anti-inflammatory, and keeping it elevated seems to decrease some pro-inflammatory cytokines like tumor necrosis factor and interleukin 6 and to allow other anti-inflammatory cytokines like interleukin 10 to be increased,” he explained during a press briefing.
The phase III trial included 504 patients with active psoriatic arthritis despite treatment with conventional disease-modifying anti-rheumatic drugs or biologic agents.
One-quarter of the patients had already been exposed to biologic treatment.
At baseline, patients were randomized to one of the two doses of apremilast or placebo. At week 16, those who had not reached a 20% improvement in swollen and tender joints were re-randomized to one of the active treatments if they had been in the placebo group, or remained at the same dose if in the active treatment groups.
After 4 months, 31.3% of patients receiving 20 mg of apremilast twice daily experienced a 20% reduction in symptoms according to criteria of the American College of Rheumatology (ACR), compared with 19.4% of those given placebo (P=0.0140).
In addition, 40% of patients receiving 30 mg of the drug twice daily had ACR20 responses, compared with placebo at that time point (P<0.0001).
At 6 months, all patients were re-randomized to 20 mg or 30 mg of apremilast, and they have now been followed for 1 year, with results for their arthritic symptoms that are “very respectable,” Kavanaugh said.
“Another important outcome for patients with arthritis of the hands and feet is functional status, as measured on the Health Assessment Questionnaire, or HAQ, with scores from zero to 3,” he said.
“Zero means ‘I can do everything I want to do,’ and 3 means ‘I can’t take care of myself at all,’ and the baseline HAQ of 1.21 in this study reflects considerable functional impairment,” he said.
After 52 weeks, there was a .35 point improvement in HAQ, “which is a level at which patients can certainly say they feel better and can do their daily activities,” he noted.
The investigators also assessed effects of the treatment on the skin manifestations of disease using the Psoriasis Area and Severity Index (PASI).
In the 30 mg group, 37% had 75% improvements in PASI scores, as did 25% of those in the 20 mg group. Those improvements were sustained out through a year, Kavanaugh said.
With regard to safety, “the overall safety profile of apremilast appears to be pretty good,” he noted.
All phosphodiesterase inhibitors can cause gastrointestinal adverse effects, but generally these occur early and decrease in frequency over time.
In this study, events such as diarrhea and nausea occurring in the second 6 months ranged from 0.6% to 3% in the 20 mg group and from 0% to 1.8% in the 30 mg group.
There were no new safety signals after 6 months regarding cardiac events, malignancies, or opportunistic infections, and no significant laboratory abnormalities were seen throughout the study.
“One tangible result of this could be that, if this drug is approved, we won’t have to monitor lab tests to look for toxicity issues,” Kavanaugh said.
“These results are encouraging for us as clinicians as well as for our patients. We have had more therapies in the past 10 years than we ever had, but success breeds success and we’re happy to see even more new treatments,” he said.
Apremilast is also being evaluated for use in psoriasis, ankylosing spondylitis, and rheumatoid arthritis.