CHICAGO -- Apremilast, an investigative oral agent, appears to provide similar benefit in psoriatic arthritis, even if the patient is already taking methotrexate, and in ankylosing spondylitis, according to two studies reported here.
"Because a large proportion of psoriatic arthritis patients are treated with methotrexate, the comparable efficacy and tolerability of apremilast as immunotherapy or in combination with methotrexate is of interest," said Georg A. Schett, MD, from the Friedrich-Alexander University Erlangen-Nuremberg, Germany, at the annual meeting of the American College of Rheumatology (ACR).
In a placebo-controlled substudy looking specifically at how apremilast treatment was affected by methotrexate over 12 weeks, Schett and colleagues found that:
- 10.3% of 29 placebo patients on methotrexate achieved an ACR20 improvement in their disease state compared with 12.8% of the 39 placebo patients not taking methotrexate
- 46.7% of the 30 patients taking apremilast (20 mg twice daily) and methotrexate achieved an ACR20 compared with 41% of the 39 patients who took only apremilast ( 20 mg twice daily)
- 36.7% of the 30 patients who took apremlast at 40 mg once daily and methotrexate, achieved an ACR20 compared with 35.1% of the 37 patients who took only apremilast (40 mg once daily)
Action Points
- Note that these studies were published as abstracts and were presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.
- Explain that an investigative, oral biologic agent (apremilast) appears to provide similar benefit in psoriatic arthritis even if the patient is already taking methotrexate.
- Note that in another placebo-controlled study of patients with ankylosing spondylitis, apremilast may be a modulator of biomarkers of bone biology.
Schett said that none of the differences in treatment arms were statistically significant.
He noted that apremilast is a phospodiesterase-4 inhibitor, which interrupts the inflammatory cascade mediated by phospodiesterase-4 in immune cells. The orally administered molecule appears to be a pluripotent immunomodulator, he suggested.
Schett said that the most commonly reported adverse events in the study were gastrointestinal complaints "which tended to be more frequent in subjects treated with methotrexate."
"There is no evidence that treatment response differed among subjects treated, and not treated, with methotrexate. There was no additional benefit or risk associated with combination of apremilast and methotrexate therapy," Schett concluded.
Commenting on the study was Lisa Mandl, MD, MPH, of the Hospital for Special Surgery in New York who said, "apremilast might be useful as an alternative for treatment of psoriatic arthritis."
However, the fact that apremilast is an oral drug may not make a different to patients, "who are getting relief from psoriatic arthritis with injected drugs [and] don't really mind the needles," she told MedPage Today.
In another placebo-controlled study, apremilast for the treatment of ankylosing spondylitis proved to potentially be an effective, well tolerated modulator of biomarkers of bone biology.
Peter Taylor, PhD, from the Kennedy Institute of Rheumatology at Oxford University, U.K., and colleagues investigated the use of three different doses of apremilast -- 10 mg, 20 mg, and 30 mg, all taken twice daily -- among patients diagnosed with ankylosing spondylitis. The patients were about 40-years -old and had experienced the disease for about 18 years.
After 85 days of treatment, patients taking apremilast had decreased scores on the Bath Ankylosing Spondylitis Activity Index by more than 1.5 points compared with a decrease of about 0.75 points with placebo from baseline (P=0.139).
These differences did not achieve statistical significance. In addition, the scores rebounded when treatment was discontinued. Taylor noted that the downward trend in the scores had not reached a treatment plateau when therapy was discontinued.
Also, there was a mean change from baseline for receptor activator of nuclear factor kB Ligand (RANKL) in the apremilast group compared with the placebo group (73.2 versus 108.2; P=0.016).
But given the current lack of oral disease-modifying drugs available for ankylosing spondylitis, these pilot data support further research of apremilast in axial inflammation, the group concluded.
Désirée van der Heijde, MD, PhD, from Leiden University in the Netherlands, and a moderator of the ACR session, told MedPage Today that apremilast treatment for ankylosing spondylitis warranted further investigation.
Disclosures
The studies were supported by Celgene.
Schett had no disclosures. Co-authors of his study are employees of Celgene.
Taylor disclosed commercial interests with Celgene. None of his co-authors had disclosures.
Mandl had no disclosures.
Van der Heijde has disclosed commercial interests with Wyeth, Abbott, Centocor, Schering Plough, UCB, Chugai, Roche, and Bristol-Myers Squibb.
Primary Source
American College of Rheumatology
Source Reference: Schett G, et al "Oral apremilast is effective with and without concomitant methotrexate therapy in the treatment of subjects with active psoriatic arthritis" ACR 2011; Abstract 780.
Secondary Source
American College of Rheumatology
Source Reference: Pathan E, et al "Efficacy and safety of apremilast, an oral phosphodiesterase inhibitor, in ankylosing spondylitis" ACR 2011; Abstract 1652.