Arthritis & Rheumatism, Volume 60,
October 2009 Abstract Supplement
The 2009 ACR/ARHP Annual Scientific Meeting
Philadelphia October 16-21, 2009.
Apremilast Is Active in the Treatment of Psoriatic Arthritis (PsA)
Schett1, Georg, Wollenhaupt2, J., Papp3, Kim, Joos4, Rik, De Vlam5, Kurt L., Rodrigues6, Jude F., Vessey7, Adele
University of Erlangen-Nuremberg, Erlangen, Germany,
Klinikum Eilbek, Hamburg, Germany,
Probity Medical Research, Waterloo, ON,
ZNA Rheumatology Department, Merksen, Belgium,
University Hospitals Leuven, Leuven, Belgium,
Clinical Research and Arthritis Centre. Windsor, ON,
Celgene Corporation, Summit, NJ
Apremilast (APL) is a novel oral phosphodiesterase-4 inhibitor that suppresses multiple pro-inflammatory mediators and cytokines implicated in the pathogenesis of PsA.
This was a phase II randomized, double-blind, placebo (PBO) controlled, multicenter study conducted in North America and Europe. Subjects with joint involvement of >=6 months' duration, and with PsA satisfying Moll & Wright criteria with >=3 tender joints (TJ) and swollen joints (SJ) were randomized to APL 20mg BID, APL 40mg QD, or PBO for 12 weeks' treatment. Stable doses of NSAIDs, corticosteroids (<=10 mg/day prednisone or equivalent), and methotrexate were allowed. A total of 126 subjects were then treated in an active-drug extension for 12 weeks (24 weeks total) including 40 PBO subjects who received the two dose regimens of APL in a 1:1 ratio.
Two hundred four subjects were enrolled [53% M, 47% F; mean age 51 (2181)]. Mean duration of PsA was 7.8 years; mean TJ count of 22, mean SJ count of 10 at baseline. Baseline characteristics were well-balanced between treatment groups. One hundred sixty eight subjects completed the 12 week treatment phase. Primary endpoint, ACR20 at 12 weeks, was met by APL 20 mg BID and 40 mg QD. Efficacy results are given in the table below. In evaluable subjects, response was maintained at 24 weeks (ACR20 40% and 39.1% for 20 mg BID and 40 mg QD, respectively). PBO subjects switched to APL in the extension achieved similar responses at 24 weeks to subjects originally allocated to APL (ACR20 35% and 40% for PBO to 20 mg BID and PBO to 40 mg QD, respectively).
|Treatment Group (N)||Placebo (68)||APL 20mg BID (69)||APL 40mg QD (67)|
|** p = 0.002|
The 5 most common adverse events (AEs) were nausea, diarrhea, headache, nasopharyngitis, and fatigue. Discontinuations due to AEs were 9% and 6% of APL subjects (20 mg BID, 40 mg QD, respectively), vs 3% in PBO group. Discontinuations due to lack of efficacy were 7 and 0% of APL subjects (20 mg BID, 40 mg QD, respectively), vs 15% in the PBO group. Eight subjects reported a serious AE (SAE) during the 12 week study period (4 in 20 mg BID, 0 in 40 mg QD, 4 in PBO); 7 subjects reported an SAE in the extension. There was no obvious difference in infections between APL and PBO groups and there were no deaths.
APL significantly improved signs and symptoms of PsA in this study. The majority of the AEs were mild to moderate and did not lead to discontinuation. Larger, longer-term studies are needed to characterize the optimum dose, efficacy and safety of APL for treatment of PsA.
To cite this abstract, please use the following information:
Schett, Georg, Wollenhaupt, J., Papp, Kim, Joos, Rik, De Vlam, Kurt L., Rodrigues, Jude F., et al; Apremilast Is Active in the Treatment of Psoriatic Arthritis (PsA) [abstract]. Arthritis Rheum 2009;60 Suppl 10 :1258