Session Information
Session Type: Late-Breaking Abstracts
Background/Purpose: Apremilast, an oral phosphodiesterase 4 inhibitor, works intracellularly to modulate a network of pro- and anti-inflammatory mediators, including those implicated in the etiopathogenesis of psoriatic arthritis (PsA). This phase 3 study (PALACE 1) compared the efficacy and safety of apremilast with placebo (PBO) in subjects with active PsA despite previous DMARDs and biologics.
Methods: Subjects were randomized 1:1:1 to PBO, apremilast 20 mg BID, or apremilast 30 mg BID stratified by baseline DMARD use. At wk 16, subjects with <20% reduction from baseline in swollen and tender joint counts were re-randomized to apremilast 20 mg BID or 30 mg BID (PBO group), or remained on their initial dose (apremilast groups). All subjects then continued assigned treatment through wk 24. Stable concurrent treatment with MTX, sulfasalazine, leflunomide or a combination was allowed.
Results: 504 subjects were randomized and comparable across treatment groups for demographics, disease characteristics, and prior/concurrent therapy. Of note, 23.6% of patients had prior biologic exposure, including 9.3% considered biologic failures. At baseline, 64.9% were taking DMARDs (54.2%, MTX). At wk 16, a significantly greater proportion of subjects treated with apremilast 20 mg BID (31.3%; P=0.0140) and 30 mg BID (41.0%; P<0.0001) achieved an ACR20 vs PBO (19.4%) (Table). In subjects receiving apremilast 30 mg BID, higher ACR20 responses were seen in subjects receiving apremilast monotherapy and in biologic-naïve subjects compared with the overall population response. At wk 24, apremilast was associated with significant differences vs PBO in ACR20, ACR50, ACR70, HAQ-DI, SF-36 Physical Function scores, DAS-28, and EULAR response. In general, response rates were higher with apremilast 30 mg BID. Apremilast was generally well tolerated. Adverse events (AEs) occurring in ≥5% of any treatment group were diarrhea (PBO, 2.4%; apremilast 20 mg BID, 11.3%; and apremilast 30 mg BID, 19.0%), nausea (6.5%, 9.5%, and 18.5%), headache (4.8%, 10.1%, and 10.7%), and upper respiratory tract infection (3.6%, 6.0%, and 4.2%). The majority (>95%) of AEs were mild or moderate; discontinuations due to AEs were similar across all treatment arms (5-7%). Serious AEs occurred in 7 (PBO), 8 (apremilast 20 mg BID), and 9 (apremilast 30 mg BID) subjects. No opportunistic infections (including TB) or lymphoma were observed, and there was not a greater risk of cardiovascular events.
Conclusion: Apremilast significantly improved signs and symptoms of PsA and resulted in statistically and clinically meaningful improvements in physical function. Apremilast was generally well tolerated and no new safety or laboratory signals were detected.
Table. Primary and select secondary end points
|
|
PBO (n=165) |
Apremilast |
Apremilast |
|
ACR20 at wk 16, % |
19.4 |
31.3*
|
41.0†
|
|
APR alone (n=172) |
10.5 |
31.5*
|
50.8†
|
|
APR+DMARDs (n=317) |
24.1 |
31.2‡
|
35.0‡
|
|
ACR20 at wk 16 Biologic-naïve subjects (n=363) |
23.7 |
31.2‡ |
43.3* |
|
APR alone (n=89) |
11.5 |
24.1‡
|
58.8*
|
|
APR+DMARDs (n=274) |
27.2 |
33.3‡
|
37.2‡
|
|
Select secondary end points at wk 24 |
|
|
|
|
ACR50, % |
4.2 |
15.3*
|
19.9†
|
|
ACR70, % |
0.6 |
5.5*
|
11.2†
|
|
HAQ-DI, LS mean change from baseline (SE) |
-0.077 (0.037) |
-0.212 (0.037)*
|
-0.260 (0.037)*
|
|
DAS-28, LS mean improvement from baseline (SE) |
0.20 (0.087) |
0.66 (0.087)*
|
0.91 (0.087) †
|
|
Good or moderate EULAR response achievement, % |
29.1 |
45.4*
|
51.6†
|
|
SF-36 Physical Function, LS mean change from baseline (SE) |
1.46 (0.671) |
3.50 (0.675)*
|
5.06 (0.674)†
|
Efficacy analyses were conducted using the per-protocol population (N=489); last observation carried forward was used for missing data.
*P<0.05; †P≤0.0001;‡P=non-significant vs. PBO.
Disclosure:
A. Kavanaugh,
Celgene,
2,
Celgene,
5;
P. J. Mease,
Abbott Laboratories,
2,
Amgen,
2,
BiogenIdec,
2,
BMS,
2,
Genentech and Biogen IDEC Inc.,
2,
Janssen Pharmaceutica Product, L.P.,
2,
Eli Lilly and Company,
2,
Pfizer Inc,
2,
UCB,
2,
Celgene,
2,
Novartis Pharmaceutical Corporation,
2,
Roche Pharmaceuticals,
2,
Abbott Laboratories,
5,
Amgen,
5,
BiogenIdec,
5,
BMS,
5,
Genentech and Biogen IDEC Inc.,
5,
Janssen Pharmaceutica Product, L.P.,
5,
Eli Lilly and Company,
5,
Pfizer Inc,
5,
UCB,
5,
Celgene,
5,
Novartis Pharmaceutical Corporation,
5,
Roche Pharmaceuticals,
5,
Abbott Laboratories,
8,
Amgen,
8,
BiogenIdec,
8,
BMS,
8,
Genentech and Biogen IDEC Inc.,
8,
Janssen Pharmaceutica Product, L.P.,
8,
Eli Lilly and Company,
8,
Pfizer Inc,
8,
UCB,
8;
J. J. Gomez-Reino,
BMS,
8,
Pfizer Inc,
8,
Roche Pharmaceuticals,
8,
Schering-Plough,
8,
UCB,
8,
Roche Pharmaceuticals,
2,
Schering-Plough,
2;
A. Adewale,
None;
J. Wollenhaupt,
Abbott Laboratories,
5,
BMS,
5,
MSD,
5,
Pfizer Inc,
5,
UCB,
5;
C. Hu,
Celgene,
1,
Celgene,
3;
R. Stevens,
Celgene,
1,
Celgene,
3.
« Back to 2012 ACR/ARHP Annual Meeting
ACR Meeting Abstracts - https://acrabstracts.org/abstract/apremilast-an-oral-phosphodiesterase-4-inhibitor-in-patients-with-psoriatic-arthritis-results-of-a-phase-3-randomized-controlled-trial/