Session Information
Session Type: Abstract Submissions (ACR)
Background/Purpose: Apremilast (APR), an oral phosphodiesterase 4 inhibitor, works intracellularly to modulate inflammatory mediators. PALACE 1, 2, and 3 compared the efficacy and safety of APR with placebo (PBO) in pts with active PsA despite prior DMARDs and/or biologics. The overall safety and tolerability of APR was assessed in a pooled analysis of PALACE 1, 2, and 3.
Methods: Pts were randomized 1:1:1 to PBO, APR 20 mg BID (APR20), or APR 30 mg BID (APR30) stratified by BL DMARD use. At wk 16, pts with <20% reduction from BL in swollen/tender joint counts qualified for protocol-defined early escape; those on PBO were re-randomized to APR20 or APR30 and those on APR remained on the initial APR dose. At wk 24, all remaining PBO pts were re-randomized to APR20 or APR30 through wk 52. Pts taking concurrent DMARDs were allowed to continue stable doses (MTX, sulfasalazine, leflunomide, or a combination). The analysis comprises data from the APR-exposure periods (wks 0-≥52).
Results: 1,493 pts received study drug (PBO, 495; APR20, 501; APR30, 497) and were included in the safety population. The APR-exposure period included 720 pts treated with APR20 (766.4 pt-yrs) and 721 with APR30 (769.0 pt-yrs). No new safety findings were identified; previously identified AEs were reported at a lower rate for wks 24-52 vs 0-24 (Table). The most common AEs were diarrhea (14.3%), nausea (12.6%), headache (10.1%), URTI (10.3%), and nasopharyngitis (7.4%). Diarrhea, nausea, and headache appeared to increase in a dose-dependent manner. Most AEs were mild/moderate in severity. Discontinuations due to AEs (APR20, 7.5%; APR30, 8.3%) were low, occurring primarily in the first 24 wks of treatment. Nausea and diarrhea were predominantly mild and occurred at a reduced incidence after the first month of dosing, with the highest incidence reported in the first 2 wks of treatment. Most cases resolved within 30 days despite continued therapy. The proportion of pts with severe nausea (APR20, 0.3%; APR30, 0.4%) and diarrhea (APR20, 0.6%; APR30, 0.3%) was low. GI AEs leading to APR discontinuation with ≥52 wks of exposure were 4% over 52 wks, with nausea (1.7%) and diarrhea (1.5%) being the most common. In the 24-≥52 wk period, no new severe AEs were reported for diarrhea, nausea, URTI, and nasopharyngitis vs 0-24 wks. Serious AEs occurred in 6.8% (APR20) and 7.2% (APR30) of pts. One death occurred (APR20) due to multiorgan failure not suspected to be treatment-related. Exposure-adjusted incidence rates of major adverse cardiac events, serious infections including systemic opportunistic infection, or malignancies were comparable to PBO. There were no clinically meaningful effects on laboratory measurements.
Conclusion: APR demonstrated an acceptable safety profile and was generally well tolerated for up to 52 wks with no new safety concerns identified with long-term exposure. These data do not indicate a need for laboratory monitoring.
Disclosure:
P. J. Mease,
Celgene,
2,
Merck Pharmaceuticals,
2,
Novartis Pharmaceutical Corporation,
2,
Abbvie,
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,
5,
Merck Pharmaceuticals,
5,
Novartis Pharmaceutical Corporation,
5,
Abbvie,
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,
Abbvie,
8,
Amgne,
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;
A. Kavanaugh,
AbbVie Inc., Amgen, Astra-Zeneca, BMS, Celgene, Centocor-Janssen, Pfizer, Roche, and UCB,
2,
AbbVie Inc., Amgen, Astra-Zeneca, BMS, Celgene, Centocor-Janssen, Pfizer, Roche, and UCB,
5;
D. D. Gladman,
Janssen, Abbvie, Amgen, Pfizer, UCB, Novartis, Lily, Celgene,
2,
Janssen, Abbvie, Amgen, Pfizer, UCB, Novartis, Lily, Celgene,
5;
A. O. Adebajo,
None;
J. J. Gomez-Reino,
BMS, Pfizer, Roche, Schering-Plough, UCB SA,
5,
BMS, Roche, Schering-Plough, Wyeth,
8,
Roche, Schering-Plough,
2;
J. Wollenhaupt,
Abbott Laboratories, Bristol-Myers Squibb, MSD, Pfizer, UCB,
5;
M. Cutolo,
BMS, Sanofi and Actelion,
2;
G. Schett,
Celgene,
2,
Abbott Laboratories, UCB, Roche,
5;
E. Lespessailles,
Novartis, Lilly, Servier, Amgen,
2,
Novartis, Lilly,
8;
K. Shah,
Celgene Corporation,
3;
C. Hu,
Celgene Corporation,
3;
R. M. Stevens,
Celgene Corporation,
3;
C. J. Edwards,
Pfizer,
2,
Pfizer, Samsung, Roche, Celgene,
5,
Roche, Pfizer, Abbott, Glaxo-SmithKline,
8;
C. A. Birbara,
Amgen, Lilly, Pfizer, Incyte, Merck, Bristol-Myers Squibb,
2.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/long-term-safety-and-tolerability-of-apremilast-an-oral-phosphodiesterase-4-inhibitor-in-patients-with-psoriatic-arthritis-pooled-safety-analysis-of-three-phase-3-randomized-controlled-trials/