Session Information
Session Type: Abstract Submissions (ACR)
Background/Purpose: Apremilast (APR), an oral phosphodiesterase 4 inhibitor, works intracellularly to modulate pro- and anti-inflammatory mediators. The PALACE 1, 2, and 3 trials compared the efficacy and safety of APR with placebo (PBO) in pts with active PsA despite prior DMARDs and/or biologics.
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 and tender joint counts (SJC/TJC) 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). Given the relative weighting of SJC/TJC in the ACR20 composite index and their clinical importance, we examined these measures across the 3 trials.
Results: APR resulted in statistically significant and clinically meaningful improvement in ACR20 response (primary endpoint) in all 3 PALACE trials. Median percent reductions (improvement) in SJC/TJC were statistically significant vs PBO at wk 16 in all 3 trials; SJC (PBO, APR20, APR30, respectively): -16.7%, -39.3% (P=0.0035), -50.0% (P<0.0001) (PALACE 1); -33.3%, -50.0% (P=0.0029), -53.9% (P=0.0009) (PALACE 2); 20.0%, -36.4% (P=0.0301), -50.0% (P=0.0014) (PALACE 3); TJC: -7.0%, -23.3% (P=0.0007), -42.9% (P<0.0001) (PALACE 1); -8.7%, -36.2% (P<0.0001), -33.3% (P=0.0015) (PALACE 2); -8.6%, -30.0% (P=0.0001), -43.7% (P<0.0001) (PALACE 3). Pts receiving APR20 and APR30 for 24 wks had median percent reductions in SJC in PALACE 1, 2, and 3, respectively, of -53.8% and -66.7%; -71.4% and -75.0%; and 61.3% and -69.2%. Median percent reductions in TJC for APR20 and APR30 were 46.2% and -59.4%; -51.0% and -47.1%; and -53.3% and -55.0%. In pts receiving APR for 52 wks, sustained improvements in SJC/TJC were observed at wk 52, with SJC improvements up to -87.5% and TJC improvements up to -70.0% (Figure). Pts randomized to APR at wks 16 and 24 demonstrated results consistent with those originally randomized to APR. No new safety findings were identified and the incidence of pts experiencing any AE was comparable over the 0-24 and 0-52 wk periods. No imbalance in the exposure-adjusted incidence rates of major adverse cardiac events, serious infections including systemic opportunistic infection, or malignancies between APR and PBO was observed. No cases of TB (novel or reactivation) were reported in the APR treatment groups; TB screening was not required per protocol.
Conclusion: Over 52 wks, APR continued to demonstrate efficacy in the treatment of PsA, including clinically meaningful improvements in SJC and TJC. APR demonstrated an acceptable safety profile and was generally well tolerated for up to 52 wks.
Disclosure:
M. Cutolo,
BMS, Sanofi and Actelion,
2;
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;
D. D. Gladman,
Janssen, Abbvie, Amgen, Pfizer, UCB, Novartis, Lily, Celgene,
2,
Janssen, Abbvie, Amgen, Pfizer, UCB, Novartis, Lily, Celgene,
5;
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;
A. O. Adebajo,
None;
J. J. Gomez-Reino,
BMS, Pfizer, Roche, Schering-Plough, and UCB SA,
5,
BMS, Roche, Schering-Plough, and Wyeth,
8,
Roche and Schering-Plough,
2;
J. Wollenhaupt,
Abbott Laboratories, Bristol-Myers Squibb, MSD, Pfizer, and UCB,
5;
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/apremilast-an-oral-phosphodiesterase-4-inhibitor-is-associated-with-long-term-52-week-improvement-in-tender-and-swollen-joint-counts-in-patients-with-psoriatic-arthritis-results-from-three-phase/