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 baseline (BL) DMARD use. At wk 16, pts with <20% reduction from BL in swollen and 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. Patients taking concurrent DMARDs were allowed to continue stable doses (MTX, sulfasalazine, leflunomide, or a combination).
Results: APR administration resulted in statistically significant and clinically meaningful improvement in ACR20 response (primary endpoint) in all 3 PALACE trials. APR30 was associated with significant improvements in Health Assessment Questionnaire-Disability Index (HAQ-DI) (P≤0.03) and SF-36 Physical Functioning (PF) domain (P≤0.05) vs PBO at wk 24 across all 3 trials. For those pts originally randomized to APR and completing 52 wks of study, improvements were maintained or increased over 52 wks (Table). At wk 52, mean changes in HAQ-DI were -0.369 (APR20) and -0.318 (APR30) in PALACE 1; -0.192 (APR20) and -0.330 (APR30) in PALACE 2; and -0.332 (APR20) and -0.350 (APR30) in PALACE 3. Mean changes from BL exceeded minimal clinically important differences (MCID) thresholds‡ of ≥0.13 or ≥0.3 in pts treated with APR20 and APR30 for 52 wks, and the proportion of APR20 and APR30 pts achieving MCID was maintained between wks 24 and 52. Mean changes in SF-36 PF were 6.98 (APR20) and 5.69 (APR30) in PALACE 1; 4.05 (APR20) and 4.97 (APR30) in PALACE 2; and 5.68 (APR20) and 5.87 (APR30) in PALACE 3. Mean changes from BL exceeded MCID of ≥2.5 in pts treated with APR20 and APR30 for 52 wks, and the proportion of APR20 and APR30 pts achieving MCID was maintained between wks 24 and 52. 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.
Conclusion: Over 52 wks, APR continued to demonstrate meaningful clinical response in PsA pts, including measures of physical function. APR demonstrated an acceptable safety profile and was generally well tolerated for up to 52 wks.
Disclosure:
G. Schett,
Celgene,
2,
Abbott Laboratories, UCB, Roche,
5;
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, UCB,
5;
M. Cutolo,
BMS, Sanofi and Actelion,
2;
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-physical-function-in-patients-with-psoriatic-arthritis-results-from-three-phase-3-randomized/