Session Information
Session Type: Abstract Submissions (ACR)
Background/Purpose: Apremilast (APR), a phosphodiesterase 4 inhibitor, helps regulate the immune response that causes inflammation and skin disease associated with psoriatic arthritis (PsA). PALACE 1, a phase 3 randomized trial with an open-label extension, compared the efficacy/safety of APR with placebo (PBO) in pts with active PsA despite prior conventional DMARDs and/or biologics.
Methods: Pts were randomized (1:1:1) to receive PBO, APR 20 mg BID (APR20), or APR 30 mg BID (APR30) stratified by baseline DMARD use (yes/no). Pts whose swollen/tender joint counts had not improved ≥20% at Wk 16 were considered non-responders and were re-randomized (1:1) to APR20 or APR30 (PBO pts) or continued on their initial dose (APR pts). At Wk 24, all remaining PBO pts were re-randomized to APR20 or APR30. Double-blind APR treatment continued to Wk 52; pts could continue to receive APR during an open-label, long-term treatment phase. The analysis reports safety findings from the APR-exposure period (Wks 0 to ≤104).
Results: 504 pts were randomized and received ≥1 dose of study medication (PBO: n=168; APR20: n=168; APR30: n=168). A total of 490 (410.3 pt-years) and 344 (306.2 pt-years) pts received APR in the Wk 0 to ≤52 and Wk >52 to ≤104 APR-exposure periods, respectively. During the Wk >52 to ≤104 period, AEs occurring in ≥5% of APR-exposed pts were nasopharyngitis and URTI (Table). Most AEs were mild/moderate in severity between Wks >52 to ≤104 and in general, no increase was seen in the incidence or severity of AEs with longer term exposure. During the Wk >52 to ≤104 exposure period, diarrhea and nausea occurred at lower rates (1.7% and 1.2%, respectively) than in the Wk 0 to ≤52 period (15.3% and 12.4%, respectively). Serious AEs occurred in 6.4% (APR20 ) and 4.7% (APR30) over the Wk >52 to ≤104 APR-exposure period.Through Wk 104, serious infections were reported by 5 pts receiving APR during Wks 0 to ≤52 and 3 pts receiving APR during Wks >52 to ≤104; none were opportunistic infections. No cases of tuberculosis (new or reactivation) were reported with either APR dose. Discontinuations due to AEs occurred at a lower rate in the combined APR-exposure pts during the Wk >52 to ≤104 (1.5%) APR-exposure period than in Wks 0 to ≤52 (8.2%). Discontinuation rates due to diarrhea and nausea also decreased over the Wk >52 to ≤104 APR-exposure period. Marked laboratory abnormalities were generally infrequent and returned to baseline with continued treatment or were associated with a concurrent medical condition.
Conclusion: APR demonstrated an acceptable safety profile and was generally well tolerated for up to 104 wks, with no new safety concerns identified with long-term exposure. These data continue to support that specific laboratory monitoring is not needed with APR.
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APR-Exposure Period* Wks 0 to ≤52 |
APR-Exposure Period* Wks >52 to ≤104 |
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Patients, n (%) |
APR20 n=245 |
APR30 n=245 |
APR20 n=173 |
APR30 n=171 |
|
≥1 AE |
171 (69.8) |
178 (72.7) |
108 (62.4) |
101 (59.1) |
|
≥1 serious AE |
14 (5.7) |
21 (8.6) |
11 (6.4) |
8 (4.7) |
|
≥1 serious infection |
2 (0.8) |
3 (1.2) |
2 (1.2) |
1 (0.6) |
|
AE leading to drug withdrawal |
17 (6.9) |
23 (9.4) |
2 (1.2) |
3 (1.8) |
|
Death |
1 (0.4)µ |
0 (0.0) |
0 (0.0) |
1 (0.6)‡ |
|
AEs in ≥5% of patients, any treatment group, n (%) |
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|
Diarrhea |
28 (11.4) |
47 (19.2) |
3 (1.7) |
3 (1.8) |
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Nausea |
24 (9.8) |
37 (15.1) |
3 (1.7) |
1 (0.6) |
|
Headache |
22 (9.0) |
24 (9.8) |
6 (3.5) |
8 (4.7) |
|
URTI |
20 (8.2) |
15 (6.1) |
15 (8.7) |
8 (4.7) |
|
Nasopharyngitis |
18 (7.3) |
16 (6.5) |
7 (4.0) |
12 (7.0) |
|
*Includes all patients who received APR during the time interval relative to the start of APR. µMultiorgan failure not suspected to be treatment related. ‡Patient died in a motor vehicle accident on study day 489 while receiving APR 30. |
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Disclosure:
P. J. Mease,
Abbott, Amgen, Biogen Idec, Bristol-Myers Squibb, Genentech, Janssen, Eli Lilly, Pfizer Inc, UCB, Celgene Corporation, Novartis, and Roche,
2,
Abbott, Amgen, Biogen Idec, Bristol-Myers Squibb, Genentech, Janssen, Eli Lilly, Pfizer Inc, UCBCelgene Corporation, Novartis, and Roche ,
5,
Abbott, Amgen, Biogen Idec, Bristol-Myers Squibb, Genentech, Janssen, Eli Lilly, Pfizer Inc, and UCB,
8;
A. O. Adebajo,
None;
D. D. Gladman,
Abbvie, Amgen, Celgene, Janssen, Pfizer, UCB,
2,
Abbvie, Amgen, BMS, Celgene, Eli Lilly, Janssen, Novartis, Pfizer, UCB,
5;
J. J. Gomez-Reino,
Bristol-Myers Squibb, Pfizer Inc, Roche, Schering-Plough, and UCB SA,
9,
Bristol-Myers Squibb, Roche, Schering-Plough, and Wyeth,
9,
Roche and Schering-Plough,
2;
S. Hall,
Celgene Corporation, Pfizer, UCB, Bristol-Myers Squibb, Glaxo-Smith Kline, Roche, Janssen, Novartis, Merck,
2,
Celgene Corporation, Pfizer, UCB, Bristol-Myers Squibb, Glaxo-Smith Kline, Roche, Janssen, Novartis, Merck,
5;
A. Kavanaugh,
Abbott, Amgen, Astra-Zeneca, Bristol-Myers Squibb, Celgene Corporation, Centocor-Janssen, Pfizer Inc, Roche, and UCB,
2;
E. Lespessailles,
Amgen, Eli Lilly, Novartis, and Servier,
2,
Amgen, Eli Lilly, Novartis, and Servier,
8;
G. A. Schett,
Abbott, Celgene Corporation, Roche, and UCB,
2,
Abbott, Celgene Corporation, Roche, and UCB,
5;
K. Shah,
Celgene Corporation,
1,
Celgene Corporation,
3;
R. M. Stevens,
Celgene Corporation,
1,
Celgene Corporation,
3;
L. Teng,
Celgene Corporation,
1,
Celgene Corporation,
3;
J. Wollenhaupt,
Abbott, Bristol-Myers Squibb, MSD, Pfizer Inc, and UCB,
2,
Abbott, Bristol-Myers Squibb, MSD, Pfizer Inc, and UCB,
5.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/long-term-104-week-safety-profile-of-apremilast-an-oral-phosphodiesterase-4-inhibitor-in-patients-with-psoriatic-arthritis-results-from-a-phase-3-randomized-controlled-trial-and-open-label-exte/