SAT0562 Long-Term (104-Week) Efficacy and Safety of Apremilast Monotherapy in Dmard-Naïve Patients with Psoriatic Arthritis: A Phase 3, Randomized, Controlled Trial and Open-Label Extension (Palace 4)

Abstract

BackgroundApremilast (APR) is an oral phosphodiesterase 4 inhibitor that helps regulate the immune response that causes joint inflammation and other manifestations of psoriatic arthritis (PsA), including skin disease.ObjectivesCompare the efficacy and safety of APR monotherapy with placebo (PBO) in patients with active PsA who were DMARD-naïve for up to 104 weeks.MethodsPatients were randomized (1:1:1) to PBO, APR 20 mg BID (APR20), or APR 30 mg BID (APR30). Patients whose swollen/tender joint counts (SJC/TJC) had not improved by ≥20% at Week 16 were considered non-responders and were required to be re-randomized (1:1) to APR20 or APR30 if they were initially randomized to PBO, or continued on their initial APR dose. At Week 24, all remaining PBO patients were re-randomized to APR20 or APR30. Double-blind treatment continued to Week 52; patients could continue to receive APR for up to 4 additional years.Results527 patients were included in the modified intent-to-treat population in which patients who were randomized in error and did not receive study medication were excluded (PBO: n=176; APR20: n=175; APR30: n=176). At Week 52, a modified ACR20 response was achieved by 58.0% (119/205 [APR30]) and 55.4% (107/193; [APR20]) of patients (Table); $≈ $84% of patients completing 1 year of APR treatment were maintained on therapy at the data cutoff during their second year of APR exposure. At Week 104, patients taking APR demonstrated sustained improvements, as shown by modified ACR20/ACR50/ACR70 response rates, SJC/TJC mean percent change, HAQ-DI mean change, proportion of patients with HAQ-DI exceeding the MCID ≥0.30 threshold, changes in MASES and dactylitis severity scores, and PASI-50/PASI-75 responses (Table). During Weeks >52 to ≤104, the most common adverse events (AEs) among APR-exposed patients were upper respiratory tract infection (4.8%) and nasopharyngitis (3.2%); serious AEs occurred in 5.3%. In general, no change in the types of AEs and no increase in the incidence/severity of AEs were seen with longer-term exposure. Diarrhea and nausea occurred at lower rates in Weeks >52 to ≤104 vs. Weeks 0 to ≤52.ConclusionsOver 104 weeks, APR monotherapy demonstrated sustained response and improvements in PsA signs/symptoms, including enthesitis, dactylitis, physical function, and psoriasis. The ACR20 response was 61% for patients receiving APR30 therapy for 2 years. APR continued to demonstrate an acceptable safety profile and was generally well tolerated.Disclosure of InterestA. Wells Grant/research support from: Celgene Corporation, C. Edwards Grant/research support from: Celgene Corporation, Pfizer Inc, Roche, and Samsung, Consultant for: Celgene Corporation, Pfizer Inc, Roche, and Samsung, Speakers bureau: Abbott, Glaxo-SmithKline, Pfizer Inc, and Roche, A. Adebajo: None declared, A. Kivitz Grant/research support from: Amgen, Janssen, Eli Lilly, Novartis, Pfizer Inc, and UCB, Consultant for: Amgen, Janssen, Eli Lilly, Novartis, Pfizer Inc, and UCB, Speakers bureau: Pfizer Inc, P. Bird Grant/research support from: C...

Apremilast in the treatment of psoriatic arthritis: a perspective review

“…With apremilast 20 mg; 5.6% in year 1, 1.7% in year 2. With apremilast 30 mg; 5.2% in year 1, 3.5% in year 2 [Wells et al 2015] Comparative efficacy There has been considerable interest in the comparative efficacy of apremilast versus both traditional DMARD and biologic therapies. An indirect comparison and cost per responder analysis for adalimumab, methotrexate and apremilast in the treatment of methotrexate-naïve patients with PsA has been carried out [Betts et al 2016].…”

“…An indirect comparison and cost per responder analysis for adalimumab, methotrexate and apremilast in the treatment of methotrexate-naïve patients with PsA has been carried out [Betts et al 2016]. The number needed to treat (NNT) to achieve an ACR20 response in methotrexatenaïve patients to be 2.63 for adalimumab, 6.69 for apremilast and 8.31 for methotrexate based on data from the Adalimumab Effectiveness in Psoriatic Arthritis (APEPT) trial for adalimumab [Mease et al 2005], PALACE 4 for apremilast [Wells et al 2015] and the Methotrexate in Psoriatic Arthritis (MIPA) trial for methotrexate [Kingsley et al 2012].…”

“…For those with baseline enthesitis, the percentage achieving a MASES score of 0 was 39.4% at 52 weeks and 58.3% at week 104 (apremilast 20 mg bd). For apremilast 30 mg, the percentage achieving a 0 score was 51.2% at week 52 and 61.4% at week 104 [Wells et al . 2015].…”

What does evidence-based medicine tell us about treatments for different subtypes of psoriatic arthritis? A systematic literature review on randomized controlled trials

“…Enthesitis was included among the primary outcomes in three RCTs [66, 120, 130], dactylitis in two RCTs [66, 130] and BASDAI in one RCT [127]. For the secondary outcomes, 20 additional studies included enthesitis and dactylitis [12, 13, 17, 18, 20, 24–27, 29, 30, 32, 39, 48, 67, 68, 80, 85, 87, 103] and three studies included BASDAI [17, 32, 80]. Studies on brodalumab, ustekinumab and the tight control of PsA trial used BASDAI as a secondary outcome [80].…”

Management of Common Side Effects of Apremilast

“…1 Pooled analyses of safety data from ESTEEM and PALACE were recently presented by Crowley et al, 5 including a total of 1905 patients, over 30% of whom had greater than 3 years of apremilast use for a total apremilast exposure period of 3527.5 patient years. Other analyses of ESTEEM or PALACE data [5][6][7][8][9][10][11][12][13][14][15][16] prior to this pooled analysis will not be discussed here to avoid redundancy in our interpretation of the data. Long-term extension phases for ESTEEM and PALACE are planned for a total of 5 years (data pending).…”