Melissa McIlraith

THU0435 DAS-28 Remission and Improvements in Skin Disease over 3 Years of Treatment with Apremilast: Results from The Palace 3 Study in Dmard/biologic-Experienced Active PsA Patients

Background Treatment goals for active psoriatic arthritis (PsA) include long-term control of both skin and joint symptoms. Achievement of remission in 28-joint count Disease Activity Score (DAS-28) using C-reactive protein (CRP), clinically important changes in DAS-28 (CRP), reduction in swollen joint count (SJC), or decrease in skin disease may be used as goals of treatment.1 PALACE 3 (NCT01212770) included PsA patients with active joint disease with an active skin lesion at the time of enrollment. Objectives Assess long-term treatment responses across PsA manifestations in patients treated with apremilast (APR) for 3 years. Methods Patients were stratified by baseline DMARD use (yes/no) and psoriasis involvement of the body surface area (<3%/≥3%) and randomized (1:1:1) to placebo (PBO), APR 30 mg BID (APR30), or APR 20 mg BID (APR20). After a PBO-controlled phase of 24 wks, all patients were treated with APR30 or APR20 and could enroll in long-term follow-up. Efficacy assessments in years 2 and 3 were conducted at Wks 65, 78, 91, 104, 117, 130, 143, and 156. Results 505 patients were randomized and received ≥1 dose of study medication (PBO: n=169; APR30: n=167; APR20: n=169). A total of 89% (249/281) of patients starting the third year of APR therapy completed the Wk 156 visit. Patients treated with APR30 demonstrated sustained decreases in disease activity at Wk 156, as shown by mean decreases in DAS-28 (CRP) of −1.58; 79.1% achieved a good/moderate EULAR response and 41.0% achieved DAS-28 (CRP) remission. Sustained relief across PsA manifestations, including SJC, a marker of inflammation, was also demonstrated (Table); at Wk 156, APR30 resulted in a mean 78.3% decrease in SJC, 65.5% of patients had a swollen joint count of 0 or 1. Decreases in disability and maintenance of functionality were demonstrated by sustained decreases in HAQ-DI scores (Table). Continued effect on skin disease was shown by decreases in skin involvement, as measured by the PASI; 54.7% of APR30 patients had a baseline PASI >5 and 27.3% had a baseline PASI >10; at 156 wks, 64.7% had a PASI <3, and 83.8% had a PASI of ≤5. PASI-75 and PASI-50 also signified clinically significant relief (Table). No new safety concerns were identified after 156 wks of APR treatment. During Wks >104 to ≤156 of APR exposure, adverse events (AEs) occurring in ≥5% of patients were nasopharyngitis and urinary tract infection; most AEs were mild or moderate in severity. Serious AEs occurred in 7.8% of APR patients during Wks >104 to ≤156, similar to rates seen for the earlier study periods; few discontinuations due to AEs (2.1%) occurred over Wks >104 to ≤156. Conclusions Over 156 wks, among patients continuing in the study, APR demonstrated sustained and clinically important improvements in PsA signs/symptoms, including physical function and associated psoriasis. APR was generally well tolerated and continued to demonstrate an acceptable safety profile with long-term use. References Gossec et al. Ann Rheum Dis. 2015 Dec 7. doi: 10.1136/annrheumdis-2015-208337. [Epub ahead of print]. Disclosure of Interest C. Edwards Grant/research support from: Celgene Corporation, Pfizer Inc, Roche, Samsung, Consultant for: Celgene Corporation, Pfizer Inc, Roche, Samsung, Speakers bureau: Abbott, Glaxo-SmithKline, Pfizer Inc, Roche, F. Blanco Grant/research support from: Celgene Corporation, J. Crowley Grant/research support from: AbbVie, Amgen, Celgene, Janssen, Merck, and Pfizer, Consultant for: AbbVie, Amgen, Speakers bureau: AbbVie, M. McIlraith Employee of: Celgene Corporation, K. Shah Employee of: Celgene Corporation, L. Teng Employee of: Celgene Corporation, C. Birbara Grant/research support from: Amgen, Bristol-Myers Squibb, Incyte, Eli Lilly, Merck, Pfizer Inc

SAT0436 Durability of apremilast response in patients with psoriatic arthritis: long-term (208-week) results from the palace 1 trial

Background Optimizing treatment choice in psoriatic arthritis (PsA) necessitates an understanding of the long-term effects of therapies across varied manifestations of this complex disease. Data from 4 years of apremilast (APR) treatment in PALACE 1 were used to examine disease control across markers of active inflammation, such as SJC, as well as improvements in patient (pt) functionality, as assessed using the HAQ-DI. Objectives Evaluate long-term outcomes with APR treatment after ≥1 DMARD or biologic in pts with active PsA. Methods Pts were randomized (1:1:1) to placebo (PBO), APR 30 mg BID (APR30), or APR 20 mg BID (APR20). The PBO-controlled phase continued to Wk 24, at which time all remaining PBO pts were re-randomized to APR30 or APR20. Double-blind APR treatment continued to Wk 52; pts could continue APR for up to 4 additional years in an open-label extension. Results 504 pts were randomized and received ≥1 dose of study medication (PBO: n=168; APR30: n=168; APR20: n=168); 86.9% (225/259) of pts entering the third year completed 208 wks of APR treatment; overall, this is 44.6% (225/504) of pts randomized at baseline (BL). At Wk 52, 53.2% of APR30 pts achieved a modified ACR20 response (Table), regardless of when APR was started (BL, Wk 16, or Wk 24). At Wk 208, a sustained response rate was observed in APR30 pts, as shown by an ACR20 response rate of 67.5%. Marked improvements in SJC were seen throughout the study, with a mean percent decrease of −84.2% at Wk 208; TJC reductions were consistent (Table). Functionality is of paramount importance to pts; large improvements were seen in HAQ-DI score, with a mean change of −0.47. Pts also note fatigue as a disease- or treatment-related impairment; a mean improvement of 5.7 was seen in FACIT-F score at Wk 208 (Table), and the pt population reached a mean score of 35.7. In addition, long-term treatment led to the maintenance of the proportions meeting the minimal clinically important difference in HAQ-DI score change, achieving ACR50/ACR70 responses and reaching PASI-75 and PASI-50 responses (Table). No new safety concerns were identified with APR treatment up to 208 wks. During Wks >156 to ≤208, the only adverse event (AE) occurring in ≥5% of APR30-exposed pts was URTI (5.2%); most AEs were mild/moderate in severity. Among APR30-exposed pts, serious AEs occurred in 6.7% of pts in Wks >156 to ≤208, consistent with earlier data. Importantly, few discontinuations due to AEs occurred throughout the long-term treatment period. Conclusions APR30 demonstrated sustained, clinically meaningful improvements in signs and symptoms of PsA, physical function, and associated psoriasis over 208 wks. APR30 continued to demonstrate a favorable safety profile and was generally well tolerated. Disclosure of Interest A. Kavanaugh Grant/research support from: Abbott, Amgen, AstraZeneca, BMS, Celgene Corporation, Centocor-Janssen, Pfizer, Roche, UCB, D. Gladman Grant/research support from: AbbVie, Amgen, BMS, Celgene Corporation, Janssen, Novartis, Pfizer, UCB, Consultant for: AbbVie, Amgen, BMS, Celgene Corporation, Janssen, Novartis, Pfizer, UCB, J. Gomez-Reino Grant/research support from: Roche and Schering-Plough, Consultant for: BMS, Pfizer, Roche, Schering-Plough, UCB, S. Hall Consultant for: Boehringer Ingelheim, MSD, Roche, Schering-Plough, Servier, Wyeth, Paid instructor for: Amgen, AstraZeneca, Boehringer Ingelheim, Centocor, GSK, MSD, Pfizer, Sanofi Aventis, Sanofi Pasteur, Schering-Plough, Serono, Wyeth, Speakers bureau: Boehringer Ingelheim, GSK, MSD, Pfizer, Roche, Sanofi Aventis, Schering-Plough, Wyeth, E. Lespessailles Grant/research support from: Amgen, Eli Lilly, Novartis, Servier, Speakers bureau: Amgen, Eli Lilly, Novartis, Servier, P. Mease Grant/research support from: Abbott, Amgen, Biogen Idec, BMS, Celgene Corporation, Genentech, Janssen, Eli Lilly, Novartis, Pfizer, Roche, UCB, Consultant for: Abbott, Amgen, Biogen Idec, BMS, Celgene Corporation, Genentech, Janssen, Eli Lilly, Novartis, Pfizer, Roche, UCB, Speakers bureau: Abbott, Amgen, Biogen Idec, BMS, Genentech, Janssen, Eli Lilly, Pfizer, UCB, G. Schett Grant/research support from: Abbott, Celgene Corporation, Roche, UCB, Consultant for: Abbott, Celgene Corporation, Roche, UCB, M. McIlraith Employee of: Celgene Corporation, N. Delev Employee of: Celgene Corporation, M. Paris Employee of: Celgene Corporation, L. Teng Employee of: Celgene Corporation, J. Wollenhaupt Grant/research support from: Abbott, BMS, MSD, Pfizer, UCB, Consultant for: Abbott, BMS, MSD, Pfizer, UCB

FRI0513 Long-term (156 weeks) improvements in physical function of dmard-naÏve and dmard/biologic-experienced psoriatic arthritis patients treated with apremilast: data from a large database of 4 phase iii clinical trials

Background Improving and preserving patient (pt) physical function is an important goal for psoriatic arthritis (PsA). Objectives To evaluate apremilasts (APR) effects on physical function/functional status for up to 3 yrs in DMARD/biologic-experienced (PALACE 1–3 [PAL1–3] pooled data) and DMARD-naive (PALACE 4 [PAL4]) pts with active PsA. Methods Pts were randomized (1:1:1) to placebo (PBO), APR 30 mg BID (APR30), or 20 mg BID (APR20) at baseline (BL). The primary endpoint was at Wk16; a long-term extension is ongoing. A detailed study design has been previously presented. Assessed were mean change from BL HAQ-DI scores and proportions of pts reaching HAQ-DI MCID and reaching scores ≤1.0 (below clinically significant disability), ≤0.5 (minimal disability), and ≤0.25 (general population). Wk16 data were analyzed by LOCF. Wk156 data are as observed. Mean change and MCID outcomes are for all pts receiving APR30 at any time during the study; disability level data are for pts randomized to APR30 at BL. Results PAL1–3 (biologic/DMARD-experienced) and PAL4 (DMARD-naïve) pts had similar BL SJC/TJC and DAS-28 (CRP), indicating active PsA. PAL1–3 pts had longer mean duration of PsA and psoriasis, higher PASI scores, and greater corticosteroid use at BL. Despite differences, BL physical disability was clinically significant in both populations (mean HAQ-DI, PAL1–3: 1.2; PAL4: 1.1). Marked disability at BL was seen in some pts randomized to APR30, with HAQ-DI scores up to 2.63–2.88. More PAL1–3 vs PAL4 APR30 pts had BL HAQ-DI >1.0 (60% vs 54%), >1.5 (marked difficulty/need for assistive devices, 31%vs 21%), and >1.75 (major disability, 19% vs 10%), highlighting need for early, effective treatment (tx). Few APR30 pts had BL scores ≤0.5 (18–22%) or ≤0.25 (10–14%). At Wk16, physical function significantly improved with APR30 vs PBO (mean HAQ-DI change, PAL1–3: −0.23 vs −0.08; PAL4: −0.21 vs 0.03; both P<0.0001) and more APR30 vs PBO pts reached HAQ-DI MCID ≥0.30 and ≥0.35. As early as Wk16, overall disability levels also shifted; more APR30 vs PBO pts achieved HAQ-DI ≤1.0 (PAL1–3: 56% vs 48%; PAL4: 60% vs 52%). At Wk156, marked achievement of HAQ-DI ≤1.0, ≤0.5, and ≤0.25 was observed in both populations (Table). LOCF analyses confirmed Wk156 results. Conclusions With APR30 tx, physical disability improved early; functionality was maintained for up to 3 yrs. Most pts achieved HAQ-DI ≤1.0; many attained minimal/mild physical impairment. Over 40% of pts receiving APR30 earlier in the tx paradigm had functional ability similar to population norms after 3 yrs; shorter disease duration and no prior DMARD/biologics use in this population suggests that earlier APR tx may increase the likelihood of maximal functionality for some pts. Disclosure of Interest P. Mease Grant/research support from: Abbott, Amgen, Biogen Idec, BMS, Celgene Corporation, Genentech, Janssen, Eli Lilly, Novartis, Pfizer, Roche, UCB, Consultant for: Abbott, Amgen, Biogen Idec, BMS, Celgene Corporation, Genentech, Janssen, Eli Lilly, Novartis, Pfizer, Roche, UCB, Speakers bureau: Abbott, Amgen, Biogen Idec, BMS, Genentech, Janssen, Eli Lilly, Pfizer, UCB, A. Wells Grant/research support from: Celgene Corporation, J. Wollenhaupt Grant/research support from: Abbott, BMS, MSD, Pfizer, UCB, Consultant for: Abbott, BMS, MSD, Pfizer, UCB, S. Hall Consultant for: Boehringer Ingelheim, MSD, Roche, Schering-Plough, Servier, Wyeth, Paid instructor for: Amgen, AstraZeneca, Boehringer Ingelheim, Centocor, GSK, MSD, Pfizer, Sanofi Aventis, Sanofi Pasteur, Schering-Plough, Serono, Wyeth, Speakers bureau: Boehringer Ingelheim, GSK, MSD, Pfizer, Roche, Sanofi Aventis, Schering-Plough, Wyeth, F. Van den Bosch Consultant for: AbbVie, Celgene Corporation, Merck, Pfizer, UCB, Janssen, E. Lespessailles Grant/research support from: Amgen, Eli Lilly, Novartis, Servier, Speakers bureau: Amgen, Eli Lilly, Novartis, Servier, M. McIlraith Employee of: Celgene Corporation, D. Nguyen Employee of: Celgene Corporation, L. Teng Employee of: Celgene Corporation, C. Edwards Grant/research support from: Celgene Corporation, Pfizer, Roche, Samsung, Consultant for: Celgene Corporation, Pfizer, Roche, Samsung, Speakers bureau: Abbott, GSK, Pfizer, Roche

THU0449 Assessment of Disability Levels in A Cohort of 1,489 Patients with Active Psoriatic Arthritis, and The Effect of Apremilast Treatment: Pooled Data from 3 Phase III, Randomized, Controlled Trials

Background Psoriatic arthritis (PsA) reduces physical function and QoL; a treatment goal is to improve/maintain functionality. PALACE 1 (NCT01172938), 2 (NCT01212757), and 3 (NCT01212770) compared apremilast (APR) efficacy/safety with placebo (PBO) in patients (pts) with active PsA despite prior conventional DMARDs and/or biologics, providing one of the largest databases (N=1,489) examining physical disability in pts with moderate/severe PsA. Objectives Assess APR 30 mg BID (APR30) treatment impact on disability using the HAQ-DI over 104 wks with PALACE 1–3 pooled data. Methods Pts were randomized (1:1:1) to PBO, APR30, or APR 20 mg BID (APR20) stratified by baseline (BL) DMARD use (yes/no). At Wk 24, all remaining PBO pts were re-randomized to APR30 or APR20. HAQ-DI scores were collected at BL and Wks 16, 24, 40, 52 65, 78, 91, and 104. Mean change, proportion reaching MCID, and disability levels were calculated; HAQ-DI cutoff levels were ≤1.0 (clinically significant disability1), ≤0.5 (MDA criteria2), and ≤0.25. Score shift categories were examined in 0.25 increments to clarify pt disability level. Wk 16 data, compared with PBO, are analyzed by intent-to-treat/LOCF methodology. Other data shown are as observed to Wk 104. Mean change and MCID outcomes are for all pts receiving treatment with APR30 at any time during the study; for disability level and category shift assessments, data are shown for pts randomized to APR at BL. Results Pts exhibited significant BL physical disability (mean HAQ-DI=1.2); 60% of APR30 pts had a score >1.0, and 31% >1.5, noting marked difficulty/need for assistive devices in performing activities of daily living. Major disability was noted in 19% with BL HAQ-DI >1.75. As early as Wk 16, physical function improved with APR30; pts exhibited a mean HAQ-DI change of −0.23 (vs −0.08 PBO; P<0.0001), 56% achieved HAQ-DI ≤1.0 at Wk 16 (vs 48% PBO pts), and 29% achieved HAQ-DI ≤0.5 (vs 25% PBO pts). Fewer PBO vs APR30 pts reached the MCID of −0.13 (prespecified analysis; 37% vs 47%; P<0.005) or −0.30 (prespecified analysis)/−0.353 (post hoc analysis) (26% vs 36% for both; P<0.005). At Wk 52, decreases in disability were maintained (APR30 mean change in HAQ-DI=−0.33); 48% of APR30 pts achieved MCID −0.30 and −0.35. Importantly, at Wk 52, 58% of all APR30 pts achieved HAQ-DI ≤1.0, 34% ≤0.5, and 24% ≤0.25 (Table). Among pts with greater BL disability (HAQ-DI ≥1.5), 64% improved by ≥1 shift category and 47% by ≥2. At Wk 104, 50% of APR30 pts achieved MCID of −0.30 and −0.35, with 64% achieving HAQ-DI ≤1.0, 38% ≤0.5, and 28% ≤0.25; LOCF analysis confirmed Wk 104 results. Conclusions In APR30 pts, physical function improved at Wk 16 and was sustained with long-term treatment. Most pts achieved HAQ-DI MCID −0.30 or −0.35 and HAQ-DI scores ≤1.0, with many obtaining HAQ-DI ≤0.5, defined as minimal disease in recent criteria. These data indicate improvement and long-term maintenance of functionality with APR treatment. References Arthritis Rheum. 2003;48:59–63. Ann Rheum Dis. 2010;69:48–53. J Rheumatol. 2011;38:2461–5. Disclosure of Interest P. Mease Grant/research support from: Abbott, Amgen, Biogen Idec, Bristol-Myers Squibb, Genentech, Janssen, Eli Lilly, Pfizer Inc, UCB, Celgene Corporation, Novartis, Roche, Consultant for: Abbott, Amgen, Biogen Idec, Bristol-Myers Squibb, Genentech, Janssen, Eli Lilly, Pfizer Inc, UCB, Celgene Corporation, Novartis, Roche, J. Wollenhaupt Grant/research support from: Abbott, Bristol-Myers Squibb, MSD, Pfizer Inc, and UCB, Consultant for: Abbott, Bristol-Myers Squibb, MSD, Pfizer Inc, and UCB, S. Hall Grant/research support from: Celgene Corporation, Pfizer, UCB, Bristol-Myers Squibb, Glaxo-Smith Kline, Roche, Janssen, Novartis, Merck, Consultant for: Celgene Corporation, Pfizer, UCB, Bristol-Myers Squibb, Glaxo-Smith Kline, Roche, Janssen, Novartis, Merck, F. Van den Bosch Grant/research support from: Celgene Corporation, E. Lespessailles Grant/research support from: Amgen, Celgene, Eli Lilly, Novartis, and Servier, Speakers bureau: Amgen, Eli Lilly, Novartis, and Servier, M. McIlraith Employee of: Celgene Corporation, L. Teng Employee of: Celgene Corporation, C. Edwards Grant/research support from: Celgene Corporation, Pfizer Inc, Roche, Samsung, Consultant for: Celgene Corporation, Pfizer Inc, Roche, Samsung, Speakers bureau: Abbott, Glaxo-SmithKline, Pfizer Inc, Roche