Lichen Teng

THU0432 Long-Term (104-Week) Safety Profile of Apremilast, An Oral Phosphodiesterase 4 Inhibitor, In Patients with Psoriatic Arthritis: Pooled Safety Analysis of Three Phase 3, Randomized, Controlled Trials

Background Apremilast (APR), a phosphodiesterase 4 inhibitor, helps regulate the immune responses in psoriatic arthritis (PsA). PALACE 1-3 compared APR efficacy/safety with placebo (PBO) in patients (pts) with active PsA despite prior conventional DMARDs and/or biologics. Objectives Overall APR safety/tolerability was assessed in a pooled analysis of PALACE 1-3, with APR exposure ≤104 wks. Methods Pts were randomized (1:1:1) to PBO, APR 20 mg BID (APR20), or APR 30 mg BID (APR30) stratified by baseline DMARD use (yes/no). The PBO-controlled phase continued to Wk 24, with an early escape option at Wk 16. Double-blind APR treatment continued to Wk 52; pts could continue to receive APR during an open-label, long-term treatment phase. We report safety findings from the APR-exposure period (Wks 0 to ≤104). Results 1493 pts were randomized and received ≥1 dose of study medication (PBO: n=495; APR20: n=501; APR30: n=497). A total of 1441 (1209.3 pt-yrs) and 1028 (907.7 pt-yrs) pts received APR in the Wk 0 to ≤52 and Wk >52 to ≤104 periods, respectively. During Wks 0 to ≤52, AEs occurring in ≥5% of APR-exposed pts were diarrhea, nausea, headache, URTI, and nasopharyngitis (Table). Most AEs were mild/moderate in severity during the Wk 0 to ≤104 APR-exposure period; in general, no increase was seen in the incidence/severity of AEs with longer term exposure. During Wks >52 to ≤104, diarrhea (2.9%), nausea (1.8%), and headache (3.0%) occurred at lower rates vs Wks 0 to ≤52 (Table). In Wks 0 to ≤52, 87 pts reported serious AEs (SAEs) vs 71 pts in Wks >52 to ≤104. In few system organ classes, there were numerically more pts reporting SAEs but it did not indicate any specific organ involvement. The vast majority of the SAEs were reported by 1 pt each. There was no increase in cardiac, malignant neoplasm, opportunistic infection, or psychiatric disorder related SAEs and no cases of tuberculosis (new/reactivation) reported with either APR dose. Discontinuations due to AEs occurred at a lower rate (2.3%) during Wks >52 to ≤104. Marked laboratory abnormalities were generally infrequent and most returned to baseline with continued treatment or were associated with a concurrent medical condition. Conclusions 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 the lack of a need for specific laboratory monitoring with APR. 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, and Roche, Consultant for: Abbott, Amgen, Biogen Idec, Bristol-Myers Squibb, Genentech, Janssen, Eli Lilly, Pfizer Inc, UCB, Celgene Corporation, Novartis, and Roche, Speakers bureau: Abbott, Amgen, Biogen Idec, Bristol-Myers Squibb, Genentech, Janssen, Eli Lilly, Pfizer Inc, and UCB, A. Adebajo: None declared, D. Gladman Grant/research support from: AbbVie, Amgen, Bristol-Myers Squibb, Celgene Corporation, Janssen, Pfizer Inc, Novartis, and UCB, Consultant for: AbbVie, Amgen, Bristol-Myers Squibb, Celgene Corporation, Janssen, Pfizer Inc, Novartis, and UCB, J. Gomez-Reino Grant/research support from: Roche and Schering-Plough, Consultant for: Bristol-Myers Squibb, Pfizer Inc, Roche, Schering-Plough, and UCB SA, Speakers bureau: Bristol-Myers Squibb, Roche, Schering-Plough, and Wyeth, S. Hall Consultant for: Boehringer Ingelheim, MSD, Roche Schering Plough, Servier, and Wyeth., Paid instructor for: Amgen, AstraZeneca, Boehringer Ingelheim, Centocor, GlaxoSmithKline, MSD, Pfizer, Sanofi Aventis, Sanofi Pasteur, Schering-Plough, Serono, and Wyeth, Speakers bureau: Boehringer Ingelheim, GlaxoSmithKline, MSD, Pfizer, Roche, Sanofi Aventis, Schering-Plough, and Wyeth;, A. Kavanaugh Grant/research support from: Abbott, Amgen, Astra-Zeneca, Bristol-Myers Squibb, Celgene Corporation, Centocor-Janssen, Pfizer Inc, Roche, and UCB, E. Lespessailles Grant/research support from: Amgen, Eli Lilly, Novartis, and Servier, Speakers bureau: Amgen, Eli Lilly, Novartis, and Servier, G. Schett Grant/research support from: Abbott, Celgene Corporation, Roche, and UCB, Consultant for: Abbott, Celgene Corporation, Roche, and UCB, K. Shah Employee of: Celgene Corporation, L. Teng Employee of: Celgene Corporation, 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

Early and sustained efficacy with apremilast monotherapy in biological-naïve patients with psoriatic arthritis: a phase IIIB, randomised controlled trial (ACTIVE)

Objective Evaluate apremilast efficacy across various psoriatic arthritis (PsA) manifestations beginning at week 2 in biological-naïve patients with PsA. Methods Patients were randomised (1:1) to apremilast 30 mg twice daily or placebo. At week 16, patients whose swollen and tender joint counts had not improved by ≥10% were eligible for early escape. At week 24, all patients received apremilast through week 52. Results Among 219 randomised patients (apremilast: n=110; placebo: n=109), a significantly greater American College of Rheumatology 20 response at week 16 (primary outcome) was observed with apremilast versus placebo (38.2% (42/110) vs 20.2% (22/109); P=0.004); response rates at week 2 (first assessment) were 16.4% (18/110) versus 6.4% (7/109) (P=0.025). Improvements in other efficacy outcomes, including 28-joint count Disease Activity Score (DAS-28) using C reactive protein (CRP), swollen joint count, Health Assessment Questionnaire-Disability Index (HAQ-DI), enthesitis and morning stiffness severity, were observed with apremilast at week 2. At week 16, apremilast significantly reduced PsA disease activity versus placebo, with changes in DAS-28 (CRP) (P<0.0001), HAQ-DI (P=0.023) and Gladman Enthesitis Index (P=0.001). Improvements were maintained with continued treatment through week 52. Over 52 weeks, apremilast’s safety profile was consistent with prior phase 3 studies in psoriasis and PsA. During weeks 0–24, the incidence of protocol-defined diarrhoea was 11.0% (apremilast) and 8.3% (placebo); serious adverse event rates were 2.8% (apremilast) and 4.6% (placebo). Conclusions In biological-naïve patients with PsA, onset of effect with apremilast was observed at week 2 and continued through week 52. The safety profile was consistent with previous reports. Trial registration number NCT01925768; Results.

Apremilast monotherapy in DMARD-naive psoriatic arthritis patients: results of the randomized, placebo-controlled PALACE 4 trial

Abstract Objectives The PALACE 4 trial evaluated apremilast monotherapy in patients with active PsA who were DMARD-naive. Methods Eligible patients were randomized (1:1:1) to placebo, apremilast 20 mg twice a day or apremilast 30 mg twice a day. At week 16 or 24, placebo patients were rerandomized to apremilast. Double-blind apremilast treatment continued to week 52, with extension up to 4 years. The primary endpoint was the proportion of patients achieving ⩾20% improvement in ACR response criteria (ACR20) at week 16; secondary endpoints included the mean change in the HAQ Disability Index (HAQ-DI) score at week 16. Results A total of 527 patients with mean disease duration of 3.4 years and high disease activity were randomized and received treatment. More apremilast patients achieved ACR20 response at week 16 [placebo, 15.9%; 20 mg, 28.0% (P = 0.0062); 30 mg, 30.7% (P = 0.0010)]. The mean HAQ-DI improvements were −0.17 (20 mg; P = 0.0008) and −0.21 (30 mg; P < 0.0001) vs 0.03 (placebo). Both apremilast doses showed significant ACR50 responses vs placebo at week 16 and improvements in secondary efficacy measures (swollen/tender joint counts) and psoriasis assessments, with sustained improvements through week 52. Common adverse events (AEs) over 52 weeks were diarrhoea, nausea, headache and upper respiratory tract infection; most events were mild or moderate. Serious AEs and AEs leading to discontinuation were comparable between groups. Laboratory abnormalities were infrequent and transient. Conclusions In DMARD-naive patients, apremilast monotherapy improved PsA signs/symptoms over 52 weeks and was generally well tolerated. Trial registration ClinicalTrials.gov (http://clinicaltrials.gov), NCT01307423.

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

OP0309 Characterisation of clinical benefits in subjects classified as acr20 non-responders at week 104 of apremilast treatment: subanalysis of 3 long-term, phase iii trials

Background The PALACE 1, 2, and 3 trials evaluated the efficacy and safety of apremilast (APR) in subjects with active psoriatic arthritis (PsA) despite prior conventional disease-modifying anti-rheumatic drugs and/or biologics. Objectives The aim of this analysis is to further characterise the clinical benefits associated with long-term APR exposure in subjects who failed to achieve an ACR20 response at Week 104. Methods Subjects were randomised (1:1:1) to receive placebo (PBO), APR 30 mg BID (APR30), or APR 20 mg BID at baseline. Subjects who were randomised to APR30 at baseline and classified as ACR20 non-responders (ACR20NRs) at Week 104 were considered for this analysis. At Weeks 24, 52, and 104, ACR core components were examined as well as the proportions of subjects achieving PASI-75/PASI-50 among those with psoriasis involvement ≥3% of the body surface area at baseline, and dactylitis count and MASES of 0 among those with dactylitis or enthesitis at baseline. Safety is described for the overall PALACE 1–3 population. Results A total of 109 subjects randomised to APR30 treatment at baseline were ACR20NRs at Week 104. Baseline ACR core components were similar for ACR20NRs and ACR20 responders at Week 104. Among these ACR20NRs, several core components of ACR response, including swollen/tender joint counts and Physician’s Global Assessment of Disease Activity (visual analogue scale) scores, showed sustained improvements from baseline through Week 104 (table 1). Importantly, of the 109 ACR20NRs at Week 104, 50.0% achieved a PASI-50 response after continued treatment with APR30 through Week 104 (table 1). Among ACR20NRs with baseline dactylitis (n=44) or enthesitis (n=74), 68.2% achieved a dactylitis count of 0% and 33.8% achieved a MASES of 0 at Week 104. More limited improvements in Subject’s Global Assessment of Disease Activity, Subject’s Assessment of Pain, Health Assessment Questionnaire-Disability Index, and C-reactive protein outcomes most commonly had an impact on subjects’ ability to achieve an ACR20 response. In the overall subject population, no new safety concerns were identified through 104 weeks.Abstract OP0309 – Table 1 Conclusions ACR20NRs receiving APR30 demonstrated significant improvements in core PsA domains. The data may explain why subjects who failed to achieve an ACR20 response remained on long-term APR treatment. These findings suggest that some subjects with PsA may experience meaningful clinical improvement that is not completely captured by the assessment of ACR20 response criteria. Outcome measures specifically designed for PsA subjects, may be more suitable to evaluate treatment response in PsA subjects. 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, 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, A. Kavanaugh Grant/research support from: Abbott, Amgen, AstraZeneca, BMS, Celgene Corporation, Centocor-Janssen, Pfizer, Roche, UCB, P. Nakasato Employee of: Celgene Corporation, B. Guerette Employee of: Celgene Corporation, L. Teng Employee of: Celgene Corporation, P. Nash Grant/research support from: Celgene Corporation

AB0946 Improvements in work productivity with up to 104 weeks of apremilast monotherapy: results from a phase 3b, randomised, controlled study in biologic-naÏve subjects with active psoriatic arthritis

Background Psoriatic arthritis (PsA) patients may experience disease manifestations across multiple domains and impaired functioning in daily activities at home and work. The phase 3b ACTIVE study is evaluating the efficacy of apremilast (APR) monotherapy in biologic-naïve subjects with active PsA who may have had exposure to 1 prior conventional DMARD. Objectives To assess work productivity through Week 104. Methods Subjects were randomised (1:1) to receive APR 30 mg BID or placebo (PBO). Subjects who did not improve by ≥10% in swollen and tender joint counts at Week 16 were eligible for early escape. At Week 24, all remaining PBO subjects were switched to APR. Work productivity and activity impairment were assessed at baseline (BL) and Week 16 using the 6-item, self-administered Work Productivity and Activity Impairment Questionnaire: Psoriatic Arthritis (WPAI:PsA). WPAI:PsA includes 4 subscale scores (Absenteeism, Presenteeism, Work Productivity Loss, and Activity Impairment), each ranging from 0% to 100%; higher scores indicate greater impairment. Work-related subscales were evaluated only among employed subjects, while activity impairment was evaluated among all subjects, regardless of employment. Correlations were examined at Week 16 between WPAI:PsA subscale scores and the SF-36v2 domain scores for Physical Functioning (PF), Bodily Pain (Pain), and Vitality (VIT), as well as associations with ACR20 response. Improvement in work productivity was assessed through Week 104. Results BL characteristics were similar between APR and PBO subjects with WPAI:PsA scores included in this analysis. At Week 16, APR significantly improved work productivity and the ability to carry out daily activities vs PBO, with significantly greater mean improvements observed in the overall Work Productivity Loss (p=0.001) and Activity Impairment (p<0.001) scores (table 1). Estimated mean change in the Absenteeism score was similar with APR vs PBO (p=0.679). By contrast, the Presenteeism score showed significant improvement with APR vs worsening with PBO (−10.8% vs 4.1%; p=0.002). At Week 16, statistically significant correlations were observed between WPAI:PsA subscale scores (except Absenteeism) and the SF-36v2 domain scores for PF, Pain, and VIT, as were associations with ACR20 response. Among subjects randomised to APR at BL, improvements in Week 16 WPAI:PsA subscale score were generally maintained through Week 104 in those continuing APR.Abstract AB0946 – Figure 1 Results are from an analysis of covariance model, adjusted with BL WPAI: PsA subscale score, BL prednisone use (yes/no), and previous DMARD use (yes/no). LS mean is estimated using the observed margins of the covariates. WPAI: PsA scores were evaluated for subjects with values at both BL and Week 16. Absenteeism, Presenteeism, and Work Productivity Loss were evaluated only among employed subjects. Activity Impairment scores were evaluated among all randomised subjects with scores at BL and Week 16, regardless of employment status. CI=confidence interval; LS=least square. Conclusions In biologic-naïve subjects with PsA, APR monotherapy contributed to an overall improvement in work productivity at Week 16, which correlated with SF-36v2 PF, Pain, and VIT scores and was associated with ACR20 response; improvements in WPAI:PsA subscale scores were generally maintained to Week 104. 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, D. Gladman Grant/research support from: AbbVie, Amgen, BMS, Celgene Corporation, Janssen, Novartis, Pfizer, and UCB, Consultant for: AbbVie, Amgen, BMS, Celgene Corporation, Janssen, Novartis, Pfizer, and UCB, E. Davenport: None declared, X. Zhou: None declared, B. Guerette Employee of: Celgene Corporation, L. Teng Employee of: Celgene Corporation, S. Kaura Employee of: Celgene Corporation, P. Nash Grant/research support from: Celgene Corporation

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

AB0785 Consistent safety profile with up to 4 years of apremilast treatment: analysis of data from 1493 patients with psoriatic arthritis in 3 large, phase iii, long-term studies

Background Apremilast (APR), an oral phosphodiesterase 4 inhibitor, regulates immune activity in psoriatic arthritis (PsA) patients. Safety data were pooled from the phase 3 PALACE 1, 2, and 3 studies. Objectives Evaluate the long-term safety of APR treatment for up to 4 years in patients with active PsA despite prior conventional DMARDs and/or biologics. Methods Patients were randomized at baseline (1:1:1) to placebo (PBO), APR 30 mg BID (APR30), or APR 20 mg BID (APR20). PBO patients were re-randomized to APR30 or APR20 at Week 16 (early escape) or Week 24. Double-blind APR treatment continued to Week 52; patients could continue APR during an open-label, long-term treatment phase for up to 5 years treatment. Visits in years 2, 3, and 4 were scheduled at 13-week intervals. Safety was assessed at each visit throughout the study, and results are summarized here by exposure. Results A total of 1493 patients were randomized and received ≥1 dose of study medication (PBO: n=495; APR30: n=497; APR20: n=501). At the 4-year data cut, the numbers of patients receiving APR30 and APR20 in each exposure period were 1441 in Weeks 0 to ≤52, 1028 in Weeks >52 to ≤104, 865 in Weeks >104 to ≤156, and 767 in Weeks >156 to ≤208. During the 0- to ≤52-week APR-exposure period, adverse events (AEs) occurring in ≥5% of APR30-exposed patients were diarrhea, nausea, headache, upper respiratory tract infection, and nasopharyngitis (Table). Most diarrhea and nausea AEs were reported within the first 2 weeks of treatment and usually resolved within 4 weeks; the frequency of gastrointestinal AEs decreased with longer APR30 exposure, and the frequency of other common AEs either decreased or remained stable with prolonged exposure (Table). Most AEs were mild/moderate in severity. During Weeks >156 to ≤208 of APR exposure, the discontinuation rate due to AEs was 1.7% with APR30, and the rate of serious AEs (SAEs) was 7.0%, consistent with earlier periods; most SAEs occurred in 1 patient each. Rates were very low for major cardiac events, malignant neoplasms, and serious opportunistic infections, comparable to the first year of treatment. Rates of depression remained very low in Weeks >156 to ≤208. Marked laboratory abnormalities were infrequent, and most returned to baseline with continued treatment. Conclusions APR30 demonstrated a favorable safety profile and was well tolerated for up to 208 weeks, marked by the lack of accumulation of immunosuppression or need for specific laboratory monitoring. The incidence of AEs remained stable or decreased with long-term exposure to APR30. 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, 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, A. Kavanaugh Grant/research support from: Abbott, Amgen, AstraZeneca, BMS, Celgene Corporation, Centocor-Janssen, Pfizer, Roche, UCB, E. Lespessailles Grant/research support from: Amgen, Eli Lilly, Novartis, Servier, Speakers bureau: Amgen, Eli Lilly, Novartis, Servier, G. Schett Grant/research support from: Abbott, Celgene Corporation, Roche, UCB, Consultant for: Abbott, Celgene Corporation, Roche, UCB, 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

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