J. Wollenhaupt

Clinical efficacy and safety of abatacept in methotrexate-naive patients with early rheumatoid arthritis and poor prognostic factors

Objectives: To assess the efficacy and safety of abatacept in methotrexate-naive patients with early rheumatoid arthritis (RA) and poor prognostic factors. Methods: In this double-blind, phase IIIb study, patients with RA for 2 years or less were randomly assigned 1 : 1 to receive abatacept (∼10 mg/kg) plus methotrexate, or placebo plus methotrexate. Patients were methotrexate-naive and seropositive for rheumatoid factor (RF), anti-cyclic citrullinated protein (CCP) type 2 or both and had radiographic evidence of joint erosions. The co-primary endpoints were the proportion of patients achieving disease activity score in 28 joints (DAS28)-defined remission (C-reactive protein) and joint damage progression (Genant-modified Sharp total score; TS) at year 1. Safety was monitored throughout. Results: At baseline, patients had a mean DAS28 of 6.3, a mean TS of 7.1 and mean disease duration of 6.5 months; 96.5% and 89.0% of patients were RF or anti-CCP2 seropositive, respectively. At year 1, a significantly greater proportion of abatacept plus methotrexate-treated patients achieved remission (41.4% vs 23.3%; p<0.001) and there was significantly less radiographic progression (mean change in TS 0.63 vs 1.06; pu200a=u200a0.040) versus methotrexate alone. Over 1 year, the frequency of adverse events (84.8% vs 83.4%), serious adverse events (7.8% vs 7.9%), serious infections (2.0% vs 2.0%), autoimmune disorders (2.3% vs 2.0%) and malignancies (0.4% vs 0%) was comparable for abatacept plus methotrexate versus methotrexate alone. Conclusions: In a methotrexate-naive population with early RA and poor prognostic factors, the combination of abatacept and methotrexate provided significantly better clinical and radiographic efficacy compared with methotrexate alone and had a comparable, favourable safety profile.

European League Against Rheumatism (EULAR) recommendations for the management of psoriatic arthritis with pharmacological therapies: 2015 update

Background Since the publication of the European League Against Rheumatism recommendations for the pharmacological treatment of psoriatic arthritis (PsA) in 2012, new evidence and new therapeutic agents have emerged. The objective was to update these recommendations. Methods A systematic literature review was performed regarding pharmacological treatment in PsA. Subsequently, recommendations were formulated based on the evidence and the expert opinion of the 34 Task Force members. Levels of evidence and strengths of recommendations were allocated. Results The updated recommendations comprise 5 overarching principles and 10 recommendations, covering pharmacological therapies for PsA from non-steroidal anti-inflammatory drugs (NSAIDs), to conventional synthetic (csDMARD) and biological (bDMARD) disease-modifying antirheumatic drugs, whatever their mode of action, taking articular and extra-articular manifestations of PsA into account, but focusing on musculoskeletal involvement. The overarching principles address the need for shared decision-making and treatment objectives. The recommendations address csDMARDs as an initial therapy after failure of NSAIDs and local therapy for active disease, followed, if necessary, by a bDMARD or a targeted synthetic DMARD (tsDMARD). The first bDMARD would usually be a tumour necrosis factor (TNF) inhibitor. bDMARDs targeting interleukin (IL)12/23 (ustekinumab) or IL-17 pathways (secukinumab) may be used in patients for whom TNF inhibitors are inappropriate and a tsDMARD such as a phosphodiesterase 4-inhibitor (apremilast) if bDMARDs are inappropriate. If the first bDMARD strategy fails, any other bDMARD or tsDMARD may be used. Conclusions These recommendations provide stakeholders with an updated consensus on the pharmacological treatment of PsA and strategies to reach optimal outcomes in PsA, based on a combination of evidence and expert opinion.

Sustained disease remission and inhibition of radiographic progression in methotrexate-naive patients with rheumatoid arthritis and poor prognostic factors treated with abatacept: 2-year outcomes

Objective To assess the efficacy and safety of abatacept plus methotrexate versus methotrexate alone in early erosive rheumatoid arthritis (RA). Methods The AGREE was a 2-year phase IIIb multinational study in early (≤2 years) RA. During the double-blind period (year 1), patients were randomly assigned 1:1 to receive abatacept+methotrexate or methotrexate alone; all patients received open-label abatacept+methotrexate during year 2. Clinical outcomes assessed included 28-joint disease activity score (DAS28) defined remission, low disease activity score (LDAS), American College of Rheumatology (ACR) responses and physical function. Radiographic outcomes were assessed using the Genant-modified Sharp total score (TS). Safety was monitored throughout. Results Of the 459 patients completing year 1, 433 patients (94.3%) completed year 2. DAS28-defined remission, LDAS, ACR and physical function were sustained through year 2 in the original abatacept+methotrexate group, with 55.2% in remission at 2 years. Upon introduction of abatacept in the methotrexate-alone group, additional patients achieved DAS28-defined remission (44.5% vs 26.9%), LDAS (60.4% vs 43.2%) and improved ACR 70 (49.8% vs 31.7%) for year 2 versus year 1. Less radiographic progression was observed at 2 years in the original abatacept+methotrexate group than the methotrexate-alone group (change in TS 0.84 vs 1.75, p<0.001). No new safety issues were seen. Similar rates of serious adverse events, serious infections and autoimmune events were observed in years 1 and 2. Conclusions The AGREE trial was the first to examine the impact of T-cell co-stimulation modulation with abatacept in patients with early erosive RA. Early treatment with abatacept+methotrexate resulted in greater sustainable clinical, functional and radiographic benefits than methotrexate alone, with acceptable safety and tolerability. Trial Registration: NCT00122382

Effect of different imputation approaches on the evaluation of radiographic progression in patients with psoriatic arthritis: results of the RAPID-PsA 24-week phase III double-blind randomised placebo-controlled study of certolizumab pegol

Objectives To report the effect of different imputation methodologies on the assessment of radiographic progression in clinical trials. Methods The 216-week RAPID-psoriatic arthritis (PsA) (NCT01087788) trial of certolizumab pegol (CZP) in patients with active PsA was double-blind and placebo-controlled until week 24. A primary end point was change from baseline in modified Total Sharp Score(s) (mTSS). Prespecified imputation methodology in patients with fewer than two analysable mTSS used minimum observed baseline score for missing baseline values and maximum observed week 24 score for missing week 24 values. Post hoc analyses used alternative methods of imputation in patients with fewer than two analysable mTSS. mTSS non-progressors were defined as patients with ≤0 (predefined) or ≤0.5 (post hoc) change in mTSS from baseline to week 24. Baseline mTSS and C-reactive protein levels as predictors of radiographic progression were investigated. Results 409 patients were randomised. Baseline demographics were similar between groups. Prespecified imputation analysis inappropriately overestimated radiographic progression (least squares mean placebo, 28.9; CZP, 18.3; p≥0.05). Multiple post hoc analyses demonstrated that CZP inhibited radiographic progression compared with placebo, particularly in patients with high baseline mTSS and C-reactive protein levels. mTSS non-progression rate was higher in CZP than placebo groups in all analyses. Conclusions Inappropriate prespecified imputation methodology resulted in an unrealistic assessment of progression in all arms. Methodologies for imputing missing radiographic data can greatly affect assessment and reporting of mTSS progression.

Effect of certolizumab pegol over 96 weeks in patients with psoriatic arthritis with and without prior antitumour necrosis factor exposure.

Objective Previous reports of RAPID-PsA (NCT01087788) demonstrated efficacy and safety of certolizumab pegol (CZP) over 24u2005weeks in patients with psoriatic arthritis (PsA), including patients with prior antitumour necrosis factor (TNF) therapy. We report efficacy and safety data from a 96-week data cut of RAPID-PsA. Methods RAPID-PsA was placebo-controlled to week 24, dose-blind to week 48 and open-label to week 216. We present efficacy data including American College of Rheumatology (ACR)/Psoriasis Area and Severity Index (PASI) responses, HAQ-DI, pain, minimal disease activity (MDA), modified total Sharp score (mTSS) and ACR responses in patients with/without prior anti-TNF exposure, in addition to safety data. Results Of 409 patients randomised, 273 received CZP from week 0. 54 (19.8%) CZP patients had prior anti-TNF exposure. Of patients randomised to CZP, 91% completed week 24, 87% week 48 and 80% week 96. ACR responses were maintained to week 96: 60% of patients achieved ACR20 at week 24, and 64% at week 96. Improvements were observed with both CZP dose regimens. ACR20 responses were similar in patients with (week 24: 59%; week 96: 63%) and without (week 24: 60%; week 96: 64%) prior anti-TNF exposure. Placebo patients switching to CZP displayed rapid clinical improvements, maintained to week 96. In patients with ≥3% baseline skin involvement (60.8% week 0 CZP patients), PASI responses were maintained to week 96. No progression of structural damage was observed over the 96-week period. In the Safety Set (n=393), adverse events occurred in 345 patients (87.8%) and serious adverse events in 67 (17.0%), including 6 fatal events. Conclusions CZP efficacy was maintained to week 96 with both dose regimens and in patients with/without prior anti-TNF exposure. The safety profile was in line with that previously reported from RAPID-PsA, with no new safety signals observed with increased exposure. Trial registration number NCT01087788.

SAT0408 Long-Term Safety and Tolerability 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), an oral phosphodiesterase 4 inhibitor, works intracellularly to regulate inflammatory mediators. PALACE 1, 2, and 3 compared the efficacy and safety of APR with placebo (PBO) in patients with active PsA despite prior conventional DMARDs and/or biologics. Objectives The overall safety and tolerability of APR was assessed in a pooled analysis of PALACE 1, 2, and 3, with APR exposure ≥52 wks. Methods Patients were randomized 1:1:1 to PBO, APR 20 mg BID (APR20), or APR 30 mg BID (APR30) stratified by baseline (BL) DMARD use (yes/no). Patients with <20% reduction from BL in swollen or tender joint counts were required to be re-randomized to APR20 or APR30 if initially randomized to PBO, or continued on their initial APR dose. At Wk 24, all remaining PBO patients were re-randomized to APR20 or APR30. Patients taking concurrent DMARDs were allowed to continue stable doses (MTX, sulfasalazine, leflunomide, or a combination). Results 1,493 patients received study medication (PBO: 495; APR20: 501; APR30: 497) and were included in the safety population. The APR-exposure period included 720 patients treated with APR20 (766.4 patient-yrs) and 721 with APR30 (769.0 patient-yrs). The nature, incidence, and severity of AEs were comparable through the 24-wk and 52-wk periods (Table). The most common AEs were diarrhea (14.3%), nausea (12.6%), headache (10.1%), URTI (10.3%), and nasopharyngitis (7.4%). Most AEs were mild or moderate in severity. Discontinuations due to AEs (APR20: 7.5%; APR30: 8.3%) were low, occurring primarily in the first 24 wks of treatment. Serious AEs (SAEs) occurred in 6.8% (APR20) and 7.2% (APR30) of patients. One death occurred (APR20) due to multiorgan failure not suspected to be treatment-related. Diarrhea and nausea were predominantly mild and occurred at a reduced incidence after the first month of dosing, with the highest incidence reported in the first 2 wks of treatment. Most cases resolved within 30 days despite continued therapy and without medical intervention. Discontinuation due to GI AEs was 4% through Wk 52, with nausea (1.7%) and diarrhea (1.5%) being the most common. There was 1 case of diarrhea and 1 case of nausea reported as an SAE in the 0 to ≥24-wk period, and no additional cases reported in the 0 to ≥52-wk period. Exposure-adjusted incidence rates of major adverse cardiac events, serious infections including systemic opportunistic infection, or malignancies were comparable to PBO. Laboratory abnormalities were infrequent and transient with no trends or patterns observed. Conclusions APR demonstrated an acceptable safety profile and was generally well tolerated through 52 wks; the nature, incidence, and severity of AEs were comparable through the 24-wk and 52-wk periods. These data do not indicate a need for laboratory monitoring. Disclosure of Interest P. Mease Grant/research support: Celgene Corporation, Novartis, and Roche, Consultant for: Abbott, Amgen, Biogen Idec, Bristol-Myers Squibb, Genentech, Janssen, Eli Lilly, Pfizer Inc, and UCB, A. Kavanaugh Grant/research support: Abbott, Amgen, Astra-Zeneca, Bristol-Myers Squibb, Celgene Corporation, Centocor-Janssen, Pfizer Inc, Roche, and UCB, D. Gladman Grant/research support: AbbVie, Amgen, Bristol-Myers Squibb, Celgene Corporation, Janssen, Pfizer Inc, Novartis, and UCB, A. Adebajo: None declared, J. Gomez-Reino Grant/research support: 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, J. Wollenhaupt Grant/research support: Abbott, Bristol-Myers Squibb, MSD, Pfizer Inc, and UCB, M. Cutolo Grant/research support: Actelion, Bristol-Myers Squibb, and G. Schett Grant/research support: Abbott, Celgene Corporation, Roche, E. Lespessailles Grant/research support: Amgen, Eli Lilly, Novartis, and Servier, K. Shah Employee of: Celgene Corporation, C. Hu Employee of: Celgene Corporation, R. Stevens Employee of: Celgene Corporation, C. Edwards Grant/research support: Celgene Corporation, Pfizer Inc, Roche, and Samsung, Speakers bureau: Abbott, Glaxo-SmithKline, Pfizer Inc, and Roche, C. Birbara Grant/research support: Amgen, Bristol-Myers Squibb, Incyte, Eli Lilly, Merck, and DOI 10.1136/annrheumdis-2014-eular.5589

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

AB0758 Change in Weight from Baseline during the Palace Clinical Trial Program with Apremilast, an Oral Phosphodiesterase 4 Inhibitor: Pooled Results from 3 Phase 3, Randomized, Controlled Trials

Background PALACE 1, 2, and 3 assessed the efficacy/safety of apremilast (APR) in pts with active PsA despite prior DMARDs and/or biologics. Objectives Assess weight change from BL in PALACE 1, 2, and 3. 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). Pts with <20% reduction from BL in SJC or TJC at Wk 16 were required to be re-randomized to APR20 or APR30 if initially randomized to PBO, or continued on their initial APR dose. At Wk 24, all remaining PBO pts were re-randomized to APR20 or APR30. The pooled analysis comprises data for the PBO-controlled period (Wks 0 to 24) and the APR-exposure period (Wks 0 to ≥52) up to cutoff date, 3/1/2013. Results During the PBO-controlled period, 495 pts received PBO, 501 received APR20, and 497 received APR30. At cutoff, 720 pts had received APR20 and 721 had received APR30. At BL, mean/median weight was 86.4/84.0 (PBO), 86.1/84.0 (APR20), and 84.5/83.0 (APR30) kg. Weight decrease was reported as an AE in a small proportion of pts during the PBO-controlled (PBO: 0.4%; APR20: 1.0%; APR30: 1.4%) and APR-exposure (APR20: 1.4%; APR30: 1.8%) periods. No pts in the PBO-controlled period and 2/1441 pt (APR20, 1; APR30, 1) in the APR-exposure period discontinued due to weight decrease. Weight loss has been reported with other PDE4 inhibitors. An additional analysis using observed weight measurements collected at selected visits assessed any changes from BL weight. In the PBO-controlled period, most pts remained within 5% of their BL weight (PBO: 92.1%; APR20: 83.5%; APR30: 86.4%). A larger proportion of APR-treated pts experienced weight loss (APR20: 57.9%; APR30: 56.8%) vs PBO (40.1%). Weight loss >5% was experienced by 3.9% (PBO), 12.7% (APR20), and 11.0% (APR30) (Table). At the end of the PBO-controlled period, mean/median weight change from BL was 0.09/0.0 (PBO), -1.16/-0.60 (APR20), and -0.96/-0.60 (APR30) kg. In the APR-exposure period (Wks 0 to ≥52), most pts remained within 5% of BL weight (APR20: 77.0%; APR30: 75.8%); 57.3% (APR20) and 57.1% (APR30) experienced weight loss. Weight loss did not lead to any overt medical sequelae or manifestations through the APR-exposure period. In an analysis to determine the relationship between weight loss and gastrointestinal (GI) AEs, weight loss was not associated with diarrhea or nausea/vomiting. Conclusions APR was associated with a low rate of weight decrease reported as an AE. The incidence of observed weight loss was higher with APR vs PBO, although most pts remained within 5% of their BL weight. Observed weight loss did not appear to be dose-dependent and did not lead to overt clinical sequelae. No association between weight loss and incidence of other AEs, including GI AEs, was apparent. Disclosure of Interest P. Mease Grant/research support: for Abbott, Amgen, Biogen Idec, Bristol-Myers Squibb, Genentech, Janssen, Eli Lilly, Pfizer Inc, and UCB, Consultant for: Celgene Corporation, Novartis, and Roche, D. Gladman Grant/research support: AbbVie, Amgen, Bristol-Myers Squibb, Celgene Corporation, Janssen, Pfizer Inc, Novartis, and UCB, A. Kavanaugh Grant/research support: Abbott, Amgen, Astra-Zeneca, Bristol-Myers Squibb, Celgene Corporation, Centocor-Janssen, Pfizer Inc, Roche, and UCB, A. Adebajo: None declared, J. Gomez-Reino Grant/research support: Roche and Schering-Plough, Consultant for: Bristol-Myers Squibb, Roche, Schering-Plough, and Wyeth, Speakers bureau: Bristol-Myers Squibb, Pfizer Inc, Roche, Schering-Plough, and UCB SA, J. Wollenhaupt: None declared, G. Schett Grant/research support: Abbott, Celgene Corporation, Roche, K. Shah Employee of: Celgene Corporation, C. Hu Employee of: Celgene Corporation, R. Stevens Employee of: Celgene Corporation, C. Edwards Grant/research support: Celgene Corporation, Pfizer Inc, Roche, and Samsung, Speakers bureau: Abbott, Glaxo-SmithKline, Pfizer Inc, and Roche, C. Birbara Grant/research support: Amgen, Bristol-Myers Squibb, Incyte, Eli Lilly, Merck, and DOI 10.1136/annrheumdis-2014-eular.2391

OP0078 Apremilast, an Oral Phosphodiesterase 4 Inhibitor, is Associated with Long-Term (52-WEEK) Improvement in Measures of Disease Activity in Patients with Psoriatic Arthritis: Results from 3 Phase 3, Randomized, Controlled Trials

Background Apremilast (APR), an oral phosphodiesterase 4 inhibitor, works intracellularly to regulate inflammatory mediators. The PALACE 1, 2, and 3 trials compared the efficacy and safety of APR with placebo (PBO) in patients with active psoriatic arthritis (PsA) despite prior conventional disease-modifying antirheumatic drugs (DMARDs) and/or biologics. Objectives Evaluate the impact of APR over 52 weeks on PsA disease activity. Methods Patients 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). Patients with <20% reduction from baseline in swollen or tender joint counts at Week 16 were required to be re-randomized to APR20 or APR30 if 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. This analysis reports data over 52 weeks. Disease activity was evaluated using the DAS-28 (CRP), modified PsARC response, and good or moderate EULAR response. Results At Week 16, a significantly greater proportion of patients treated with APR achieved a modified ACR20 response vs PBO (primary endpoint). In patients initially randomized to APR and completing 52 weeks, ACR20 response was sustained over 52 weeks. APR20 and APR30 demonstrated improvement in disease activity vs PBO at Week 16, as measured by the DAS-28 (CRP), modified PsARC response, and good or moderate EULAR response. Among patients who were continuously treated with APR through 52 weeks sustained improvements were observed at Week 52 (Table). The most common adverse events reported during the PBO-controlled period (PAL 1-3; pooled) were diarrhea (12.2%), nausea (10.1%), and headache (8.0%). The safety profile of APR through 52 weeks was similar to that observed with APR for up to 24 weeks of treatment (PBO-controlled period). Conclusions APR demonstrated clinically meaningful improvements in measures of PsA disease activity through Week 52. APR demonstrated an acceptable safety profile and was generally well tolerated through 52 weeks. Disclosure of Interest A. Kavanaugh Grant/research support: Abbott, Amgen, Astra-Zeneca, Bristol-Myers Squibb, Celgene Corporation, Centocor-Janssen, Pfizer Inc., Roche, and UCB, M. Cutolo Grant/research support: Actelion, Bristol-Myers Squibb, and Sanofi-Aventis, Consultant for: Actelion, Bristol-Myers Squibb, and Sanofi-Aventis, P. Mease Grant/research support: Abbott, Amgen, Biogen Idec, Bristol-Myers Squibb, Genetech, Janssen, Eli Lilly, Pfizer Inc.,Celgene Corporation, Novartis, Roche and UCB, Consultant for: Abbott, Amgen, Biogen Idec, Bristol-Myers Squibb, Genetech, Janssen, Eli Lilly, Pfizer Inc., Celgene Corporation, Novartis, Roche and UCB, Speakers bureau: Abbott, Amgen, Biogen Idec, Bristol-Myers Squibb, Genetech, Janssen, Eli Lilly, Pfizer Inc., and UCB, D. Gladman Grant/research support: 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, A. Adebajo: None declared, J. Gomez-Reino Grant/research support: 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, J. Wollenhaupt Grant/research support: Abbott, Bristol-Myers Squibb, MSD, Pfizer Inc., and UCB, Consultant for: Abbott, Bristol-Myers Squibb, MSD, Pfizer Inc., and UCB, G. Schett Grant/research support: Abbott, Celgene Corporation, Roche, and UCB, Consultant for: Abbott, Celgene Corporation, Roche, and UCB, E. Lespessailles Grant/research support: Amgen, Eli Lilly, Novartis, and Servier, Speakers bureau: Amgen, Eli Lilly, Novartis, and Servier, C. Hu Employee of: Celgene Corporation, R. Stevens Employee of: Celgene Corporation, C. Edwards Grant/research support: 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, C. Birbara Grant/research support: Bristol-Myers Squibb, Incyte, Eli Lilly, Merck, and Pfizer Inc. DOI 10.1136/annrheumdis-2014-eular.1827

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