A. Adebajo

Treatment of psoriatic arthritis in a phase 3 randomised, placebo-controlled trial with apremilast, an oral phosphodiesterase 4 inhibitor

Objectives Apremilast, an oral phosphodiesterase 4 inhibitor, regulates inflammatory mediators. Psoriatic Arthritis Long-term Assessment of Clinical Efficacy 1 (PALACE 1) compared apremilast with placebo in patients with active psoriatic arthritis despite prior traditional disease-modifying antirheumatic drug (DMARD) and/or biologic therapy. Methods In the 24-week, placebo-controlled phase of PALACE 1, patients (N=504) were randomised (1:1:1) to placebo, apremilast 20 mg twice a day (BID) or apremilast 30 mg BID. At week 16, patients without ≥20% reduction in swollen and tender joint counts were required to be re-randomised equally to either apremilast dose if initially randomised to placebo or remained on their initial apremilast dose. Patients on background concurrent DMARDs continued stable doses (methotrexate, leflunomide and/or sulfasalazine). Primary outcome was the proportion of patients achieving 20% improvement in modified American College of Rheumatology response criteria (ACR20) at week 16. Results At week 16, significantly more apremilast 20 mg BID (31%) and 30 mg BID (40%) patients achieved ACR20 versus placebo (19%) (p<0.001). Significant improvements in key secondary measures (physical function, psoriasis) were evident with both apremilast doses versus placebo. Across outcome measures, the 30-mg group generally had higher and more consistent response rates, although statistical comparison was not conducted. The most common adverse events were gastrointestinal and generally occurred early, were self-limiting and infrequently led to discontinuation. No imbalance in major adverse cardiac events, serious or opportunistic infections, malignancies or laboratory abnormalities was observed. Conclusions Apremilast was effective in the treatment of psoriatic arthritis, improving signs and symptoms and physical function. Apremilast demonstrated an acceptable safety profile and was generally well tolerated. Clinical trial registration number NCT01172938.

Longterm (52-week) Results of a Phase III Randomized, Controlled Trial of Apremilast in Patients with Psoriatic Arthritis

Objective. To evaluate the efficacy and safety of apremilast, an oral phosphodiesterase 4 inhibitor, over 52 weeks in patients with active psoriatic arthritis (PsA) despite prior treatment. Methods. Patients were randomized to placebo (n = 168), apremilast 20 mg BID (n = 168), or apremilast 30 mg BID (n = 168). Patients whose swollen and tender joint counts had not improved by ≥ 20% at Week 16 were considered nonresponders and were required to be re-randomized (1:1) to apremilast 20 mg BID or 30 mg BID if they were initially randomized to placebo, or continued their initial treatment of apremilast dose. At Week 24, all remaining patients treated with placebo were re-randomized to apremilast 20 mg BID or 30 mg BID. Results. An American College of Rheumatology 20 (ACR20) response at Week 16 was attained by significantly more patients receiving apremilast 20 mg BID (30.4%, p = 0.0166) or 30 mg BID (38.1%, p = 0.0001) than placebo (19.0%). Among patients receiving apremilast continuously for 52 weeks (n = 254), ACR20 response at Week 52 was observed in 63.0% (75/119, 20 mg BID) and 54.6% (71/130, 30 mg BID) of patients. Response was also maintained across secondary outcomes, including measures of PsA signs and symptoms, skin psoriasis severity, and physical function. The nature, incidence, and severity of adverse events were comparable over the 24-week and 52-week periods. The most common adverse events, diarrhea and nausea, generally occurred early and were self-limited. Conclusion. Continuous apremilast treatment resulted in sustained improvements in PsA for up to 52 weeks. Apremilast had an acceptable safety profile and was generally well tolerated. Clinical trial registration: NCT01172938.

Effect of Psoriatic Arthritis According to the Affected Categories of the International Classification of Functioning, Disability and Health

Objective. To determine the categories of the International Classification of Functioning, Disability and Health (ICF) checklist and core sets of rheumatoid arthritis and ankylosing spondylitis frequently occurring in people with psoriatic arthritis (PsA) and to compare the number of such categories with scores on self-report measures of participation restrictions and activity limitations. Methods. Data were collected from 94 patients with PsA attending rheumatology clinics in 6 centers. For each ICF category affected by PsA in at least 30% of patients, the percentage of such patients was determined for Body Structures, Body Functions, Activities and Participation, and Environmental Factors. A count of all affected categories by ICF chapter was compared to patient self-report scores on a number of functional and health status instruments using Spearman’s correlation. Results. There were 25 categories in the Body Functions section, 6 categories in the Body Structures section, and 51 categories in the Activities and Participation section that were relevant in at least 30% of participants. Thirteen Environmental Factors were facilitating and 1 Environmental Factor (climate) was a barrier in at least 30% of participants. The number of involved Activities and Participation categories by chapter did not correlate in predictable ways with self-report measures of participation restrictions and activity limitations. Conclusion. PsA is associated with a wide range of impairments, limitations, and restrictions across the ICF categories. People with PsA find environmental factors to be helpful more often than to be barriers. The unexpected pattern of correlation between ICF chapters and self-report measures suggests the need for a better way of quantitatively representing the ICF concepts.

A Delphi Exercise to Identify Characteristic Features of Gout — Opinions from Patients and Physicians, the First Stage in Developing New Classification Criteria

Objective. To identify a comprehensive list of features that might discriminate between gout and other rheumatic musculoskeletal conditions, to be used subsequently for a case-control study to develop and test new classification criteria for gout. Methods. Two Delphi exercises were conducted using Web-based questionnaires: one with physicians from several countries who had an interest in gout and one with patients from New Zealand who had gout. Physicians rated a list of potentially discriminating features that were identified by literature review and expert opinion, and patients rated a list of features that they generated themselves. Agreement was defined by the RAND/UCLA disagreement index. Results. Forty-four experienced physicians and 9 patients responded to all iterations. For physicians, 71 items were identified by literature review and 15 more were suggested by physicians. The physician survey showed agreement for 26 discriminatory features and 15 as not discriminatory. The patients identified 46 features of gout, for which there was agreement on 25 items as being discriminatory and 7 items as not discriminatory. Conclusion. Patients and physicians agreed upon several key features of gout. Physicians emphasized objective findings, imaging, and patterns of symptoms, whereas patients emphasized severity, functional results, and idiographic perception of symptoms.

SAT0389 Apremilast, an Oral Phosphodiesterase 4 Inhibitor, is Associated with Long-Term (52-Week) Improvements in Enthesitis and Dactylitis in Patients with Psoriatic Arthritis: Results from the Palace 4 Phase 3, Randomized, Controlled Trial

Background Apremilast (APR), an oral phosphodiesterase 4 inhibitor, works intracellularly to regulate inflammatory mediators. PALACE 4 compared the efficacy/safety of APR with placebo (PBO) in patients (pts) with active PsA who were DMARD-naïve. Objectives Evaluate the impact of APR treatment over 52 wks on enthesitis and dactylitis among PALACE 4 pts. Methods Pts were randomized 1:1:1 to PBO, APR 20 mg BID (APR20), or APR 30 mg BID (APR30). 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 the initial APR dose. At Wk 24, all remaining PBO pts were re-randomized to APR20 or APR30. The analysis comprises data from Wks 0-52. Enthesitis was evaluated based on MASES (range 0-13), which indicates the number of painful entheses out of 13 entheses sites. The dactylitis count (range 0-20) is the number of digits (hands and feet) with dactylitis present; each digit is rated as 0 (no dactylitis) or 1 (dactylitis present). Results At Wk 16, a significantly greater proportion of pts receiving APR20 or APR30 achieved the modified ACR20 response vs PBO (primary endpoint). In pts initially randomized to APR and with enthesitis (n=228) and dactylitis (n=173) at BL, APR was associated with improvements in enthesitis and dactylitis over 52 wks, as evidenced by reductions in the MASES and dactylitis count. At Wk 16, median percent changes in MASES were 0.0% (PBO), -20.0% (APR20; P=0.2948), and -50.0% (APR30; P=0.0008). In pts initially randomized to APR and completing 52 wks, median percent changes in MASES were -66.7% (APR20) and -75% (APR30) (Table); 39.6% (APR20) and 45.9% (APR30) of pts achieved a score of 0, indicating no pain at any of the entheses assessed. Median percent changes in dactylitis count at Wk 16 were -50.0% (PBO), -70.8% (APR20; P=0.0691), and -69.2% (APR30; P=0.1494). In pts initially randomized to APR and completing 52 wks, both doses resulted in a median 100% decrease in the dactylitis count; a dactylitis count of 0 was achieved in 68.6% (APR20) and 68.8% (APR30) of pts. The most common AEs reported during the PBO-controlled period were nausea (12.6%), diarrhea (9.4%), and headache (6.0%). The safety profile of APR for up to 52 wks was similar to that observed with APR for up to 24 wks of treatment (PBO-controlled period). Conclusions Among pts continuously treated with APR through 52 wks, sustained improvements in both enthesitis and dactylitis were observed in pts with active PsA, who had enthesitis and dactylitis at BL. APR demonstrated an acceptable safety profile and was generally well tolerated for up to 52 wks. Disclosure of Interest 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-Smith Kline, Pfizer Inc., and Roche, A. Wells Grant/research support: Celgene Corporation, A. Adebajo: None declared, A. Kivitz Grant/research support: 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: Celgene Corporation, K. Shah Employee of: Celgene Corporation, C. Hu Employee of: Celgene Corporation, R. Stevens Employee of: Celgene Corporation, J. Aelion Grant/research support: Ardea, AstraZeneca, Bristol-MyersSquibb, CelgeneCorporation, CentocorGalapagos, Genetech, GlaxoSmithKline, HumanGenomeSciences, Janssen, Eli Lilly, Merck, Mesoblast, Novartis, NovoNordisk, PfizerInc., Roche, UCB Biosciences, Sanofi-Aventis, Takeda, and Vertex, Consultant for: Ardea, AstraZeneca, Bristol-MyersSquibb, CelgeneCorporation, CentocorGalapagos, Genetech, GlaxoSmithKline, HumanGenomeSciences, Janssen, Eli Lilly, Merck, Mesoblast, Novartis, NovoNordisk, PfizerInc., Roche, UCB Biosciences, Sanofi-Aventis, Takeda, and Vertex, Speakers bureau: AbbVie, Amgen, and UCB DOI 10.1136/annrheumdis-2014-eular.1574

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

The pattern of rheumatic disorders seen amongst patients attending urban and rural clinics in West Africa

SummaryThere is a growing interest in the study of the pattern of rheumatic disorders in Africa. This has led to our studying the pattern of rheumatic disorders seen among patients attending both urban and rural clinics in West Africa. A wide spectrum of rheumatic diseases was observed among those attending both clinics. Osteoarthritis and soft tissue lesions were most commonly seen while inflammatory joint disease and connective tissue disorders were less commonly observed. We consider that these observations have significant rheumatological health care implications for West Africa and may provide useful aetiopathogenic clues.

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