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

BackgroundApremilast (APR) is an oral phosphodiesterase 4 inhibitor that helps regulate the immune response that causes joint inflammation and other manifestations of psoriatic arthritis (PsA), including skin disease. Primary findings from the PALACE 4 study (NCT01307423) demonstrated greater efficacy with APR vs. placebo in DMARD-naive patients with active PsA.1,2ObjectivesDescribe the long-term efficacy and safety of APR monotherapy in DMARD-naïve patients in PALACE 4 for up to 156 weeks.MethodsPatients were randomized (1:1:1) to placebo, APR 30 mg BID (APR30), or APR 20 mg BID (APR20). Patients whose swollen joint count (SJC) and tender joint counts (TJC) had not improved by ≥20% at Week 16 were considered non-responders and required to be re-randomized (1:1) to APR30 or APR20 if they were initially randomized to placebo, or continued on their initial APR dose. At Week 24, all patients remaining on placebo were re-randomized to APR30 or APR20. Double-blind treatment continued to Week 52 with open-label APR for up to 4 additional years.ResultsA total of 527 patients were randomized and received ≥1 dose of placebo (n=176), APR30 (n=176), and APR20 (n=175). Of the patients entering the third year of therapy, 88.0% (272/309) completed the Week 156 visit. At Week 52, 58.0% (119/205) of patients receiving APR30 and 55.4% (107/193) receiving APR20 achieved a 20% improvement in modified American College of Rheumatology (ACR20) response (Table). At Week 156, rates of improvement in PsA signs and symptoms and physical function were sustained, as shown by modified ACR20/ACR50/ACR70 responses, mean percent change in SJC/TJC, mean change in Health Assessment Questionnaire-Disability Index (HAQ-DI) score, proportion of patients with HAQ-DI exceeding the minimal clinically important differences (MCID) ≥0.30 threshold, achievement of Maastricht Ankylosing Spondylitis Enthesitis Score (MASES) of 0 and dactylitis count of 0, and 75% and 50% reduction from baseline Psoriasis Area and Severity Index (PASI-75 and PASI-50) responses (Table). During Weeks >104 to ≤156, the most common adverse events (AEs) among APR-exposed patients were upper respiratory tract infection (3.2%) and nasopharyngitis (3.9%); serious AEs occurred in 5.2% of APR patients, and no opportunistic infections occurred. In general, no change in the types of AEs and no increase in the incidence and severity of AEs were seen with longer-term exposure.ConclusionsOver 156 weeks, APR monotherapy demonstrated sustained response and improvements in PsA signs and symptoms, including SJC, TJC, enthesitis, dactylitis, physical function, and psoriasis. APR continued to demonstrate an acceptable safety profile and was generally well tolerated.ReferencesEdwards et al. Arthritis Rheum. 2014;66(11 Suppl)S694–5. Abstract 1572.Wells et al. Arthritis Rheum. 2014;66(11 Suppl)S264–5. Abstract 602.Disclosure of InterestA. Wells Grant/research support from: Celgene Corporation, C. Edwards Grant/research support from: Celgene Corporation, Pfizer Inc, Roche, Samsung, Speakers bureau: Ab...

Background:Upadacitinib (UPA), an oral JAK inhibitor selective for JAK1, demonstrated efficacy in patients (pts) with moderate to severe rheumatoid arthritis (RA) with an inadequate response (IR) to csDMARDs or bDMARDs in the SELECT-NEXT1 and SELECT-BEYOND2 trials, respectively.Objectives:To investigate the speed of response to UPA across disease measures in csDMARD- and bDMARD-IR pts.Methods:661 pts in NEXT and 498 in BEYOND received UPA 15 mg or UPA 30 mg once daily (QD) or placebo (PBO) for 12 weeks (wks)1,2. Time to first achievement of clinically meaningful outcomes, including ACR20/50, DAS28-CRP≤3.2 and Low Disease Activity (LDA) measures of CDAI (≤10) and SDAI (≤11) was evaluated. The cumulative incidences of ACR20/50, DAS28-CRP≤3.2 and LDA by CDAI and SDAI over 12 wks were estimated. Hazard ratios between UPA and PBO were obtained using Cox proportional hazards model with treatment group, corresponding baseline values and main stratification factors, without control for multiple comparisons. All analyses were based on observed data without imputation.Table 1Summary of Median Time (in Weeks) to Achieve First Response Over 12 WeeksHR, hazard ratio, NE (not estimatable) indicates that the response was not reached within the 12-week period. ***p<0.001Results:Pts had a disease duration of 7 and 13 years in NEXT and BEYOND respectively.1,2 In BEYOND, pts were treatment-refractory as evidenced by 53% having received ≥2 prior bDMARDs2. Median times to achieve ACR20 were similar, irrespective of pt population, being 4 wks for UPA 15 mg QD and 2–3 wks for UPA 30 mg QD vs 12 wks on PBO (p<0.001). In general, the median times to achieve ACR50 and DAS28-CRP≤3.2 for UPA 15 mg and 30 mg QD were ~12 wks and ~8 wks for both csDMARD-IR and bDMARD-IR pts, whereas the median was not reached for pts on PBO during the first 12 wks (p<0.001, table 1). The median time to LDA by CDAI and SDAI was ~12 wks across UPA doses and populations, but was not reached for pts receiving PBO within that time. Pts receiving UPA were 2–4 times more likely to achieve clinical responses vs pts receiving PBO. In general, both UPA doses performed similarly across pt populations, with numerically quicker responses observed in pts receiving UPA 30 mg vs UPA 15 mg QD. Median times to achieve 20% and 50% improvements in tender and swollen joint counts were 1–2 wks and 2–4 wks respectively, for both UPA doses, irrespective of pt population. Median times to achieve 20% improvements in morning stiffness duration and severity were approximately 2 wks in each of the UPA arms vs 4 wks on PBO (p<0.001).Conclusions:Pts receiving UPA at either 15 mg or 30 mg QD were more likely to achieve clinical responses at significantly earlier time points when compared with pts receiving PBO. Irrespective of being csDMARD-IR or bDMARD-IR, times to achieve various clinical responses were consistent between pt populations.References[1]Burmester, et al. Arthritis Rheumatol2017;69S10.[2]Genovese, et al. Arthritis Rheumatol2017;69S10.Acknowledgements:AbbVie: Study sponsor, study...

disease in patients with psoriatic arthritis (PsA). Objectives: To compare the presence of CV risk factors and disease in patients with PsA and the normal population. Further to estimate the 10-year risk of a fatal CV event by using the Systematic Coronary Evaluation (SCORE) algorithm. 1 Methods: Patients and control subjects were recruited from the Nord-Trøndelag Health Study (HUNT) 3, and the diagnoses of PsA (n=338) were verified according to the Classification of Psoriatic Arthritis (CASPAR) criteria. 2 The control group (n=50468) consisted of other individuals enrolled in the HUNT 3 study. Age and sex adjusted prevalence rates of CV risk factors and co morbidity were calculated. Results: Mean (SD) age was 54.3±11.9 years and 53.9±16.1 years in PsA and controls, respectively (p=0.58) and the gender ratio was nearly equally distributed in both groups (p=0.31). Patients with PsA were more often smokers compared to controls (p=0.02). The other traditional CV risk factors included in the SCORE CV risk algorithm (age, gender, systolic blood pressure and total cholesterol/HDL) were comparable between PsA patients and controls. Of untraditional CV risk factors; CRP, body mass index (BMI) and triglycerides were elevated in PsA patients compared to controls, (p<0.001, p<0.001 and p=0.01, respectively). The mean calculated CV risk (SD) in PsA patients was low (1.45±1.79) and comparable to controls (1.59±1.95) (p=0.63). The distribution across CV risk classes (low, moderate and high + very high) was comparable amongst PsA patients and controls (figure 1). There was no difference in the prevalence of established CV disease in the PsA cohort and the control group (p=0.2). Conclusions:The low CV risk in patients with PsA was related to low levels of traditional risk factors. Although, PsA patients had elevated levels of untraditional CV risk factors such as CRP, BMI and triglycerides, which are not included in the SCORE risk algorithm. Whether these factors will affect long term CV outcome is not known.Background: Apremilast (APR), an oral phosphodiesterase 4 inhibitor, works intracellularly to regulate inflammatory mediators. PALACE 4 compared APR efficacy/safety with placebo (PBO) in patients (pts) with active PsA who were DMARD-naïve. Objectives: Evaluate the impact of APR over 52 wks on physical function 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. This analysis reports data for Wks 0-52.

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 Assess safety and tolerability of APR for up to 52 wks. 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 baseline (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 analysis reports data from the APR-exposure period (Wks 0 to 52). Results 526 pts received PBO, APR20, or APR30 and were included in the safety population;. In the APR-exposure period, 252 pts received APR20 (192.8 pt-yrs) and 252 received APR30 (196.8 pt-yrs). Through Wk 52, AEs occurring in ≥5% of APR-exposed pts were nausea, diarrhea, headache, and URTI (Table). The nature, incidence, and severity of AEs were comparable over the 24-wk and 52-wk periods. Nearly 90% of AEs were mild/moderate in severity. Serious AEs (SAEs) occurred in 6.3% (APR20) and 2.4% (APR30) over 52 wks with no change in the type of SAEs reported between the 24-wk and 52-wk exposure periods. Through Wk 52, serious infections were reported by 1 pt receiving APR20 (chronic tonsillitis) and 2 pts receiving APR30 (gallbladder empyema; acute pyelonephritis); none were opportunistic infections. No deaths occurred. Discontinuation due to AEs in combined APR-exposed pts was 5.2% over 52 wks. No SAEs of diarrhea or nausea were reported. Most diarrhea and nausea events were generally reported within the first 2 wks of treatment and usually resolved in 4 wks without medical intervention. Discontinuation due to diarrhea and nausea was <2% in the combined APR group. Three cases of cancer were reported during the study: 2 cases of skin cancer (PBO, 1; APR30, 1) and 1 case of prostate cancer (APR20). The mean baseline BMI was 28.6 kg/m2 for the study population. Observed weight measurements were prospectively collected at selected study visits. At the end of the 52-wk APR-exposure period, the mean (median) weight loss was 0.91 kg (0.25 kg) in the APR20 and 1.19 kg (1.30 kg) in the APR30 group. Marked laboratory abnormalities generally were infrequent and returned to BL 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 52 wks; the nature, incidence, and severity of AEs were comparable over the 24-wk and 52-wk periods. Similar to data from other phase 3 trials assessing pts previously treated with DMARDs, these data do not indicate a need for laboratory monitoring. Disclosure of Interest A. Adebajo: None declared, A. Wells Grant/research support: Celgene Corporation, C. Edwards Grant/research support: Celgene Corporation, Pfizer Inc, Roche, and Samsung, Cons...