INTRODUCTION • Psoriasis is a chronic, systemic in� ammatory disease that is associated with signi� cant impairments in quality of life (QOL), which may include physical discomfort, pruritus, and emotional distress.1-4 • Apremilast is an oral, small-molecule phosphodiesterase 4 inhibitor that has demonstrated ef� cacy and safety vs. placebo (PBO) in the LIBERATE global phase 3b trial in patients with moderate to severe plaque psoriasis.5 • Ef� cacy was maintained for up to 104 weeks in patients who continued treatment with apremilast 30 mg twice daily (APR) in the LIBERATE trial.6 • To further understand the clinical pro� le of APR, the effect of long-term APR treatment on patient-reported outcomes assessed at 104 weeks was evaluated in the LIBERATE patient population. METHODS Patients Key Inclusion Criteria • Adults ≥18 years of age • Chronic plaque psoriasis for ≥12 months • Candidates for phototherapy who had no prior exposure to biologics for the treatment of psoriatic arthritis or psoriasis • Moderate to severe plaque psoriasis, as de� ned by Psoriasis Area and Severity Index (PASI) score ≥12, psoriasis-involved body surface area (BSA) ≥10%, and static Physician Global Assessment (sPGA) score ≥3 • Inadequate response, inability to tolerate, or contraindication to ≥1 conventional systemic agent for the treatment of psoriasis Key Exclusion Criteria • Prior treatment with >3 systemic agents for the management of psoriasis • Other clinically signi� cant or major uncontrolled diseases • Serious infections, including latent, active, or history of incompletely treated tuberculosis Study Design • LIBERATE consisted of 2 treatment phases: a 16-week randomized, double-blind, PBO-controlled phase and an 88-week APR extension phase for an overall treatment duration of 104 weeks (Figure 1). – Patients were randomized (1:1:1) to PBO, APR, or etanercept 50 mg once weekly (ETN). – At Week 16, all patients in the PBO and ETN groups switched to APR, and patients in the APR group continued APR. Treatment with APR was maintained from Weeks 16 to 104 (APR extension phase). Figure 1. Study Design Follow-up Phase 4 Weeks Week ‒5 Week 16 Primary End Point Week 32 Topicals/Phototherapy* for Non-responders Week 104 Week 0 Apremilast Extension Phase Placebo-Controlled Phase Screening Period Etanercept 50 mg QW + Placebo Tablets Dose Titration Apremilast 30 mg BID + Placebo Injection Apremilast 30 mg BID Apremilast 30 mg BID Apremilast 30 mg BID No Dose Titration Placebo Tablets + Placebo Injection R AN D O M IZ E (1 :1 :1 ) Screening Week 52 Analysis ClinicalTrials.gov: NCT01690299 Note: LIBERATE was not powered for APR vs. ETN comparisons. *Starting at Week 32, all non-responders (57 – Pruritus visual analog scale (VAS; 0–100 mm); MCID de� ned as a decrease from baseline ≥20%8 – 36-Item Short Form Health Survey version 2 (SF-36v2) Mental and Physical Component Summary scores (MCS and PCS); both MCIDs de� ned as an increase of ≥2.5 points from baseline9 – Patient Health Questionnaire-8 (PHQ-8); MCID de� ned as achievement of score ≤4 (no signi� cant depressive symptoms)10 Safety Assessments • Safety was assessed based on adverse events (AEs), vital signs, clinical laboratory assessments, and physical examinations. Statistical Analysis • Achievement of MCID on the DLQI at Week 16 and Week 104 was a prespeci� ed exploratory end point, whereas achievement of MCID on the pruritus VAS, the MCS and PCS, and the PHQ-8 were post hoc analyses. • All MCID analyses were performed using the modi� ed intent-to-treat (mITT) population, which included all randomized patients who received ≥1 dose of study medication and had an evaluation at baseline and at the speci� ed time point. • End points were analyzed using descriptive statistics, including proportions of patients achieving each end point by treatment group; associated 95% con� dence intervals (CIs) were calculated. All data were analyzed as observed, with no imputation for missing values. • The safety population consisted of all patients who were randomized and received ≥1 dose of study medication. Descriptive statistics were used for summaries of treatment-emergent AEs and other safety assessments. RESULTS Patients • The mITT population consisted of 250 patients (PBO, n=84; APR, n=83; ETN, n=83). • Patient demographics and baseline disease characteristics were generally comparable between treatment groups (Table 1). Table 1. Patient Demographics and Baseline Disease Characteristics PBO n=84 APR n=83 ETN n=83 Age, mean (SD), years 43.4 (14.9) 46.0 (13.6) 47.0 (14.1) Male, n (%) 59 (70.2) 49 (59.0) 49 (59.0) White, n (%) 80 (95.2) 79 (95.2) 75 (90.4) Body mass index, mean (SD), kg/m2 29.6 (6.6) 29.1 (5.9) 29.9 (6.9) Weight, mean (SD), kg 89.5 (23.1) 88.5 (19.8) 88.1 (20.5) Duration of psoriasis, mean (SD), years 16.6 (12.1) 19.7 (12.7) 18.1 (11.7) PASI score (0–72), mean (SD) 19.4 (6.8) 19.3 (7.0) 20.3 (7.9) PASI score >20, n (%) 32 (38.1) 28 (33.7) 34 (41.0) Body surface area, mean (SD), % 27.3 (16.1) 27.1 (15.6) 28.4 (15.7) Body surface area >20%, n (%) 42 (50.0) 45 (54.2) 47 (56.6) sPGA of 4 (severe), n (%) 23 (27.4) 17 (20.5) 13 (15.7) Prior use of conventional systemic medications, n (%) 70 (83.3) 66 (79.5) 58 (69.9) VAS scores* (0–100 mm), mean (SD), mm Pruritus 62.5 (22.7) 62.6 (25.7) 57.2 (27.7) Skin discomfort/pain 43.9 (31.2) 51.8 (30.8) 47.3 (32.8) Patient global assessment of psoriasis disease activity, mean (SD) 53.6 (21.6) 60.9 (24.6) 55.6 (24.2) DLQI score* (0–30), mean (SD) 11.4 (6.3) 13.6 (6.7) 12.5 (7.0) PHQ-8* (0–24), mean (SD) 4.8 (4.4) 5.8 (5.0) 5.0 (5.2) SF-36v2,* mean (SD) MCS (0–100) 44.3 (11.0) 42.8 (12.6) 45.6 (10.8) PCS (0–100) 50.8 (7.8) 46.1 (9.0) 46.2 (9.1) *n=number of patients randomized; number of patients with scores available at baseline differs from randomized n for the following parameters: VAS (PBO, n=81; APR, n=79; ETN, n=78); DLQI and SF-36v2 MCS and PCS (PBO, n=81; APR, n=81; ETN, n=80); PHQ-8 (PBO, n=81; APR, n=82; ETN, n=80). RESULTS (cont’d) Patient-Reported Outcomes DLQI MCID Achievement: Week 16 and Week 104 • At Week 16, a higher proportion of patients in the APR and ETN groups achieved DLQI MCID compared with the PBO group; response was generally maintained at Week 104 among patients who continued APR or who were switched at Week 16 from PBO to APR (PBO/APR) or from ETN to APR (ETN/APR) and remained on APR at Week 104 (Figure 2). Figure 2. Achievement of DLQI MCID at Week 16 and Week 104 59 70 75 69 80 68 0 20 40 60 80 100 n/m= Pa ti en ts A ch ie vi ng D LQ I M C ID ( % ) PBO/APR APR/APR ETN/APRPBO APR ETN 35/59 28/40 48/64 25/36 52/65 27/40 Week 16 Week 16Week 16Week 104 Week 104Week 104 Includes patients in the mITT population with a DLQI score >5 at baseline, with a value at baseline and at the speci� ed time point. MCID=≥5-point decrease from baseline; n/m=number of patients achieving DLQI MCID/number of patients with evaluable data at the time point. Pruritus VAS MCID Achievement at Week 16 and Week 104 • At Week 16, a higher proportion of patients in the APR and ETN groups achieved pruritus VAS MCID compared with the PBO group. Response was maintained at Week 104 in the APR/APR group and in patients who switched at Week 16 from ETN or PBO to APR (Figure 3). Figure 3. Achievement of Pruritus VAS MCID at Week 16 and Week 104 60 77 87 80 89 80 0 20 40 60 80 100 n/m= Pa ti en ts A ch ie vi ng P ru ri tu s VA S M C ID ( % ) PBO/APR APR/APR ETN/APRPBO APR ETN 42/70 37/48 60/69 32/40 67/75 37/46 Week 16 Week 16Week 16Week 104 Week 104Week 104 Includes patients in the mITT population with a value at baseline and at the speci� ed time point. MCID=improvement ≥20% from baseline; n/m=number of patients achieving pruritus improvement ≥20% from baseline/number of patients with evaluable data at the time point. MCS and PCS MCID Achievement at Week 16 and Week 104 • The proportions of patients achieving the MCID for the MCS were generally similar among the treatment groups at Week 16. At Week 104, MCS response was maintained in PBO/APR patients and was comparable between APR/APR and ETN/APR patients at Week 104 (Figure 4A). • At Week 16, the proportion of patients achieving PCS MCID was lowest in the PBO group. At Week 104, PCS response was comparable between the APR/APR and ETN/APR groups and remained lower in the PBO/APR group (Figure 4B). RESULTS (cont’d) Figure 4. Achievement of MCID on MCS (A) and PCS (B) at Week 16 and Week 104 51 54 59 45 53 45 0 40 20 60 80 100 n/m= Pa ti en ts A ch ie vi ng SF -3 6v 2 M C S M C ID ( % ) PBO/APR APR/APR MCS MCIDA. PCS MCIDB. ETN/APRPBO APR ETN 36/70 26/48 42/71 18/40 41/77 21/47 Week 16 Week 16Week 16Week 104 Week 104Week 104 29 31 41 48 60 49 0 40 20 60 80 100 n/m= Pa ti en ts A ch ie vi ng SF -3 6v 2 PC S M C ID ( % ) PBO/APR APR/APR ETN/APRPBO APR ETN 20/70 15/48 29/71 19/40 46/77 23/47 Week 16 Week 16Week 16Week 104 Week 104Week 104 Includes patients in the mITT population with a baseline value and a value at the speci� ed time point. MCID=improvement ≥2.5 from baseline; n/m=number of patients achieving SF-36v2 MCS or PCS MCID/number of patients with evaluable data at the time point. PHQ-8 MCID Achievement • At Week 16 and Week 104, proportions of patients achieving the MCID for PHQ-8 (i.e., score ≤4 [no signi� cant depressive symptoms]) were generally similar among the treatment groups; response was maintained at Week 104 in the APR/APR group and in patients who switched at Week 16 from ETN or PBO to APR (Figure 5). Figure 5. Achievement of PHQ-8 MCID at Week 16 and Week 104 33 40 34 33 43 49 0 20 40 60 80 100 n/m= Pa ti en ts A ch ie vi ng P H Q -8 M C ID ( % ) PBO/APR APR/APR ETN/APRPBO APR ETN 23/70 19/48 24/71 13/40 32/75 23/47 Week 16 Week 16Week 16Week 104 Week 104Week 104 Includes patients in the mITT population with a baseline value and a value at the speci� ed time point. MCID=score ≤4; n/m=number of patients achieving PHQ-8 score ≤4/number of patients with evaluable data at the time point. Safety • During the PBO-controlled period (Weeks 0 to 16), AEs occurring in ≥5% of patients in any treatment group were diarrhea, nausea, upper respiratory tract infection, nasopharyngitis, headache, and tension headache (Table 2). • During the APR extension phase (Weeks 16 to 104), AEs that occurred in ≥5% of patients in any treatment group included those observed during the PBO-controlled period as well as arthralgia, rebound psoriasis, pain in extremity, bronchitis, psoriasis, and sinusitis. • Most AEs were mild or moderate in severity, did not increase with prolonged APR exposure, and did not lead to study discontinuation. RESULTS (cont’d) Table 2. Summary of Safety During Weeks 0 to 165 PBO-Controlled Phase Weeks 0 to 16* PBO n=84 APR n=83 ETN n=83 Patients, n (%)§ ≥1 AE 45 (53.6) 59 (71.1) 44 (53.0) ≥1 Serious AE 0 (0.0) 3 (3.6) 2 (2.4) ≥1 Severe AE 2 (2.4) 3 (3.6) 3 (3.6) AE leading to drug withdrawal 2 (2.4) 3 (3.6) 2 (2.4) AEs reported by ≥5% of patients in any treatment group Diarrhea 3 (3.6) 9 (10.8) 1 (1.2) Nausea 1 (1.2) 9 (10.8) 4 (4.8) Upper respiratory tract infection 2 (2.4) 6 (7.2) 2 (2.4) Nasopharyngitis 8 (9.5) 4 (4.8) 8 (9.6) Headache 3 (3.6) 11 (13.3) 5 (6.0) Tension headache 4 (4.8) 5 (6.0) 3 (3.6) *Each patient is counted once for each applicable category. §Safety population. • No clinically meaningful changes were reported in laboratory parameters. • No cases of tuberculosis (new or reactivation) were reported during the trial. CONCLUSIONS • In biologic-naive patients with moderate to severe psoriasis, improvements in patient-reported outcomes, including QOL and pruritus, were generally maintained with continued APR treatment up to 104 weeks. • AEs were consistent with the known safety pro� le of APR. REFERENCES 1. Reich K. J Eur Acad Dermatol Venereol. 2012;26(Suppl 2):3-11. 2. Owczarek K, Jaworski M. Postepy Dermatologii i Alergologii. 2016;33:102-108. 3. Meyer N, et al. J Eur Acad Dermatol Venereol. 2010;24:1075-1082. 4. Reich A, et al. Acta Derm Venereol. 2010;90:257-263. 5. Reich K, et al. J Eur Acad Dermatol Venereol. 2017;31:507-517. 6. Reich K, et al. Safety and ef� cacy of apremilast through 104 weeks in patients with moderate to severe psoriasis who continued on apremilast or switched from etanercept treatment in the LIBERATE study. Presented at: Annual Meeting of the American Academy of Dermatology; March 3-7, 2017; Orlando, FL. 7. Basra MK, et al. Dermatology. 2015;230:27-33. 8. Reich A, et al. Acta Derm Venereol. 2013;93:609-610 [abstract IL26]. 9. Strand V, et al. Health Qual Life Outcomes. 2013;11:82. 10. Kroenke K, et al. J Affect Disord. 2009;114:163-173. ACKNOWLEDGMENTS The authors acknowledge � nancial support for this study from Celgene Corporation. The authors received editorial support in the preparation of this poster from Amy Shaberman, PhD, of Peloton Advantage, LLC, Parsippany, NJ, USA, funded by Celgene Corporation, Summit, NJ, USA. The authors, however, directed and are fully responsible for all content and editorial decisions for this poster. CORRESPONDENCE Shane Chapman – Michael.Shane.Chapman@hitchcock.org DISCLOSURES SC: Nothing to disclose. JC: Celgene Corporation – employment. SM: Nothing to disclose. Presented at: the Winter Clinical Dermatology Conference – Hawaii; January 12–17, 2018; Maui, HI. Sustained Improvement in Patient-Reported Outcomes With Continued Apremilast Treatment Over 104 Weeks in Patients With Moderate to Severe Psoriasis Shane Chapman, MD1; Joshua Cirulli, PharmD2; Sandy McBride, MD3 1Dartmouth–Hitchcock Medical Center, Lebanon, NH, USA; 2Celgene Corporation, Summit, NJ, USA; 3Royal Free London NHS Foundation Trust, London, UK