Effect of Apremilast on Patient-Reported Outcomes in Patients With Moderate to Severe Plaque Psoriasis in the ESTEEM 1 Trial

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1 1152 Effect of Apremilast on Patient-Reported Outcomes in Patients With Moderate to Severe Plaque Psoriasis in the ESTEEM 1 Trial April W. Armstrong, MD, MPH 1 ; Christopher E.M. Griffiths, MD 2 ; Tom Tencer, PhD 3 ; Stan Li, MS 3 ; Frank Zhang, MD, MPH 3 1 University of Colorado, Denver, CO, USA; 2 Dermatology Centre, University of Manchester, Manchester, UK; 3 Celgene Corporation, Warren, NJ, USA Presented at: the 73rd Annual Meeting of the American Academy of Dermatology; March 20-24, 2015; San Francisco, CA. This study was sponsored by Celgene Corporation.

2 Abstract Background: Apremilast (APR), an oral phosphodiesterase 4 inhibitor, works intracellularly to regulate inflammatory mediators. The ESTEEM 1 study compared the efficacy and safety of APR vs. placebo (PBO) in patients with a diagnosis of moderate to severe plaque psoriasis (Psoriasis Area and Severity Index [PASI] 12; body surface area 10%, static Physician Global Assessment 3), and who were also candidates for phototherapy and/or systemic therapy. The objective of this analysis was to determine the proportion of patients with a clinically meaningful improvement in patient-reported outcomes (PRO) associated with APR during the first 16 weeks of ESTEEM 1 using the 36-item Short Form Health Survey version 2 mental component summary (SF-36v2 MCS) score, Dermatology Life Quality Index (DLQI) score, and pruritus visual analog scale (pruritus VAS) score. Methods: Patients with moderate to severe plaque psoriasis were randomized (2:1) to APR 30 mg (APR30) or PBO. All patients were treated blindly until Week 16, when the primary endpoint was assessed. Pre-specified secondary endpoints, including change from baseline in the SF-36v2 MCS, DLQI, and pruritus VAS scores, were also analyzed at Week 16. Clinical meaningfulness of these PRO improvements was assessed using the percentage of patients who met the minimum clinically important differences (MCID) of each instrument, which were defined as an improvement from baseline of 2.5 for the SF-36v2 MCS score, 5 for the DLQI among patients whose baseline DLQI score was >5, and a change of 20% for the pruritus VAS score. Results: 844 patients (mean age: 46.0 years; male: 67.9%) were randomized to PBO (n=282) or APR30 (n=562). At Week 16, the percentage of patients achieving MCID in PRO was significantly improved with APR30 vs. PBO, as measured by the SF-36v2 MCS (44.3% vs. 30.1%; P<0.0001), DLQI (70.2% vs. 33.5%; P<0.0001), and pruritus VAS (70.6% vs. 33.7%; P<0.0001). Among APR30 PASI-75 responders at Week 16, a significantly higher percentage of patients compared to placebo achieved MCID improvement in SF-36v2 MCS (52.2% vs. 30.1%; and P<0.0001) and >90% of patients achieved MCID improvements in DLQI or pruritus VAS score. Conclusion: APR30 treatment resulted in significantly improved PRO, as measured by SF-36v2 MCS, DLQI, and pruritus VAS scores, over 16 weeks of treatment in patients with moderate to severe plaque psoriasis.

3 Background Apremilast, an oral PDE4 inhibitor, works intracellularly to regulate inflammatory mediators. 1 Apremilast was approved by the FDA in 2014 and by the EC in 2015 for the treatment of psoriasis and psoriatic arthritis. 2,3 ESTEEM is a phase 3 clinical trial program comprising 2 randomized placebo-controlled studies evaluating the efficacy, safety, and tolerability of apremilast for the treatment of moderate to severe plaque psoriasis. The ESTEEM 1 study compared the efficacy and safety of apremilast versus placebo in patients with a diagnosis of moderate to severe plaque psoriasis (Psoriasis Area and Severity Index [PASI] 12, body surface area 10%, static Physician Global Assessment 3) who were also candidates for phototherapy and/or systemic therapy at baseline. EC=European Commission; ESTEEM=Efficacy and Safety Trial Evaluating the Effects of Apremilast in Psoriasis; FDA=US Food and Drug Administration; PDE4=phosphodiesterase Schafer P. Biochem Pharmacol. 2012;83: ; 2. Otezla [package insert]. Summit, NJ: Celgene Corporation, 2014; 3. Otezla (apremilast) summary of product characteristics. Uxbridge, UK: Celgene Europe Ltd.; January 2015.

4 Objective The objective of this analysis was to determine whether there were clinically meaningful improvements associated with apremilast in patient-reported outcomes (PRO) during the first 16 weeks of ESTEEM 1 using the 36-item Short Form Health Survey version 2 Mental Component Summary (SF-36v2 MCS), Dermatology Life Quality Index (DLQI), and pruritus visual analog scale (VAS).

5 Methods Patients with moderate to severe plaque psoriasis were randomized (2:1) to apremilast 30 mg twice daily (BID) or placebo. Treatment was blinded for all patients until Week 16, when the primary end point was assessed. Pre-specified secondary end points, including change from baseline in SF-36v2 MCS, DLQI, and pruritus VAS scores, were also analyzed at Week 16. The extent that these PRO improvements were clinically meaningful was determined using the percentage of patients who met the minimum clinically important difference (MCID) for each instrument, defined as an improvement from baseline of 2.5 for the SF-36v2 MCS score, 5 for the DLQI score among patients whose baseline DLQI score was >5, and a change of 20% for the pruritus VAS score Finlay AY, Khan GK. Clin Exp Dermatol.1994;19: ; 2. Basra MKA, et al. Br J Dermatol. 2008;159: ; 3. Reich A, et al. Acta Dermatol Venereol. 2013; 93:

6 Results 844 patients (mean age: 46.0 years; male: 67.9%) were randomized to placebo (n=282) or apremilast 30 mg BID (n=562). Apremilast 30 mg BID was associated with a significantly higher percentage of patients who achieved an MCID at Week 16 (Figure). Among patients receiving apremilast 30 mg BID who were PASI-75 responders at Week 16, more than 90% achieved the MCID for the DLQI or the pruritus VAS. Patients Achieving MCID Change From Baseline (%) SF-36v2 MCS DLQI Pruritus VAS n= P< vs. placebo. Note: DLQI response among patients with baseline DLQI total score >5. Placebo Apremilast 30 mg BID Apremilast 30 mg BID/ PASI-75 Responders

7 Conclusion Apremilast 30 mg BID resulted in significantly improved PRO measures, including the SF-36v2 MCS, DLQI, and pruritus VAS scores, over 16 weeks of treatment in patients with moderate to severe plaque psoriasis.