Secukinumab is superior to ustekinumab in clearing skin of patients with moderate-to-severe plaque psoriasis: CLARITY, a randomized, controlled, Phase IIIb trial

Secukinumab is superior to ustekinumab in clearing skin of patients with moderate-to-severe plaque psoriasis: CLARITY, a randomized, controlled, Phase IIIb trial

Presenters: Bagel J1, Nia J2, Hashim P2, Patekar M3, de Vera A3, Hugot S3, Sheng K4, Xia S5, Muscianisi E4, Blauvelt A6, Lebwohl M2

Affiliations: 1Psoriasis Treatment Center of Central New Jersey, East Windsor, NJ; 2Icahn School of Medicine at Mount Sinai, New York, NY; 3Novartis Pharma AG, Basel, Switzerland; 4Novartis Pharmaceuticals Corporation, East Hanover, NJ; 5Novartis Beijing Novartis Pharma Co. Ltd, Shanghai, China; 6Oregon Medical Research Center, Portland, OR

Background/Objective: Secukinumab, a fully human anti-interleukin-17A monoclonal antibody, has previously demonstrated superior efficacy to ustekinumab in the Phase IIIb CLEAR study of moderate-to-severe plaque psoriasis. Here, we report 16-week results from CLARITY, the second head-to-head trial comparing secukinumab with ustekinumab.

Methods: In this ongoing multicenter, head-to-head, double-blind, parallel-group, Phase IIIb study (NCT02826603), patients were randomized 1:1 to receive subcutaneous secukinumab 300mg or ustekinumab per label. The co-primary objectives were to demonstrate the superiority of secukinumab over ustekinumab at Week 12 in relation to the proportion of patients with 1) 90-percent or more improvement from baseline Psoriasis Area and Severity Index (PASI 90) and 2) a score of 0/1 (clear/almost clear) on the Investigator’s Global Assessment (IGA mod 2011 0/1). Key secondary objectives included demonstrating the superiority of secukinumab over ustekinumab with respect to PASI 75 at Week 4; PASI 75 and 100 at Week 12; PASI 75, 90, 100; and IGA mod 2011 0/1 at Week 16. Missing values were handled by multiple imputation.

Results: At Week 12, both co-primary objectives were met, secukinumab 300 mg (n=550) was significantly superior to ustekinumab (n=552) for the proportion of patients achieving both PASI 90 (66.5% vs. 47.9%; P<0.0001) and IGA mod 2011 0/1 (72.3% vs 55.4%; P<0.0001) response rates. Additionally, all key secondary objectives were met. At Week 4, PASI 75 response rates were significantly superior with secukinumab 300mg compared to ustekinumab (40.2% vs 16.3%; P<0.0001). At Week 16, secukinumab 300mg demonstrated significantly superior response rates compared to ustekinumab for PASI 75 (91.7% vs. 79.8%; P<0.0001), PASI 90 (76.6% vs. 54.2%; P<0.0001), PASI 100 (45.3% vs. 26.7%; P<0.0001), and IGA mod 2011 0/1 (78.6% vs. 59.1%; P<0.0001). Furthermore, at Week 12, patients receiving secukinumab 300mg compared to ustekinumab had significantly greater PASI 75 (88.0% vs. 74.2%; P<0.0001) and PASI 100 (38.1% vs. 20.1%; P<0.0001) responses. Safety findings were consistent with the known safety profile of secukinumab.

Conclusion: Secukinumab demonstrated superior results with greater improvements compared to ustekinumab across all study outcomes at Weeks 4, 12, and 16 in patients with moderate-to-severe plaque psoriasis.

Funding: This research was sponsored by Novartis Pharma AG, Basel, Switzerland.

Efficacy of brodalumab in ustekinumab-naive and -experienced patients with moderate-to-severe plaque psoriasis

Efficacy of brodalumab in ustekinumab-naive and -experienced patients with moderate-to-severe plaque psoriasis

Presenters: Hsu S1, Green L2, Keegan BR3, Kircik L4, Rastogi S5, Pillai R6, Israel RJ5

Affiliations: 1Temple University School of Medicine, Philadelphia, PA; 2George Washington University School of Medicine, Washington, DC; 3Psoriasis Treatment Center of Central New Jersey/Windsor Dermatology, East Windsor, NJ; 4Icahn School of Medicine at Mount Sinai, New York, NY; 5Valeant Pharmaceuticals North America LLC, Bridgewater, NJ; 6Dow Pharmaceutical Sciences, Petaluma, CA

Background/Objective: Brodalumab is a fully human anti–interleukin-17 receptor A (IL-17RA) monoclonal antibody that has shown efficacy in patients with moderate-to-severe plaque psoriasis. We evaluated the efficacy of brodalumab in a post-hoc analysis of a subset of patients with prior exposure to ustekinumab, a human anti-IL-12 and -IL-23 monoclonal antibody approved for the treatment of moderate-to-severe plaque psoriasis who were enrolled in a Phase III, multicenter, randomized, double-blind, placebo-controlled study (AMAGINE-1).

Methods: During the induction phase, patients received brodalumab 210mg weekly for the first three weeks and every two weeks (Q2W) thereafter for 12 weeks. After 12 weeks, patients who achieved a static physician’s global assessment (sPGA) score of 0 or 1 continued to the withdrawal phase and were rerandomized 1:1 to receive brodalumab 210mg Q2W or placebo for up to 52 weeks. Beginning at Week 16, all rerandomized patients who experienced return of disease (sPGA ?3) qualified for retreatment with their induction dose of brodalumab 210mg and were imputed as nonresponders at the time of qualification. Skin clearance was monitored by the Psoriasis Area and Severity Index (PASI) and the sPGA.

Results: Of 167 patients who were randomized to brodalumab 210mg in the induction phase and continued into the withdrawal phase, 19.2 percent had taken ustekinumab prior to the start of the trial (n=32). Among patients receiving continuous brodalumab 210mg, rates of 100-percent reduction in PASI score (PASI 100) were 65.2 percent (n=43/66) and 76.5 percent (n=13/17) in ustekinumab-naive and -experienced patients, respectively (rates for placebo were 0 [n=0/69] and 0 [n=0/15], respectively). Similarly, rates of PASI 75 and PASI 90 were 84.8 percent (n=56/66) and 75.8 percent (n=50/66), respectively, in ustekinumab-naive patients and 94.1 percent (n=16/17) and 88.2 percent (n=15/17), respectively, in ustekinumab-experienced patients (rates for placebo were 0 [n=0 of 69] and 0 [n=0 of 69], respectively, in ustekinumab-naive patients and 0 [n=0/15] and 0 [n=0/15], respectively, in ustekinumab-experienced patients).

Conclusion: Brodalumab 210mg was associated with improved skin clearance efficacy in both patients with and without prior ustekinumab exposure.

Funding: This study was sponsored by Amgen Inc.

Long-term efficacy of brodalumab for the treatment of moderate-to-severe psoriasis: data from a pivotal Phase III clinical trial

Long-term efficacy of brodalumab for the treatment of moderate-to-severe psoriasis: data from a pivotal Phase III clinical trial

Presenters: Menter A1, Sobell J2, Silverberg JI3, Lebwohl M4, Rastogi S5, Pillai R6, Israel RJ5

Affiliations: 1Baylor University Medical Center, Dallas, TX; 2SkinCare Physicians, Chestnut Hill, MA; 3Northwestern University Feinberg School of Medicine, Chicago, IL; 4Icahn School of Medicine at Mount Sinai, New York, NY; 5Valeant Pharmaceuticals North America LLC, Bridgewater, NJ; 6Dow Pharmaceutical Sciences, Petaluma, CA

Background/Objective: Brodalumab is a fully human anti-interleukin-17 receptor A (IL-17RA) monoclonal antibody that antagonizes the action of specific inflammatory cytokines involved in psoriasis. Pivotal Phase III clinical trials demonstrated the efficacy and safety of brodalumab through 52 weeks of treatment in patients with moderate-to-severe psoriasis. We evaluated the efficacy of brodalumab in psoriasis from Week 52 through Week 120. Data were derived from the long-term, open-label extension study of a 52-week, randomized, double-blind, placebo- and active comparator-controlled clinical trial (AMAGINE-2).

Methods: Patients received brodalumab 210mg or 140mg every two weeks (Q2W), ustekinumab, or placebo during a 12-week induction phase, followed by a maintenance phase through Week 52. During the maintenance phase, patients receiving brodalumab were rerandomized to a different dose and interval of brodalumab (210mg or 140mg Q2W, Q4W, or Q8W), patients receiving placebo were switched to brodalumab 210mg Q2W, and patients receiving ustekinumab continued on ustekinumab. At Week 52, patients who received brodalumab during the maintenance phase continued receiving their maintenance dose of brodalumab, and patients who were taking ustekinumab switched to brodalumab 210mg Q2W. Data are presented for patients who received brodalumab 210mg Q2W (the FDA-approved dose) through Week 120 of the long-term extension phase.

Results: A total of 1,392 patients received brodalumab 210mg Q2W in the long-term extension phase. At Week 52, rates (95% confidence interval [CI]) of these patients for Psoriasis Area and Severity Index (PASI) 75-percent improvement (PASI 75), PASI 90, and PASI 100 were 90.6 percent (88.9%-92.2%), 77.6 percent (75.2%-79.9%), and 53.3 percent (50.5%-56.0%), respectively. Similarly, at Week 120, corresponding responder rates (95% CI) were 88.4 percent (86.0%-90.6%), 76.8 percent (73.6%-79.7%), and 56.2 percent (52.7%-59.7%), respectively. Success rates (95% CI), based on static physician’s global assessment score of 0 or 1, were 79.2 percent (76.8%-81.4%) and 76.6 percent (73.5%-79.6%) at Weeks 52 and 120, respectively. The patients who received continuous brodalumab 210mg Q2W (n=334) achieved Static Physician’s Global Assessment Score of 0 or 1, PASI 75, PASI 90, and PASI 100 response of 79.2, 86.5, 76.4, and 59.0 percent, respectively, through Week 120.

Conclusion: Treatment with brodalumab resulted in substantial psoriatic lesion clearing for more than two years in most patients with moderate-to-severe psoriasis.

Funding: This study was sponsored by Amgen Inc.

Incidence of inflammatory bowel disease in patients treated with secukinumab: pooled analysis of 21 randomized controlled Phase III and IV clinical trials of psoriasis, psoriatic arthritis, and ankylosing spondylitis

Incidence of inflammatory bowel disease in patients treated with secukinumab: pooled analysis of 21 randomized controlled Phase III and IV clinical trials of psoriasis, psoriatic arthritis, and ankylosing spondylitis

Presenters: Schreiber S1, Colombel JF2, Feagan BG3, Blauvelt A4, Reich K5, Deodhar A6, McInnes IB7, Porter B8, Gupta AD9, Pricop L8, Fox T10

Affiliations: 1Department of Internal Medicine, University Hospital Schleswig-Holstein, Kiel, Germany; Institute of Clinical Molecular Biology, University of Kiel, Germany; 2Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, New York; 3University of Western Ontario, Ontario, Canada; 4Oregon Medical Research Center, Portland, Oregon; 5Dermatologikum Hamburg and Georg-August-University, Göttingen, Germany; 6Oregon Health & Science University, Portland, OR; 7Institute of Infection Immunity and Inflammation, University of Glasgow, Glasgow, UK; 8Novartis Pharmaceuticals Corporation, East Hanover, NJ; 9Novartis Healthcare Pvt. Ltd., Hyderabad, India; 10Novartis Pharma AG, Basel, Switzerland

Background/Objective: Inflammatory bowel disease (IBD) such as Crohn’s disease (CD) and ulcerative colitis (UC) are common comorbidities associated with psoriasis, psoriatic arthritis (PsA), and ankylosing spondylitis (AS). Compared to the general population, epidemiological studies have shown that patients with psoriasis or PsA are at a 2- to 4-fold increased risk of developing CD and a 2- to 3-fold increased risk of developing UC. Additionally, in patients with AS, there is a 3- to 5-fold increased risk of IBD compared with the general population. Secukinumab is approved for the treatment of psoriasis, PsA, and AS and is a fully human monoclonal antibody that neutralizes interleukin-17A. Here, we report the pooled incidence of IBD, CD, and UC in patients with psoriasis, PsA, or AS who received IL-17A inhibition with secukinumab. The data reported herein are based on results from 21 Phase III/IV clinical trials of secukinumab for psoriasis, PsA, or AS.

Methods: This analysis evaluated pooled data from 14 Phase III and one Phase IV psoriasis trials, three Phase III PsA trials, and three Phase III AS trials. Patients with a history of IBD but not active IBD were eligible for enrollment in these trials. Data from all patients that received at least one dose of secukinumab were included in this analysis. IBD reporting includes cases of CD, UC, and IBD not otherwise specified (NOS).

Results: A total of 7,355 patients receiving secukinumab were assessed for the presence of IBD: 5,181 with psoriasis, 1,380 with PsA, and 794 with AS. Over the entire treatment period, the mean total exposure to secukinumab was 10,416.9 patient-years in patients with psoriasis, 3,866.9 patient-years in patients with PsA, and 1,943.1 patient-years in patients with AS. The exposure-adjusted incidence rate (EAIR) per 100 patient-years (95% confidence interval [CI]) of CD, UC, and IBD NOS in secukinumab-treated patients were 0.05 [0.02, 0.11], 0.13 [0.07, 0.23], and 0.01 [0.00, 0.05], respectively, in the psoriasis studies; 0.08 [0.02, 0.23], 0.08 [0.02, 0.23], and 0.05 [0.01, 0.19], respectively in the PsA studies; and 0.4 [0.2, 0.8], 0.2 [0.1, 0.5], and 0.1 [0.0, 0.3], respectively, in the AS studies. Additionally, the incidence of IBD, CD, and UC did not increase over time.

Conclusion: Pooled data from 21 studies indicated that the observed exposure-adjusted incidence rates of IBD, CD, and UC with secukinumab were low and did not increase over time in patients with moderate-to-severe plaque psoriasis, PsA, or AS.

Funding: This research was sponsored by Novartis Pharma AG, Basel, Switzerland.

Clinical efficacy of tildrakizumab, an anti–IL-23p19 monoclonal antibody, in patients with chronic plaque psoriasis over two years of treatment: Results from long-term extensions to two Phase III clinical studies (reSURFACE 1 and reSURFACE 2)

Clinical efficacy of tildrakizumab, an anti–IL-23p19 monoclonal antibody, in patients with chronic plaque psoriasis over two years of treatment: Results from long-term extensions to two Phase III clinical studies (reSURFACE 1 and reSURFACE 2)

Presenters: Papp K1, Reich K2, Blauvelt A3, Thaçi D4, Sinclair R5, Tyring SK6, Cichanowitz N7, Green S7, Li Q,7 La Rosa C7

Affiliations: 1Probity Medical Research, Waterloo, ON, Canada; 2SCIderm Research Institute and Dermatologikum Hamburg, Hamburg, Germany; 3Oregon Medical Research Center, Portland, Oregon; 4Comprehensive Center for Inflammation Medicine, University Medical School Schleswig-Holstein, University of Lübeck, Lübeck, Germany; 5University of Melbourne, Melbourne, VIC, Australia; 6Department of Dermatology, University of Texas, Houston, Texas; 7Merck & Co., Inc., Kenilworth, New Jersey

Background/Objective: Tildrakizumab is a high-affinity, humanized, anti-IL-23p19 monoclonal antibody that has demonstrated efficacy in the treatment of chronic plaque psoriasis in two Phase III studies (reSURFACE 1 and 2). Extensions of these studies are ongoing. In this analysis, we present preliminary data evaluating maintenance of response in patients who were responders to tildrakizumab upon entering the extension periods and who maintained response a year into the extensions (a total of at least 2 years of treatment).

Methods: The reSURFACE base studies are three-part, double-blinded, randomized, placebo-controlled studies in adult patients with moderate-to-severe chronic plaque psoriasis (body surface area involvement ?10%, Physician’s Global Assessment [PGA] score ?3, and Psoriasis Area and Severity Index [PASI] ?12). Tildrakizumab 200mg and 100mg were evaluated for 64 weeks (reSURFACE 1; NCT01722331) and 52 weeks (reSURFACE 2; NCT01729754), respectively. Patients were eligible for the optional long-term extensions if they completed the base studies and achieved PASI ?50 at the end of the base studies (for reSURFACE 1 only, patients had to have received an active dose of tildrakizumab within 12 weeks of the end of the base study). Patients received the same dose of tildrakizumab (200mg or 100mg every 12 weeks) as they received at the completion of the base studies. Administration was open label after database lock for the base studies. The full analysis set (patients with at least 1 dose of extension treatment based on assigned treatment) was the primary efficacy population. The efficacy objective during the extension period was evaluation of maintenance of efficacy endpoints (i.e., proportion of PASI 50, 75, 90, and 100 responders 1 year into the extension among PASI 50, 75, 90, and 100 responders at the start of the extension) prespecified to be based on observed data. No statistical analyses were planned for comparison between doses.

Results: In reSURFACE 1, 772 patients entered, 638 completed the base study, and 506 entered the extension; in reSURFACE 2, 1,090 patients entered, 756 patients completed the base study, and 731 entered the extension. In reSURFACE 1, in patients entering the extension on tildrakizumab 200mg, PASI 50/75/90/100 was maintained by 97%/91%/82%/63% (out of 255/208/135/70 patients with data at 1 year); in patients on tildrakizumab 100mg, PASI 50/75/90/100 was maintained by 98%/90%/74%/53% (out of 219/195/121/70 patients with data at 1 year). In patients entering the extension on tildrakizumab 200 mg in reSURFACE 2, PASI 50/75/90/100 was maintained by and 97%/88%/84%/70% (out of 330/293/191/97 patients with data at 1 year); for those on tildrakizumab 100mg, PASI 50/75/90/100 was maintained by 99%/92%/84%/66% (out of 352/327/249/125 patients with data at 1 year).

Conclusion: Tildrakizumab 100mg and 200mg demonstrated maintenance of efficacy in the treatment of moderate-to-severe chronic plaque psoriasis for at least two years of treatment.

Funding: Study sponsored by Merck & Co. Analyses previously presented at the 26th European Academy of Dermatology and Venereology Congress, Geneva, Switzerland, 2017.

Sustained and improved efficacy of tildrakizumab from Week 28 to Week 52 in treating moderate-to-severe plaque psoriasis

Sustained and improved efficacy of tildrakizumab from Week 28 to Week 52 in treating moderate-to-severe plaque psoriasis

Presenters: Elewski B1, Menter M2, Crowley J3, Tyring J4, Zhao Y5, Lowry S5, Rozzo S5, Mendelsohn A5, Parno J5, Gordon K6

Affiliations: 1Department of Dermatology, The University of Alabama at Birmingham, Birmingham, AL; 2Division of Dermatology, Baylor University Medical Center, Dallas, TX; 3Bakersfield Dermatology, Bakersfield, CA; 4Department of Dermatology, University of Texas Health Science Center, Houston, TX; 5Sun Pharmaceuticals, Princeton, NJ; 6Medical College of Wisconsin, Milwaukee, WI

Introduction: Two Phase III, double-blind, randomized controlled trials (reSURFACE 1: NCT01722331; reSURFACE 2: NCT01729754) have demonstrated efficacy and safety of tildrakizumab, a high affinity, humanized, IgG1 ?, anti-interleukin-23 monoclonal antibody, in the treatment of adult patients with moderate-to-severe plaque psoriasis over 28 weeks. This analysis evaluated longer-term data from these two trials to examine whether the efficacy is sustained or improved from Week 28 to Week 52.

Methods: Both trials randomized adult patients with moderate-to-severe plaque psoriasis to receive tildrakizumab 100mg or 200mg at Weeks 0 and 4, then every 12 weeks after Week 4. At Week 28, patients with a Psoriasis Area and Severity Index (PASI) response of at least 50 percent were re-randomized, based on their Week 28 PASI response, to receive a higher dose, a lower dose, or an unchanged dose of tildrakizumab or placebo (randomized withdrawal in reSURFACE 1 per the trial designs). The current analysis evaluated only patients treated with the same dose of tildrakizumab (100mg or 200mg) throughout the first 52 weeks. Four mutually exclusive groups were created based on Week 28 PASI response: PASI 100, PASI 90–99, PASI 75–89 and PASI 50–74. PASI responses at Week 52 (observed data) were analyzed for each Week 28 PASI-response group.

Results: This analysis included 352 patients on tildrakizumab 100mg (men: 69.9%; mean baseline age: 44.9 years) and 313 on tildrakizumab 200mg (men: 67.1%; mean baseline age: 46.4 years). The proportions of patients achieving PASI 100, PASI 90–99, PASI 75–89 and PASI 50–74 at Week 28 were 25.9 percent, 38.4 percent, 25.3 percent, and 10.5 percent, respectively, for those on the 100mg dose, and 24.6 percent, 24.3 percent, 19.5 percent and 31.6 percent, respectively, for those on the 200mg dose. Among patients who achieved Week 28 PASI of at least 90 with either dose of tildrakizumab, 88.9 to 89.4 percent maintained PASI of at least 90 at Week 52. Overall, 91.1 percent of patients on the 100mg dose and 93.9 percent on the 200mg dose with Week 28 PASI of at least 75 maintained PASI of at least 75 at Week 52. In addition, 39.3 to 40.4 percent of patients with Week 28 PASI 75 to 89 remained PASI 75 to 89 at Week 52 and 33.7 to 41.0 percent improved to PASI of at least 90. Among patients with Week 28 PASI 50 to 74, 20.2 to 29.7 percent achieved PASI of at least 90 and 52.5 to 64.9 percent achieved PASI of at least 75 at Week 52. Overall, only 2.6 percent of patients on the 100mg (n=9/352) or 200mg (n=8/313) dose had Week 52 PASI less than 50.

Conclusion: Among patients with moderate-to-severe plaque psoriasis treated with tildrakizumab 100mg or 200mg at Weeks 0 and 4, then every 12 weeks after Week 4, those who achieved Week 28 PASI of at least 50 and continued on the same dose had sustained or improved efficacy from Week 28 to Week 52. The majority patients who achieved Week 28 PASI of at least 75 or 90 maintained PASI 75 or 90 at Week 52. More than half of partial responders (PASI 50–74) at Week 28 eventually achieved PASI of at least 75 and at least one in five achieved PASI of at least 90 at Week 52.

Efficacy and safety of ixekizumab in a randomized, double-blinded, placebo-controlled, Phase IIIb clinical trial in patients with moderate-to-severe genital psoriasis

Efficacy and safety of ixekizumab in a randomized, double-blinded, placebo-controlled, Phase IIIb clinical trial in patients with moderate-to-severe genital psoriasis

Presenters: Ryan C1, Menter A2, Guenther L3, Blauvelt A4, Bissonnette R5, Yang FE6, Potts Bleakman A6; Amato DA6

Affiliations: 1Department of Dermatology, St. Vincent’s University Hospital, Dublin, Ireland; 2Menter Cosmetic Institute, Dallas, TX; 3Guenther Dermatology Research Centre, Ontario, Canada; 4Oregon Medical research Center, Portland, OR; 5Innovaderm Research, Quebec, Canada; 6Eli Lilly and Company, Indianapolis, IN

Background/Objectives: Genital psoriasis (gen-pso) is common among patients with plaque psoriasis. The condition negatively impacts quality of life and sexual health. Ixekizumab (IXE), a high-affinity monoclonal antibody that selectively targets interleukin-17A, is approved for the treatment of plaque psoriasis. This study’s objective was to evaluate the effect of IXE on gen-pso compared to placebo (PBO) during 12 weeks of treatment.

Methods: Patients with moderate-to-severe gen-pso (n=149) were randomized in a 1:1 ratio to receive either PBO (n=74) or 80mg IXE every two weeks (Q2W) following a starting dose of 160mg IXE (n=75). The primary endpoint was the percentage of patients achieving a 0 or 1 score on the 6-point static Physician’s Global Assessment of Genitalia (sPGA-G [0,1]) at Week 12. Major secondary endpoints included the percentage of patients achieving a 0 or 1 score on the 6-point overall sPGA (sPGA [0,1]), at least a three-point improvement on the 11-point Genital Itch (gen-itch) Numeric Rating Scale (NRS) for patients with a baseline score of at least 3, and a 0 or 1 score for the 5-point Sexual Frequency Questionnaire Item 2 (SFQ-item 2 [0,1]) (indicating that the frequency of sexual activity is never or rarely limited by gen-pso) for patients with a baseline SFQ-Item 2 score of at least 2. Treatment comparisons were made using logistic regression analysis with non-responder imputation for missing data. Clinicaltrials.gov ID: NCT02718898.

Results: IXE Q2W treatment led to significantly greater sPGA-G (0, 1) response rates (73.3%) than PBO (8.1%) at Week 12 (p<0.001). Similarly, overall sPGA (0, 1) response rates were significantly greater with IXE Q2W (73.3%) compared to PBO (2.7%, p<0.001). IXE Q2W led to significantly greater gen-itch NRS response rate (59.7%) at Week 12 versus PBO (8.3%, p<0.001). Significantly more patients achieved SFQ-item 2 (0, 1) with IXE Q2W (78.4%) than PBO (21.4%, p<0.001). Significant improvements in response rates were observed by Week 1 for sPGA-G (0,1) (p<0.01), overall sPGA (0,1) (p<0.001), and SFQ-item 2 (0, 1) (p<0.05), and by Week 2 for gen-itch NRS (p<0.001). Frequencies of treatment-emergent adverse events (TEAEs) through Week 12 were 56.0 percent and 44.6 percent in IXE Q2W and PBO groups, respectively; the majority were mild or moderate in severity. Common TEAEs in the IXE Q2W population included upper respiratory tract infections, injection site reactions, headache, oropharyngeal pain, and pruritus. No cases of candidiasis were reported, no deaths occurred, and only one (1.4%) serious adverse event was reported in a patient receiving PBO.

Conclusion: IXE Q2W was superior to PBO for the primary and all major secondary endpoints as early as Week 1 and safety outcomes were comparable to previously reported IXE Phase III trials. These results indicate that IXE is an efficacious treatment of moderate-to-severe gen-pso and minimizes how often gen-pso limits the frequency of sexual activity.

Certolizumab pegol is effective for chronic plaque psoriasis across patient subgroups: a pooled analysis from ongoing, Phase III studies (CIMPASI-1 and CIMPASI-2)

Certolizumab pegol is effective for chronic plaque psoriasis across patient subgroups: a pooled analysis from ongoing, Phase III studies (CIMPASI-1 and CIMPASI-2)

Presenters: Reich K1, Blauvelt A2, Thaçi D3, Leonardi C4, Poulin Y5, Burge D6, Peterson L7, Drew J6, Arendt C8, Gottlieb AB9

Affiliations: 1Dermatologikum Hamburg and SCIderm Research Institute, Hamburg, Germany; 2Oregon Medical Research Center, Portland, OR; 3University of Lübeck, Lübeck, Germany; 4Central Dermatology and Saint Louis University School of Medicine, St. Louis, MO; 5Centre de Recherche Dermatologique du Québec Métropolitain, Québec, Canada; 6Dermira, Inc., Menlo Park, CA; 7UCB Pharma, Raleigh, NC; 8UCB Pharma, Brussels, Belgium; 9New York Medical College at Metropolitan Hospital, New York, NY

Background/Objective: CIMPASI-1 (NCT02326298) and CIMPASI-2 (NCT02326272) are ongoing Phase III trials of certolizumab pegol (CZP) in adults with moderate-to-severe chronic plaque psoriasis. This prespecified, pooled subgroup analysis is assessing efficacy of CZP to Week 48 across demographic and baseline disease characteristic subgroups.

Methods: Patients are at least 18 years old with moderate-to-severe plaque psoriasis for at least six months (Psoriasis Area and Severity Index [PASI] ?12, Body Surface Area Affected [BSA] ?10%, Physician’s Global Assessment [PGA] ?3 on a 5-point scale), had no prior exposure to CZP or less than two biologics, and were candidates for systemic psoriasis therapy. The coprimary endpoints were PASI 75 (?75% reduction in PASI) and PGA 0/1 (clear/almost clear with ?2 category improvement in PGA) at Week 16. Subgroup analyses based on age, sex, weight, body mass index (BMI), duration of psoriasis, baseline PASI, and baseline BSA affected were performed at Week 48. PASI 75, PGA 0/1, and PASI 90 (?90% reduction in PASI) responses were summarized at Week 16 using a logistic regression model with multiple imputation (overall population) and descriptively at Week 48 based on nonresponse imputation (subgroups).

Results: Patients are being randomized to CZP 400mg every two weeks (Q2W; n=175), CZP 200mg Q2W (following 400mg loading dose at Weeks 0, 2, and 4; N=186), or placebo (n=100). So far, at Week 16 PASI 75 responder rates for CZP 400mg Q2W and CZP 200mg Q2W were 82.0 percent and 76.7 percent, respectively, versus 9.9 percent for placebo (both p<0.0001), and PGA 0/1 responder rates for CZP 400mg Q2W and CZP 200mg Q2W were 65.3 percent and 56.8 percent, respectively, versus 2.7 percent for placebo (both p<0.0001). At Week 48, CZP 400mg Q2W and CZP 200mg Q2W responder rates were 83.6 percent and 70.7 percent for PASI 75, 68.9 percent and 61.0 percent for PGA 0/1, and 61.6 percent and 50.0 percent for PASI 90. Efficacy was observed for both CZP 400mg Q2W and 200mg Q2W across demographic and baseline disease characteristic subgroups. CZP is generally well tolerated and there have been few serious treatment-emergent adverse events (TEAEs) or discontinuations due to TEAEs; no new safety signals have been observed.

Conclusion: In this pooled analysis of CIMPASI-1 and CIMPASI-2, treatment with either dose of CZP thus far is resulting in statistically significant and clinically meaningful improvements in signs and symptoms of psoriasis at Week 16 that have been maintained at Week 48. The safety profile for CZP is consistent with the anti-TNF class in psoriasis and the known safety profile of CZP. Similar to the overall population, PASI 75, PGA 0/1, and PASI 90 responder rates have been numerically greater for CZP 400 mg Q2W versus 200 mg Q2W across most subgroups at Week 48.

Long-term safety of adalimumab (HUMIRA) in adult patients from global clinical trials across multiple indications: an updated analysis in 29,987 patients representing 56,951 patient-years

Long-term safety of adalimumab (HUMIRA) in adult patients from global clinical trials across multiple indications: an updated analysis in 29,987 patients representing 56,951 patient-years

Presenters: Burmester GR1, Panaccione R2, Gordon KB3, Rosenbaum J4, Arikan D5, Lau W5, Tarzynski-Potempa R5

Affiliations: 1Charité – University Medicine Berlin, Berlin, Germany; 2University of Calgary, Calgary, AB, Canada; 3Medical College of Wisconsin, Milwaukee, WI; 4Oregon Health & Science University and Legacy Devers Eye Institute, Portland, OR; 5AbbVie, North Chicago, IL

Background/Objective: Adalimumab is an anti–tumor necrosis factor-? (TNF-?) agent indicated for the treatment of immune-mediated diseases. The long-term safety of adalimumab was previously reported in 23,458 patients representing up to 12 years of clinical trial exposure in rheumatoid arthritis (RA), juvenile idiopathic arthritis, ankylosing spondylitis (AS), psoriatic arthritis (PsA), plaque psoriasis (Ps), and Crohn’s disease (CD). Here, we report an updated analysis examining the long-term safety of adalimumab in adult patients with RA, AS, non-radiographic axial spondyloarthritis (nr-axSpA), peripheral SpA (pSpA), PsA, Ps, hidradenitis suppurativa (HS), CD, ulcerative colitis (UC), and non-infectious uveitis (UV).

Methods: Safety data from 78 clinical trials of adalimumab (RA, 33; AS, 5; nr-axSpA, 2; pSpA, 1; PsA, 3; Ps, 13; HS, 3; CD, 11; UC, 4; UV, 2; other, 1) were included in these analyses, including randomized, controlled, open-label, and long-term extension studies conducted in Europe, North America, South America, Asia, Australia, New Zealand, and South Africa through December 31, 2016. Adalimumab postmarketing surveillance data were not included in this analysis. Safety assessments included all adverse events (AEs) and serious AEs (SAEs) that occurred after the first adalimumab study dose and up to 70 days (5 half-lives) after the last study dose.

Results: This analysis included 29,987 patients, representing 56,951 patient-years of exposure. The majority of adalimumab exposure was in RA studies (24,922 PYs). The most frequently reported SAE of interest was infection (highest incidences in CD: 6.9, RA: 4.6, UV: 4.1, and UC: 3.5). The overall standardized mortality ratio was 0.65, 95 percent CI (0.5, 0.74). For most of the adalimumab populations (AS, PsA, Ps, UC, CD, and RA), the observed number of deaths was below what would be expected in an age- and sex-adjusted population. For HS, nr-axSpA, pSpA, and UV studies, the small size of these trials precluded accurate assessment of the standardized mortality ratio, and the 95 percent CIs all included 1.0.

Conclusion: This analysis of data from clinical trials of adalimumab demonstrated an overall safety profile consistent with previous findings and with the TNF inhibitor class. No new safety signals or tolerability issues with adalimumab treatment were identified, and, for most indications, the mortality rate was below what would be expected in an age- and sex-adjusted population. Efficacy and safety data continue to support the well-established benefits of adalimumab for the approved indications.

Impact on quality of life and satisfaction with apremilast in patients with moderate plaque psoriasis: 52-week results of the UNVEIL study

Impact on quality of life and satisfaction with apremilast in patients with moderate plaque psoriasis: 52-week results of the UNVEIL study

Presenters: Gold LS1, Forman S2, Lebwohl M3, Jackson JM4, Goncalves J5, Levi E5, Bagel J6

Affiliations: 1Henry Ford Health System, West BloomTeld, MI; 2Forward Clinical Trials, Tampa, FL; 3Icahn School of Medicine at Mount Sinai, New York, NY; 4University of Louisville, Forefront Dermatology, Louisville, KY; 5Celgene Corporation, Summit, NJ; 6Psoriasis Treatment Center of Central New Jersey, East Windsor, NJ

Background/Objective: Patients with moderate plaque psoriasis (i.e., 5–10% psoriasis-involved body surface area [BSA]) often receive no treatment or are undertreated with topical monotherapy. Patients with moderate psoriasis often report substantial impairments in disease-related quality of life (QoL), despite having lower psoriasis-involved BSA. Among the symptoms of psoriasis, pruritus is a key contributor to QoL impairments. Apremilast, an oral, small-molecule phosphodiesterase 4 inhibitor, improved QoL and disease severity, with acceptable tolerability, in Phase III clinical studies of patients with moderate-to-severe psoriasis. Evaluating Apremilast in a Phase IV Trial of Efficacy and Safety in Patients With Moderate Plaque Psoriasis (UNVEIL; ClinicalTrials.gov: NCT02425826), the first prospective, randomized, placebo (PBO)-controlled trial in systemic- and biologic-naive patients with moderate plaque psoriasis, demonstrated that apremilast 30mg twice-daily (APR) was effective, generally well tolerated, and had a positive impact on QoL during the 16-week, double-blind, PBO-controlled phase. The improvements in QoL and pruritus as well as treatment satisfaction are described for the open-label APR treatment phase (Weeks 16 to 52) of UNVEIL.

Methods: UNVEIL is a Phase IV, multicenter, randomized, PBO-controlled, double-blind study. Adult men and women with chronic plaque psoriasis for at least six months before screening were included in the study. Moderate plaque psoriasis at screening and baseline as defined by a BSA of 5 to 10 percent and static Physician’s Global Assessment (sPGA) of 3 (moderate) based on a scale ranging from 0 (clear) to 5 (very severe). Subject selected had no prior exposure to systemic or biologic treatments for psoriasis, psoriatic arthritis, or any other condition that could affect the assessment of psoriasis. Exclusion criteria included presence of inflammatory or dermatologic conditions, including forms of psoriasis other than plaque psoriasis. Individuals who had undergone topical therapy within two weeks or phototherapy within four weeks of randomization were also excluded. Patients were randomized (2:1) to receive APR or PBO during Weeks 0 to 16; patients in the PBO group were switched to APR at Week 16. All patients continued taking APR through Week 52. An unmedicated moisturizer was the only topical therapy permitted during the study.

Patients completed the Dermatology Life Quality Index (DLQI), Pruritus Visual Analog Scale (VAS), and Treatment Satisfaction Questionnaire for Medication (TSQM) version II. QoL was assessed with the DLQI, a validated instrument containing ten items pertaining to the skin and designed to assess QoL in a dermatology clinical setting. QoL endpoints included mean change from baseline in DLQI total score at Week 16 and Week 52, proportion of patients with baseline DLQI greater than 5 who achieved DLQI response (i.e., minimal clinically important difference [MCID] defined as a 5-point improvement from baseline in DLQI total score among patients with baseline DLQI >5). Pruritus was assessed on a 100mm VAS ranging from “no itch” (0) to “itch as severe as can be imagined” (100). Pruritus endpoints included mean change from baseline in pruritus VAS at Week 16 and Week 52. Treatment satisfaction was assessed using the TSQM Version II, a validated, self-administered, 11-question instrument designed to evaluate patient satisfaction with current treatment. An algorithm was used to transform scores to a 0- to 100-scale for effectiveness, side effects, convenience, and global satisfaction, with higher scores indicating greater satisfaction. Mean TSQM scores for effectiveness, side effects, convenience, and global satisfaction were assessed at Week 16 and Week 52. Safety was evaluated based on adverse events (AEs), vital signs, clinical laboratory testing, and complete physical examinations. QOL, pruritus, and treatment satisfaction assessments at Week 16 were conducted for the intent-to-treat (ITT) population, which included all randomized patients. At Week 52, efficacy analyses were performed in the modified ITT population (all patients who entered the APR extension phase and were treated). Safety assessments were conducted in all randomized patients who received one dose of study medication. Changes from baseline in DLQI total score and pruritus VAS score at Week 16 were compared between the APR and PBO groups using a two-way analysis of covariance (ANOVA) model with treatment and site as factors and baseline value as a covariate. The proportions of patients achieving a DLQI response at Week 16 were compared between groups using a two-sided Cochran-Mantel-Haenszel test stratified by site. Mean TSQM scores at Week 16 were compared between treatment groups by ANOVA with treatment and site as factors. QOL, pruritus, and treatment satisfaction parameters at Week 52 were evaluated descriptively. The last-observation-carried-forward (LOCF) methodology was used to impute missing values. Safety assessments were summarized using frequencies and percentages.

Results: A total of 221 patients were randomized to study treatment, constituting the ITT population; 185 patients (84%) completed the PBO-controlled phase (Weeks 0–16) and 136/185 patients (74%) completed the APR treatment phase (Weeks 16–52). Demographics and baseline disease characteristics were generally similar between treatment groups. At baseline, mean DLQI total score was comparable between treatment groups, and mean pruritus VAS score was slightly higher in the PBO group. At Week 16, improvement from baseline in DLQI total score was significantly greater with APR than with PBO (-4.8 vs. -2.4; P=0.0008). Significantly more patients with a baseline DLQI total score greater than 5 who received APR versus PBO achieved the DLQI MCID at Week 16 (63.8% vs. 34.5%; P=0.0009). At Week 52, improvement in DLQI total score was maintained in patients who were randomized to APR and then continued on APR during the open-label APR treatment phase (mean change from baseline: -4.4). Patients who switched from PBO to APR at Week 16 achieved similar improvements in DLQI total score at Week 52 (mean change from baseline: -5.1). Among patients who were initially randomized to APR at baseline, the percentages of patients who achieved DLQI MCID at Week 16 were maintained over 52 weeks. At Week 16, mean change from baseline in pruritus VAS score was -19.2mm in the APR group and -10.2mm in the PBO group (P=0.0016). The improvement in pruritus VAS score was maintained at Week 52 in patients who continued on APR, and mean VAS score improved in those switched from PBO to APR. At Week 16, treatment effectiveness, as measured by the TSQM, was significantly greater with APR than with PBO (P<0.0001). Global satisfaction also favored APR over PBO (P<0.0001), whereas satisfaction with side effects (P=0.34) and convenience (P=0.63) did not differ between treatment groups. At Week 52, levels of satisfaction were maintained on all domains. The most common AEs reported with APR treatment from 0 to 52 weeks included diarrhea, nausea, headache, and nasopharyngitis; most AEs were mild or moderate in severity. Exposure-adjusted incidence rates (EAIR) per 100 patient-years did not increase with longer exposure up to 52 weeks. No new safety or tolerability signals were observed up to 52 weeks.

Conclusion: APR improved QoL and reduced pruritus at Week 16 in systemic- and biologic-naive patients with moderate plaque psoriasis (BSA 5–10%); these improvements were maintained over 52 weeks with continued APR treatment. The beneficial effects of APR on QoL and pruritus were consistent with those previously reported in patients with moderate-to-severe plaque psoriasis in randomized Phase III trials. Global treatment satisfaction was greater with APR than with PBO at Week 16, and satisfaction remained high over 52 weeks of APR treatment. The safety and tolerability of APR was consistent with previous studies. No new safety or tolerability issues were observed with APR treatment up to Week 52.

Funding/Disclosures: The authors acknowledge financial support for this study from Celgene Corporation. Linda Stein Gold is an investigator and/or consultant for Celgene Corporation. Seth Forman provides research support for Celgene Corporation. Mark Lebwohl is affiliated with Mount Sinai, which receives funds from Celgene Corporation. J. Mark Jackson is a consultant, receives honoraria from, provides research support and/or other support to Celgene Corporation. Joana Goncalves and Eugenia Levi are employees of the Celgene Corporation. Jerry Bagel is an advisory board member, speaker, consultant, and/or provider of research support for Celgene Corporation.