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.

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.

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.

Efficacy and safety of apremilast in systemic- and biologic-naive patients with moderate plaque psoriasis (52-week results of the UNVEIL study)

Presenters: Strober B¹, Forman S², Bagel J³, Lebwohl M⁴, Stein Gold L⁵, Jackson JM⁶, Goncalves J⁷, Levi E⁷, Callis Duffin K⁸

Affiliations: ¹University of Connecticut, Farmington, CT, and Probity Medical Research, Waterloo, ON, Canada; ²Forward Clinical Trials, Tampa, FL; ³Psoriasis Treatment Center of Central New Jersey, East Windsor, NJ; ⁴Icahn School of Medicine at Mount Sinai, New York, NY; ⁵Henry Ford Health System, West Bloomfield, MI; ⁶University of Louisville, Forefront Dermatology, Louisville, KY; ⁷Celgene Corporation, Summit, NJ; ⁸University of Utah, Salt Lake City, UT

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. Apremilast, an oral, small-molecule phosphodiesterase 4 inhibitor, has been shown to be effective and has demonstrated acceptable tolerability in patients with moderate-to-severe psoriasis (BSA 10%) in the Efficacy and Safety Trial Evaluating the Effects of Apremilast in Psoriasis (ESTEEM) Phase III clinical trial program. Evaluating Apremilast in a Phase IV Trial of Efficacy and Safety in Patients With Moderate Plaque Psoriasis (UNVEIL) (ClinicalTrials.gov: NCT02425826) is the first prospective randomized, placebo (PBO)-controlled trial to demonstrate the clinical efficacy and safety of an oral systemic treatment (apremilast) in systemic- and biologic-naive patients with moderate plaque psoriasis. Apremilast 30mg twice-daily (APR) was clinically effective and well tolerated during the 16-week, double-blind, PBO-controlled phase. The efficacy and safety results of the open-label APR treatment phase up to Week 52 are presented.

Methods: UNVEIL is a Phase IV, multicenter, randomized, PBO-controlled, double-blind study. Men and women at least 18 years of age with chronic plaque psoriasis for six months before screening were included in the study. Subjects had moderate plaque psoriasis at screening and baseline as defined by 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). Included subjects had no prior exposure to systemic or biologic treatments for psoriasis, psoriatic arthritis, or any other condition that could affect the assessment of psoriasis. Potential subjects with an inflammatory or dermatologic condition, including forms of psoriasis other than plaque psoriasis, were excluded. Persons using 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.

The primary efficacy endpoint was the mean percentage change from baseline at Week 16 in PGAxBSA, which represents the product of sPGA and BSA scores. Overall BSA affected by psoriasis is estimated based on the patient’s palm area, which equates to approximately one percent of total BSA. For the 6-point sPGA for plaques in all involved areas, the severity of erythema, scaling, and plaque elevation were each scored; scores were averaged and rounded to the nearest whole number. The secondary efficacy endpoint was the proportions of patients achieving a 75-percent reduction from baseline in PGAxBSA score (PGAxBSA-75) and the sPGA response, defined as a score of 0 (clear) or 1 (almost clear). Quality of life (QOL) was assessed with the Dermatology Life Quality Index (DLQI). Safety was evaluated based on adverse events (AEs), vital signs, clinical laboratory testing, and complete physical examinations. Efficacy and QOL assessments were conducted for the intent-to-treat (ITT) population, which included all randomized patients; safety assessments were conducted in all randomized patients who received one dose of study medication. Mean percentage change from baseline in PGAxBSA and change from baseline in DLQI total score at Week 16 were compared between APR and PBO using a two-sided analysis of covariance model (ANOVA) with treatment and site as factors and baseline value as covariate. PGAxBSA-75 and sPGA responses at Week 16 were evaluated with two-sided Cochran-Mantel-Haenszel tests stratified by site. Efficacy and QOL parameters at Week 52 were evaluated descriptively. Week 16 and Week 52 APR/APR analyses were performed with the ITT population. Week 52 PBO/APR analyses were performed with the modified ITT population (all patients who entered the APR extension phase). The last-observation-carried-forward 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 and constitute 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 the mean pruritus Visual Analog Scale (VAS) score was slightly higher in the PBO group. At Week 16, significantly greater improvement in PGAxBSA occurred in patients receiving APR (-48.1%) versus PBO (-10.2%). At Week 52, improvement was maintained in the APR/APR group and emerged in the PBO/APR group after switching to APR. Significantly more patients treated with APR achieved PGAxBSA-75 response at Week 16 (35.4%) versus PBO (12.3%). PGAxBSA-75 response was maintained in the open-label APR treatment phase. Significantly more patients treated with APR achieved an sPGA score of 0 or 1 at Week 16 (30.4%) versus PBO (9.6%). Long-term sPGA response was maintained with APR treatment in the open-label treatment phase. Improvement in DLQI was significantly greater with APR (-4.8) than PBO (-2.4) at Week 16. DLQI improvement was maintained in patients continuing on APR for up to 52 weeks and developed after patients were switched from PBO to APR. Most AEs were mild or moderate. The most common AEs (reported in 5% of patients in either treatment group during the PBO-controlled period) included diarrhea, headache, nausea, upper respiratory tract infection, decreased appetite, and vomiting.

Conclusion: APR was clinically effective in systemic- and biologic-naive patients with moderate plaque psoriasis (BSA of 5–10%). APR significantly improved PGAxBSA score, PGAxBSA-75 response rate, sPGA 0 or 1 response rate, and DLQI total score at Week 16 compared with PBO. Clinical responses were maintained with continued APR treatment through Week 52 and emerged in patients who switched from PBO to APR at Week 16. The incidence of AEs, based on EAIR per 100 patient-years, did not increase with longer exposure to APR. Safety and tolerability were consistent with previous studies; no new safety or tolerability issues were observed up to 52 weeks.

Funding/Disclosures: The authors acknowledge financial support for this study from Celgene Corporation. Bruce Strober receives honoraria as a consultant, payments (to the University of Connecticut) as an investigator, and is an advisory board member of Celgene Corporation. Seth Forman receives research support from the Celgene Corporation. Jerry Bagel is an advisory board member, speaker, consultant, and/or receives research support from the Celgene Corporation. Mark Lebwohl is an investigator and/or consultant for the Celgene Corporation. J. Mark Jackson receives research, honoraria, consulting, and/or other support from Celgene Corporation. Joana Goncalves and Eugenia Levi are employees of the Celgene Corporation. Kristina Callis Duffin is a consultant, steering committee member, advisory board member, has received grants, and/or has received honoraria from the Celgene Corporation.

Sustained improvement in patient-reported outcomes with continued apremilast treatment over 104 weeks in patients with moderate-to-severe psoriasis

Presenters: Chapman S¹, Cirulli J², McBride S³

Affiliations: ¹Dartmouth–Hitchcock Medical Center, Lebanon, NH; ²Celgene Corporation, Summit, NJ; ³Royal Free London NHS Foundation Trust, London, UK

Background/Objective: Psoriasis is a chronic, systemic, inflammatory disease that is associated with significant impairments in quality of life (QoL), which can include physical discomfort, pruritus, and emotional distress. Apremilast is an oral, small-molecule phosphodiesterase 4 inhibitor that has demonstrated efficacy and safety versus placebo (PBO) in the LIBERATE global Phase IIIb trial in patients with moderate-to-severe plaque psoriasis. Efficacy was maintained for up to 104 weeks in patients who continued treatment with apremilast 30mg twice-daily (APR) in the LIBERATE trial. To further understand the clinical profile 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: Adults 18 years of age or older with chronic plaque psoriasis for at least 12 months and who were candidates for phototherapy with no prior exposure to biologics for the treatment of psoriatic arthritis or psoriasis were included. Included patients had moderate-to-severe plaque psoriasis, as defined by Psoriasis Area and Severity Index (PASI) score 12, psoriasis-involved Body Surface Area (BSA) 10 percent, and static Physician Global Assessment (sPGA) score 3. Patients included in the study had inadequate response, inability to tolerate, or contraindication to one conventional systemic agent for the treatment of psoriasis. Patients who were excluded had prior treatment with more than three systemic agents for the management of psoriasis, other clinically significant or major uncontrolled diseases, and/or serious infections, including latent, active, or history of incompletely treated tuberculosis. LIBERATE consisted of two 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. Patients were randomized (1:1:1) to PBO, APR, or etanercept 50mg 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).

At Weeks 16 and 104, the proportion of patients achieving response, defined as the minimal clinically important difference (MCID), was evaluated for the following patient-reported outcomes: 1) Dermatology Life Quality Index (DLQI) MCID defined as an at least 5-point decrease from baseline in patients with baseline DLQI score over 5; 2) pruritus Visual Analog Scale (VAS; 0–100mm) MCID defined as an at least 20 percent decrease from baseline; 3) 36-Item Short Form Health Survey version 2 (SF-36v2) Mental and Physical Component Summary scores (MCS and PCS)–both MCIDs defined as an increase of at least 2.5 points from baseline; and 4) Patient Health Questionnaire-8 (PHQ-8)–MCID defined as achievement of score 4 (no significant depressive symptoms). Safety was assessed based on adverse events (AEs), vital signs, clinical laboratory assessments, and physical examinations. Achievement of MCID on the DLQI at Week 16 and Week 104 was a prespecified exploratory endpoint, 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 modified intent-to-treat (mITT) population, which included all randomized patients who received one dose of study medication and had an evaluation at baseline and at the specified time point. Endpoints were analyzed using descriptive statistics, including proportions of patients achieving each endpoint by treatment group; associated 95-percent confidence 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 one dose of study medication. Descriptive statistics were used for summaries of treatment-emergent AEs and other safety assessments.

Results: 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. 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. 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.

At Week 16 and Week 104, proportions of patients achieving the MCID for PHQ-8 (i.e., score 4 [no significant 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. During the PBO-controlled period (Weeks 0 to 16), AEs occurring in five percent of patients in any treatment group were diarrhea, nausea, upper respiratory tract infection, nasopharyngitis, headache, and tension headache. During the APR extension phase (Weeks 16–104), AEs that occurred in five percent 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. No clinically meaningful changes were reported in laboratory parameters. No cases of tuberculosis (new or reactivation) were reported during the trial.

Conclusion: 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 profile of APR.

Funding/Dislcosures: The authors acknowledge financial support for this study from Celgene Corporation. Joshua Cirulli is an employee of the Celgene Corporation.