BACKGROUND:Genital psoriasis is highly prevalent among patients with psoriasis, is often stigmatized, causes pain and discomfort and negatively impacts quality of life. Apremilast is an oral phosphodiesterase 4 inhibitor approved for treating psoriasis and has demonstrated safety and efficacy in treating genital psoriasis, as seen in the primary 16-week DISCREET results. OBJECTIVES:To assess the efficacy and safety of apremilast 30 mg twice daily in patients with moderate to severe genital psoriasis over the 32-week study duration. METHODS:DISCREET was a phase 3, multicentre, randomized, double-blind trial that evaluated apremilast 30 mg twice daily versus placebo in a 16-week placebo-controlled phase (randomization 1:1) followed by a 16-week apremilast extension phase. Patients had moderate to severe genital psoriasis, defined as a modified static Physician's Global Assessment of Genitalia (genital PGA) score of ≥3. They also either had disease inadequately controlled by or were intolerant to topical therapy. We report the results through Week 32. RESULTS:Of 289 patients randomized, 229 continued to the apremilast extension phase (Weeks 16-32): 110 in the placebo/apremilast group and 119 in the apremilast/apremilast group. At 32 weeks, 51.8% (95% CI: 42.6, 60.9) of patients in the placebo/apremilast group and 40.3% (95% CI: 32.0, 49.3) of patients in the apremilast/apremilast group had achieved a modified genital PGA response (score of 0/1 with ≥2-point reduction from baseline). At Week 32, similar improvements in skin, genital signs and symptoms and quality of life were observed in patients who started apremilast at Week 16 or at randomization. Frequently reported treatment-emergent adverse events during all-apremilast exposure were diarrhoea (25.4%), nausea (19.4%) and headache (17.9%). CONCLUSIONS:Apremilast is an effective oral systemic therapy in patients with moderate to severe genital psoriasis and has shown consistent clinical efficacy, lessening of symptoms and quality-of-life benefit in DISCREET. CLINICAL TRIAL ID:NCT03777436.

Background: Genital psoriasis can be stigmatizing, is highly prevalent among patients with psoriasis, and has limited treatment options. Apremilast is a unique oral immunomodulating phosphodiesterase 4 inhibitor approved for psoriasis treatment. Objective: To assess the efficacy and safety of apremilast 30 mg twice daily in patients with genital psoriasis. Methods: DISCREET, a phase 3, placebo-controlled trial (NCT03777436), randomized patients with moderate-to-severe genital psoriasis (stratified by affected body surface area \10% or >= 10%) to apremilast or placebo for a 16-week period, followed by an apremilast extension period. Week 16 results are presented. Results: Patients were randomized to apremilast (n = 143) or placebo (n = 146). At Week 16, 39.6% and 19.5% of apremilast and placebo patients, respectively, achieved a modified static Physician Global Assessment of Genitalia response (primary endpoint; score of 0/1, >= 2 -point reduction); treatment difference was significant (20.1%, P = .0003). Improvements in genital signs and symptoms, skin involvement, and quality of life were observed. Common treatment-emergent adverse events were diarrhea, headache, nausea, and nasopharyngitis. Conclusions: Apremilast demonstrated statistically and clinically meaningful genital Physician Global Assessment responses and improvement of signs, symptoms, severity, and quality of life in this first randomized, controlled study of an oral systemic treatment in patients with genital psoriasis. ( J Am Acad Dermatol 2024;90:485-93.)

Background: Obesity is prevalent in psoriasis patients and may interfere with treatment efficacy. Apremilast is an oral immunomodulator of phosphodiesterase 4 indicated for psoriasis treatment.

Background: Genital psoriasis remains highly stigmatized, underdiagnosed, and undertreated. Apremilast is an oral immunomodulating phosphodiesterase 4 inhibitor approved in multiple countries for psoriasis. The phase 3 DISCREET trial (NCT03777436) evaluated apremilast 30 mg BID (APR) for the treatment of genital psoriasis.

To the Editor: Mild-to-moderate psoriasis often involves special areas such as the scalp.1Lebwohl M.G. Bachelez H. Barker J. et al.Patient perspectives in the management of psoriasis: results from the population-based Multinational Assessment of Psoriasis and Psoriatic Arthritis Survey.J Am Acad Dermatol. 2014; 70: 871-881Abstract Full Text Full Text PDF PubMed Scopus (403) Google Scholar Patients can experience substantial quality-of-life impairment despite limited overall skin involvement.1Lebwohl M.G. Bachelez H. Barker J. et al.Patient perspectives in the management of psoriasis: results from the population-based Multinational Assessment of Psoriasis and Psoriatic Arthritis Survey.J Am Acad Dermatol. 2014; 70: 871-881Abstract Full Text Full Text PDF PubMed Scopus (403) Google Scholar In the phase 3 ADVANCE study (NCT03721172), apremilast demonstrated efficacy and tolerability in adults with mild-to-moderate psoriasis (static Physician's Global Assessment [sPGA] 2-3, psoriasis-involved body surface area [BSA] 2%-15%, and Psoriasis Area and Severity Index 2-15) inadequately controlled with/intolerant to ≥1 topical therapy.2Stein Gold L. Papp K. Leonardi C. et al.Efficacy and safety of apremilast in patients with mild to moderate plaque psoriasis: results of a phase 3, multicenter, randomized, double-blind, placebo-controlled trial.J Am Acad Dermatol. 2022; 86: 77-85Abstract Full Text Full Text PDF PubMed Scopus (16) Google Scholar Patients were randomized 1:1 to apremilast 30 mg BID or placebo for 16 weeks, followed by a 16-week extension phase. We present efficacy and safety of apremilast during the extension phase. Of 595 randomized patients (apremilast: 297; placebo: 298), 84.5% entered (apremilast: 257; placebo: 246) and 73.4% (n = 437) completed the extension phase, including 221 patients continuing apremilast treatment. Of 503 patients, 66 (13.1%) discontinued. The primary endpoint was met: 21.6% of apremilast-treated patients achieved an sPGA score of 0 (clear) or 1 (almost clear) and a ≥2-point reduction from baseline at week 16 vs 4.1% with placebo (P < .0001).2Stein Gold L. Papp K. Leonardi C. et al.Efficacy and safety of apremilast in patients with mild to moderate plaque psoriasis: results of a phase 3, multicenter, randomized, double-blind, placebo-controlled trial.J Am Acad Dermatol. 2022; 86: 77-85Abstract Full Text Full Text PDF PubMed Scopus (16) Google Scholar At week 32, the sPGA response was maintained by 30.2% (64 of 212) of patients continuing apremilast (apremilast/apremilast) and 34.3% (72 of 210) of patients initially randomized to placebo (placebo/apremilast) using data as observed (DAO); apremilast/apremilast: 24.9% (64 of 257) and placebo/apremilast: 29.3% (72 of 246) using nonresponder imputation. Improvements in secondary endpoints observed at week 16 (Supplementary Material, available via Mendeley at https://data.mendeley.com/datasets/wf4g3yxvzz/1) were sustained up to week 32 in patients continuing apremilast (DAO: BSA-75: 49.1% [104 of 212] [Fig 1]; Whole Body Itch Numeric Rating Scale response: 51.9% [95 of 183] and 62.1% [110 of 177] [Supplementary Fig 1, available via Mendeley at https://data.mendeley.com/datasets/wf4g3yxvzz/1]; Scalp Physician's Global Assessment response: 49.7% [78 of 157] and 58.6% [78 of 133]; Dermatology Life Quality Index: –5.8 [n = 212] and –6.7 [n = 207] [Supplementary Fig 2, available via Mendeley at https://data.mendeley.com/datasets/wf4g3yxvzz/1]). At week 32, 29.3% of patients continuing apremilast achieved Psoriasis Area and Severity Index-75, comparable to the 27.2% of patients who switched from placebo to apremilast (nonresponder imputation; Fig 2). BSA-75, Whole Body Itch Numeric Rating Scale, and Scalp Physician's Global Assessment responses at week 32 analyzed with nonresponder imputation were consistent with DAO (Supplementary Fig 3, available via Mendeley at https://data.mendeley.com/datasets/wf4g3yxvzz/1).Fig 2Proportions of patients with psoriasis achieving PASI-75 response based on NRI analysis. Bars represent two-sided 95% CIs. NRI, Nonresponder imputation; PASI, Psoriasis Area and Severity Index; PASI-75, ≥75% reduction from baseline in PASI score.View Large Image Figure ViewerDownload Hi-res image Download (PPT) During the apremilast-exposure period (0-32 weeks), 544 patients received ≥1 apremilast dose (total apremilast exposure: 234.3 person-years). Most (93.2%) patients with treatment-emergent adverse events during this period had mild/moderate treatment-emergent adverse events. The most common treatment-emergent adverse events (≥5%) were diarrhea (14.3%, 78 of 544), headache (12.9%, 70 of 544), nausea (12.7%, 69 of 544), upper respiratory tract infection (8.5%, 46 of 544), and nasopharyngitis (6.8%, 37 of 544), consistent with the known apremilast safety profile.3Papp K. Reich K. Leonardi C.L. et al.Apremilast, an oral phosphodiesterase 4 (PDE4) inhibitor, in patients with moderate to severe plaque psoriasis: results of a phase III, randomized, controlled trial (Efficacy and Safety Trial Evaluating the Effects of Apremilast in Psoriasis [ESTEEM 1]).J Am Acad Dermatol. 2015; 73: 37-49Abstract Full Text Full Text PDF PubMed Scopus (448) Google Scholar,4Paul C. Cather J. Gooderham M. et al.Efficacy and safety of apremilast, an oral phosphodiesterase 4 inhibitor, in patients with moderate to severe plaque psoriasis over 52 weeks: a phase III, randomized, controlled trial (ESTEEM 2).Br J Dermatol. 2015; 173: 1387-1399Crossref PubMed Scopus (345) Google Scholar Although topical therapies are commonly prescribed for mild-to-moderate psoriasis, systemic treatment may benefit patients with intractable pruritus or special area involvement (eg, the scalp).5Menter A. Strober B.E. Kaplan D.H. et al.Joint AAD-NPF guidelines of care for the management and treatment of psoriasis with biologics.J Am Acad Dermatol. 2019; 80: 1029-1072Abstract Full Text Full Text PDF PubMed Scopus (498) Google Scholar Bothersome symptoms and psoriasis locations can impair quality of life.1Lebwohl M.G. Bachelez H. Barker J. et al.Patient perspectives in the management of psoriasis: results from the population-based Multinational Assessment of Psoriasis and Psoriatic Arthritis Survey.J Am Acad Dermatol. 2014; 70: 871-881Abstract Full Text Full Text PDF PubMed Scopus (403) Google Scholar Per current guidelines, mild-to-moderate psoriasis may require systemic treatment in patients with high disease burden or psoriasis inadequately controlled with topicals. Efficacy results may be biased by lack of an active comparator and reporting DAO findings. Improvements in sPGA, BSA, whole-body itch Numeric Rating Scale, Scalp Physician's Global Assessment, and Dermatology Life Quality Index were maintained through week 32 with apremilast treatment. These findings demonstrate that continued apremilast treatment results in sustained clinical improvements in overall disease severity, scalp psoriasis, itch, and quality of life for patients with mild-to-moderate psoriasis. Qualified researchers may request data from Amgen clinical studies. Complete details are available at http://www.amgen.com/datasharing. Linda Stein Gold has received honoraria, grants, and/or research funding as a speaker, investigator, and/or advisory board member for AbbVie, Amgen Inc, Arcutis, Celgene Corporation, Dermira, Dermavant, Eli Lilly, Galderma, LEO Pharma, Novartis, Pfizer, Regeneron, Sanofi Genzyme, UCB, and Valeant. Kim Papp has received honoraria, grants, and/or research funding as a speaker, investigator, advisory board member, data safety monitoring board member, and/or consultant for AbbVie, Actelion, Amgen Inc, Astellas Pharma US, Boehringer Ingelheim, Bausch Health, Celgene Corporation, Dermira, Dow Pharmaceuticals, Eli Lilly, Frontier, Galderma, Janssen, Kyowa Hakko Kirin Pharma, LEO Pharma, MedImmune, Merck & Co, Inc, Novartis, Pfizer, Regeneron, Roche Laboratories, Sanofi Genzyme, Takeda Pharmaceuticals, UCB, and Valeant and is a steering committee member for PSLOAR, PURE. David Pariser is a honoraria, investigator, advisory board, or data monitoring board member for Amgen Inc, AO Biome, Asana, Brickel Biotech, Celgene Corporation, Dermavant, Dermira, Eli Lilly, Menlo Therapeutics, Merck, Novartis, Ortho, Regeneron, Atacama, Biofrontera, Bristol Myers Squibb, LEO Pharma, Pfizer, Sanofi, and Valeant. Neal Bhatia is an advisor, consultant, investigator, and/or speaker for AbbVie, Actavis, Allergan, Amgen Inc, Aqua, Bayer, Biofrontera, BioPharmX, Castle, Cipher, Dermira, Encore, Exeltis, Ferndale, Foamix, Galderma, Intraderm, ISDIN, LaRoche-Posay, LEO Pharma, Novan, Novartis, PharmaDerm, Pfizer, Promius, Regeneron, Sanofi, Sun Pharma, and Valeant. Howard Sofen has received honoraria, grants, and/or research funding as an investigator and/or advisory board member for AbbVie, Amgen Inc, Celgene Corporation, Dermira, Dermavant, Eli Lilly, Galderma, LEO Pharma, Novartis, Pfizer, and UCB. Lorne Albrecht has received honoraria, grants, and/or research funding as a speaker, investigator, advisory board member, and/or consultant for AbbVie, Amgen Inc, Arcutis, Boehringer Ingelheim, Bausch Health/Valeant, Celgene Corporation, Dermira, Dermavant, Eli Lilly, Galderma, Janssen, LEO Pharma, MedImmune, Merck & Co, Novartis, Pfizer, Regeneron, Roche Laboratories, Sanofi Genzyme, and UCB. Melinda Gooderham has received honoraria, grants, and/or research funding as a speaker, investigator, advisory board member, data safety monitoring board member, and/or consultant AbbVie, Amgen Inc, Akros, Arcutis, Bausch/Valeant, Boehringer Ingelheim, Celgene Corporation, Dermira, Dermavant, Eli Lilly, Galderma, Janssen, Kyowa Hakko Kirin Pharma, LEO Pharma, MedImmune, Merck & Co, Novartis, Pfizer, Regeneron, Roche Laboratories, Sanofi Genzyme, Takeda Pharmaceuticals USA Inc, and UCB. Mindy Chen, Maria Paris, Sue Cheng, and Hernan Picard are employees and stockholders for Amgen Inc. Yao Wang was employed at time of study. Kristina Callis Duffin has received honoraria, grants, and/or research funding as investigator, advisory board member, consultant, and nonpromotional speaker for Novartis and has received honoraria, grants, and/or research funding as an investigator, advisory board member, and/or consultant for AbbVie, Amgen Inc, Boehringer Ingelheim, Celgene Corporation, Eli Lilly, Janssen, Novartis, Pfizer, Regeneron, and UCB. Lawrence Green is an investigator, speaker, and/or consultant for AbbVie, Amgen Inc, Arcutis, Dermavant, MC2, Novartis, Lilly, OrthoDerm, Sun Pharma, and UCB. Writing support was funded by Amgen and provided by Kristin Carlin, BSPharm, MBA, of Peloton Advantage, LLC, an OPEN Health company, and Dawn Nicewarner, PhD, employee of and stockholder in Amgen Inc.

Objective To assess apremilast’s impact on patient quality of life (QoL) in active Behçet’s syndrome and correlations between improvement in patients’ QoL and efficacy measures in the phase 3 RELIEF study. Methods QoL measures included Behçet’s Disease QoL (BDQoL), 36-Item Short-Form Health Survey V.2 (SF-36v2) Physical/Mental Component Summary (PCS/MCS) and eight subscale scores, focusing on Physical Functioning (PF). Pearson’s correlation coefficients assessed relationships between efficacy endpoints (oral ulcer count, oral ulcer pain, Behçet’s Syndrome Activity Scale (BSAS), Behçet’s Disease Current Activity Form (BDCAF)) and QoL endpoints for apremilast at Week 12. Results Apremilast (n=104) demonstrated significantly greater improvements versus placebo (n=103) in SF-36v2 PCS (3.1 vs 0.9), MCS (4.6 vs ─0.7) and PF (2.9 vs 0.14), respectively (all p<0.05). Mild correlations were observed in improvements of SF-36v2 measures (PCS, MCS, PF) with oral ulcer count (r=−0.11, PCS), and change in oral ulcer pain from baseline (r=−0.28, PCS; r=−0.10, PF) and BSAS (r=−0.38, PCS; r=−0.20, PF; r=−0.16, MCS). Correlations among BDCAF and SF-36v2 components and BDQoL were variable. BDQoL showed mild/moderate correlations with SF-36v2 components (r=−0.18, PCS; r=−0.13, PF; r=−0.45, MCS). Conclusions Apremilast was associated with significant improvements in QoL measures of SF-36v2 PCS, MCS and PF and BDQoL in patients with Behçet’s syndrome. Correlations of improvement among QoL endpoints support the beneficial clinical effects of apremilast in Behçet’s syndrome. Trial registration number NCT02307513.

Background: In ADVANCE (NCT03721172), apremilast 30 mg BID (APR) demonstrated significantly greater sPGA response vs. PBO at Week 16 (22% vs. 4%; P < .0001) in patients with mild-to-moderate psoriasis. The Physician Global Assessment and Body Surface Area Composite Tool (PGA × BSA) is a simple, sensitive measure of psoriasis severity for patients with BSA<10%. We performed a post hoc analysis of the efficacy results from ADVANCE using the PGA×BSA. Methods: This current post hoc analysis included all randomized patients. Missing data were imputed by multiple imputation. PGAxBSA-50/75/90 was 50%, 75% and 90% improvement in PGAxBSA from baseline. Results: Of 595 randomized patients (APR: 297; PBO: 298), baseline characteristics were similar for mean BSA (APR: 6.4; PBO: 6.3), sPGA score 2 (APR 31%; PBO: 31%), sPGA score 3 (APR: 69%; PBO: 70%), and mean PGA×BSA (APR: 17.6; PBO: 17.5). At Week 16, significantly more patients achieved PGAxBSA-50/75/90 response with APR vs. PBO: PGA×BSA-50, 67% vs. 26% (P < .0001), difference 41%, 95%CI (32.7,48.5) PGA×BSA-75, 46% vs. 13% (P < .0001), difference 33%, 95%CI (25.8,40.2) PGA×BSA-90, 27% vs. 3% (P < .0001), difference 24%, 95%CI (18.3,29.6) A significant improvement from baseline at Week 16 in PGA×BSA was observed with APR vs PBO: Mean % change (SE) in PGA×BSA, -51.8 (4.2) vs. 1.97 (4.3); difference (95%CI): -53.8 (-65.4, -42.2), P < .0001. Conclusions: The PGA×BSA Composite Tool appeared to be a sensitive and a relevant measure for mild-to-moderate psoriasis that showed significantly greater treatment differences at 50%, 75%, and 90% response thresholds at Week 16 with APR compared with PBO in ADVANCE.

Background: In ADVANCE, apremilast 30 mg BID (APR) demonstrated efficacy in mild-to-moderate psoriasis vs placebo (PBO). We report subgroup analyses by baseline psoriasis-involved BSA (≤5%, >5%).

OBJECTIVES:Apremilast efficacy and safety was assessed in a prespecified subgroup of Japanese patients with oral ulcers associated with Behçet's syndrome from a Phase 3 randomized, placebo-controlled, double-blind study of apremilast (RELIEF).METHODS:The primary end point was area under the curve for number of oral ulcers during the 12-week placebo-controlled phase (AUCWk0-12). Key secondary end points were change from baseline in oral ulcer pain, complete oral ulcer resolution, and measures of disease activity and quality of life (QoL).RESULTS:Thirty-nine Japanese patients were randomised (apremilast 30 mg BID: n = 19; placebo: n = 20). Improvements at Week 12 were observed for apremilast vs. placebo in AUCWk0-12 for the number of oral ulcers (115.9 vs. 253.3; nominal P = 0.0168); 57.9% vs. 25.0% achieved complete oral ulcer resolution, 47.4% vs. 0.0% achieved oral ulcer resolution by Week 6 and maintained oral ulcer-free status for ≥6 additional weeks; mean change from baseline in BSAS was -10.5 vs. 0.5. Favourable effects were observed for apremilast vs. placebo in other secondary end points, including QoL. Clinical benefits were sustained over 28 weeks of continued apremilast treatment. Adverse events were consistent with apremilast's known safety profile.CONCLUSIONS:Apremilast reduced the number of oral ulcers and overall disease activity in this Japanese subgroup with Behçet's syndrome.

BACKGROUND:Patients with mild-to-moderate psoriasis may have substantial quality-of-life impairment. OBJECTIVE:To evaluate apremilast 30 mg twice daily for mild-to-moderate psoriasis. METHODS:Phase 3, double-blind, placebo-controlled study in adults with mild-to-moderate psoriasis inadequately controlled or intolerant to ≥ 1 topical psoriasis therapy (NCT03721172). The primary endpoint was the achievement of static Physician Global Assessment score of 0 (clear) or 1 (almost clear) and ≥ 2-point reduction at week 16. RESULTS:Five hundred ninety-five patients were randomized (apremilast: 297; placebo: 298). The primary endpoint was met, with a significantly greater static Physician Global Assessment response rate observed at week 16 in the apremilast group compared with the placebo group (21.6% vs 4.1%; P < .0001). All secondary endpoints were met with the achievement of body surface area-75 (33.0% vs 7.4%), body surface area ≤ 3% (61.0% vs 22.9%), ≥ 4-point reduction in Whole Body Itch Numeric Rating Scale (43.2% vs 18.6%), Scalp Physician Global Assessment 0 or 1 and ≥ 2-point reduction (44.0% vs 16.6 %), and changes from baseline in body surface area, Psoriasis Area and Severity Index, and Dermatology Life Quality Index (all P < .0001). The most commonly reported adverse events (≥ 5%) with apremilast were diarrhea, headache, nausea, nasopharyngitis, and upper respiratory tract infection, consistent with prior studies. LIMITATIONS:The study lacked an active-comparator arm. CONCLUSION:Apremilast demonstrated efficacy in mild-to-moderate psoriasis and safety consistent with the established safety profile of apremilast.

BackgroundThe small-molecule phosphodiesterase 4 inhibitor apremilast modulates cytokines that are up-regulated in Behcet's syndrome. In a phase 2 trial involving patients with Behcet's syndrome, apremilast reduced the incidence and severity of oral ulcers. Data on the efficacy and safety of apremilast in patients with Behcet's syndrome who had active oral ulcers and had not previously received biologic agents are limited. MethodsIn a phase 3 trial, we randomly assigned, in a 1:1 ratio, patients who had Behcet's syndrome with active oral ulcers but no major organ involvement to receive either apremilast at a dose of 30 mg or placebo, administered orally, twice daily for 12 weeks, followed by a 52-week extension phase. The primary end point was the area under the curve (AUC) for the total number of oral ulcers during the 12-week placebo-controlled period (with lower values indicating fewer ulcers). There were 13 secondary end points, including complete response of oral ulcers, change from baseline in pain associated with oral ulcers, disease activity, and change from baseline in the Behcet's Disease Quality of Life score (range, 0 to 30, with higher scores indicating greater impairment in quality of life). Safety was also assessed. ResultsA total of 207 patients underwent randomization (104 patients to the apremilast group and 103 to the placebo group). The AUC for the number of oral ulcers was 129.5 for apremilast, as compared with 222.1 for placebo (least-squares mean difference, -92.6; 95% confidence interval [CI], -130.6 to -54.6; P<0.001). The change from baseline in the Behcet's Disease Quality of Life score was -4.3 points in the apremilast group, as compared with -1.2 points in the placebo group (least-squares mean difference, -3.1 points; 95% CI, -4.9 to -1.3). Adverse events with apremilast included diarrhea, nausea, and headache. ConclusionsIn patients with oral ulcers associated with Behcet's syndrome, apremilast resulted in a greater reduction in the number of oral ulcers than placebo but was associated with adverse events, including diarrhea, nausea, and headache. (Funded by Celgene; ClinicalTrials.gov number, NCT02307513.) In a phase 3 trial involving patients with Behcet's syndrome, the small-molecule phosphodiesterase 4 inhibitor apremilast reduced the number of oral ulcers and pain of ulcers and improved quality-of-life measures as compared with placebo over 12 weeks. Adverse events included diarrhea, nausea, and headache.