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Robert M Day - One of the best experts on this subject based on the ideXlab platform.

  • long term safety and tolerability of Apremilast in patients with psoriasis pooled safety analysis for 156 weeks from 2 phase 3 randomized controlled trials esteem 1 and 2
    Journal of The American Academy of Dermatology, 2017
    Co-Authors: Jeffrey J Crowley, Robert M Day, Joana Carla Soares Goncalves, Rongdean Chen, Kim Papp, Diamant Thaci, P Joly, Ketty Peris, K Shah
    Abstract:

    Background Randomized, controlled trials demonstrated efficacy and safety of Apremilast for moderate-to-severe plaque psoriasis and psoriatic arthritis. Objective Assess long-term safety of oral Apremilast in psoriasis patients. Methods Safety findings are reported for 0 to ≥156 weeks from the Efficacy and Safety Trial Evaluating the Effects of Apremilast in Psoriasis (ESTEEM) 1 and 2. Results The 0 to ≥156–week Apremilast-exposure period included 1184 patients treated twice daily with Apremilast 30 mg (1902.2 patient-years). During 0 to ≤52 weeks, the adverse events (AEs) that occurred in ≥5% of patients included diarrhea, nausea, upper respiratory tract infection, nasopharyngitis, tension headache, and headache. From 0 to ≥156 weeks, no new AEs (affecting ≥5% of the population) were reported. AEs, serious AEs, and study drug discontinuations caused by AEs did not increase with long-term exposure. During the 0 to ≥156–week period, the rates of major cardiac events (exposure-adjusted incidence rate [EAIR] 0.5/100 patient-years), malignancies (EAIR 1.2/100 patient-years), depression (EAIR 1.8/100 patient-years), or suicide attempts (EAIR 0.1/100 patient-years) did not increase in comparison with the rates found during the 0 to ≤52–week period. No serious opportunistic infections, reactivation of tuberculosis, or clinically meaningful effects on laboratory measurements were reported. Limitations This study had a high dropout rate (21% of patients ongoing >156 weeks); most were unrelated to safety concerns. Conclusions Apremilast demonstrated an acceptable safety profile and was generally well tolerated for ≥156 weeks.

  • Apremilast an oral phosphodiesterase 4 inhibitor in the treatment of japanese patients with moderate to severe plaque psoriasis efficacy safety and tolerability results from a phase 2b randomized controlled trial
    Journal of Dermatology, 2017
    Co-Authors: Mamitaro Ohtsuki, Robert M Day, Yukari Okubo, Mayumi Komine, Shinichi Imafuku, Peng Chen, Rosemary Petric, Allan Maroli, Osamu Nemoto
    Abstract:

    Apremilast, an oral, small-molecule phosphodiesterase 4 inhibitor, works intracellularly within immune cells to regulate inflammatory mediators. This phase 2b randomized, placebo-controlled study evaluated efficacy and safety of Apremilast among Japanese patients with moderate to severe plaque psoriasis. In total, 254 patients were randomized to placebo, Apremilast 20 mg b.i.d. (Apremilast 20) or Apremilast 30 mg b.i.d. (Apremilast 30) through week 16; thereafter, all placebo patients were re-randomized to Apremilast 20 or 30 through week 68. Efficacy assessments included achievement of 75% or more reduction from baseline in Psoriasis Area and Severity Index score (PASI-75; primary) and achievement of static Physician Global Assessment (sPGA; secondary) score of 0 (clear) or 1 (minimal) at week 16. Safety was assessed through week 68. At week 16, PASI-75 response rates were 7.1% (placebo), 23.5% (Apremilast 20; P = 0.0032 vs placebo) and 28.2% (Apremilast 30; P = 0.0003 vs placebo); sPGA response rates (score of 0 or 1) were 8.8% (placebo), 23.9% (Apremilast 20; P = 0.0165 vs placebo) and 29.6% (Apremilast 30; P = 0.0020 vs placebo). Responses were maintained with Apremilast through week 68. Most common adverse events (AEs) with placebo, Apremilast 20 and Apremilast 30 (0-16 weeks) were nasopharyngitis (8.3%, 11.8%, 11.8%), diarrhea (1.2%, 8.2%, 9.4%), and abdominal discomfort (1.2%, 1.2%, 7.1%), respectively. Exposure-adjusted incidence of these AEs did not increase with continued Apremilast treatment (up to 68 weeks). Apremilast demonstrated efficacy and safety in Japanese patients with moderate to severe plaque psoriasis through 68 weeks that was generally consistent with prior studies.

  • the efficacy and safety of Apremilast etanercept and placebo in patients with moderate to severe plaque psoriasis 52 week results from a phase iiib randomized placebo controlled trial liberate
    Journal of The European Academy of Dermatology and Venereology, 2017
    Co-Authors: K Reich, Melinda Gooderham, L Green, Anthony Bewley, Zuoshun Zhang, I Khanskaya, Robert M Day, Joana Carla Soares Goncalves, K Shah, Vincent Piguet
    Abstract:

    Background Apremilast, an oral, small-molecule phosphodiesterase 4 inhibitor, has demonstrated efficacy in patients with moderate-to-severe psoriasis. Objective Evaluate efficacy and safety of Apremilast vs. placebo in biologic-naive patients with moderate-to-severe plaque psoriasis and safety of switching from etanercept to Apremilast in a phase IIIb, randomized, double-blind, placebo-controlled study (NCT01690299). Methods Two hundred and fifty patients were randomized to placebo (n = 84), Apremilast 30 mg BID (n = 83) or etanercept 50 mg QW (n = 83) through Week 16; thereafter, all patients continued or switched to Apremilast through Week 104. The primary efficacy endpoint was achievement of PASI-75 at Week 16 with Apremilast vs. placebo. Secondary endpoints included achievement of PASI-75 at Week 16 with etanercept vs. placebo and improvements in other clinical endpoints vs. placebo at Week 16. Outcomes were assessed through Week 52. This study was not designed for Apremilast vs. etanercept comparisons. Results At Week 16, PASI-75 achievement was greater with Apremilast (39.8%) vs. placebo (11.9%; P < 0.0001); 48.2% of patients achieved PASI-75 with etanercept (P < 0.0001 vs. placebo). PASI-75 response was maintained in 47.3% (Apremilast/Apremilast), 49.4% (etanercept/Apremilast) and 47.9% (placebo/Apremilast) of patients at Week 52. Most common adverse events (≥5%) with Apremilast, including nausea, diarrhoea, upper respiratory tract infection, nasopharyngitis, tension headache and headache, were mild or moderate in severity; diarrhoea and nausea generally resolved in the first month. No new safety or tolerability issues were observed through Week 52 with Apremilast. Conclusion Apremilast demonstrated significant efficacy vs. placebo at Week 16 in biologic-naive patients with psoriasis, which was sustained over 52 weeks, and demonstrated safety consistent with the known safety profile of Apremilast. Switching from etanercept to Apremilast did not result in any new or clinically significant safety findings, and efficacy was maintained with Apremilast through Week 52.

  • Apremilast an oral phosphodiesterase 4 inhibitor in the treatment of palmoplantar psoriasis results of a pooled analysis from phase ii psor 005 and phase iii efficacy and safety trial evaluating the effects of Apremilast in psoriasis esteem clinical
    Journal of The American Academy of Dermatology, 2016
    Co-Authors: Robert Bissonnette, Robert M Day, Joana Carla Soares Goncalves, Rongdean Chen, David M Pariser, Norman Wasel, Michael Sebastian
    Abstract:

    Background Difficult-to-treat palmoplantar psoriasis has a disproportionately negative impact on quality of life. Objective We evaluated the efficacy and safety of Apremilast in palmoplantar psoriasis. Methods A post hoc analysis of data pooled from phase IIb (PSOR-005) and phase III (Efficacy and Safety Trial Evaluating the Effects of Apremilast in Psoriasis [ESTEEM] 1 and 2) clinical studies was conducted to determine the effect of Apremilast 30 mg twice daily versus placebo at week 16 in a subset of patients with moderate to severe plaque psoriasis with active palmoplantar psoriasis (baseline Palmoplantar Psoriasis Physician Global Assessment [PPPGA] score ≥1). Results Significantly more patients taking Apremilast with moderate to severe palmoplantar psoriasis (baseline PPPGA score ≥3) achieved PPPGA score 0 (clear) or 1 (almost clear) compared with placebo at week 16 (48% vs 27%; P  = .021). At week 16, 46% of the Apremilast group with baseline PPPGA score 1 or higher achieved a PPPGA score of 0 versus 25% of the placebo group ( P P Limitations This post hoc analysis was limited to 16 weeks and did not assess palmoplantar pustules, lesion localization, or surface area involvement. Conclusion Apremilast may be a useful oral treatment option for patients with moderate to severe palmoplantar plaque psoriasis.

  • Apremilast an oral phosphodiesterase 4 inhibitor in patients with difficult to treat nail and scalp psoriasis results of 2 phase iii randomized controlled trials esteem 1 and esteem 2
    Journal of The American Academy of Dermatology, 2016
    Co-Authors: Phoebe Rich, Melinda Gooderham, Robert M Day, Joana Carla Soares Goncalves, Rongdean Chen, H Bachelez, Jeffrey J Crowley
    Abstract:

    Background In the phase III double-blind Efficacy and Safety Trial Evaluating the Effects of Apremilast in Psoriasis (ESTEEM) 1 and 2, Apremilast, an oral phosphodiesterase 4 inhibitor, demonstrated efficacy in moderate to severe psoriasis. Objective We sought to evaluate efficacy of Apremilast in nail/scalp psoriasis in ESTEEM 1 and 2. Methods A total of 1255 patients were randomized (2:1) to Apremilast 30 mg twice daily or placebo. At week 16, placebo patients switched to Apremilast through week 32, followed by a randomized withdrawal phase to week 52. A priori efficacy analyses included patients with nail (target nail Nail Psoriasis Severity Index score ≥1) and moderate to very severe scalp (Scalp Physician Global Assessment score ≥3) psoriasis at baseline. Results At baseline, 66.1% and 64.7% of patients had nail psoriasis; 66.7% and 65.5% had moderate to very severe scalp psoriasis in ESTEEM 1 and 2. At week 16, Apremilast produced greater improvements in Nail Psoriasis Severity Index score versus placebo; mean percent change: −22.5% versus +6.5% (ESTEEM 1; P P  = .0052). At week 16, Apremilast produced greater NAPSI-50 response (50% reduction from baseline in target nail Nail Psoriasis Severity Index score) versus placebo (both studies P P Limitations Baseline randomization was not stratified for nail/scalp psoriasis. Conclusion Apremilast reduces the severity of nail/scalp psoriasis.

Kim Papp - One of the best experts on this subject based on the ideXlab platform.

  • long term safety and tolerability of Apremilast in patients with psoriasis pooled safety analysis for 156 weeks from 2 phase 3 randomized controlled trials esteem 1 and 2
    Journal of The American Academy of Dermatology, 2017
    Co-Authors: Jeffrey J Crowley, Robert M Day, Joana Carla Soares Goncalves, Rongdean Chen, Kim Papp, Diamant Thaci, P Joly, Ketty Peris, K Shah
    Abstract:

    Background Randomized, controlled trials demonstrated efficacy and safety of Apremilast for moderate-to-severe plaque psoriasis and psoriatic arthritis. Objective Assess long-term safety of oral Apremilast in psoriasis patients. Methods Safety findings are reported for 0 to ≥156 weeks from the Efficacy and Safety Trial Evaluating the Effects of Apremilast in Psoriasis (ESTEEM) 1 and 2. Results The 0 to ≥156–week Apremilast-exposure period included 1184 patients treated twice daily with Apremilast 30 mg (1902.2 patient-years). During 0 to ≤52 weeks, the adverse events (AEs) that occurred in ≥5% of patients included diarrhea, nausea, upper respiratory tract infection, nasopharyngitis, tension headache, and headache. From 0 to ≥156 weeks, no new AEs (affecting ≥5% of the population) were reported. AEs, serious AEs, and study drug discontinuations caused by AEs did not increase with long-term exposure. During the 0 to ≥156–week period, the rates of major cardiac events (exposure-adjusted incidence rate [EAIR] 0.5/100 patient-years), malignancies (EAIR 1.2/100 patient-years), depression (EAIR 1.8/100 patient-years), or suicide attempts (EAIR 0.1/100 patient-years) did not increase in comparison with the rates found during the 0 to ≤52–week period. No serious opportunistic infections, reactivation of tuberculosis, or clinically meaningful effects on laboratory measurements were reported. Limitations This study had a high dropout rate (21% of patients ongoing >156 weeks); most were unrelated to safety concerns. Conclusions Apremilast demonstrated an acceptable safety profile and was generally well tolerated for ≥156 weeks.

  • 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
    Journal of The American Academy of Dermatology, 2015
    Co-Authors: Kim Papp, K Reich, Robert M Day, R Stevens, Craig L Leonardi, Leon H Kircik, Sergio Chimenti, Richard G Langley, Kenneth B Gordon, Neil J Korman
    Abstract:

    Background Apremilast works intracellularly to regulate inflammatory mediators. Objective ESTEEM 1 evaluated efficacy/safety of Apremilast at 30 mg twice a day for moderate to severe plaque psoriasis. Methods This phase III, multicenter, double-blind, placebo-controlled study randomized adults (2:1) to Apremilast or placebo. At week 16, the placebo group switched to Apremilast through week 32, followed by a randomized treatment withdrawal phase to week 52. Binary end points were analyzed using χ 2 test; continuous end points used analysis of covariance. Results In all, 844 patients were randomized (n = 282, placebo; n = 562, Apremilast). At week 16, significantly more patients taking Apremilast achieved 75% or greater reduction from baseline Psoriasis Area and Severity Index score (PASI-75) (33.1%) versus placebo (5.3%, P Limitations Data were limited to 52 weeks and may not generalize to nonplaque psoriasis. Conclusions Apremilast was effective in moderate to severe plaque psoriasis.

  • efficacy and safety of Apremilast in subjects with moderate to severe plaque psoriasis results from a phase ii multicenter randomized double blind placebo controlled parallel group dose comparison study
    Journal of The European Academy of Dermatology and Venereology, 2013
    Co-Authors: Kim Papp, Roland Kaufmann, Diamant Thaci, D Sutherland, P Rohane
    Abstract:

    Background  Apremilast, a small molecule specific inhibitor of phosphodiesterase 4, works intracellularly to modulate pro-inflammatory and anti-inflammatory mediator production. Objective  Assess Apremilast efficacy and safety in moderate to severe plaque psoriasis. Methods  Phase II, 12-week, multicenter, double-blind, placebo-controlled, parallel-group, dose-comparison study of 259 subjects randomized 1 : 1 : 1 to placebo, Apremilast 20 mg QD or Apremilast 20 mg BID. Results  More subjects receiving Apremilast 20 mg BID achieved ≥ 75% reduction in Psoriasis Area and Severity Index (PASI-75) vs. placebo (24.4% vs. 10.3%; P = 0.023). A similar proportion of subjects receiving Apremilast 20 mg QD and placebo achieved PASI-75 at week 12 [9/87 (10.3%, each group)]. Mean per cent reduction in PASI from baseline was 17.4% for placebo, 30.3% for Apremilast 20 mg QD (P = 0.021 vs. placebo) and 52.1% for Apremilast 20 mg BID (P   90%) were mild to moderate and did not lead to study discontinuation. Serious adverse events occurred in four placebo subjects (panic attack, hospitalization for rehabilitation, hospitalization for alcoholism, worsening psoriasis), one receiving Apremilast 20 mg QD (knee surgery) and in one receiving Apremilast 20 mg BID (worsening psoriasis). The panic attack was considered treatment-related; both cases of worsening psoriasis occurred after medication discontinuation. No deaths or opportunistic infections were reported. Conclusion  Apremilast 20 mg BID for 12 weeks was effective and well tolerated in subjects with moderate to severe plaque psoriasis.

  • oral Apremilast in the treatment of active psoriatic arthritis results of a multicenter randomized double blind placebo controlled study
    Arthritis & Rheumatism, 2012
    Co-Authors: Georg Schett, R Stevens, Adele Vessey, Kim Papp, J Wollenhaupt, R Joos, Jude F Rodrigues, Kurt De Vlam
    Abstract:

    Objective To evaluate the efficacy and safety of Apremilast, a novel, orally available small molecule that specifically targets phosphodiesterase 4, in the treatment of active psoriatic arthritis (PsA). Methods This phase II, multicenter, randomized, double-blind, placebo-controlled study included the following: a 12-week treatment phase, with patients receiving placebo, Apremilast 20 mg twice per day, or Apremilast 40 mg once per day; a 12-week treatment-extension phase, with patients in the placebo group re-randomized to receive Apremilast; and a 4-week observational phase after treatment cessation. The primary end point was the proportion of patients achieving the American College of Rheumatology criteria for 20% improvement (ACR20) at week 12. Safety assessments included adverse events (AEs), physical examinations, vital signs, laboratory parameters, and electrocardiograms. Results Of the 204 patients with PsA who were randomized to a treatment group, 165 completed the treatment phase. At the end of the treatment phase (week 12), 43.5% of patients receiving Apremilast 20 mg twice per day (P 40% of patients in each group (patients receiving Apremilast 20 mg twice per day, patients receiving Apremilast 40 mg once per day, and patients in the placebo group re-randomized to receive Apremilast) achieved the ACR20 level of improvement. Most patients in the treatment phase (84.3%) and treatment-extension phase (68.3%) reported ≥1 AE. Diarrhea, headache, nausea, fatigue, and nasopharyngitis were reported most frequently; most events were mild or moderate. No clinically relevant laboratory or electrocardiographic abnormalities were reported. Conclusion Treatment with Apremilast at a dosage of 20 mg twice per day or 40 mg once per day demonstrated efficacy in comparison with placebo and was generally well tolerated in patients with active PsA. The balance of efficacy, tolerability, and safety supports further study of Apremilast in PsA.

  • Efficacy of Apremilast in the treatment of moderate to severe psoriasis: a randomised controlled trial
    Lancet (London England), 2012
    Co-Authors: Kim Papp, Les Rosoph, Richard G Langley, Jennifer Clay Cather, Howard Sofen, Robert Matheson, Robert M Day
    Abstract:

    Summary Background Apremilast, a small-molecule inhibitor of phosphodiesterase 4, works intracellularly to modulate proinflammatory and anti-inflammatory mediator production, and doses of 20 mg twice daily have shown efficacy in the treatment of moderate to severe plaque psoriasis in a 12-week phase 2 study. We assessed the clinical efficacy and safety of different doses of Apremilast in the treatment of patients with moderate to severe plaque psoriasis. Methods In this phase 2b, multicentre, randomised, placebo-controlled, dose-ranging study, patients (aged ≥18 years) with moderate to severe psoriasis were randomly assigned (in a 1:1:1:1 ratio) to receive oral placebo or Apremilast 10, 20, or 30 mg twice daily at 35 US and Canadian sites between Sept 24, 2008, and Oct 21, 2009. At week 16, patients in the placebo group were assigned Apremilast 20 or 30 mg twice daily until week 24. Randomisation was generated with a permuted-block randomisation list via interactive voice response system. For the first 16 weeks, treatment assignment was concealed from both investigators and participants. During weeks 16–24, investigators and participants all knew that treatment was active, but the dose was concealed. The primary endpoint was the proportion of patients achieving at least 75% reduction from baseline psoriasis area and severity index (PASI-75) at week 16. Analyses were by intention to treat; missing values were imputed by last-observation-carried-forward. This trial is registered with ClinicalTrials.gov, number NCT00773734. Findings 89 patients were randomly assigned Apremilast 10 mg, 87 Apremilast 20 mg, and 88 Apremilast 30 mg twice daily; 88 were assigned placebo. At week 16, PASI-75 was achieved in five patients (6%) assigned placebo, ten (11%) assigned Apremilast 10 mg, 25 (29%) assigned 20 mg, and 36 (41%) assigned 30 mg. Apremilast 10 mg did not differ significantly from placebo in achievement of the endpoint (odds ratio 2·10; 95% CI 0·69–6·42); for both Apremilast 20 mg (6·69; 2·43–18·5; p Interpretation Apremilast, given orally at 20 or 30 mg twice daily, seems to be efficacious, safe, and tolerable for patients with moderate to severe plaque psoriasis. Our results support continuing, longer-term studies. Funding Celgene Corporation.

Joana Carla Soares Goncalves - One of the best experts on this subject based on the ideXlab platform.

  • Efficacy and Safety of Apremilast in Systemic- and Biologic-Naive Patients With Moderate Plaque Psoriasis: 52-Week Results of UNVEIL.
    Journal of drugs in dermatology : JDD, 2018
    Co-Authors: Linda Stein Gold, Joana Carla Soares Goncalves, Jerry Bagel, Mark Lebwohl, J. Mark Jackson, Rongdean Chen, Eugenia Levi, Kristina Callis Duffin
    Abstract:

    BACKGROUND: Many patients with moderate plaque psoriasis are undertreated despite broadening treatment options. In the phase IV UNVEIL study, oral Apremilast demonstrated efficacy and safety in systemic-naive patients with chronic moderate plaque psoriasis with lower psoriasis-involved body surface area (BSA; 5%-10%) during the 16-week, double-blind, placebo-controlled phase. We describe efficacy and safety of Apremilast in this population through week 52 in UNVEIL. METHODS: Patients with moderate plaque psoriasis (BSA 5%-10%; static Physician's Global Assessment [sPGA] score of 3 [moderate]) and naive to systemic therapies for psoriasis were randomized (2:1) to receive Apremilast 30 mg twice daily or placebo for 16 weeks. At week 16, patients continued on Apremilast (Apremilast/Apremilast) or were switched from placebo to Apremilast (placebo/Apremilast) through week 52 (open-label Apremilast treatment phase). Efficacy assessments included the product of sPGA and BSA (PGAxBSA) (mean percentage change from baseline; ≥75% reduction from baseline [PGAxBSA-75]), sPGA response (achievement of score of 0 [clear] or 1 [almost clear]), and the Dermatology Life Quality Index (DLQI; mean change from baseline). RESULTS: A total of 136 patients completed the 52-week analysis period (placebo/Apremilast, n=50/64; Apremilast/Apremilast, n=86/121). At week 52, improvements in all efficacy end points observed at week 16 were maintained in the Apremilast/Apremilast group (mean percentage change from baseline in PGAxBSA: -55.5%; PGAxBSA-75: 42.1%; sPGA response: 33.1%; mean change from baseline in DLQI score: -4.4); similar improvements emerged in the placebo/Apremilast group after switching to Apremilast. The most common adverse events (≥5% of patients) through week 52 were diarrhea (28.0%), nausea (19.0%), headache (15.2%), nasopharyngitis (10.4%), upper respiratory tract infection (7.1%), vomiting (5.7%), and decreased appetite (5.2%). CONCLUSIONS: Apremilast was effective in systemic-naive patients with moderate plaque psoriasis with BSA 5%-10%; efficacy was sustained through week 52. No new safety signals emerged with continued Apremilast exposure. ClinicalTrials.gov: NCT02425826 J Drugs Dermatol. 2018;17(2):221-228. THIS ARTICLE HAD BEEN MADE AVAILABLE FREE OF CHARGE. PLEASE SCROLL DOWN TO ACCESS THE FULL TEXT OF THIS ARTICLE WITHOUT LOGGING IN. NO PURCHASE NECESSARY. PLEASE CONTACT THE PUBLISHER WITH ANY QUESTIONS.

  • efficacy and safety of Apremilast in patients with moderate plaque psoriasis with lower bsa week 16 results from the unveil study
    Journal of Drugs in Dermatology, 2017
    Co-Authors: Bruce E Strober, Joana Carla Soares Goncalves, Jerry Bagel, Mark Lebwohl, J. Mark Jackson, Rongdean Chen, Eugenia Levi, Stein Gold L, Callis Duffin K
    Abstract:

    INTRODUCTION: Many options are available for patients with moderate to severe plaque psoriasis. Patients with moderate disease, however, are often undertreated and do not achieve satisfactory clearance. UNVEIL (NCT02425826) assessed efficacy and safety of Apremilast in patients with chronic moderate plaque psoriasis. METHODS: Patients with psoriasis body surface area (BSA) 5% to 10% and static Physician's Global Assessment (sPGA) score of 3 (moderate) without prior exposure to systemics were randomized (2:1) to Apremilast 30 mg twice daily or placebo for 16 weeks. The primary efficacy endpoint was mean percentage change in the product of sPGA and BSA scores (PGAxBSA). RESULTS: Of 221 patients (placebo, n=73; Apremilast, n=148), >80% had received prior topical therapy. At week 16, Apremilast yielded a significantly greater percentage change from baseline in PGAxBSA (-48.1%) vs placebo (-10.2^; P less than 0.0001). Dermatology Life Quality Index scores were significantly improved with Apremilast (-4.8) vs placebo (-2.4; P=0.0008). Mean improvements in the Treatment Satisfaction Questionnaire for Medication, version II, were greater with Apremilast vs placebo for global satisfaction (63.2 vs 48.7; P less than 0.0001) and treatment effectiveness (57.3 vs 38.8; P less than 0.0001). Most adverse events were mild or moderate; most common were diarrhea, headache, nausea, upper respiratory tract infection, decreased appetite, and vomiting. CONCLUSION: Apremilast was effective and well tolerated, significantly improved quality of life, and was associated with high patient satisfaction in systemic-naive, post-topical patients with moderate plaque psoriasis. ClinicalTrials.gov: NCT02425826 J Drugs Dermatol. 2017;16(8):801-808. .

  • long term safety and tolerability of Apremilast in patients with psoriasis pooled safety analysis for 156 weeks from 2 phase 3 randomized controlled trials esteem 1 and 2
    Journal of The American Academy of Dermatology, 2017
    Co-Authors: Jeffrey J Crowley, Robert M Day, Joana Carla Soares Goncalves, Rongdean Chen, Kim Papp, Diamant Thaci, P Joly, Ketty Peris, K Shah
    Abstract:

    Background Randomized, controlled trials demonstrated efficacy and safety of Apremilast for moderate-to-severe plaque psoriasis and psoriatic arthritis. Objective Assess long-term safety of oral Apremilast in psoriasis patients. Methods Safety findings are reported for 0 to ≥156 weeks from the Efficacy and Safety Trial Evaluating the Effects of Apremilast in Psoriasis (ESTEEM) 1 and 2. Results The 0 to ≥156–week Apremilast-exposure period included 1184 patients treated twice daily with Apremilast 30 mg (1902.2 patient-years). During 0 to ≤52 weeks, the adverse events (AEs) that occurred in ≥5% of patients included diarrhea, nausea, upper respiratory tract infection, nasopharyngitis, tension headache, and headache. From 0 to ≥156 weeks, no new AEs (affecting ≥5% of the population) were reported. AEs, serious AEs, and study drug discontinuations caused by AEs did not increase with long-term exposure. During the 0 to ≥156–week period, the rates of major cardiac events (exposure-adjusted incidence rate [EAIR] 0.5/100 patient-years), malignancies (EAIR 1.2/100 patient-years), depression (EAIR 1.8/100 patient-years), or suicide attempts (EAIR 0.1/100 patient-years) did not increase in comparison with the rates found during the 0 to ≤52–week period. No serious opportunistic infections, reactivation of tuberculosis, or clinically meaningful effects on laboratory measurements were reported. Limitations This study had a high dropout rate (21% of patients ongoing >156 weeks); most were unrelated to safety concerns. Conclusions Apremilast demonstrated an acceptable safety profile and was generally well tolerated for ≥156 weeks.

  • the efficacy and safety of Apremilast etanercept and placebo in patients with moderate to severe plaque psoriasis 52 week results from a phase iiib randomized placebo controlled trial liberate
    Journal of The European Academy of Dermatology and Venereology, 2017
    Co-Authors: K Reich, Melinda Gooderham, L Green, Anthony Bewley, Zuoshun Zhang, I Khanskaya, Robert M Day, Joana Carla Soares Goncalves, K Shah, Vincent Piguet
    Abstract:

    Background Apremilast, an oral, small-molecule phosphodiesterase 4 inhibitor, has demonstrated efficacy in patients with moderate-to-severe psoriasis. Objective Evaluate efficacy and safety of Apremilast vs. placebo in biologic-naive patients with moderate-to-severe plaque psoriasis and safety of switching from etanercept to Apremilast in a phase IIIb, randomized, double-blind, placebo-controlled study (NCT01690299). Methods Two hundred and fifty patients were randomized to placebo (n = 84), Apremilast 30 mg BID (n = 83) or etanercept 50 mg QW (n = 83) through Week 16; thereafter, all patients continued or switched to Apremilast through Week 104. The primary efficacy endpoint was achievement of PASI-75 at Week 16 with Apremilast vs. placebo. Secondary endpoints included achievement of PASI-75 at Week 16 with etanercept vs. placebo and improvements in other clinical endpoints vs. placebo at Week 16. Outcomes were assessed through Week 52. This study was not designed for Apremilast vs. etanercept comparisons. Results At Week 16, PASI-75 achievement was greater with Apremilast (39.8%) vs. placebo (11.9%; P < 0.0001); 48.2% of patients achieved PASI-75 with etanercept (P < 0.0001 vs. placebo). PASI-75 response was maintained in 47.3% (Apremilast/Apremilast), 49.4% (etanercept/Apremilast) and 47.9% (placebo/Apremilast) of patients at Week 52. Most common adverse events (≥5%) with Apremilast, including nausea, diarrhoea, upper respiratory tract infection, nasopharyngitis, tension headache and headache, were mild or moderate in severity; diarrhoea and nausea generally resolved in the first month. No new safety or tolerability issues were observed through Week 52 with Apremilast. Conclusion Apremilast demonstrated significant efficacy vs. placebo at Week 16 in biologic-naive patients with psoriasis, which was sustained over 52 weeks, and demonstrated safety consistent with the known safety profile of Apremilast. Switching from etanercept to Apremilast did not result in any new or clinically significant safety findings, and efficacy was maintained with Apremilast through Week 52.

  • Apremilast an oral phosphodiesterase 4 inhibitor in the treatment of palmoplantar psoriasis results of a pooled analysis from phase ii psor 005 and phase iii efficacy and safety trial evaluating the effects of Apremilast in psoriasis esteem clinical
    Journal of The American Academy of Dermatology, 2016
    Co-Authors: Robert Bissonnette, Robert M Day, Joana Carla Soares Goncalves, Rongdean Chen, David M Pariser, Norman Wasel, Michael Sebastian
    Abstract:

    Background Difficult-to-treat palmoplantar psoriasis has a disproportionately negative impact on quality of life. Objective We evaluated the efficacy and safety of Apremilast in palmoplantar psoriasis. Methods A post hoc analysis of data pooled from phase IIb (PSOR-005) and phase III (Efficacy and Safety Trial Evaluating the Effects of Apremilast in Psoriasis [ESTEEM] 1 and 2) clinical studies was conducted to determine the effect of Apremilast 30 mg twice daily versus placebo at week 16 in a subset of patients with moderate to severe plaque psoriasis with active palmoplantar psoriasis (baseline Palmoplantar Psoriasis Physician Global Assessment [PPPGA] score ≥1). Results Significantly more patients taking Apremilast with moderate to severe palmoplantar psoriasis (baseline PPPGA score ≥3) achieved PPPGA score 0 (clear) or 1 (almost clear) compared with placebo at week 16 (48% vs 27%; P  = .021). At week 16, 46% of the Apremilast group with baseline PPPGA score 1 or higher achieved a PPPGA score of 0 versus 25% of the placebo group ( P P Limitations This post hoc analysis was limited to 16 weeks and did not assess palmoplantar pustules, lesion localization, or surface area involvement. Conclusion Apremilast may be a useful oral treatment option for patients with moderate to severe palmoplantar plaque psoriasis.

Rongdean Chen - One of the best experts on this subject based on the ideXlab platform.

  • Efficacy and Safety of Apremilast in Systemic- and Biologic-Naive Patients With Moderate Plaque Psoriasis: 52-Week Results of UNVEIL.
    Journal of drugs in dermatology : JDD, 2018
    Co-Authors: Linda Stein Gold, Joana Carla Soares Goncalves, Jerry Bagel, Mark Lebwohl, J. Mark Jackson, Rongdean Chen, Eugenia Levi, Kristina Callis Duffin
    Abstract:

    BACKGROUND: Many patients with moderate plaque psoriasis are undertreated despite broadening treatment options. In the phase IV UNVEIL study, oral Apremilast demonstrated efficacy and safety in systemic-naive patients with chronic moderate plaque psoriasis with lower psoriasis-involved body surface area (BSA; 5%-10%) during the 16-week, double-blind, placebo-controlled phase. We describe efficacy and safety of Apremilast in this population through week 52 in UNVEIL. METHODS: Patients with moderate plaque psoriasis (BSA 5%-10%; static Physician's Global Assessment [sPGA] score of 3 [moderate]) and naive to systemic therapies for psoriasis were randomized (2:1) to receive Apremilast 30 mg twice daily or placebo for 16 weeks. At week 16, patients continued on Apremilast (Apremilast/Apremilast) or were switched from placebo to Apremilast (placebo/Apremilast) through week 52 (open-label Apremilast treatment phase). Efficacy assessments included the product of sPGA and BSA (PGAxBSA) (mean percentage change from baseline; ≥75% reduction from baseline [PGAxBSA-75]), sPGA response (achievement of score of 0 [clear] or 1 [almost clear]), and the Dermatology Life Quality Index (DLQI; mean change from baseline). RESULTS: A total of 136 patients completed the 52-week analysis period (placebo/Apremilast, n=50/64; Apremilast/Apremilast, n=86/121). At week 52, improvements in all efficacy end points observed at week 16 were maintained in the Apremilast/Apremilast group (mean percentage change from baseline in PGAxBSA: -55.5%; PGAxBSA-75: 42.1%; sPGA response: 33.1%; mean change from baseline in DLQI score: -4.4); similar improvements emerged in the placebo/Apremilast group after switching to Apremilast. The most common adverse events (≥5% of patients) through week 52 were diarrhea (28.0%), nausea (19.0%), headache (15.2%), nasopharyngitis (10.4%), upper respiratory tract infection (7.1%), vomiting (5.7%), and decreased appetite (5.2%). CONCLUSIONS: Apremilast was effective in systemic-naive patients with moderate plaque psoriasis with BSA 5%-10%; efficacy was sustained through week 52. No new safety signals emerged with continued Apremilast exposure. ClinicalTrials.gov: NCT02425826 J Drugs Dermatol. 2018;17(2):221-228. THIS ARTICLE HAD BEEN MADE AVAILABLE FREE OF CHARGE. PLEASE SCROLL DOWN TO ACCESS THE FULL TEXT OF THIS ARTICLE WITHOUT LOGGING IN. NO PURCHASE NECESSARY. PLEASE CONTACT THE PUBLISHER WITH ANY QUESTIONS.

  • efficacy and safety of Apremilast in patients with moderate plaque psoriasis with lower bsa week 16 results from the unveil study
    Journal of Drugs in Dermatology, 2017
    Co-Authors: Bruce E Strober, Joana Carla Soares Goncalves, Jerry Bagel, Mark Lebwohl, J. Mark Jackson, Rongdean Chen, Eugenia Levi, Stein Gold L, Callis Duffin K
    Abstract:

    INTRODUCTION: Many options are available for patients with moderate to severe plaque psoriasis. Patients with moderate disease, however, are often undertreated and do not achieve satisfactory clearance. UNVEIL (NCT02425826) assessed efficacy and safety of Apremilast in patients with chronic moderate plaque psoriasis. METHODS: Patients with psoriasis body surface area (BSA) 5% to 10% and static Physician's Global Assessment (sPGA) score of 3 (moderate) without prior exposure to systemics were randomized (2:1) to Apremilast 30 mg twice daily or placebo for 16 weeks. The primary efficacy endpoint was mean percentage change in the product of sPGA and BSA scores (PGAxBSA). RESULTS: Of 221 patients (placebo, n=73; Apremilast, n=148), >80% had received prior topical therapy. At week 16, Apremilast yielded a significantly greater percentage change from baseline in PGAxBSA (-48.1%) vs placebo (-10.2^; P less than 0.0001). Dermatology Life Quality Index scores were significantly improved with Apremilast (-4.8) vs placebo (-2.4; P=0.0008). Mean improvements in the Treatment Satisfaction Questionnaire for Medication, version II, were greater with Apremilast vs placebo for global satisfaction (63.2 vs 48.7; P less than 0.0001) and treatment effectiveness (57.3 vs 38.8; P less than 0.0001). Most adverse events were mild or moderate; most common were diarrhea, headache, nausea, upper respiratory tract infection, decreased appetite, and vomiting. CONCLUSION: Apremilast was effective and well tolerated, significantly improved quality of life, and was associated with high patient satisfaction in systemic-naive, post-topical patients with moderate plaque psoriasis. ClinicalTrials.gov: NCT02425826 J Drugs Dermatol. 2017;16(8):801-808. .

  • long term safety and tolerability of Apremilast in patients with psoriasis pooled safety analysis for 156 weeks from 2 phase 3 randomized controlled trials esteem 1 and 2
    Journal of The American Academy of Dermatology, 2017
    Co-Authors: Jeffrey J Crowley, Robert M Day, Joana Carla Soares Goncalves, Rongdean Chen, Kim Papp, Diamant Thaci, P Joly, Ketty Peris, K Shah
    Abstract:

    Background Randomized, controlled trials demonstrated efficacy and safety of Apremilast for moderate-to-severe plaque psoriasis and psoriatic arthritis. Objective Assess long-term safety of oral Apremilast in psoriasis patients. Methods Safety findings are reported for 0 to ≥156 weeks from the Efficacy and Safety Trial Evaluating the Effects of Apremilast in Psoriasis (ESTEEM) 1 and 2. Results The 0 to ≥156–week Apremilast-exposure period included 1184 patients treated twice daily with Apremilast 30 mg (1902.2 patient-years). During 0 to ≤52 weeks, the adverse events (AEs) that occurred in ≥5% of patients included diarrhea, nausea, upper respiratory tract infection, nasopharyngitis, tension headache, and headache. From 0 to ≥156 weeks, no new AEs (affecting ≥5% of the population) were reported. AEs, serious AEs, and study drug discontinuations caused by AEs did not increase with long-term exposure. During the 0 to ≥156–week period, the rates of major cardiac events (exposure-adjusted incidence rate [EAIR] 0.5/100 patient-years), malignancies (EAIR 1.2/100 patient-years), depression (EAIR 1.8/100 patient-years), or suicide attempts (EAIR 0.1/100 patient-years) did not increase in comparison with the rates found during the 0 to ≤52–week period. No serious opportunistic infections, reactivation of tuberculosis, or clinically meaningful effects on laboratory measurements were reported. Limitations This study had a high dropout rate (21% of patients ongoing >156 weeks); most were unrelated to safety concerns. Conclusions Apremilast demonstrated an acceptable safety profile and was generally well tolerated for ≥156 weeks.

  • Apremilast an oral phosphodiesterase 4 inhibitor improves patient reported outcomes in the treatment of moderate to severe psoriasis results of two phase iii randomized controlled trials
    Journal of The European Academy of Dermatology and Venereology, 2017
    Co-Authors: Diamant Thaci, Rongdean Chen, Yves Poulin, Alexa B Kimball, Peter Foley, E Levi, Steven R. Feldman
    Abstract:

    Background Apremilast, an oral phosphodiesterase 4 inhibitor, has an acceptable safety profile and is effective for treatment of plaque psoriasis and psoriatic arthritis. Objectives To evaluate the impact of Apremilast on health-related quality of life (HRQOL), general functioning and mental health using patient-reported outcome (PRO) assessments among patients with moderate to severe plaque psoriasis in the ESTEEM 1 and 2 trials. Methods A total of 1255 patients were randomized (2 : 1) to Apremilast 30 mg BID or placebo for 16 weeks; all received Apremilast through Week 32. PRO assessments included the Dermatology Life Quality Index (DLQI), 36-Item Short-Form Health Survey version 2 mental/physical component summary scores (SF-36v2 MCS/PCS), Patient Health Questionnaire-8 (PHQ-8), EuroQol-5D (EQ-5D) and Work Limitations Questionnaire-25 (WLQ-25). Post hoc analyses examined relationships between Psoriasis Area and Severity Index (PASI) scores and PHQ-8 in the Apremilast-treated population at Week 16. Results Treatment with Apremilast improved all HRQOL PROs at Week 16 (vs. placebo), except the SF-36v2 PCS, and improvements were sustained through Week 32. Mean DLQI and SF-36v2 MCS improvements exceeded minimal clinically important differences. Changes at Week 16 in PHQ-8 and PASI were weakly correlated, and only 35.8% of patients who achieved a ≥75% reduction from baseline in PASI score (PASI-75) with Apremilast treatment also achieved PHQ-8 scores of 0–4. Conclusions Apremilast led to improvements in HRQOL PROs vs. placebo in patients with moderate to severe plaque psoriasis.

  • Apremilast an oral phosphodiesterase 4 inhibitor in the treatment of palmoplantar psoriasis results of a pooled analysis from phase ii psor 005 and phase iii efficacy and safety trial evaluating the effects of Apremilast in psoriasis esteem clinical
    Journal of The American Academy of Dermatology, 2016
    Co-Authors: Robert Bissonnette, Robert M Day, Joana Carla Soares Goncalves, Rongdean Chen, David M Pariser, Norman Wasel, Michael Sebastian
    Abstract:

    Background Difficult-to-treat palmoplantar psoriasis has a disproportionately negative impact on quality of life. Objective We evaluated the efficacy and safety of Apremilast in palmoplantar psoriasis. Methods A post hoc analysis of data pooled from phase IIb (PSOR-005) and phase III (Efficacy and Safety Trial Evaluating the Effects of Apremilast in Psoriasis [ESTEEM] 1 and 2) clinical studies was conducted to determine the effect of Apremilast 30 mg twice daily versus placebo at week 16 in a subset of patients with moderate to severe plaque psoriasis with active palmoplantar psoriasis (baseline Palmoplantar Psoriasis Physician Global Assessment [PPPGA] score ≥1). Results Significantly more patients taking Apremilast with moderate to severe palmoplantar psoriasis (baseline PPPGA score ≥3) achieved PPPGA score 0 (clear) or 1 (almost clear) compared with placebo at week 16 (48% vs 27%; P  = .021). At week 16, 46% of the Apremilast group with baseline PPPGA score 1 or higher achieved a PPPGA score of 0 versus 25% of the placebo group ( P P Limitations This post hoc analysis was limited to 16 weeks and did not assess palmoplantar pustules, lesion localization, or surface area involvement. Conclusion Apremilast may be a useful oral treatment option for patients with moderate to severe palmoplantar plaque psoriasis.

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  • Apremilast for the treatment of moderate to severe palmoplantar psoriasis results from a double blind placebo controlled randomized study
    Journal of The European Academy of Dermatology and Venereology, 2018
    Co-Authors: Robert Bissonnette, Melinda Gooderham, R Haydey, Les Rosoph, C W Lynde, M Bukhalo, Joseph F Fowler, I Delorme, A Gagnehenley, Y Poulin
    Abstract:

    Background Palmoplantar psoriasis is a variant of psoriasis vulgaris which can severely impair quality of life. Objectives The main objectives of this double-blind, placebo-controlled, randomized study were to assess the efficacy and impact on quality of life and work productivity of Apremilast for the treatment of moderate-to-severe palmoplantar psoriasis. Methods A total of 100 patients with moderate-to-severe palmoplantar psoriasis were randomized to either Apremilast 30 mg bid or placebo for 16 weeks. At Week 16, all patients received Apremilast 30 mg bid until Week 32. The primary endpoint was the proportion of patients who achieved a Palmoplantar Psoriasis Physician Global Assessment (PPPGA) of 0/1 at Week 16. Results There was no significant difference in the proportion of patients who achieved a PPPGA of 0/1 at Week 16 between patients randomized to Apremilast (14%) and placebo (4%; P = 0.1595). After 32 weeks of treatment with Apremilast, 24% of patients achieved a PPGA of 0/1. In addition, Apremilast was superior to placebo in achieving Palmoplantar Psoriasis Area Severity Index (PPPASI) 75 (Apremilast: 22%; placebo: 8%; P = 0.0499), in improving PPPASI (Apremilast: −7.4 ± 7.1; placebo: −3.6 ± 5.9; P = 0.0167), Dermatology Life Quality Index score (Apremilast: −4.3 ± 5.1; placebo: −0.8 ± 4.5; P = 0.0004) and in reducing activity impairment (Apremilast: −11.0 ± 22.3; placebo: 2.5 ± 25.5; P = 0.0063). Conclusion Despite the absence of a significant difference between Apremilast and placebo in proportion of patients achieving a PPPGA of 0/1, the presence of significant differences observed for several secondary endpoints suggests that Apremilast may have a role in the treatment of moderate-to-severe palmoplantar psoriasis.

  • Safety and efficacy of Apremilast through 104 weeks in patients with moderate to severe psoriasis who continued on Apremilast or switched from etanercept treatment: findings from the LIBERATE study.
    Journal of the European Academy of Dermatology and Venereology : JEADV, 2018
    Co-Authors: K Reich, Melinda Gooderham, L Green, Anthony Bewley, J. Soung, R. Petric, J. Marcsisin, J. Cirulli, R. Chen, Vincent Piguet
    Abstract:

    BACKGROUND Apremilast, an oral phosphodiesterase-4 inhibitor, has demonstrated efficacy in patients with moderate to severe psoriasis. OBJECTIVE To evaluate long-term efficacy and safety of Apremilast in biologic-naive patients with moderate to severe plaque psoriasis and safety of switching from etanercept to Apremilast in the phase 3b LIBERATE trial. METHODS Two hundred fifty patients were randomized to placebo, Apremilast 30 mg BID or etanercept 50 mg QW through Week 16; thereafter, all patients continued or switched to Apremilast through Week 104 (extension phase). Skin, scalp and nail involvement at Weeks 16, 52 and 104 were assessed using the Psoriasis Area and Severity Index (PASI; 0-72), Scalp Physician Global Assessment (ScPGA; 0-5) and Nail Psoriasis Severity Index (NAPSI; 0-8); patient-reported outcomes (PROs) were assessed using the Dermatology Life Quality Index (DLQI; 0-32) and pruritus visual analog scale (VAS; 0-100 mm). RESULTS The Apremilast-extension phase (Weeks 16-104) included 226 patients in the placebo/Apremilast (n = 73), Apremilast/Apremilast (n = 74) and etanercept/Apremilast (n = 79) groups, and at Week 104, 50.7%, 45.9% and 51.9% of these patients, respectively, maintained ≥75% reduction from baseline in PASI score (based on last-observation-carried-forward analysis). Across treatment groups, ScPGA 0 (clear) or 1 (minimal) was achieved by 50.0%-59.2% of patients; NAPSI mean change from baseline was -48.1% to -51.1%; DLQI score ≤5 was achieved by 66.0%-72.5% of patients; and pruritus VAS mean change from baseline was -24.4 to -32.3. AEs in ≥5% of patients (diarrhoea, nausea, nasopharyngitis, upper respiratory tract infection and headache) did not increase with prolonged Apremilast exposure. CONCLUSIONS Apremilast demonstrated significant and sustained improvements in skin, scalp, nails and PROs (pruritus and quality of life) over 104 weeks in patients with moderate to severe plaque psoriasis. Safety was consistent with the known safety profile of Apremilast.

  • the efficacy and safety of Apremilast etanercept and placebo in patients with moderate to severe plaque psoriasis 52 week results from a phase iiib randomized placebo controlled trial liberate
    Journal of The European Academy of Dermatology and Venereology, 2017
    Co-Authors: K Reich, Melinda Gooderham, L Green, Anthony Bewley, Zuoshun Zhang, I Khanskaya, Robert M Day, Joana Carla Soares Goncalves, K Shah, Vincent Piguet
    Abstract:

    Background Apremilast, an oral, small-molecule phosphodiesterase 4 inhibitor, has demonstrated efficacy in patients with moderate-to-severe psoriasis. Objective Evaluate efficacy and safety of Apremilast vs. placebo in biologic-naive patients with moderate-to-severe plaque psoriasis and safety of switching from etanercept to Apremilast in a phase IIIb, randomized, double-blind, placebo-controlled study (NCT01690299). Methods Two hundred and fifty patients were randomized to placebo (n = 84), Apremilast 30 mg BID (n = 83) or etanercept 50 mg QW (n = 83) through Week 16; thereafter, all patients continued or switched to Apremilast through Week 104. The primary efficacy endpoint was achievement of PASI-75 at Week 16 with Apremilast vs. placebo. Secondary endpoints included achievement of PASI-75 at Week 16 with etanercept vs. placebo and improvements in other clinical endpoints vs. placebo at Week 16. Outcomes were assessed through Week 52. This study was not designed for Apremilast vs. etanercept comparisons. Results At Week 16, PASI-75 achievement was greater with Apremilast (39.8%) vs. placebo (11.9%; P < 0.0001); 48.2% of patients achieved PASI-75 with etanercept (P < 0.0001 vs. placebo). PASI-75 response was maintained in 47.3% (Apremilast/Apremilast), 49.4% (etanercept/Apremilast) and 47.9% (placebo/Apremilast) of patients at Week 52. Most common adverse events (≥5%) with Apremilast, including nausea, diarrhoea, upper respiratory tract infection, nasopharyngitis, tension headache and headache, were mild or moderate in severity; diarrhoea and nausea generally resolved in the first month. No new safety or tolerability issues were observed through Week 52 with Apremilast. Conclusion Apremilast demonstrated significant efficacy vs. placebo at Week 16 in biologic-naive patients with psoriasis, which was sustained over 52 weeks, and demonstrated safety consistent with the known safety profile of Apremilast. Switching from etanercept to Apremilast did not result in any new or clinically significant safety findings, and efficacy was maintained with Apremilast through Week 52.

  • Apremilast an oral phosphodiesterase 4 inhibitor in patients with difficult to treat nail and scalp psoriasis results of 2 phase iii randomized controlled trials esteem 1 and esteem 2
    Journal of The American Academy of Dermatology, 2016
    Co-Authors: Phoebe Rich, Melinda Gooderham, Robert M Day, Joana Carla Soares Goncalves, Rongdean Chen, H Bachelez, Jeffrey J Crowley
    Abstract:

    Background In the phase III double-blind Efficacy and Safety Trial Evaluating the Effects of Apremilast in Psoriasis (ESTEEM) 1 and 2, Apremilast, an oral phosphodiesterase 4 inhibitor, demonstrated efficacy in moderate to severe psoriasis. Objective We sought to evaluate efficacy of Apremilast in nail/scalp psoriasis in ESTEEM 1 and 2. Methods A total of 1255 patients were randomized (2:1) to Apremilast 30 mg twice daily or placebo. At week 16, placebo patients switched to Apremilast through week 32, followed by a randomized withdrawal phase to week 52. A priori efficacy analyses included patients with nail (target nail Nail Psoriasis Severity Index score ≥1) and moderate to very severe scalp (Scalp Physician Global Assessment score ≥3) psoriasis at baseline. Results At baseline, 66.1% and 64.7% of patients had nail psoriasis; 66.7% and 65.5% had moderate to very severe scalp psoriasis in ESTEEM 1 and 2. At week 16, Apremilast produced greater improvements in Nail Psoriasis Severity Index score versus placebo; mean percent change: −22.5% versus +6.5% (ESTEEM 1; P P  = .0052). At week 16, Apremilast produced greater NAPSI-50 response (50% reduction from baseline in target nail Nail Psoriasis Severity Index score) versus placebo (both studies P P Limitations Baseline randomization was not stratified for nail/scalp psoriasis. Conclusion Apremilast reduces the severity of nail/scalp psoriasis.

  • 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
    British Journal of Dermatology, 2015
    Co-Authors: C Paul, Melinda Gooderham, K Shah, J Cather, Yves Poulin, Ulrich Mrowietz, C Ferrandiz, Jeffrey J Crowley, Rm Stevens, Rm Day
    Abstract:

    SummaryBackground Apremilast, an oral phosphodiesterase 4 inhibitor, regulates immune responses associated with psoriasis. Objectives ESTEEM 2 evaluated the efficacy and safety of Apremilast 30 mg twice daily for moderate-to-severe plaque psoriasis. Methods This phase III, double-blind, placebo-controlled trial randomized adults to Apremilast or placebo (2 : 1). At week 16, placebo patients switched to Apremilast. At week 32, Apremilast patients achieving ≥ 50% reduction in Psoriasis Area and Severity Index (PASI 50) were rerandomized (1 : 1) to continue Apremilast or receive placebo. Upon loss of 50% of PASI improvement obtained at week 32, patients rerandomized to placebo resumed Apremilast. Results The modified intention-to-treat population (full analysis set) included 137 placebo and 274 Apremilast patients. At week 16, significantly more Apremilast patients achieved PASI 75 (28·8%), PASI 50 (55·5%) and static Physician's Global Assessment score of 0 or 1 (20·4%) vs. placebo (5·8%, 19·7%, 4·4%, respectively; P < 0·001). Most patients rerandomized to Apremilast at week 32 had a PASI 50 response at week 52 (80%). Patients treated with Apremilast showed significant improvements in quality of life (as assessed by the Dermatology Life Quality Index) and pruritus at week 16 compared with placebo (P < 0·001). The exposure-adjusted incidence of adverse events did not increase with continued Apremilast treatment for up to 52 weeks. The most common adverse events were nausea, diarrhoea, nasopharyngitis and upper respiratory tract infection. Conclusions Apremilast was effective in the treatment of moderate-to-severe plaque psoriasis over 52 weeks.