BackgroundTyrosine kinase 2 (TYK2) is an intracellular enzyme involved in IL-23 signaling that is... more BackgroundTyrosine kinase 2 (TYK2) is an intracellular enzyme involved in IL-23 signaling that is important in the pathogenesis of immune-mediated diseases, including psoriasis, psoriatic arthritis, and systemic lupus erythematosus (SLE). Deucravacitinib is a first-in-class, oral, selective, allosteric TYK2 inhibitor approved in multiple countries for the treatment of adults with plaque psoriasis. Deucravacitinib uniquely binds to the TYK2 regulatory domain rather than the more conserved catalytic domain at which Janus kinase (JAK) 1/2/3 inhibitors bind. Deucravacitinib was efficacious compared with placebo in phase 2 trials in psoriatic arthritis and SLE.[1,2]Furthermore, deucravacitinib was significantly more efficacious than placebo or apremilast and was well tolerated in patients with moderate to severe plaque psoriasis, as observed in the phase 3 POETYK PSO-1 and PSO-2 trials.[3,4]Patients who completed the psoriasis trials could enroll in the ongoing open-label, 240-week long-term extension (LTE) trial.ObjectivesThis analysis examined whether changes occurred in blood laboratory parameters upon deucravacitinib treatment in the phase 3 POETYK PSO-1, PSO-2, and LTE trials and, if so, assessed how these compared with signature laboratory changes seen with JAK 1/2/3 inhibitors.MethodsPOETYK PSO-1 (NCT03624127) and PSO-2 (NCT03611751) were 52-week, double-blind trials that randomized patients with moderate to severe plaque psoriasis 2:1:1 to deucravacitinib 6 mg once daily, placebo, or apremilast 30 mg twice daily. Patients receiving placebo switched to deucravacitinib at Week 16, and patients receiving apremilast who failed to achieve ≥50% reduction from baseline in Psoriasis Area and Severity Index (PASI 50; PSO-1) or ≥75% reduction from baseline in PASI (PASI 75; PSO-2) at Week 24 switched to deucravacitinib. At Week 52, all eligible patients enrolled in the LTE trial (NCT04036435) and received open-label deucravacitinib 6 mg once daily. Changes from baseline in hematologic parameters (lymphocytes, neutrophils, platelets, hemoglobin) and lipid and chemistry parameters (cholesterol, creatinine, CPK, ALT) known to be impacted by JAK 1/2/3 inhibitors were assessed through Week 100 (LTE at Week 48). CTCAE grade ≥3 laboratory abnormalities and treatment discontinuations due to laboratory abnormalities were also evaluated.ResultsPatients (n=1519) received ≥1 dose of deucravacitinib in PSO-1, PSO-2, and/or the LTE through the cutoff date of 1 October 2021. In total, 1179 (77.6%) and 584 (38.4%) patients had ≥52 and ≥104 weeks, respectively, of continuous deucravacitinib exposure at the cutoff date, and the median duration of exposure was 682.0 days (97 weeks). No trends for clinically meaningful changes from baseline were observed in any laboratory parameters from Weeks 0–52 in PSO-1 or in the LTE. Grade 3 or 4 abnormalities over 100 weeks of deucravacitinib treatment were rare; incidence rates were comparable with placebo and apremilast through Week 52, and no increases were seen in the LTE. Two patients discontinued deucravacitinib treatment due to laboratory abnormalities (1 lymphopenia, 1 abnormal hepatic function).ConclusionNo trends for clinically meaningful changes from baseline were observed with deucravacitinib treatment in hematologic, lipid, or chemistry parameters, including signature laboratory changes associated with JAK 1/2/3 inhibitors, for up to 100 weeks. Treatment discontinuations and grade 3 or 4 laboratory abnormalities were rare, consistent with those in the parent studies, and comparable to the incidence rates seen with placebo and apremilast. These results suggest that laboratory monitoring in patients with plaque psoriasis is not warranted with deucravacitinib treatment.References[5]Mease PJ, et al.Ann Rheum Dis. 2022;81:815-822.[6] Morand E, et al.Arthritis Rheumatol. 2022 Nov 11. doi: 10.1002/art.42391. Epub ahead of print.[7] Armstrong AW, et al.J Am Acad Dermatol.2023;88:29-39.[8] Strober B, et al.J Am Acad Dermatol.2023;88:40-51.AcknowledgementsThese clinical trials were sponsored by Bristol Myers Squibb.Disclosure of InterestsNeil J Korman Speakers bureau: AbbVie, Eli Lilly, Janssen, Novartis, Regeneron, and Sanofi Genzyme, Consultant of: AbbVie, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly, Janssen, Leo Pharma, Novartis, Principia, Regeneron, Sanofi Genzyme, Sun Pharma, and UCB, Grant/research support from: AbbVie, Amgen, Argenx, Bristol Myers Squibb, Celgene, Chemocentryx, Eli Lilly, Galderma, Kyowa Hakko Kirin, Leo Pharma, Menlo, Principia, Prothena, Rhizen, Syntimmune, Trevi, and XBiotech, Thierry Passeron Consultant of: AbbVie, Almirall, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly, Galderma, Incyte, Janssen, Leo Pharma, Novartis, Pfizer, Sanofi Genzyme, Sun Pharma, and UCB, Kenneth B Gordon Consultant of: Almirall, Amgen, Dermira, Leo Pharma, Pfizer, and Sun Pharma, Grant/research support from: AbbVie, Boehringer Ingelheim,…
Journal of the American Association of Nurse Practitioners, Sep 1, 2018
Objective: Atopic dermatitis is a chronic, relapsing inflammatory skin disease characterized by i... more Objective: Atopic dermatitis is a chronic, relapsing inflammatory skin disease characterized by intense pruritus, excoriations and limited therapies. Dupilumab, a monoclonal antibody against interleukin-4 receptor alpha, is a promising new treatment option for atopic dermatitis. We sought to systematically summarize the efficacy, safety, and influence on quality of life of dupilumab for the treatment of moderate-to-severe atopic dermatitis in adults. Results: A total of 7 RCTs containing 2705 subjects were identified. Significantly more patients receiving dupilumab (611/1789) achieved Investigator's Global Assessment response compared with the control (89/916; RR, 3.95; P < 0.001). Dupilumab was significantly more effective in reducing Eczema Area and Severity Index, peak pruritus numerical rating scale score, and body surface area. Treatment duration rather than administration frequency slightly influenced the efficacy. Dupilumab treatment also contributed to marked improvement in patients' quality of life and psychological symptoms. Incidence of adverse events was similar in dupilumab group and control group. Conclusions: Dupilumab is effective and safe for the treatment of moderate-tosevere atopic dermatitis in adults. This meta-analysis supports the role of dupilumab as a primary targeted biologic therapy in adult patients with moderate-to-severe atopic dermatitis. Materials and Methods: We searched Pubmed, Embase, and the Cochrane Library for eligible trials. Only double-blinded randomized controlled trials (RCTs) investigating the efficacy and safety of dupilumab in treating moderate-to-severe atopic dermatitis were included in this analysis. We made a comparison of dupilumab with control based on the pooled relative risk (RR), weighted mean difference, and their corresponding 95% confidence intervals of different measurements.
Journal of The American Academy of Dermatology, Jul 1, 2020
Background: Many patients with psoriasis are bothered by symptoms in highly visible, pruritic are... more Background: Many patients with psoriasis are bothered by symptoms in highly visible, pruritic areas, such as the scalp. Objective: To evaluate the efficacy and safety of apremilast for moderate to severe scalp psoriasis. Methods: This phase 3b, double-blind, placebo-controlled study randomized adults with moderate to severe scalp psoriasis who had inadequate response/intolerance to at least 1 topical scalp psoriasis therapy (NCT03123471). The primary endpoint was the proportion of patients who achieved Scalp Physician Global Assessment response, defined as score of 0 (clear) or 1 (almost clear), with at least a 2-point reduction, at week 16.
Journal of The American Academy of Dermatology, 2022
BACKGROUND Patients with mild-to-moderate psoriasis may have substantial quality-of-life impairme... more BACKGROUND Patients with mild-to-moderate psoriasis may have substantial quality-of-life impairment. OBJECTIVE To evaluate apremilast 30 mg BID 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 achievement of static Physician Global Assessment (sPGA) score of 0 (clear) or 1 (almost clear) and ≥2-point reduction at Week 16. RESULTS 595 patients were randomized (apremilast: 297; placebo: 298). The primary endpoint was met, with significantly greater sPGA response rate observed at Week 16 in the apremilast group compared with the placebo group (21.6% vs. 4.1%; P<0.0001); all secondary endpoints were met (achievement of BSA-75 [33.0% vs. 7.4%], BSA ≤3% [61.0% vs. 22.9%], ≥4-point reduction in Whole Body Itch NRS [43.2% vs. 18.6%], Scalp PGA 0 or 1 and ≥2-point reduction [44.0% vs. 16.6%], and changes from baseline in BSA, PASI, and DLQI; all P<0.0001). 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.
Journal of The European Academy of Dermatology and Venereology, Mar 31, 2017
Background Continuous treatment is recommended for patients with moderate-to-severe psoriasis; ho... more Background Continuous treatment is recommended for patients with moderate-to-severe psoriasis; however, treatment may need to be interrupted in routine clinical practice. Objective To assess outcomes in patients continuously treated with ixekizumab versus those who interrupted therapy and were subsequently retreated with ixekizumab (IXE). Methods This analysis used data pooled from two phase 3 trials, UNCOVER-1 and UNCOVER-2. Patients were randomized to placebo (PBO), IXE every 4 (Q4W) or IXE every 2 weeks (Q2W) for 12 weeks. Patients with a static Physician's Global Assessment (sPGA) 0, 1 at Week 12 were rerandomized to IXEQ4W, IXE every 12 weeks (not presented) or PBO. We examined outcomes in patients who were continuously treated (IXEQ2W/IXEQ4W; IXEQ4W/IXEQ4W) or withdrawn (IXEQ2W/PBO; IXEQ4W/PBO), and in patients who were withdrawn and retreated with IXEQ4W for 24 weeks after disease relapse (sPGA ≥3). Results A total of 1226 treated patients achieved an sPGA 0, 1 at Week 12 and entered the maintenance phase; of these patients, 402 and 416 were rerandomized to PBO and IXEQ4W, respectively. Among patients interrupting treatment, 157 (82.2%) of IXEQ4W/PBO and 176 (83.4%) of IXEQ2W/PBO had an sPGA ≥3 by Week 60; median time to relapse was approximately 20 weeks irrespective of induction dose. At Week 60, continuously treated patients maintained high levels of PASI and sPGA responses (90.0% PASI 75 IXEQ2W/IXEQ4W; 81.9% sPGA 0, 1 IXEQ2W/IXEQ4W, non-responder imputation). After 24 weeks of retreatment with IXEQ4W (IXEQ2W/PBO/IXEQ4W and IXEQ4W/PBO/IXEQ4W), 87.0% (107 of 123) and 95.1% (97 of 102) (observed), respectively, of patients recaptured PASI 75 and 70.7% (104 of 147) and 82.3% (107 of 130) (observed) recaptured an sPGA 0, 1. Overall, adverse events in continuously treated and retreated patients were comparable. Conclusion High levels of response were sustained with continuous ixekizumab treatment through 60 weeks. Most patients who were withdrawn experienced disease relapse, and most of those patients recaptured response after 24 weeks of retreatment.
• To assess the durability of the initial clinical response to certolizumab pegol in patients wit... more • To assess the durability of the initial clinical response to certolizumab pegol in patients with moderate to severe plaque psoriasis over 48 weeks in phase 3 trials.
Journal of The European Academy of Dermatology and Venereology, Jun 28, 2017
auf psoriasisbedingte Hautläsionen hat der IL-17A-Antikörper Ixekizumab bereits unter Beweis gest... more auf psoriasisbedingte Hautläsionen hat der IL-17A-Antikörper Ixekizumab bereits unter Beweis gestellt. Nun wurde getestet, wie zügig sich unter der Therapie die Lebensqualität bessert.
ASN002 is an oral dual inhibitor of Janus kinase and spleen tyrosine kinase, which are involved i... more ASN002 is an oral dual inhibitor of Janus kinase and spleen tyrosine kinase, which are involved in the pathogenesis of atopic dermatitis (AD) through their regulatory role on T helper (Th)1, Th2 and Th17/Th22 pathways.
Background In the long-term extension study of the ERASURE and FIXTURE trials, the efficacy of se... more Background In the long-term extension study of the ERASURE and FIXTURE trials, the efficacy of secukinumab (a fully human anti-interleukin-17A monoclonal antibody) was demonstrated to have been maintained through to year 3 of treatment in moderate-to-severe plaque psoriasis. Objectives To assess the efficacy and safety of secukinumab through to year 5 of treatment in moderate-to-severe plaque psoriasis. Methods Responders with ≥ 75% improvement in Psoriasis Area and Severity Index (PASI 75) from two core trials-ERASURE and FIXTURE-were randomized 2 : 1 at year 1 (end of core trials) to either the same dose (300 or 150 mg, continuous treatment) or placebo (treatment withdrawal) every 4 weeks, until year 3 or relapse (> 50% reduction in maximal PASI from core study baseline). Partial responders (achieving PASI 50 but not PASI 75) at year 1 continued at the same dose as in the core trials. At year 3, all patients received open-label secukinumab treatment, with those on secukinumab 300 mg continuing on their dose, while those on secukinumab 150 mg or placebo received secukinumab 150 or 300 mg based on the physician's discretion. The study is registered on ClinicalTrials.gov with the identifier NCT01544595. Results Most patients randomized to placebo at year 1 relapsed, but the response was rapidly recaptured upon reinitiation of treatment. PASI responses were sustained with secukinumab through to year 5. The PASI responses for the 300 mg responders + partial responders group at year 1 (PASI 75/90/100: 86.8%/72.8%/45.9%) trended downwards until year 3 (PASI 75/90/100: 82.3%/58.4%/32.7%) and then remained stable through year 4 (PASI 75/90/100: 83.3%/60.1%/32.2%) until year 5 (PASI 75/90/100: 81.1%/62.8%/35.1%). Dermatology Life Quality Index showed sustained benefit up to year 5. Absolute PASI responses were maintained throughout the study. The most common adverse events (AEs) were infections and infestations, nasopharyngitis, and upper respiratory tract infections (URTIs). The overall exposure-adjusted incidence rate (EAIR; with 95% confidence interval) for all AEs was 139.9 (130.3-149.9). EAIRs for Crohn's disease and neutropenia were 0.1 (0.0-0.3) and 0.5 (0.3-0.8), respectively. Conclusions The 4-year extension of two pivotal phase III trials demonstrated that secukinumab treatment was effective through to year 5 and improved quality of life in patients with moderate-to-severe plaque psoriasis. The most common AEs were infections and infestations, nasopharyngitis, and URTIs. The safety profile was consistent with that in the secukinumab phase II/III clinical development programme. What is already known about this topic? • Secukinumab has shown efficacy in moderate-to-severe plaque psoriasis. • ERASURE and FIXTURE were the key, phase III, pivotal trials that investigated the efficacy and safety of secukinumab. Their primary results have been published.
What is this summary about? This is a summary of a paper published in a medical journal that desc... more What is this summary about? This is a summary of a paper published in a medical journal that describes the results of a study called POETYK PSO-2, which investigated a new treatment for plaque psoriasis. Plaque psoriasis appears on the body as dry, discolored, patches of skin that can be flaky and covered in scales. This can make the skin itch, crack or bleed and make it difficult for people with psoriasis to perform basic everyday tasks. Treatments are available, but some do not always reduce symptoms or may need to be injected or taken multiple times a day, which can be difficult to do, or can have undesirable side effects. Researchers are looking for new treatments for psoriasis. What happened in the study? Deucravacitinib is a once-daily pill taken by mouth (orally) that was studied as a treatment for moderate to severe plaque psoriasis in two large studies conducted globally, PSO-1 and PSO-2. POETYK PSO-2 was a Phase 3 research study, which is a study that tests a treatment in ...
BackgroundTyrosine kinase 2 (TYK2) is an intracellular enzyme involved in IL-23 signaling that is... more BackgroundTyrosine kinase 2 (TYK2) is an intracellular enzyme involved in IL-23 signaling that is important in the pathogenesis of immune-mediated diseases, including psoriasis, psoriatic arthritis, and systemic lupus erythematosus (SLE). Deucravacitinib is a first-in-class, oral, selective, allosteric TYK2 inhibitor approved in multiple countries for the treatment of adults with plaque psoriasis. Deucravacitinib uniquely binds to the TYK2 regulatory domain rather than the more conserved catalytic domain at which Janus kinase (JAK) 1/2/3 inhibitors bind. Deucravacitinib was efficacious compared with placebo in phase 2 trials in psoriatic arthritis and SLE.[1,2]Furthermore, deucravacitinib was significantly more efficacious than placebo or apremilast and was well tolerated in patients with moderate to severe plaque psoriasis, as observed in the phase 3 POETYK PSO-1 and PSO-2 trials.[3,4]Patients who completed the psoriasis trials could enroll in the ongoing open-label, 240-week long-term extension (LTE) trial.ObjectivesThis analysis examined whether changes occurred in blood laboratory parameters upon deucravacitinib treatment in the phase 3 POETYK PSO-1, PSO-2, and LTE trials and, if so, assessed how these compared with signature laboratory changes seen with JAK 1/2/3 inhibitors.MethodsPOETYK PSO-1 (NCT03624127) and PSO-2 (NCT03611751) were 52-week, double-blind trials that randomized patients with moderate to severe plaque psoriasis 2:1:1 to deucravacitinib 6 mg once daily, placebo, or apremilast 30 mg twice daily. Patients receiving placebo switched to deucravacitinib at Week 16, and patients receiving apremilast who failed to achieve ≥50% reduction from baseline in Psoriasis Area and Severity Index (PASI 50; PSO-1) or ≥75% reduction from baseline in PASI (PASI 75; PSO-2) at Week 24 switched to deucravacitinib. At Week 52, all eligible patients enrolled in the LTE trial (NCT04036435) and received open-label deucravacitinib 6 mg once daily. Changes from baseline in hematologic parameters (lymphocytes, neutrophils, platelets, hemoglobin) and lipid and chemistry parameters (cholesterol, creatinine, CPK, ALT) known to be impacted by JAK 1/2/3 inhibitors were assessed through Week 100 (LTE at Week 48). CTCAE grade ≥3 laboratory abnormalities and treatment discontinuations due to laboratory abnormalities were also evaluated.ResultsPatients (n=1519) received ≥1 dose of deucravacitinib in PSO-1, PSO-2, and/or the LTE through the cutoff date of 1 October 2021. In total, 1179 (77.6%) and 584 (38.4%) patients had ≥52 and ≥104 weeks, respectively, of continuous deucravacitinib exposure at the cutoff date, and the median duration of exposure was 682.0 days (97 weeks). No trends for clinically meaningful changes from baseline were observed in any laboratory parameters from Weeks 0–52 in PSO-1 or in the LTE. Grade 3 or 4 abnormalities over 100 weeks of deucravacitinib treatment were rare; incidence rates were comparable with placebo and apremilast through Week 52, and no increases were seen in the LTE. Two patients discontinued deucravacitinib treatment due to laboratory abnormalities (1 lymphopenia, 1 abnormal hepatic function).ConclusionNo trends for clinically meaningful changes from baseline were observed with deucravacitinib treatment in hematologic, lipid, or chemistry parameters, including signature laboratory changes associated with JAK 1/2/3 inhibitors, for up to 100 weeks. Treatment discontinuations and grade 3 or 4 laboratory abnormalities were rare, consistent with those in the parent studies, and comparable to the incidence rates seen with placebo and apremilast. These results suggest that laboratory monitoring in patients with plaque psoriasis is not warranted with deucravacitinib treatment.References[5]Mease PJ, et al.Ann Rheum Dis. 2022;81:815-822.[6] Morand E, et al.Arthritis Rheumatol. 2022 Nov 11. doi: 10.1002/art.42391. Epub ahead of print.[7] Armstrong AW, et al.J Am Acad Dermatol.2023;88:29-39.[8] Strober B, et al.J Am Acad Dermatol.2023;88:40-51.AcknowledgementsThese clinical trials were sponsored by Bristol Myers Squibb.Disclosure of InterestsNeil J Korman Speakers bureau: AbbVie, Eli Lilly, Janssen, Novartis, Regeneron, and Sanofi Genzyme, Consultant of: AbbVie, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly, Janssen, Leo Pharma, Novartis, Principia, Regeneron, Sanofi Genzyme, Sun Pharma, and UCB, Grant/research support from: AbbVie, Amgen, Argenx, Bristol Myers Squibb, Celgene, Chemocentryx, Eli Lilly, Galderma, Kyowa Hakko Kirin, Leo Pharma, Menlo, Principia, Prothena, Rhizen, Syntimmune, Trevi, and XBiotech, Thierry Passeron Consultant of: AbbVie, Almirall, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly, Galderma, Incyte, Janssen, Leo Pharma, Novartis, Pfizer, Sanofi Genzyme, Sun Pharma, and UCB, Kenneth B Gordon Consultant of: Almirall, Amgen, Dermira, Leo Pharma, Pfizer, and Sun Pharma, Grant/research support from: AbbVie, Boehringer Ingelheim,…
Journal of the American Association of Nurse Practitioners, Sep 1, 2018
Objective: Atopic dermatitis is a chronic, relapsing inflammatory skin disease characterized by i... more Objective: Atopic dermatitis is a chronic, relapsing inflammatory skin disease characterized by intense pruritus, excoriations and limited therapies. Dupilumab, a monoclonal antibody against interleukin-4 receptor alpha, is a promising new treatment option for atopic dermatitis. We sought to systematically summarize the efficacy, safety, and influence on quality of life of dupilumab for the treatment of moderate-to-severe atopic dermatitis in adults. Results: A total of 7 RCTs containing 2705 subjects were identified. Significantly more patients receiving dupilumab (611/1789) achieved Investigator's Global Assessment response compared with the control (89/916; RR, 3.95; P < 0.001). Dupilumab was significantly more effective in reducing Eczema Area and Severity Index, peak pruritus numerical rating scale score, and body surface area. Treatment duration rather than administration frequency slightly influenced the efficacy. Dupilumab treatment also contributed to marked improvement in patients' quality of life and psychological symptoms. Incidence of adverse events was similar in dupilumab group and control group. Conclusions: Dupilumab is effective and safe for the treatment of moderate-tosevere atopic dermatitis in adults. This meta-analysis supports the role of dupilumab as a primary targeted biologic therapy in adult patients with moderate-to-severe atopic dermatitis. Materials and Methods: We searched Pubmed, Embase, and the Cochrane Library for eligible trials. Only double-blinded randomized controlled trials (RCTs) investigating the efficacy and safety of dupilumab in treating moderate-to-severe atopic dermatitis were included in this analysis. We made a comparison of dupilumab with control based on the pooled relative risk (RR), weighted mean difference, and their corresponding 95% confidence intervals of different measurements.
Journal of The American Academy of Dermatology, Jul 1, 2020
Background: Many patients with psoriasis are bothered by symptoms in highly visible, pruritic are... more Background: Many patients with psoriasis are bothered by symptoms in highly visible, pruritic areas, such as the scalp. Objective: To evaluate the efficacy and safety of apremilast for moderate to severe scalp psoriasis. Methods: This phase 3b, double-blind, placebo-controlled study randomized adults with moderate to severe scalp psoriasis who had inadequate response/intolerance to at least 1 topical scalp psoriasis therapy (NCT03123471). The primary endpoint was the proportion of patients who achieved Scalp Physician Global Assessment response, defined as score of 0 (clear) or 1 (almost clear), with at least a 2-point reduction, at week 16.
Journal of The American Academy of Dermatology, 2022
BACKGROUND Patients with mild-to-moderate psoriasis may have substantial quality-of-life impairme... more BACKGROUND Patients with mild-to-moderate psoriasis may have substantial quality-of-life impairment. OBJECTIVE To evaluate apremilast 30 mg BID 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 achievement of static Physician Global Assessment (sPGA) score of 0 (clear) or 1 (almost clear) and ≥2-point reduction at Week 16. RESULTS 595 patients were randomized (apremilast: 297; placebo: 298). The primary endpoint was met, with significantly greater sPGA response rate observed at Week 16 in the apremilast group compared with the placebo group (21.6% vs. 4.1%; P<0.0001); all secondary endpoints were met (achievement of BSA-75 [33.0% vs. 7.4%], BSA ≤3% [61.0% vs. 22.9%], ≥4-point reduction in Whole Body Itch NRS [43.2% vs. 18.6%], Scalp PGA 0 or 1 and ≥2-point reduction [44.0% vs. 16.6%], and changes from baseline in BSA, PASI, and DLQI; all P<0.0001). 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.
Journal of The European Academy of Dermatology and Venereology, Mar 31, 2017
Background Continuous treatment is recommended for patients with moderate-to-severe psoriasis; ho... more Background Continuous treatment is recommended for patients with moderate-to-severe psoriasis; however, treatment may need to be interrupted in routine clinical practice. Objective To assess outcomes in patients continuously treated with ixekizumab versus those who interrupted therapy and were subsequently retreated with ixekizumab (IXE). Methods This analysis used data pooled from two phase 3 trials, UNCOVER-1 and UNCOVER-2. Patients were randomized to placebo (PBO), IXE every 4 (Q4W) or IXE every 2 weeks (Q2W) for 12 weeks. Patients with a static Physician's Global Assessment (sPGA) 0, 1 at Week 12 were rerandomized to IXEQ4W, IXE every 12 weeks (not presented) or PBO. We examined outcomes in patients who were continuously treated (IXEQ2W/IXEQ4W; IXEQ4W/IXEQ4W) or withdrawn (IXEQ2W/PBO; IXEQ4W/PBO), and in patients who were withdrawn and retreated with IXEQ4W for 24 weeks after disease relapse (sPGA ≥3). Results A total of 1226 treated patients achieved an sPGA 0, 1 at Week 12 and entered the maintenance phase; of these patients, 402 and 416 were rerandomized to PBO and IXEQ4W, respectively. Among patients interrupting treatment, 157 (82.2%) of IXEQ4W/PBO and 176 (83.4%) of IXEQ2W/PBO had an sPGA ≥3 by Week 60; median time to relapse was approximately 20 weeks irrespective of induction dose. At Week 60, continuously treated patients maintained high levels of PASI and sPGA responses (90.0% PASI 75 IXEQ2W/IXEQ4W; 81.9% sPGA 0, 1 IXEQ2W/IXEQ4W, non-responder imputation). After 24 weeks of retreatment with IXEQ4W (IXEQ2W/PBO/IXEQ4W and IXEQ4W/PBO/IXEQ4W), 87.0% (107 of 123) and 95.1% (97 of 102) (observed), respectively, of patients recaptured PASI 75 and 70.7% (104 of 147) and 82.3% (107 of 130) (observed) recaptured an sPGA 0, 1. Overall, adverse events in continuously treated and retreated patients were comparable. Conclusion High levels of response were sustained with continuous ixekizumab treatment through 60 weeks. Most patients who were withdrawn experienced disease relapse, and most of those patients recaptured response after 24 weeks of retreatment.
• To assess the durability of the initial clinical response to certolizumab pegol in patients wit... more • To assess the durability of the initial clinical response to certolizumab pegol in patients with moderate to severe plaque psoriasis over 48 weeks in phase 3 trials.
Journal of The European Academy of Dermatology and Venereology, Jun 28, 2017
auf psoriasisbedingte Hautläsionen hat der IL-17A-Antikörper Ixekizumab bereits unter Beweis gest... more auf psoriasisbedingte Hautläsionen hat der IL-17A-Antikörper Ixekizumab bereits unter Beweis gestellt. Nun wurde getestet, wie zügig sich unter der Therapie die Lebensqualität bessert.
ASN002 is an oral dual inhibitor of Janus kinase and spleen tyrosine kinase, which are involved i... more ASN002 is an oral dual inhibitor of Janus kinase and spleen tyrosine kinase, which are involved in the pathogenesis of atopic dermatitis (AD) through their regulatory role on T helper (Th)1, Th2 and Th17/Th22 pathways.
Background In the long-term extension study of the ERASURE and FIXTURE trials, the efficacy of se... more Background In the long-term extension study of the ERASURE and FIXTURE trials, the efficacy of secukinumab (a fully human anti-interleukin-17A monoclonal antibody) was demonstrated to have been maintained through to year 3 of treatment in moderate-to-severe plaque psoriasis. Objectives To assess the efficacy and safety of secukinumab through to year 5 of treatment in moderate-to-severe plaque psoriasis. Methods Responders with ≥ 75% improvement in Psoriasis Area and Severity Index (PASI 75) from two core trials-ERASURE and FIXTURE-were randomized 2 : 1 at year 1 (end of core trials) to either the same dose (300 or 150 mg, continuous treatment) or placebo (treatment withdrawal) every 4 weeks, until year 3 or relapse (> 50% reduction in maximal PASI from core study baseline). Partial responders (achieving PASI 50 but not PASI 75) at year 1 continued at the same dose as in the core trials. At year 3, all patients received open-label secukinumab treatment, with those on secukinumab 300 mg continuing on their dose, while those on secukinumab 150 mg or placebo received secukinumab 150 or 300 mg based on the physician's discretion. The study is registered on ClinicalTrials.gov with the identifier NCT01544595. Results Most patients randomized to placebo at year 1 relapsed, but the response was rapidly recaptured upon reinitiation of treatment. PASI responses were sustained with secukinumab through to year 5. The PASI responses for the 300 mg responders + partial responders group at year 1 (PASI 75/90/100: 86.8%/72.8%/45.9%) trended downwards until year 3 (PASI 75/90/100: 82.3%/58.4%/32.7%) and then remained stable through year 4 (PASI 75/90/100: 83.3%/60.1%/32.2%) until year 5 (PASI 75/90/100: 81.1%/62.8%/35.1%). Dermatology Life Quality Index showed sustained benefit up to year 5. Absolute PASI responses were maintained throughout the study. The most common adverse events (AEs) were infections and infestations, nasopharyngitis, and upper respiratory tract infections (URTIs). The overall exposure-adjusted incidence rate (EAIR; with 95% confidence interval) for all AEs was 139.9 (130.3-149.9). EAIRs for Crohn's disease and neutropenia were 0.1 (0.0-0.3) and 0.5 (0.3-0.8), respectively. Conclusions The 4-year extension of two pivotal phase III trials demonstrated that secukinumab treatment was effective through to year 5 and improved quality of life in patients with moderate-to-severe plaque psoriasis. The most common AEs were infections and infestations, nasopharyngitis, and URTIs. The safety profile was consistent with that in the secukinumab phase II/III clinical development programme. What is already known about this topic? • Secukinumab has shown efficacy in moderate-to-severe plaque psoriasis. • ERASURE and FIXTURE were the key, phase III, pivotal trials that investigated the efficacy and safety of secukinumab. Their primary results have been published.
What is this summary about? This is a summary of a paper published in a medical journal that desc... more What is this summary about? This is a summary of a paper published in a medical journal that describes the results of a study called POETYK PSO-2, which investigated a new treatment for plaque psoriasis. Plaque psoriasis appears on the body as dry, discolored, patches of skin that can be flaky and covered in scales. This can make the skin itch, crack or bleed and make it difficult for people with psoriasis to perform basic everyday tasks. Treatments are available, but some do not always reduce symptoms or may need to be injected or taken multiple times a day, which can be difficult to do, or can have undesirable side effects. Researchers are looking for new treatments for psoriasis. What happened in the study? Deucravacitinib is a once-daily pill taken by mouth (orally) that was studied as a treatment for moderate to severe plaque psoriasis in two large studies conducted globally, PSO-1 and PSO-2. POETYK PSO-2 was a Phase 3 research study, which is a study that tests a treatment in ...
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