Veracity Clinical Research

The efficacy and safety of lebrikizumab, a high-affinity monoclonal antibody targeting interleukin-13, were investigated in patients with moderate-to-severe atopic dermatitis (AD) up to 52weeks in phase3 trials. This analysis evaluates safety and maintenance of response through 104weeks of lebrikizumab treatment in patients with moderate-to-severe AD who achieved clinical response with lebrikizumab at week16. ADjoin is a 100-week phase3 long-term extension study. Adult and adolescent patients with moderate-to-severe AD were enrolled into parent studies ADvocate1, ADvocate2, and ADhere. ADvocate1&2 week16 lebrikizumab clinical responders (patients who achieved Investigator's Global Assessment [IGA] [0, 1] or Eczema Area and Severity Index [EASI]75 without rescue) were re-randomized 2:2:1 to lebrikizumab 250mgQ2W, Q4W, or placebo (lebrikizumab withdrawal). Patients who completed week52 of ADvocate1&2 could enroll into ADjoin. ADhere week16 lebrikizumab clinical responders could enroll into ADjoin and were randomized 2:1 to lebrikizumab 250mgQ2W or Q4W. Analyses were performed on patients who received 104weeks of lebrikizumab treatment in parent and extension studies combined. Efficacy analyses are reported as observed from week16 for patients who were re-randomized to lebrikizumab Q2W or Q4W. Safety assessments included monitoring adverse events. IGA(0, 1) was maintained by 86.4% (Q2W) and 76.4% (Q4W) patients from ADvocate1&2 and 83.9% (Q2W) and 78.6% (Q4W) patients from ADhere at week104. EASI75 was maintained by 95.6% (Q2W) and 96.3% (Q4W) ADvocate1&2 patients and 95.1% (Q2W) and 96.0% (Q4W) ADhere patients at week104. Pruritus NRS ≥ 4-point improvement was maintained by 100% (Q2W) and 89.7% (Q4W) ADvocate1&2 patients at week104 and 81.8% (Q2W) and 90.0% (Q4W) ADhere patients at week68. During ADjoin, adverse events were reported by 62.2% of patients from ADvocate1&2 and ADhere who received lebrikizumab Q2W or Q4W, with the majority being mild (31.5%) or moderate (27.0%) in severity, and 2.2% leading to discontinuation due to adverse event. Skin and itch outcomes were maintained over 2years of continuous lebrikizumab 250mg treatment. The safety profile of lebrikizumab in ADjoin is consistent with previous lebrikizumab studies in patients with moderate-to-severe AD. ClinicalTrials.gov, NCT04392154.

Introduction: Deucravacitinib, an oral, selective, allosteric TYK2 inhibitor, was superior to placebo and apremilast in two global, phase 3 trials (POETYK PSO-1 and PSO-2) in moderate to severe plaque psoriasis. At Week 52, patients could enter the POETYK long-term extension (LTE) trial and receive open-label deucravacitinib. Long-term efficacy was maintained through 3 total years of continuous treatment with no new safety signals in the ongoing LTE. Methods: Efficacy was further evaluated through Week 208 (4 years; data cutoff, November 1, 2023) in patients from the pooled PSO-1/PSO-2 populations who received continuous deucravacitinib from Day 1, achieved ≥75% reduction from baseline in Psoriasis Area and Severity Index (PASI 75) at Week 16 (primary endpoint) or Week 24 (peak response), and entered the LTE. Maintenance of response assessments included PASI 75, PASI 90, and sPGA 0/1 (static Physician Global Assessment score of 0 [clear]/1 [almost clear]). Efficacy is reported using modified nonresponder imputation in patients who reached or discontinued before Week 208. Results: Of 513 patients who received continuous deucravacitinib from Day 1 and entered the LTE, PASI 75 was achieved by 313 (61.0%) and 336 (65.5%) patients at Week 16 and Week 24. Among Week 16 PASI 75 responders, response rates were maintained well from Week 16 to Week 208 (PASI 75: 100%, 84.4%; PASI 90: 55.7%, 57.4%; sPGA 0/1: 82.8%, 65.4%). Among Week 24 PASI 75 responders, response rates were also maintained from Week 24 to Week 208 (PASI 75: 100%, 84.6%; PASI 90: 62.7%, 58.2%; sPGA 0/1: 82.5%, 66.0%). Conclusion: Clinical efficacy was generally maintained with continuous deucravacitinib in the vast majority of Week 16 and Week 24 PASI 75 responders from the parent trials through 4 years, supporting the long-term effectiveness and treatment durability of once-daily oral deucravacitinib for moderate to severe plaque psoriasis.

Introduction: Deucravacitinib, an oral, selective, allosteric tyrosine kinase 2 inhibitor, is approved in the US and other countries for the treatment of adults with moderate-to-severe plaque psoriasis who are candidates for systemic therapy or phototherapy. In the POETYK PSO-1 (NCT03624127) and PSO-2 (NCT03611751) trials, deucravacitinib was superior to placebo and apremilast in patients with moderate to severe plaque psoriasis. This analysis evaluated deucravacitinib efficacy by baseline characteristics.
 Methods: Efficacy endpoints, including ≥75% reduction from baseline in Psoriasis Area and Severity Index (PASI 75) and static Physician’s Global Assessment score of 0 (clear) or 1 (almost clear) (sPGA 0/1), were evaluated at Week 24 by baseline subgroups including weight, sex, and PASI in the pooled PSO-1 and PSO-2 population, and at Week 52 in PSO-1 patients who received continuous deucravacitinib treatment from Day 1.
 Results: In the pooled PSO-1 and PSO-2 population, deucravacitinib (n=843) was more efficacious than apremilast (n=422) at Week 24 across subgroups defined by baseline weight (<90 kg: PASI 75, 69.8% vs 43.8%, sPGA 0/1, 60.2% vs 34.2%; ≥90 kg: PASI 75, 55.4% vs 31.5%, sPGA 0/1, 45.9% vs 25.6%), sex (male: PASI 75, 59.3% vs 33.7%, sPGA 0/1, 49.6% vs 24.7%; female: PASI 75, 70.4% vs 45.2%, sPGA 0/1, 60.9% vs 39.4%), and PASI (≤20: PASI 75, 61.6% vs 38.6%, sPGA 0/1, 53.5% vs 32.4%; >20: PASI 75, 64.7% vs 37.0%, sPGA 0/1: 53.2% vs 27.1%). Consistent efficacy was observed through Week 52 in patients who received continuous deucravacitinib treatment in PSO-1 (n=332), regardless of baseline characteristics.
 Conclusion: Deucravacitinib demonstrated consistent efficacy for up to 52 weeks regardless of baseline characteristics in patients with moderate to severe plaque psoriasis.
 
 Acknowledgments
 
 This study was sponsored by Bristol Myers Squibb
 Writing and editorial assistance was provided by Liz Rockstein, PhD, of Peloton Advantage, LLC, an OPEN Health company, funded by Bristol Myers Squibb

Introduction: Deucravacitinib, an oral, selective, allosteric tyrosine kinase 2 inhibitor, is approved by the US Food and Drug Administration for the treatment of adults with moderate-to-severe plaque psoriasis who are candidates for systemic therapy or phototherapy. In the pivotal phase 3 POETYK PSO-1 trial, deucravacitinib was superior to placebo and apremilast using multiple clinical endpoints, including PASI 75 and sPGA score of 0 or 1 (clear/almost clear skin) at Week 16. Clinical efficacy was maintained through Week 52 on continued treatment. We examined long-term clinical efficacy in patients randomized to deucravacitinib on Day 1 in PSO-1 who opted to continue treatment at Week 52 in the long-term extension (LTE) trial.
 Methods: In the 52-week POETYK PSO-1 trial, adult patients were randomized 2:1:1 to deucravacitinib 6 mg once daily, placebo, or apremilast 30 mg twice daily; upon trial completion, patients could enter the LTE and receive deucravacitinib. Efficacy endpoints included PASI 75, PASI 90, and sPGA 0/1. Maintenance of response was assessed in Week 16 PASI 75 responders continuing treatment in the LTE. Modified nonresponder imputation (mNRI) was used to impute missing data; patients discontinuing due to psoriasis worsening were imputed as nonresponders. Efficacy results used as-observed data and treatment failure rule imputation.
 Results: Of 332 patients randomized to deucravacitinib in PSO-1, 265 completed the trial and entered the LTE, including 173 Week 16 PASI 75 responders. The mNRI population included 262 deucravacitinib patients entering the LTE, including 171 Week 16 PASI 75 responders; patients failing to reach the Week 112 assessment or discontinuing as of October 1, 2021, were excluded. At Week 112 (LTE Week 60), mNRI response rates among deucravacitinib patients entering the LTE were 82.4% (PASI 75), 55.2% (PASI 90), and 66.5% (sPGA 0/1). Efficacy was maintained up to 112 weeks in Week 16 PASI 75 responders continuing treatment, including PASI 75 response rates at Weeks 16, 52, and 112 (100%, 90.1%, 91.0%, respectively), PASI 90 (62.6%, 64.9%, 63.0%), and sPGA 0/1 (84.2%, 73.7%, 73.5%).
 Conclusion: Clinical efficacy was maintained up to 112 weeks with continuous treatment, further supporting deucravacitinib as an effective treatment for patients with moderate to severe plaque psoriasis.

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Introduction: Inflammation and pain of the oral soft tissues is a common reason for presentation to a dental professional, and with a wide range of differential diagnoses, successful management often provides a significant clinical challenge. One such cause of these symptoms is burning mouth syndrome (BMS), a diagnosis of exclusion based on the presence of a burning sensation of the mouth every day over a period of at least four to six months in the absence of other clinical or laboratory finding to explain the symptoms. Burning mouth syndrome is notoriously difficult to treat and causes significant pain and psychological distress to those who suffer from it. Therefore, thorough investigation and adequate management of potential underlying causes are essential before a definitive diagnosis is made.

Background It is unclear whether primary efficacy outcomes in plaque psoriasis clinical trials represent residual disease during treatment. Objectives To evaluate supplementing dichotomous efficacy with residual disease activity. Methods This post hoc analysis used pooled, patient-level data after tildrakizumab 100 mg (N = 616) or placebo (N = 309) treatment from reSURFACE 1/2 (NCT01722331/NCT01729754) phase 3 clinical trials of patients with moderate to severe plaque psoriasis. Results Median baseline Psoriasis Area and Severity Index (PASI) was 17.9 for patients receiving tildrakizumab 100 mg. At Week 12, median PASI was 2.9, whereas dichotomous PASI 90 response rate was 36.9%, and absolute PASI <5.0, <3.0, and <1.0 were 64.0%, 50.8%, and 23.3%, respectively. At Week 28, median PASI was 1.7, whereas PASI 90 response rate was 51.9%, and absolute PASI <5.0, <3.0, and <1.0 were 75.3%, 62.8%, and 38.0%, respectively. Dermatology Life Quality Index and PASI scores were correlated through Week 28 (r = 0.51, p ≤ .0001). Conclusions Disease activity was more reliably estimated by PASI scores than percentage PASI improvement; this may partially explain efficacy disparities between clinical trials and practice. These results suggest supplementing dichotomous PASI improvement with PASI scores and consideration of patient treatment goals could facilitate clinical decisions.