Itching is a prevalent plaque psoriasis symptom. Ixekizumab, an IL-17A antagonist, has demonstrated rapid, significant improvements in itch severity over 12 weeks in Phase III psoriasis trials (UNCOVER-1, UNCOVER-2). We assessed the long-term (through 60 weeks) effect of ixekizumab maintenance therapy (80-mg ixekizumab every 4 weeks [IXEQ4W]) on itch severity, using the Itch Numeric Rating Scale, in psoriasis patients who received ixekizumab, placebo, or etanercept for 12 weeks in the Phase III UNCOVER-3 trial. After 12 weeks, patients either continued or switched to IXEQ4W. Mean improvements in itch severity achieved with 12 weeks of ixekizumab (-4.7 to -5.1) were maintained through 60 weeks with IXEQ4W (-4.9 to -5.0). Patients who initially received placebo or etanercept experienced rapid itch severity improvements after switching to ixekizumab at Week 12 (Week 12, placebo: -0.6; etanercept: -3.8; Week 60, placebo/IXEQ4W: -4.9; etanercept/IXEQ4W: -4.7). Ixekizumab maintenance therapy sustained improvements in itch severity through 60 weeks.
Publications
2018
BACKGROUND: Psoriasis (Ps) is a chronic inflammatory immune-mediated skin disease that has been identified as a risk factor for various conditions including neoplasms.
OBJECTIVE: To compare prevalence of cancer between Ps and Ps-free patients.
METHODS: Adult patients continuously enrolled for ≥12 months (≥1 month in 2014) were selected from a large United States (US) claims database (Q1:2010-Q4:2014) and classified as Ps patients (≥2 Ps diagnoses; International Classification of Diseases 9th Revision, [ICD-9] code: 696.1x) and Ps-free patients (no Ps diagnosis). Patients were exactly matched (1:1) based on age, gender, state of residence, and insurance plan type. Prevalence of cancer was compared between cohorts over patients' last 12 months of continuous healthcare plan enrollment using logistic-regression models.
RESULTS: A total of 179,066 pairs of Ps and Ps-free patients were selected. Median age was 54.0 years, 51.7% were females. Prevalence of cancer was higher among Ps patients for any type of neoplasms (OR [95% confidence interval (CI)]=1.86 [1.83; 1.89]), malignant neoplasms (OR [95% CI]=1.53 [1.49;1.57]), as well as malignant skin neoplasms (OR [95% CI]=1.87 [1.79; 1.95]), lymphatic and hematopoietic tissues (OR [95% CI]=1.70 [1.57;1.84]), genital (OR [95% CI]=1.33 [1.26;1.41]), breast (OR [95% CI]=1.32 [1.24;1.40]), digestive organs and peritoneum (OR [95% CI]=1.24 [1.13;1.35]), urinary organs (OR [95% CI]=1.49 [1.36;1.64]), respiratory and intrathoracic organs (OR [95% CI]=1.30 [1.17;1.44]), and metastatic cancer (OR [95% CI]=1.14 [1.06;1.24]), all P less than 0.01.
LIMITATIONS: Impact of Ps severity could not be assessed.
CONCLUSION: Ps patients had a higher prevalence of cancer than Ps-free patients. J Drugs Dermatol. 2018;17(2):180-186.
BACKGROUND: Two patient-reported outcome (PRO) questionnaires, the Hidradenitis Suppurativa Symptom Assessment (HSSA) and Hidradenitis Suppurativa Impact Assessment (HSIA), were developed to measure signs, symptoms and impacts of HS in treatment efficacy studies.
METHODS: In accordance with FDA guidelines and published best practices, four stages of research were conducted to create the questionnaires: concept elicitation, questionnaire construction, content evaluation and psychometric evaluation.
RESULTS: Subjects (N = 20) who participated in the concept elicitation stage reported 15 unique HS-related signs and symptoms and 51 impacts. Following this, eight sign and symptom concepts and 21 impacts were selected for construction of the HSSA and HSIA, respectively. During content evaluation, cognitive debriefing interviews with HS subjects (N = 20) confirmed subjects could read, comprehend and meaningfully respond to both questionnaires. Modifications made after this stage of work resulted in a nine-item HSSA and a 17-item HSIA. The HSSA and HSIA were subsequently entered into a US-based observational study (N = 40), and the scores produced by each were found to be reliable, construct valid, and able to distinguish among clinically distinct groups.
CONCLUSIONS: The HSSA and HSIA are content-valid, HS-specific, PRO questionnaires with demonstrated ability to generate reliable, valid scores when administered to patients with HS in a research setting.
Psoriasis is a complex chronic autoimmune skin disease with multiple comorbidities that can have a considerable impact on quality of life (QoL). As therapeutic options evolve, physicians should look to treatment guidelines and consensus statements to keep their practice and management of psoriasis patients current with worldwide standards. This article reviews the most up-to-date general guidelines available for the management of psoriasis.
BACKGROUND: Ixekizumab has demonstrated improvement in patients with moderate-to-severe psoriasis by selectively targeting interleukin-17A, which is a proinflammatory cytokine that is important in the pathogenesis of psoriasis.
OBJECTIVE: To report 4-year efficacy and safety results from the open-label extension (OLE) of this phase 2 trial.
METHODS: Analysis was by last observation carried forward. Patients received ixekizumab, 120 mg, and then 80 mg subcutaneously once every 4 weeks.
RESULTS: Of the patients who completed the randomized placebo-controlled trial, 93% entered the OLE. A 75% reduction in the Psoriasis Area Severity Index score was reported in 82% of patients at week 208 of the OLE. A static Physician's Global Assessment score of 0 or 1 was reported in 64% of patients, and a score of 0 was reported in 45% at week 208. Patients' Dermatology Life Quality Index and Itch Visual Analog Scale scores decreased when compared with baseline. Improvements were observed in other efficacy and health outcome measures. Serious adverse events were observed in 16.7% of patients, and 87% had 1 or more treatment-emergent adverse events. Three patients had serious infections. One patient reported 2 major cardiovascular events.
LIMITATIONS: The study was unblinded and lacked a placebo or active comparator.
CONCLUSIONS: Efficacy was shown to be maintained for up to 4 years of ixekizumab treatment.
INTRODUCTION: Despite a growing arsenal of therapies for psoriasis and, consequently, an increasing number of advertisements for these treatments, many psoriasis patients still remain untreated. While the primary treatment seeking motivations for these patients have been identified, it is unknown if the commercials for the medications designed to encourage patient engagement in treatment are relevant to these concerns.
METHODS: Online databases for national television advertisements were searched for psoriasis treatment commercials broadcast between 2000 and 2018. Each advertisement video was viewed 3 times and separately assessed for the content displayed or information conveyed in images, text, and voice-over speech. Additionally, references to known patient motivations for seeking treatment, including concerns about skin symptoms or appearance (embarrassment, scaling/flaking, pain, discomfort, itch, etc.) were recorded.
RESULTS: A total of 20 commercials were assessed. Of those, 100% emphasized "clear skin" as the result of the treatment that was being marketed. Bothersome skin symptoms, however, were less frequently displayed; scaling/flaking, pain/discomfort, and itch were present in 15%, 5%, and 0% of commercials, respectively. Similarly, text or images displaying sadness, shame or covering of skin were in 40%, 45% and 30% the advertisements, respectively. None (0%) of the commercials evaluated displayed images of people scratching or verbally addressed skin itching as a bothersome symptom of psoriasis.
CONCLUSIONS AND RELEVANCE: While the advertisements assessed in this study did exhibit patient concerns regarding skin appearance, skin symptoms including skin itching, flaking, pain and discomfort were not equally addressed. As these are known factors that motivate psoriasis patients to actively engage in treatment, targeted ads that better demonstrate these concerns may help prompt under-treated patients to seek care. J Drugs Dermatol. 2018;17(8):886-887.
BACKGROUND: Due to the chronic nature of psoriasis, it is important to assess the sustained response of treatments over time.
OBJECTIVE: To assess the efficacy of continuous treatment with guselkumab (an interleukin-23 blocker) through two years in the phase 3 VOYAGE 1 trial.
METHODS: Patients were randomized to placebo, guselkumab, or adalimumab at baseline. Placebo-randomized patients crossed over to guselkumab at week 16 (placebo→guselkumab) and adalimumab-randomized patients crossed over to guselkumab at week 52 (adalimumab→guselkumab); all patients received open-label guselkumab beyond week 52. Efficacy was assessed based on the Psoriasis Area and Severity Index (PASI; proportion of patients achieving ≥75%, 90%, or 100% improvement [PASI 75/90/100]) and the Investigator's Global Assessment (IGA; proportion achieving nearly clear [IGA 0/1] or completely clear [IGA 0]). As pre-specified, efficacy data were analyzed using non-responder imputation (NRI; patients with missing data counted as non-responders) after applying treatment failure rules (TFR; patients meeting TFR counted as non-responders thereafter) through week 48 and by applying TFR only from week 52 through 100. All endpoints were also analyzed using NRI and As Observed methodology for the guselkumab group through week 100.
RESULTS: The clinical responses were maintained through week 100 based on all three analyses. Based on pre-specified analyses, proportions of patients who achieved PASI 75, PASI 90, PASI 100, IGA 0/1, and IGA 0 were 94.8%, 82.1%, 49.0%, 82.4%, and 53.8%, respectively, at week 100. Results were similar for the placebo→guselkumab and adalimumab→guselkumab groups at week 100. As expected, proportions of patients achieving these endpoints were similar based on As Observed analyses and slightly lower when the more conservative NRI rules were applied.
CONCLUSIONS: High levels of efficacy were maintained through two years of continuous treatment among guselkumab-treated patients, and efficacy improved through two years among adalimumab-treated patients who crossed over to guselkumab at one year. J Drugs Dermatol. 2018;17(8):826-832.
BACKGROUND: How patients experience the symptoms/signs of psoriasis is highly relevant for assessing treatment response.
OBJECTIVES: Compare outcomes with guselkumab, placebo and adalimumab utilizing the novel, validated Psoriasis Symptoms and Signs Diary (PSSD).
METHODS: VOYAGE 1 is an ongoing, phase III, double-blinded, controlled trial of patients with moderate-to-severe psoriasis. Patients were randomized to guselkumab 100 mg every 8 weeks; placebo-to-guselkumab 100 mg every 8 weeks; or adalimumab 40 mg every 2 weeks. The PSSD was self-administered to assess symptoms (i.e. itch, skin tightness, burning, stinging and pain) and signs (i.e. dryness, cracking, scaling, shedding/flaking, redness and bleeding) of psoriasis (0-10 [absent-to-worst-imaginable]) every 24 h. Symptom and sign summary scores were derived (0-100) based on average scores of the individual symptoms and signs. Proportions of patients with clinically meaningful improvements and symptom- and sign-free scores of 0 were evaluated across treatment groups at weeks 16, 24 and 48.
RESULTS: At baseline, 652 of 837 randomized patients had PSSD scores. The proportion of patients achieving clinically meaningful improvements in PSSD summary scores was significantly higher in the guselkumab group compared with the placebo group at week 16 (P < 0.001) and compared with the adalimumab group at weeks 24 (P = 0.002) and 48 (P < 0.001). The proportions of patients achieving PSSD symptom and sign summary scores of 0 (i.e. symptom- and sign-free) were significantly higher for guselkumab vs. placebo at week 16 and vs. adalimumab at weeks 24 and 48 (all P < 0.001).
CONCLUSIONS: Based on PSSD scores, greater improvements in symptoms and signs of psoriasis were reported by patients treated with guselkumab compared with placebo at week 16 or adalimumab through 48 weeks.