Real-World Effectiveness of Dupilumab in Patients With Prurigo Nodularis: An Observational Study

Study Overview
=================
Brief Summary
-----------------
This study is a prospective, multinational, observational investigation designed to elucidate the real-world effectiveness and treatment patterns of dupilumab therapy in adult patients diagnosed with prurigo nodularis (PN). The primary objective of this study is to comprehensively characterize the real-world usage of dupilumab for the management of PN. In addition to this, the study aims to achieve several secondary objectives, including a detailed assessment of the medical history, socio-demographic and disease characteristics of dupilumab-treated PN patients, as well as the evaluation of the long-term real-world effectiveness of dupilumab therapy for PN.

Detailed Description
-----------------
The follow-up period will be 60 months or until death, loss to follow-up, or withdrawal, whichever comes first.

Official Title
-----------------
A Prospective Observational Study of Patients Receiving Dupilumab for Prurigo Nodularis

Conditions
-----------------
Prurigo Nodularis

Intervention / Treatment
-----------------
* Drug: Dupilumab


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients aged 18 years or older at the time of informed consent. Physician decision to treat the patient with dupilumab for prurigo nodularis (according to the country-specific prescribing information) made prior to and independently of the patient's participation in the study. Patients able to understand and complete study-related questionnaires. Patients provide voluntary informed consent to participate in the study before inclusion in the study. Exclusion Criteria: Patients who have a contraindication to dupilumab according to the country-specific prescribing information label. Any condition that, in the opinion of the Investigator, may interfere with the patient's ability to participate in the study, such as short life expectancy, substance abuse, severe cognitive impairment, or other comorbidities that can predictably prevent the patient from completing the schedule of visits and assessments. Patients currently participating in any interventional clinical trial. Prior use of dupilumab within 6 months of the screening visit, or within 6 months of the baseline visit if screening and baseline occur on the same day.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Patient with prurigo nodularis<br>Participants aged 18 years or older who start receiving dupilumab for prurigo nodularis (according to the country-specific prescribing information) prior to and independently of their participation in the study | Drug: Dupilumab<br>* Injection solution; subcutaneous<br>* Other names: SAR231893;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Frequency of reasons for dupilumab treatment initiation with the description of dosing |  | At baseline | 
| Duration of dupilumab treatment | The treatment duration will be measured from the start of dupilumab treatment until the date of discontinuation (e.g., lost to follow-up, death, or withdrawal). | At baseline and in 60 months | 
| Percentage of patients having dupilumab treatment modifications |  | From baseline up to month 60 | 
| Frequency of reasons for dupilumab treatment modifications |  | From baseline up to month 60 | 
| Proportion of patients who discontinued dupilumab |  | From baseline up to month 60 | 
| Frequency of reasons for dupilumab treatment discontinuation |  | From baseline up to month 60 | 
| Proportion of patients hospitalized due to PN |  | From baseline up to month 60 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Baseline Characteristics: PN-related medical history | (e.g., date of diagnosis, severity, comorbidities) | At baseline | 
| Baseline Characteristics: Socio-demographics of PN patients | (e.g., month and year of birth (where allowed) or age, gender, race (if allowed), ethnicity (if allowed), Fitzpatrick skin type) | At baseline | 
| Baseline Characteristics: Type of PN therapies received prior to initiation of dupilumab treatment |  | At baseline | 
| Proportion of patients using concomitant medication |  | At baseline | 
| Proportion of patients with a ≥ four-point improvement (reduction) in Worst Itch Numeric Rating Scale (WI-NRS) | The WI-NRS is a single-item Patient-Reported Outcomes (PRO). Patients will be asked to report the intensity of their worst pruritus (itch) using the 0 to 10 WI-NRS. Scores range from 0 to 10, with higher scores indicating greater itch intensity. | From baseline up to month 60 | 
| Mean change in WI-NRS | The WI-NRS is a single-item Patient-Reported Outcomes (PRO). Patients will be asked to report the intensity of their worst pruritus (itch) using the 0 to 10 WI-NRS. Scores range from 0 to 10, with higher scores indicating greater itch intensity. | From baseline up to month 60 | 
| Proportion of patients with a ≥ four-point improvement (reduction) in Skin Pain Numeric Rating Scale (NRS) | The Skin Pain NRS is a single-item Patient-Reported Outcomes (PRO). Patients indicate the intensity of their worst skin pain over the past 24 hours by selecting a number on the scale that ranges from 0 (No pain) to 10 (Worst pain imaginable). Scores range from 0 to10, with higher scores indicating greater pain intensity. | From baseline up to month 60 | 
| Mean change in Skin Pain NRS | The Skin Pain NRS is a single-item Patient-Reported Outcomes (PRO). Patients indicate the intensity of their worst skin pain over the past 24 hours by selecting a number on the scale that ranges from 0 (No pain) to 10 (Worst pain imaginable). Scores range from 0 to10, with higher scores indicating greater pain intensity. | From baseline up to month 60 | 
| Proportion of patients with a ≥ two-point improvement (reduction) in Sleep Disturbance Numeric Rating Scale (NRS) | The Sleep Disturbance NRS is a single-item Patient-Reported Outcomes (PRO). Patients will be asked to report the severity of their sleep disturbance using a 0 to 10 NRS. Scores range from 0 to10, with higher scores indicating worse sleep quality. | From baseline up to month 60 | 
| Mean change in Sleep Disturbance NRS | The Sleep Disturbance NRS is a single-item Patient-Reported Outcomes (PRO). Patients will be asked to report the severity of their sleep disturbance using a 0 to 10 NRS. Scores range from 0 to10, with higher scores indicating worse sleep quality. | From baseline up to month 60 | 
| Proportion of patients with Patient Global Impression of Change of PN Disease (PGIC) score of Very much better (improved) | The PGIC is a 7-point scale to assess patient health and determine if there has been an improvement or decline in clinical status. Scores range from 1 to 7, with higher score indicating worse health status. | From baseline up to month 60 | 
| Proportion of patients with PGIC score of Very much better (improved) or Moderately better (improved) | The PGIC is a 7-point scale to assess patient health and determine if there has been an improvement or decline in clinical status. Scores range from 1 to 7, with higher score indicating worse health status. | From baseline up to month 60 | 
| Mean change in PGIC | The PGIC is a 7-point scale to assess patient health and determine if there has been an improvement or decline in clinical status. Scores range from 1 to 7, with higher score indicating worse health status. | From baseline up to month 60 | 
| Proportion of patients with Patient Global Impression of Severity of PN Disease (PGIS) score of None | The PGIS is a one-item questionnaire that asks participants to provide the overall self-assessment of their disease severity on a 4-point scale for the past week. Scores range from 1 to 4, with higher score indicating worse symptom severity. | From baseline up to month 60 | 
| Proportion of patients with PGIS score of None or Mild | The PGIS is a one-item questionnaire that asks participants to provide the overall self-assessment of their disease severity on a 4-point scale for the past week. Scores range from 1 to 4, with higher score indicating worse symptom severity. | From baseline up to month 60 | 
| Mean change in PGIS | The PGIS is a one-item questionnaire that asks participants to provide the overall self-assessment of their disease severity on a 4-point scale for the past week. Scores range from 1 to 4, with higher score indicating worse symptom severity. | From baseline up to month 60 | 
| Mean change in Dermatology Life Quality Index (DLQI) | The DLQI is designed to measure the health-related quality of life of adults with a skin disease. The DLQI consists of 10 questions related to the effect of skin disease over the past week. Overall scoring ranges from 0 to 30, with a high score indicative of a poorer Health-Related Quality of Life (HRQoL) | From baseline up to month 60 | 
| Mean change in Pruritus Activity Score (PAS) | The modified PAS is a clinical-reported measure that evaluates the pruritic lesions. The modified questionnaire consists of five items: the type (visible lesions: item 1a; predominant lesions: item1b), estimated number (item 2), distribution (item 3), the representative body area and exact number of lesions (item 4), and the activity in terms of percentage of pruriginous lesions with excoriations/crusts on top (reflecting active scratching; item 5a) and the percentage of healed pruriginous lesions (reflecting healing of chronic prurigo; item 5b). The modified PAS will be completed based on the standard of care clinical assessment. | From baseline up to month 60 | 
| Proportion of patients with Investigator's Global Assessment-chronic prurigo Activity (IGA-CPG Activity) score of 0 or 1 | The IGA-CPG Activity is an instrument used to assess the overall activity of chronic prurigo lesions at a given time point, as determined by the Investigator. In this context, nodules, papules, plaques and other PN related lesions are defined as pruriginous lesions or chronic prurigo lesions. The instrument consists of a five-point scale ranging from 0 to 4. Higher scores indicate severe CPG. | From baseline up to month 60 | 
| Mean change in IGA-CPG Activity | The IGA-CPG Activity is an instrument used to assess the overall activity of chronic prurigo lesions at a given time point, as determined by the Investigator. In this context, nodules, papules, plaques and other PN related lesions are defined as pruriginous lesions or chronic prurigo lesions. The instrument consists of a five-point scale ranging from 0 to 4. Higher scores indicate severe CPG. | From baseline up to month 60 | 
| Proportion of patients with Investigator's Global Assessment-chronic prurigo Stage (IGA-CPG Stage) score of 0 or 1 | The IGA-CPG Stage is an instrument used to assess the overall number and thickness of chronic prurigo lesions at a given time point, as determined by the Investigator. In this context, nodules, papules, plaques and other PN related lesions are defined as pruriginous lesions or chronic prurigo lesions. The instrument consists of a five-point scale ranging from 0 to 4. Higher scores indicate severe CPG. | From baseline up to month 60 | 
| Mean change in IGA-CPG Stage | The IGA-CPG Stage is an instrument used to assess the overall number and thickness of chronic prurigo lesions at a given time point, as determined by the Investigator. In this context, nodules, papules, plaques and other PN related lesions are defined as pruriginous lesions or chronic prurigo lesions. The instrument consists of a five-point scale ranging from 0 to 4. Higher scores indicate severe CPG. | From baseline up to month 60 | 
| Mean change in EQ-5D-5L | The EQ-5D-5L comprises of five dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems, and extreme problems. The patient is asked to indicate their health state by ticking the box next to the most appropriate statement in each of the five dimensions. This decision results in a 1-digit number that expresses the level selected for that dimension. The digits for the five dimensions can be combined into a 5-digit number that describes the patient's health state. | From baseline up to month 60 | 
| Mean change in Hospital Anxiety and Depression Scale (HADS) total score | The HADS is a Patient-Reported Outcomes (PRO) instrument for screening anxiety and depression in non-psychiatric populations. The HADS consists of 14 items, 7 each for anxiety and depression symptoms. Patients select a response from 0 to 3 for each item, based on how they have been feeling in the past week. Scores range from 0 to 21 for each subscale. HADS anxiety (HADS-A) and HADS depression (HADS-D) scores ≤ 7 indicate no clinically relevant symptoms (normal), 8 to 10 borderline abnormal (borderline case), and 11 to 21 abnormal (maximum 21) indicating more severe symptoms. | From baseline up to month 60 | 
| Proportion of patients reported working, absenteeism score, presenteeism score, and overall impairment working score using the Work Productivity and Activity Impairment (WPAI) questionnaire | The Work Productivity and Activity Impairment General Health (WPAI-GH) is a 6-item Patient-Reported Outcomes (PRO) instrument that measures the effect of a condition on productivity during work and regular activities in the seven days prior to completion. The instrument comprises 4 domains: absenteeism, presenteeism, overall work impairment, and activity impairment due to health. WPAI-GH outcomes are expressed as impairment percentages, with higher numbers indicating greater impairment and less productivity, i.e., worse outcomes. | From baseline up to month 60 | 
| Percentage of patients experiencing AEs and SAEs |  | From baseline up to month 60 |