Comorbidities, healthcare resource utilization & treatment pattern among patients with prurigo nodularis, compared to a benchmark in Germany: A real-world evidence claims data study.

BACKGROUND: Prurigo nodularis (PN) is a rare chronic inflammatory skin disease with a high disease burden, but data on clinical and economic burden are still scarce. OBJECTIVE: To describe the real-world epidemiologic, clinical and therapeutic characteristics and related economic burden of patients with PN compared to a benchmark population in Germany. METHODS: This retrospective study was based on an excerpt of German Statutory Health Insurance data of patients with an initial PN diagnosis between 2012 and 2016. PN cohort contained no record of PN in eight quarters before the index quarter and was followed up for eight quarters (unless deceased). Benchmark cohort without PN was calculated using direct standardization and 1:1 matching to PN cohort. RESULTS: Out of 4,536,002 insured patients, 2309 incident patients with PN were identified and matched to the benchmark cohort out of 3,018,382 patients without PN. Patients were mostly between 45 and 80 years when diagnosed with PN. Higher comorbidity rates were reported for PN than benchmark, with a rising disease burden at follow-up. Most patients with PN (91.3%) were diagnosed outpatient and had >50% more outpatient visits than the benchmark cohort. Hospitalization rates were higher in PN (53.9%) versus benchmark (35.1%), yielding twice longer mean hospital stays for PN (12 days) compared to benchmark (6 days) (p < 0.001). The most common initial therapy for patients with PN was topical corticosteroids (47.6%); ≥10% of patients were treated with antidepressants, antihistamines or systemic corticosteroids. Therapy rates were higher for PN compared to benchmark (p < 0.001). Mean initial costs were twofold higher in PN versus benchmark for outpatient, inpatient and drugs. During follow-up, an increase of >70% in mean PN costs compared to benchmark was identified for outpatient, inpatient and concomitant treatments (p < 0.001). CONCLUSION: This study highlights the significantly higher clinical and economic burden incurred by PN compared to benchmark patients in Germany, reflecting the unmet medical need for PN.

Cost-effectiveness and Quality of Specialized and Routine Care in a German Cohort of Patients with Chronic Pruritus.

Chronic pruritus is a prevalent interdisciplinary symptom with a strong influence on health-related quality of life. Patients need extensive diagnostics and long-term treatment. This retrospective and prospective cohort study compared routine and university-based specialized care in terms of cost-effectiveness and patient benefit. Direct medical and non-medical costs and patient-reported outcomes (PRO; pruritus intensity, quality of life, treatment needs and benefits) were assessed. Data analyses were conducted using descriptive methods and non-parametric statistical tests. A total of 300 adult patients (54.3% female) participated in the study. Six months after the treatment start in a specialized German pruritus care unit, the total costs were significantly reduced (mean total costs 686 € vs 433 € per patient per half year (total cohort); p < 0.001; mean out-of-pocket costs 198 € vs 124 € per half year (total cohort), p < 0.001). Pruritus intensity (numerical rating  scale 5.3 vs 3.7, p < 0.001), quality of life (Dermatology Life Quality Index 8.9 vs 5.7, p < 0.001) and patient benefit (Patient Benefit Index Pruritus 1.2 vs 2.1, p < 0.001) improved significantly (total  cohort). The results of this study show, that treatment of chronic pruritus patients in a specialized itch centre leads to an improvement in patient  benefit and reduces the economic burden at the same time.

Hand Pruritus: Clinical Profile, Functional Impairment and Disease-related Burden in a Prospective Cohort Study of 395 Patients.

Human hands are complex structures essential for a variety of functions in everyday life. This study prospectively investigated the clinical features of hand pruritus and the resulting functional impairment and disease-related burden in 395 patients with chronic pruritus (210 females, median age 59 years). Moderate to very severe hand pruritus was reported by 91.2% of patients, while 79% perceived additional sensory symptoms, such as burning, pain or tingling. A long duration of pruritus occurred in most cases (>6 months: 71.4%). A considerable proportion of patients showed moderate to severe impairment in the use of their hands (40.2%), performance of daily activities (65.0%) and quality of life (45.2%). Disease severity and burden is particularly high when both the palms and the backs of the hands are affected, and when pain is present simultaneously. Pruritus located on the hands is impairing and burdensome due to the functional relevance of the hands in everyday life.

Chronic Pruritus of Unknown Origin: Clinical Profile and Disease-Related Burden.

Chronic pruritus of unknown origin is established when no underlying origin for pruritus can be determined. This retrospective cohort study aimed to determine the clinical profile and disease-related burden of chronic pruritus of unknown origin. A total of 263 patients (female/male: 154/109, median age 55 years) were included. Moderate to severe itch intensities were recorded (median average itch: 5.5/10, n = 200; median worst itch: 7.5/10, n = 199). In most cases pruritus lasted longer than 1 year (77.6%), occurred daily (68.2%), occurred in attacks (72.8%), and was often accompanied by dysaesthesias, such as burning, tingling and stinging. Quality of life was moderately impaired, while 22.2% and 12.4% of patients showed pathological anxiety and depression scores. Scratch lesions were associated with higher intensities of itch and greater impairment of quality of life, while women were more burdened by the disease than men. Chronic pruritus of unknown origin may occur at any age and the majority of patients endure severe itch with substantial disease-related burden.

Relationship Among Treatment, Pruritus, Investigator's Static Global Assessment, and Quality of Life in Patients with Atopic Dermatitis.

INTRODUCTION: The Investigator's Static Global Assessment (ISGA) is a 5-point rating scale that is recommended by the US Food and Drug Administration for assessing the severity of atopic dermatitis (AD), and ISGA success is a widely used endpoint in AD clinical studies. In this study, we seek to interpret the relationship of ISGA with treatment, pruritus, and quality of life (QoL) by conducting post hoc analyses of pooled data from two phase 3 crisaborole studies. METHODS: Patients aged ≥ 2 years with baseline ISGA of 2 (mild) or 3 (moderate) were randomly assigned 2:1 to receive crisaborole or vehicle for 28 days. Disease severity, pruritus severity, and QoL were assessed with the ISGA, Severity of Pruritus Scale (SPS), and Dermatology Life Quality Index (DLQI; patients aged ≥ 16 years), or Children's Dermatology Life Quality Index (CDLQI; patients aged 2-15 years), respectively. The effect of treatment on ISGA and the relationship between ISGA and QoL were analyzed using a longitudinal repeated-measures model. The interrelationship between treatment, disease severity, pruritus, and QoL was analyzed with a mediation model. RESULTS: Overall, 1522 patients (crisaborole, n = 1016; vehicle, n = 506) were included. Estimated longitudinal profiles indicated changes in ISGA by day 8 were large for crisaborole (effect size [ES]: - 0.68) and small for vehicle (ES: - 0.34). There was a direct relationship between ISGA and DLQI and CDLQI severity bands in the longitudinal repeated-measures model. For both QoL mediation models, treatment effects on QoL were mediated indirectly by reduction in pruritus (DLQI, 42.4%; CDLQI, 58.1%) and disease severity (DLQI, 12.2%; CDLQI, 33.1%). CONCLUSIONS: These post hoc analyses suggest that ISGA success is a clinically meaningful endpoint associated with reduction in the severity of pruritus and improvement in QoL.

Investigator's Global Assessment of Chronic Prurigo: A New Instrument for Use in Clinical Trials.

Chronic prurigo is a pruritic disease characterized by the development of pruriginous lesions due to scratching. The number of lesions is representative of the stage of the disease, while the presence of excoriations reflects the scratching activity. Aim of this study was to validate a new developed tool for the objective assessment of chronic prurigo. Investigator's Global Assessment scales for stage and activity were completed for 187 patients with chronic prurigo, who also reported patient-reported outcomes for itch intensity and quality of life. To assess the reliability and objectivity of the Investigator's Global Assessment, 5 independent raters completed the Investigator's Global Assessment scales for 8 patients twice. The scores increased with increased intensity of pruritus. The Investigator's Global Assessment stage scales correlated strongly with each other (Kendall's-tau-b 0.62) and moderately with the Investigator's Global Assessment activity scale (Kendall's-tau-b 0.47). Intra-rater test-retest reliability was excellent for all items, while the congruence among raters was very good for Investigator's Global Assessment - chronic prurigo activity (Kendall's W 0.84) and good for Investigator's Global Assessment stage scales (Kendall's W 0.747). Investigator's Global Assessment - chronic prurigo stage and activity are thus the best Investigator's Global Assessment instruments for use in assessing chronic prurigo.

Clinical Relevance of Skin Pain in Atopic Dermatitis.

Skin pain is increasingly recognized as an impactful symptom in atopic dermatitis (AD) because of its association with patient discomfort, disease burden, and reduced quality of life. Although the nature of skin pain in AD has not been systematically studied and is therefore not well understood, patients report soreness, discomfort, and tenderness that may reflect peripheral and central pain sensitization. The high prevalence of skin pain suggests that it is not adequately addressed by current therapies for AD and may be undertreated compared with other symptoms. This review discusses the clinical relevance of skin pain with respect to its experience, pathophysiology, relationship with itch, and treatment implications. Recent studies suggest that skin pain presents as a neuropathic symptom independent from itch and the “itch-scratch cycle”, and poses a unique burden to patients. Recognition of the significant consequences of skin pain and discomfort should reinforce the need to assess and treat this symptom in patients with moderate-to-severe AD. J Drugs Dermatol. 2020;19(10)921-926. doi:10.36849/JDD.2020.5498.

Analysis of 325 Patients with Chronic Nodular Prurigo: Clinics, Burden of Disease and Course of Treatment.

Chronic nodular prurigo presents with multiple pruriginous nodules and severe pruritus. This study aims to explore the treatment course and regimens in patients with chronic nodular prurigo and to analyse predictive factors contributing to therapeutic success. A total of 325 patients with chronic nodular prurigo (male 37.5%) were analysed concerning demographic data, pruritus intensity, medical history, psychological impairment, quality of life, treatment duration, regimens and outcome. These parameters were compared with 325 sex- and age-matched patients with chronic pruritus on non-lesional skin. Treatment success was dependent on duration and regime of treatment and independent of age, sex and initial itch intensity. Non-responders displayed a higher percentage of inflamed nodules, a higher portion of excoriated nodules and a higher impairment of quality of life and mood factors before initiation of treatment. Gabapentinoids and immunosuppressants proved to be the most successful therapeutic agents. Compared with patients with chronic pruritus, those with chronic nodular prurigo needed longer duration of therapy.

Quality of Life in Psoriasis Vulgaris: Use of the ItchyQoL Question-naire in a Secukinumab Phase III Trial in Patients with Psoriasis Vulgaris.

Chronic pruritus is a bothersome symptom in psoriasis vulgaris and can profoundly reduce quality of life (QoL). In this exploratory analysis of the PSORITUS study, the impact of pruritus on QoL in 130 subjects with moderate-to-severe psoriasis was assessed using the ItchyQoL questionnaire. The majority of patients (n = 127) had to scratch their itchy skin regularly, which led to painful skin and frustration (mean ± standard deviation; SD ItchyQoL scores; 4.50 ± 0.56; 3.80 ± 1.09 and 4.20 ± 0.87, respectively). Changes in either temperature or season led to a worsening of itching in most of the patients (n = 126; mean ± SD ItchyQoL score; 3.80 ± 1.02). Many patients felt ashamed (n = 125) or embarrassed (n = 127) due to their itchy skin (mean ± SD ItchyQoL scores; 3.90 ± 1.26 and 3.40 ± 1.19, respectively). The results demonstrated the ItchyQoL questionnaire as a validated tool responsive to treatment for detailed insights into chronic pruritus in patients with psoriasis.

Validation of a Comprehensive Set of Pruritus Assessment Instruments: The Chronic Pruritus Tools Questionnaire PRURITOOLS.

Few studies have validated standard measurement instruments for evaluation of chronic pruritus. The Chronic Pruritus Tools Questionnaire PRURITOOLS assembles a set of instruments for the assessment of pruritus, such as the visual analogue scale (horizontal 100-mm line), numerical rating scale (0-10), verbal rating scale, and information on pruritus quality and improvement during therapy. This study, with 40 subjects, analysed PRURITOOLS regarding convergent validity and test-retest reliability (60 min), followed by a feasibility questionnaire. Test-retest reliability for PRURITOOLS items was excellent (intraclass correlation coefficient 0.84-1). Strong to very strong correlations between the pruritus intensity scales indicated convergent validity. The feasibility questionnaire showed an overall acceptance of PRURITOOLS, and the majority of subjects (82.5%) considered it an appropriate questionnaire to measure pruritus. In conclusion, PRURITOOLS offers validated tools for rapid pruritus assessment in routine care or endpoints of clinical trials.

Humanistic burden of chronic pruritus in patients with inflammatory dermatoses: Results of the European Academy of Dermatology and Venereology Network on Assessment of Severity and Burden of Pruritus (PruNet) cross-sectional trial.

BACKGROUND: Chronic pruritus is a multifactorial, challenging symptom of global relevance. OBJECTIVE: The European Academy of Dermatology and Venereology Network on Assessment of Severity and Burden of Pruritus (PruNet) investigation aimed to analyze the severity and humanistic burden of chronic pruritus in patients suffering from inflammatory dermatoses across Europe. METHODS: Prospectively collected routine data on 552 patients (with atopic dermatitis, contact dermatitis, prurigo nodularis, psoriasis vulgaris, lichen planus, or mycosis fungoides [pruritus numeric rating scale score ≥3]) from 9 European centers (in Austria, France, Germany, Italy, Poland, Russia, Spain, Switzerland, and Turkey) were analyzed by univariate and multivariate variance analyses of various itch characteristics and quality of life (as measured by the Dermatology Life Quality Index and the ItchyQoL). RESULTS: Duration, frequency, and intensity of pruritus (according to a numeric rating scale and visual analog scale) and related impairment of quality of life differed between European centers and dermatologic diagnoses (P < .05). The country in which the center was located had a greater impact on how patients evaluated pruritus intensity and quality of life than diagnosis did (P < .001). LIMITATIONS: One center per country was included. CONCLUSION: The humanistic burden of chronic pruritus in patients with inflammatory dermatoses is high. European cross-cultural factors may have a stronger influence than a specific dermatologic diagnosis on how patients rate intensity of pruritus and quality of life.

Usability of Validated Sleep-assessment Questionnaires in Patients with Chronic Pruritus: An Interview-based Study.

Impaired sleep due to nocturnal pruritus is a common symptom in patients with chronic pruritus. However, there is no standardized, simplified instrument for assessing sleep-related problems in patients with chronic pruritus. After a literature search, we conducted 50 interviews with patients with chronic pruritus and tested 12 items most frequently used in routine sleep questionnaires. Afterwards, 2 sleep assessment questionnaires (Pittsburgh Sleep Quality Index; Regensburg Insomnia Scale) were selected for use in 88 patients with chronic pruritus with sleep impairment due to pruritus. They were completed twice; once before optimizing their individual pruritus therapy and once again after 4 weeks. During the latter survey, 21 patients reported that pruritus no longer negatively affected their sleep. These patients also achieved a significant improvement in their sleeping behaviour in the Regensburg Insomnia Scale. Therefore, the Regensburg Insomnia Scale appears to be well-suited to assessing sleep impairment in patients with chronic pruritus.

Cost-effectiveness of an 8% Capsaicin Patch in the Treatment of Brachioradial Pruritus and Notalgia Paraesthetica, Two Forms of Neuropathic Pruritus.

In brachioradial pruritus and notalgia paraesthetica, the 8% capsaicin patch is a novel and effective, but cost-intense, therapy. Routine data for 44 patients were collected 6 months retrospectively and prospectively to first patch application. The cost to health insurance and the patient, and patient-reported outcomes were analysed (visual analogue scale, numerical rating scale, verbal rating scale for pruritus symptoms, Dermatological Life Quality Index, and Patient Benefit Index). Mean inpatient treatment costs were reduced by €212.31, and mean outpatient treatment and medication costs by €100.74 per patient (p.p.). However, these reductions did not offset the high cost of the patch itself (€767.02 p.p.); thus the total cost to health insurance increased by €453.97 p.p. (p ≤ 0.01). The additional costs of therapy to the patient decreased by €441.06, thus the overall cost p.p. remained approximately the same (€3,306.03 vs. €3,318.94). Capsaicin patch therapy resulted in reduced pruritus, improved quality of life and greater patient benefit, thus long-term cost-efficiency analyses are necessary.

Assessment of severity and burden of pruritus.

Chronic pruritus is a complex multifactorial symptom associated with many different diseases that represents a diagnostic and therapeutic challenge for physicians. In order to better manage chronic pruritus, a detailed medical history, individualized diagnostic procedures and treatment approaches are necessary. Treatment should not only take itch into consideration, but also scratching-induced skin lesions and accompanying disorders such as anxiety, depression and insomnia. Various standardized questionnaires and scales have been developed to assist in the characterization and assessment of these parameters. Monodimensional scales (e.g. the visual analogue scale) represent a simple method for assessing pruritus intensity and are frequently used; however, they can easily be confounded and may indicate the level of satisfaction regarding the medical care provided rather than the itch course. The Dynamic Pruritus Score and Itch-Free Days questionnaire enable a closer assessment of patient responses to treatment. Because chronic pruritus has the potential to greatly impact the quality of life, it is important that physicians recognize it as a major issue. The Dermatology Quality of Life Index is an instrument that is used in a variety of dermatological conditions, but may be unsuitable for measuring pruritus of extracutaneous origin. The ItchyQol is a tool designed specifically for those suffering from pruritus. Additional tools, such as the Hospital Anxiety and Depression Scale, take psychiatric comorbidities into consideration. Recommendations from European (EADV-based Task Force Pruritus) and international (International Forum for the Study of Itch) expert groups focusing on assessment instruments for chronic pruritus are also provided in this article.

ItchApp©: An App-based eDiary for Assessment of Chronic Pruritus in Clinical Trials.

Performing a reliable assessment of chronic pruritus remains a challenge. Electronic diaries are often used, but many of the scales have not been validated. ItchApp© was developed for Android smartphones in order to address this lack. A total of 40 subjects with chronic pruritus completed questionnaires both on paper and with ItchApp© (verbal rating scale, numerical rating scale, dynamic pruritus score) in order to validate the software application. Strong correlations were found for test-retest reliability (intraclass correlation coefficient: 0.865-0.977) and convergent validity (Spearman's r: 0.442-0.924). A feasibility questionnaire for ItchApp© revealed a high level of user friendliness and compliance. This was confirmed in a randomized controlled trial with 68 subjects, for which the clinically important difference in the numerical rating scale values for ItchApp© was calculated (2.61 points). In summary, ItchApp© is a recently developed eDiary that can provide experts with a reliable evaluation of patients with chronic pruritus. It will be made available for future clinical trials.