Role of patient-reported outcome measures in the management of chronic urticaria and angioedema

UAS7

The UAS7, which happens to be the current, standardized prospective patient-reported measure, is a simple and validated scoring system to estimate disease activity in CSU cases. It has two parts: The number of wheals (0: none–3: >50) and the severity of the itch (0: none–3: severe). Patients are needed to record every 24 h, and the total data yields a daily UAS score of 0–6 [Table 1]. The aggregate score over a weeklong period (range 0–42) is seen as an acceptable indicator of CSU activity. Although UAS7 cutoff values have not yet been established, a score of 0 denotes a complete lack of wheals and itch, while a score of 6 denotes the minimal degree of disease activity. According to the suggested cutoff values, minor illness activity is indicated by a UAS7 score of 7–15; moderate disease activity is indicated by a UAS7 score of 16–27; and severe disease activity is indicated by a UAS7 score of 28–42.^[5]

UCT

The UCT is a 4-item retrospective (last 4 weeks) tool that measures the intensity of the medical manifestations of CSU and their impact on patient’s QoL, the frequency of therapy inadequacy to manage the symptoms, and the degree to which the medical complaints were controlled. The ultimate goal of developing the UCT was to ascertain the symptom management status in every kind of CSU. Answers are given a score between 0 and 4, with a total score between 0 and 16 denoting complete control. A UCT score of 11 or less denotes insufficient illness control, while a score of 12 or more denotes effectively managed CSU.^[6]

CU-Q2oL

The CU-Q2oL is a 23-question survey designed specifically for CSU patients that cover a variety of characteristics of how the condition affects their daily lives. It includes questions on itching, swelling, activities of normal day-to-day living, the period of rest, visible external attributes, and limits.^[7] A greater decrease in QoL associated with the health aspect is reflected by a higher CU-Q2oL score. Scores range from 23 to 115. This questionnaire which provides more details on aspects pertinent to CSU is a useful tool for documenting and analyzing changes in CSU QoL over time and/or in response to therapies.

Condition-specific QoL takes into account the perception of the affected individual on the physiological repercussions of the disease and the treatment modalities. This subjective tool is now fundamental in the assessment of, particularly, chronic diseases such as CSU and serves to compare treatments. QoL questionnaires can be used to gauge and monitor changes in several parameters including emotional changes; this is unlike symptom scoring. Given the extremely low fatality rate and unpredictable nature of CSU episodes, the management of disease control must place a high priority on the QoL. The impact of various illnesses can be examined using the general QoL questionnaires, allowing for some cross-population comparison.

USS

The USS is a PROM that uses 12 specific questions to assess the patient’s QoL, the severity of the urticaria, and the treatment’s overall effectiveness.^[8] The Likert intensity scale, varying from 0 to 7, is used in the grading of 10 questions: 0 corresponding to the absence of symptoms, impairment of QoL, medication, and 7 corresponding to the very strong manifestation of symptoms, QoL impairment, and high medication use. The remaining two questions are used to determine the amount of surface area of the body that is affected, using a scoring range from 0 to 8 to correspond to the increased surface area of the body affected by CU. The scoring for the question about oral corticosteroid use is multiplied by two as it is considered to have a significant correlation to increased disease activity. The final score comes out to be in the range of 0–93; the higher the score, the higher the impact on the patient’s QoL and disease severity.

AAS

The AAS was developed for all types of AE cases, including those with recurrent AE associated with CU and those with bradykinin-mediated recurrent AE, like hereditary AE. It is the first standardized, symptom-specific PROM for assessing disease activity in AE. It is a five-item tool where the main question is if AE had occurred within the past 24 h. If the response to that question is affirmative, further, inquiries should be made on the degree of physical discomfort, functional capacity, esthetic effect, and the general evaluation of the seriousness of the disease.^[9] The point value assigned to each element ranges from 0 (none) to 3 (severe). As a consequence, the scores obtained on the AAS may vary anywhere from 0 to 15 (for the AAS score on a daily basis), 0–105 (daily AAS score), 0–105 (over a period of 7 days), and 0–420 (AAS28) [Table 2].

AE-QoL

The AE-QoL is the first validated 17-item questionnaire aimed at measuring the consequences of AE on health-related QoL (HRQoL) from the patient’s perspective. The 17 items cover 4 spheres related to the impact of AE which is functioning, fatigue/mood, fears/shame, and food.^[10] There is a wide range of possible values, from 0 to 85. A higher score indicates a stronger disturbance in QoL. It seeks to present a thorough understanding of how recurrent AE affects several aspects of one’s HRQoL.

Application of PROM in clinical trials and studies

The inherently fluctuating nature of the symptoms accompanying CU provides a major roadblock for doctors to ascertain the degree of severity to which the illness presented itself in the clinical setting. Certain factors like autoimmunity play a key, predictive role in the therapeutic management of CSU in patients. In fact, a 6-month prospective trial for omalizumab conducted among 117 patients with CSU in Denmark found a mean baseline improvement of UA7 scores from 29.3 to 11.9 after a 3-month interval indicating the efficacy of treatment.^[11] Ever since the establishment of a validated scorer of the likes of the UAS, it has been used, since then, in several studies based on the efficacy of the medicines used for CSU.^[12]

Patients who had a UAS7 score of <16 at baseline were frequently included in omalizumab randomized controlled trials.^[13-16] At week 12, 52% of the patients had a UAS7 score below 6, and 36% of the patients had a complete response (UAS7 = 0), according to Saini et al.^[13] Likewise, 336 CSU patients with a UAS7 score of <16 were included in a study by Kaplan et al.^[14] The study had also involved the same number of patients with a UAS7 score above or equal to 16. After starting treatment, 34% of the individuals in the omalizumab group had achieved a UAS7 score of 0 as opposed to only 5% in the placebo group.^[14] Following the failure of first-line treatment with antihistamines, a second randomized controlled trial involved 49 CSU patients who had immunoglobulin E (IgE) autoantibodies toward Thyroid peroxidase (TPO) and a UAS7 score of more than 10. Patients receiving omalizumab at week 24 reported a drop in UAS7 score from baseline of 17.8 points as opposed to a reduction of 7.9 points in the placebo group.^[15,16]

AWARE was a multi-centric and non-interventional study conducted across several continents that aimed to observe the efficacy of different diagnostic approaches to CSU, and PROMs served to be an important prognostic marker as the appropriate therapy leads to a sustained improvement in the QoL.^[17]

In an Indian study, 48 individuals with CU who experienced symptoms every day had their QoL evaluated using the CU-Q2oL.^[18] The study discovered that sleep disruption, influence on daily activities, restrictions, and appearance were all affected, although to a lesser degree, than the category of physical symptoms. All in all, the study demonstrated the utility of regular application of CU-Q2oL to evaluate baseline QoL impairment and treatment outcomes, both during first and follow-up visits.

Availability of PROMs in apps

Applications developed for chronicling the daily symptoms, disease control, and regular assessments of QoL of CSU patients are highly desirable. They can help in determining the important triggers (such as stress, temperature changes, and infections), as well as the effects on everyday life (such as poor sleep, missed work or school, and other comorbidities). Moreover, apps tracking individual issues and day-to-day conditions can greatly assist the physician in formulating the optimal treatment plan. Many patients, especially those with a higher educational degree, have expressed their eagerness to avail of communication technologies and apps to keep track of their disease as well as interact daily with their physicians, as demonstrated by this UCARE CURCIT analysis study.^[19] Yet, a recent study done by Antó et al. demonstrated a global lack of such apps for patients with CSU.^[20] This study conducted both automatic and manual searches to discover five apps for CU self-evaluation which are as follows: TARGET My Hives, UrCare, UrticariApp, and SymTrac™ HIVES. However, only two allowed for the documentation of triggers, and three allowed for the input of medications used. None of the five covered comorbidities or provided individualized advice.

This reveals a dearth of availability of CU-driven apps on iOS and Android platforms for patients.

Impact of the pandemic on CSU

The COVID-19 pandemic has been a major cause of disturbance in the health-care system and patient welfare. Patients and their physicians have fallen victim to the disruptions due to travel restrictions, lockdowns, and changing management patterns in addition to the psychological aspect of dealing with the pandemic. A study conducted in 110 health-care centers reported a more than 50% decrease in CU patients visiting for treatment, with more consultations being done online than face-to-face. They also reported a CU exacerbation in one in three patients suffering from COVID-19.^[21] A study in Turkey reported markedly higher disease activity in male CSU patients as compared to female ones.^[19]

Another Turkish study successfully used PROMs for the evaluation of changes in disease activity during the pandemic period. The mean UAS7 was 7.5 ± 10.2 before the pandemic and 8.5 ± 11.2 during the pandemic indicating a slightly higher disease activity. The mean UCT score during the pandemic was found to be 11.0 ± 3.7.^[20]

Limitations of PROMS

The major limitation of all PROMs is the absence of properly validated questionnaires designed specifically for children and adolescents.^[22] Till now, generic tools like the CDLQI are utilized for measuring disease activity in this age group.^[23] Information regarding prevalence could perhaps be gathered with the help of school-based programs because childhood CSU cases seldom appear before specialists and tend to be handled by general physicians at home. CSU questionnaires, specifically those targeting the pediatric population and adolescents, need to be designed in the quest to begin clinical investigations.

Although UAS7 has emerged as the gold standard to evaluate disease progression routinely, it presents its own set of issues. As it is a prospective tool, it poses the inherent problem of assessing CSU activity when the physician encounters a CSU patient for the 1^st time. The UAS7 scoring also depends on patients themselves as they need to complete it every day, without fail until their next appointment. Furthermore, even though AE and chronic inducible urticaria (CIndU) subtypes of urticaria are associated with CSU in many patients, they are not included in the scoring.^[7] To address these apparent limitations of the UAS, the UCT came to be developed. The major benefit of the UCT happens to be its retrospective nature which renders it totally distinct from any past interactions with patients, and the relative ease of completion for patients and physicians alike. The ideal practice in the clinical setting will be to combine these two questionnaires in CU patients, as they focus on entirely different aspects, and hence, it will offer the physician a more complete picture of the disease’s activity as well as the measures to manage it.

Certain areas of CSU exist, which are improperly covered by current scoring systems, such as stress and other emotional factors. Stress happens to play a significant role in disease activity and progression of CSU as demonstrated by a pilot study that tried an innovative approach of implementing a complete treatment program, including the psychological aspect. About 75% of the patients who had reported being unaffected by standard therapy demonstrated significant improvement with next to no disease activity as opposed to pre-treatment scores. This provided support for the idea that there is a relationship between psychological variables and the manifestation of sickness.^[24]

The AEQoL, although being utilized regularly in clinical studies, has a slightly elevated respondent burden along with a complicated method and interpretation of score computation.^[22]

The CUQoL, despite serving as an excellent tool, is flawed in the sense that it takes longer and more effort to calculate its scores. Furthermore, it excludes the commonly seen influence of AE on the QoL.^[25] Due to this, people diagnosed with AE are often barred from participating in clinical studies. To account for the more accurate assessment of AE in CSU patients, there is a regular use of the AE-QoL in clinical practice and other studies.

Even though several validation studies exist for other languages, studies are yet to be published in Indian languages and this becomes a major challenge for physicians residing in the Indian subcontinent to interact with patients, especially those who are not conversant in English [Table 3].