乌鸦传媒

"Medical Journeys" is a set of clinical resources reviewed by physicians, meant for the medical team as well as the patients they serve. Each episode of this 12-part journey through a disease state contains both a physician guide and a downloadable/printable patient resource. "Medical Journeys" chart a path each step of the way for physicians and patients and provide continual resources and support, as the caregiver team navigates the course of a disease.

With unfortunately no curative therapy for chronic spontaneous urticaria (CSU) available for now, the overall goal is to achieve and maintain complete control of the signs and symptoms and prevent recurrence. However, the lack of guidance on key issues, including consensus on a definition for "treatment success" and standardization of treatment targets, has resulted in a "heterogeneity in approach" that is undermining clinical care, said the authors of a 2023 .

"Physicians face multiple challenges in the management of chronic spontaneous urticaria, including inconsistent measures of treatment success in clinical practice," wrote April Armstrong, MD, MPH, of UCLA (University of California Los Angeles) Health and the David Geffen School of Medicine at UCLA. "With a large proportion of physicians relying on their clinical experience to inform clinical decision-making, the variation in patient outcomes is unsurprising."

Clinical remission of CSU is not achieved in many patients, the team noted. The review showed that in one , investigators calculated cumulative weighted average estimates for patients remitting at years 1, 5, and 20 of 17%, 45%, and 73%, respectively. The definitions of disease severity and remission also differed between various studies, as did the conclusions about influencing factors.

"There is a need for structured, practical, and realistic guidance of progress towards remission -- i.e., 'treatment success,'" Armstrong and co-authors said. Universal definitions of "remission" and "recurrence" must be developed and research fast-tracked to identify biomarkers, and "informing physicians of updates in clinically informative biomarkers should be a priority in the coming years. As the evidence base grows, predictive biomarkers may be utilized alongside specific treatment targets, which could significantly impact clinical decision-making."

Lack of Standardized Treatment Targets

The lack of standardized treatment targets in clinical care is a reflection of the lack of standardized treatment targets in clinical research, the review authors explained. "Most measures used in clinical trials are not used in clinical practice, likely due to feasibility challenges."

"What's used in clinical trials is not necessarily feasible or appropriate for clinical practice," confirmed Jonathan Silverberg, MD, PhD, MPH, director of Clinical Research and Contact Dermatitis at George Washington University School of Medicine and Health Sciences in Washington, D.C. "I lean towards patient-reported outcomes that can be easily integrated into practice."

The 2022 for the management of urticaria, developed in partnership with the American Academy of Allergy, Asthma & Immunology, the American Academy of Dermatology, and the American College of Allergy, Asthma, and Immunology, recommends the routine use of patient-reported outcome measures (PROMs) in CSU patients at every visit, including the first.

The weekly Urticaria Activity Score (UAS7) and/or the Angioedema Activity Score should be used for the assessment of disease activity; and the Urticaria Control Test (UCT) and/or the Angioedema Control Test should be used to determine disease control. In addition, health-related quality of life (HRQoL) impairment should be measured using the Chronic Urticaria Quality-of-Life Questionnaire (CU-Q2oL) and/or the Angioedema Quality of Life Questionnaire (AE-QoL).

Complete disease control is defined in the guideline as a score of 0 on the UAS7 (UAS7=0), a score of 16 on the UCT (UCT=16), and a return to normal values on the CU-Q2oL and/or the AE-QoL.

Armstrong and co-authors, however, maintained that those targets "do not reflect the realities of clinical management nor the complexity of CSU."

There is no consensus on what the scores mean for treatment, targets are lacking for angioedema and HRQoL, and more guidance is needed on when to step down therapy. Clinicians should be provided with a list of accurately defined PROMs that measure disease activity, disease control, HRQoL, and angioedema, along with targets and all associated actions, the team suggested.

The use of PROMs in patients with CSU provides more accurate information about disease activity and control than physician assessment. Results from the of real-world data from 2,078 patients in the global Chronic Urticaria Registry indicated that scores on the UCT and the UAS7 were more clinically relevant than those from the Physician Global Assessment.

Aiming for complete response in the treatment of CSU is important, and disease control is associated with good sleep domain and HRQoL scores on the Dermatology Life Quality Index (DLQI) and the CU-Q2oL. Disease control is also associated with the presence of angioedema without wheals, episodic disease, treatment with omalizumab (Xolair), and male gender.

In another looking at the association between urticaria activity and HRQoL, investigators concluded that improved understanding about the connections between PROM scores could boost physician decision-making.

"Despite the important insights that PROMs offer to physicians, there is limited information on how these different dimensions are linked," wrote Jonathan A. Bernstein, MD, of the University of Cincinnati, and co-authors. "A holistic understanding of these associations would optimize the usefulness of PROMs and enable physicians to plan appropriate treatment strategies."

Notably, the researchers reported that the analysis of 382 patient evaluations reinforced the guideline recommendation to treat patients with CSU until complete control of the disease is achieved with a score of UAS7=0.

A complete response to treatment for itching and hives was associated with better patient HRQoL scores on the DLQI, the Overall Work Impairment (OWI), the Weekly Activity Interference Score (AIS7), and the Weekly Sleep Interference Score (SIS7). A total of 91.1% of UAS7=0 evaluations corresponded to DLQI scores of 0–1; 99.7% to SIS7 scores of 0; 99.7% to AIS7 scores of 0; and 85.3% to OWI scores of 0. This was significantly different compared with the UAS7=1–6 evaluations (61.9%, 68.5%, 67.7%, and 65.4%, respectively).

"Complete responses to treatment were associated with no impairments on the dermatology-QoL, no interferences with sleep and activity, and significantly improved capacities to work compared to patients who continued to have signs and symptoms, even for those with minimal disease activity," Bernstein and co-authors said. "Sleep disruption in patients with CSU is drastically under-appreciated. Patient assessments of the effect of therapy on sleep quality should explicitly be included as part of an integrated treatment approach."

Validated self-report measures of sleep are important, noted Wilfred R. Pigeon, PhD, of the University of Rochester Medical Center in New York. Sleep disturbance is a key driver of poor HRQoL scores and may also exacerbate symptoms, he told 乌鸦传媒.

Problems About Guideline Adherence

The review authors noted that many physicians are not following guidelines when treating patients with CSU, although the extent of non-adherence remains unclear.

In 2018, a web-based completed by 1,140 physicians in 99 countries showed that physician age, clinical experience, specialty, country, and access to drugs for CSU play a significant role in adherence. Poorly written recommendations and discrepancies between guidelines can lead to suboptimal patient care.

In the survey, more than 90% of physicians (88% of whom were allergists/clinical immunologists) said they followed the treatment guidelines, reported Pavel Kolkhir, MD, of First Moscow State Medical University, and colleagues. However, about 20% also reported deviating from the guidelines -- most often to rely on their own clinical experience.

Doctors younger than 40 and/or those with less than 19 years of clinical experience were more likely to adhere to the guidelines compared with older, more experienced physicians. Younger clinicians also administered second-generation antihistamines more frequently.

"This may point to a need to better communicate to physicians, especially experienced physicians, about the benefits of guideline adherence and to better engage them in the guideline development and review process," Kolkhir and co-authors wrote. They noted that guidelines that allow for flexibility may improve physician "buy-in" and education that is based on guidelines being a complement rather than a substitute for clinical judgement could help.

PROM Testing Via App

A more recent study indicates that patients with CSU may soon be conducting their own PROM testing using an app. An analysis of data from the (Chronic Urticaria Information and Communication Technologies) study showed that 51% of 1,841 patients responding to a 23-item questionnaire were interested in an expert-validated app to record and track symptoms. Most respondents had CSU, but 18% had chronic inducible urticaria, and 19% had both; approximately 70% were female.

Well-designed, validated apps specific to chronic urticaria could potentially improve treatment outcomes and provide valuable research information, the investigators said. "The unmet need for suitable apps from the patient's point of view remains unknown."

The , one of several skin disease and allergy apps developed by the life sciences company Moxie in consultation with dermatologists provides users with monitoring scores, reminders, and checklists in preparation for doctor visits.

Read previous installments in this series:

Part 1: Urticaria/Hives: The Search Continues for Causes

Part 2: Keys to Diagnosis of Urticaria

Part 3: Chronic Spontaneous Urticaria and Autoimmunity

Part 4: Case Study: Terrible Recurrent Itchy Wheals All Over This Woman's Body

Part 5: Managing Comorbidities in Chronic Urticaria

Part 6: What's New in the Treatment of Chronic Urticaria?

Part 7: Special Considerations in Treating Urticaria in Pregnant or Lactating Patients

Part 8: Case Study: Sudden Urticaria After a Stroke

Part 9: Managing Urticaria in Children and Elderly Patients

Part 10: Clues to Improving the Quality of Life of Patients with Chronic Urticaria