Remibrutinib in Real-world Clinical Practice - a US Sub-study

Urticaria Activity Score over 7 days UAS7 is based on 2 daily questions scored 0-3 per day, ranging from 0 (complete control) to 42 (poor control)

Urticaria Control Test is looking retrospectively for 7 days (UCT7) and consists of 4 questions. Each question is scored 0-4, with a total score range of 0 (poor control) to 16 (well controlled).

Proportion of patients with UCT score ≥12 and UAS7 score ≤6. Urticaria Control Test (UCT) consists of 4 questions scored 0 (very much) to 4 (not at all), with a total score range of 0 to 16. High scores indicates better disease control. Urticaria Activity Score over 7 days (UAS7) is based on 2 daily questions, with daily score of 0 to 6 and weekly score of 0 to 42. Lower scores suggests urticaria free and well controlled urticaria.

Change in UCT score over time. Urticaria Control Test (UCT) consists of 4 questions scored 0 (very much) to 4 (not at all), with a total score range of 0 to 16. Highest scores indicates better disease control. The study is not powered to detect any specific difference and the purpose is to estimate any observed difference descriptively.

Urticaria Activity Score over 7 days (UAS7) is based on 2 daily questions, with daily score of 0 to 6 and weekly score of 0 to 42. Lower scores suggests urticaria free and well controlled urticaria. The study is not powered to detect any specific difference and the purpose is to estimate any observed difference descriptively.

Angioedema Activity Score (AAS7) is assessing disease activity over 7 days in patients with urticaria. The score is based on 5 daily questions scored 0 (no discomfort) to 3 (severe discomfort), with weekly score ranging from 0 to 15. Higher scores indicates greater severity of angioedema.

Number of weeks without angioedema evaluated using application entries.

Number of participants with rescue medication requirement

CSU relapse by frequency and presentation

Urticaria Control Test (UCT) consists of 4 questions scored 0 (very much) to 4 (not at all), with a total score range of 0 to 16. High scores indicates better disease control. The study is not powered to detect any specific difference and the purpose is to estimate any observed difference descriptively.

Urticaria Activity Score over 7 days (UAS7) is based on 2 daily questions, with daily score of 0 to 6 and weekly score of 0 to 42. Lower scores suggests urticaria free and well controlled urticaria. The study is not powered to detect any specific difference, descriptive analysis of difference over time will be presented.

Number of participants with remibrutinib as monotherapy in cohort 2 and 3

Duration of remibrutinib as monotherapy expressed by days, weeks or months in cohort 2 and 3

Number of participants with Administration of remibrutinib as monotherapy with "on demand" sgH1-AH in cohort 2 and 3

Duration of remibrutinib therapy with "on demand" sgH1-AH expressed by days, weeks or months in cohort 2 and 3

Descriptive analysis of concomitant sgH1-AHs

Number of participants with administration of CSU-related treatment(s) outside of local and/or international guidelines

Demonstrate relationship between non-adherence to local/international guidelines and impact on patient, disease control, treatment patterns and HCRU during early and long-term follow-up

Delay of treatment escalation contrary within 2-4 weeks from up-dosed sgH1-AH when UCT <12 or UAS>6 at time points measuring UCT7 (early) / UCT (month 3 onwards) / UAS7 group.

This will be measured by time in days/months without escalation, with UCT<12 or UAS7>6 at time points measuring UCT7 / UCT (month 3 onwards) / UAS7 group

Time in days/months without escalation while UCT score is below 12 OR UAS7 score above 6. Urticaria Control Test consists of 4 questions, score below 12 indicates poor disease control. Urticaria Activity Score over 7 days is based on 2 daily questions with a maximum daily score of 6 and weekly total score up to 42. Lower scores indicates better urticaria control.

Number of patients with escalation to remibrutinib (cohort 1), time to escalate, prior medications/escalations, and disease control at time of escalation will be presented.

Number of participants receiving escalated doses of sgH1-AH above the licensed dose (2 times, 3 times, 4 times, >4 times) prior to remibrutinib switch. This will be presented for cohort 1 and 2.

Number of sgH1-AH treatment escalations and switches prior to remibrutinib escalation

Demonstrate benefit of early vs late treatment escalation to remibrutinib

Presence of angioedema will be reported through App and/or derived from AAS scores

Proportion of patients requiring corticosteroids for disease control prior to switch to remibrutinib (cohort 1 and 2)

Dermatology Life Quality Index (DLQI) score consists of 10 questions scored from 0 (no impact at all) to 3 (very much). Total score ranges from 0 to 30, with lower scores showing lowest impact of disease on quality of life.

Change over time in Chronic Urticaria Quality of Life Questionnaire (CU-Q2oL) questionnaire. CU-Q2oL consists of 20 items rated from 0 (never) to 5 (very often). Total score ranges from 0 to 25, with lower scores showing better urticaria control. The study is not powered to detect any specific difference, descriptive analysis of difference over time will be presented.

Sleep interference will be evaluated though bespoke question. Maximum score along 7 days ranges from 0 to 21, lower scores showing lowest interference of CSU with sleep.

Quality of life will be evaluated through HADS measuring anxiety and depression components, as well as change from baseline in HADS score. Hospital Anxiety and Depression Score (HADS) is a 14 item questionnaire, 7 item rating anxiety and 7 depression. Responses are rated from 0 (never) to 3 (almost all time) at each question. Total score for anxiety and total score for depression range from 0 to 21, higher scores showing higher anxious/depressive symptomatology. Descriptive analysis will be presented.

Health Care resource utilisation (HCRU) will be evaluated based on quarterly and annualized number of health care resource utilisation related to CSU.

Work productivity assessed through WPAI questionnaire which consists of 6 questions, used to calculate 4 types of scores, absenteeism (work time missed), presenteeism (impairment at work/reduced on the job effectiveness), work productivity loss (overall work impairment), and activity impairment. The scores are expressed in percentage with higher numbers indicating greater impairment and less productivity at work.

Incidence of AEs, including serious AEs in patients who initiated remibrutinib and in patients with sgH1-AH treatment alone