Observational Study of Characteristics, Treatment and Outcomes With Severe Asthma in the United States (CHRONICLE)

The CHRONICLE Study is a multi-center, non-interventional, prospective cohort study of adults
with severe asthma who do not achieve control with high-dose ICS therapy with additional
controllers and/or require systemic corticosteroid or monoclonal antibody therapy. This study
will provide a contemporary description of the epidemiology and medical management of United
States adults with severe asthma who have not achieved control with high-dose ICS therapy and
additional controllers. Additionally, the study will describe the use of and outcomes
associated with recently approved monoclonal antibody therapies for severe asthma. Patients
will be enrolled from a diverse population of academic and community-based specialist centers
across the US. Data will be collected in a naturalistic manner and patient management will
not be influenced by the study protocol. At least 1500 patients in the US with a confirmed
diagnosis of severe asthma will be enrolled by a diverse set of asthma specialists (eg,
allergists and pulmonologists who treat asthma) from academic and community-based centers.
Basic de-identified information will be collected for all patients meeting study inclusion
criteria, including those not approached for enrollment or who decline enrollment, to enable
an assessment of the enrolled and non-enrolled populations. This information will include
age, sex, insurance status, age at asthma diagnosis, class of asthma treatment per study
inclusion criteria, number of asthma exacerbations in the past 12 months, study eligibility,
whether the patient was approached for enrollment, study enrollment status, and reason for
not enrolling for those who are approached but do not enroll. Patient-reported asthma control
(Asthma Control Test [ACT]), asthma exacerbations, and treatment adherence will be solicited
monthly. Patient-reported information on asthma-related healthcare utilization, global
evaluation of treatment effectiveness (GETE), and work productivity (Work Productivity and
Activity Impairment Asthma questionnaire [WPAI-Asthma]) will be collected at baseline and
approximately every 3 months. Detailed information on asthma-related quality of life (Saint
George's Respiratory Questionnaire [SGRQ]) as well as presence of an asthma treatment plan
will be collected from patients approximately every 6 months. All of the questionnaires will
be collected via web-based surveys. Patients will then be followed until study
discontinuation or the patient withdraws from the study or death, whichever occurs first. The
expectation is that patients will be followed for a period of at least 3 years.

Inclusion Criteria:

1. Individuals with a diagnosis of severe asthma for at least 12 months prior to enrollment
and confirmed by the Investigator not to be due to alternative diagnoses.

2. Currently receiving care from specialist physicians (eg, pulmonologists and or
allergists) at the Investigator's or sub-investigator's site.

3. 18 years of age and older. 4. Meeting at least one of the following three criteria (a,
b, or c):

a. Uncontrolled on asthma treatment consistent with GINA (Global Initiative for Asthma)
Step 4 or 5, receiving high-dose ICS with additional controllers.

i. Uncontrolled is defined by meeting at least one of the following (as outlined by ATS/ERS
[American Thoracic Society/European Respiratory Society] guidelines):

1. Poor symptom control: Asthma Control Questionnaire consistently ≥1.5, ACT <20 (or "not
well controlled" by NAEPP [National Asthma Education and Prevention Program]/GINA
guidelines).

2. Frequent severe exacerbations: two or more bursts of systemic corticosteroids (≥3 days
each) in the previous 12 months.

3. Serious exacerbations: at least one hospitalization, intensive care unit stay or
mechanical ventilation in the previous 12 months.

4. Airflow limitation: after appropriate bronchodilator withhold FEV1 <80% predicted (in
the face of reduced FEV1/FVC defined as less than the lower limit of normal).

ii. For the purposes of this study, high-dose ICS will be defined as

1. ICS at a cumulative dose of >500 μg fluticasone propionate equivalents daily as defined
in Appendix A, or 2. Highest labeled dose of a combination of ICS/LABA. b. Current use of a
Food and Drug Administration (FDA)-approved monoclonal antibody agent for treatment of
severe asthma (use is not primarily for an alternative condition).

c. Use of systemic corticosteroids or other systemic immunosuppressants (any dose level)
for approximately 50% or more of the prior 12 months for treatment of severe asthma (use is
not primarily for an alternative condition).

Exclusion Criteria

1. Not willing and able to sign written informed consent. Consent can be obtained from
having a responsible, legally authorized representative acting on patient's behalf.

2. Not fluent in English or Spanish.

3. Inability to complete study follow-up or web-based PROs. If the patient does not have
email or web access, minimal assistance from others to access the web-based PRO is
permitted (ie receiving the email and/or assisting patient in navigating to the web
page); PROs must be completed by the patient.

4. Received an investigational therapy for asthma, allergy, atopic disease, or
eosinophilic disease as part of a clinical trial during the 6 months prior to
enrollment.

1. Once enrolled in the CHRONICLE Study, patients can enroll in trials of
investigational therapies (as well as other non-interventional studies) as long
as they continue to complete study follow-up. If a patient enrolls in a trial of
an investigational therapy, the identity (National Clinical Trial [NCT] number)
of the study and dates of the first and last investigational therapy
administrations will be collected. If a patient receives blinded therapy in a
trial, the Investigator will request the identity of that therapy at trial
conclusion so that treatment information collected for the current study may be
updated accordingly.