Lupus & COVID-19: Emerging Research Findings Presentation by Hospital for Special Surgery

Lupus & COVID-19: Emerging Research Findings Sebastian Sattui Cortes, MD, MS Medha Barbhaiya, MD, MPH Jillian Rose, PhD, MPH, LCSW Margaret Smith, MBA, MPH, CHES

June 24, 2020

Disclosures HSS educational activities are carried out in a manner that serves the educational component of our mission. As faculty we are committed to providing transparency in any relevant external relationships prior to giving an academic presentation. Dr. Sebastian Sattui: Member of the Clinical Advisory and Scientific Committee of the COVID-19 Global Rheumatology Alliance (C19GRA) and NY/NJ Regional Lead. Views presented here do not represent those of the C19-GRA, American College of Rheumatology or the European League Against Rheumatism Dr. Medha Barbhaiya: No relevant disclosures Jillian Rose, PhD: No relevant disclosures Margaret Smith: No relevant disclosures Confidential & Proprietary

COVID-19 and Rheumatic Diseases Dr. Sebastian Sattui

Agenda  COVID-19 Global Rheumatology Alliance (C19-GRA) Data

 C19-GRA, registries, and current numbers  Latest analysis  SLE and Plaquenil/hydroxychloroquine (HCQ)  Use of anti-rheumatic medications for COVID-19

 HCQ  Glucocorticoids (GC) (steroids, e.g., Prednisone)  Others

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Data from COVID-19 Global Rheumatology Alliance (C19-GRA)

Establishment of C19-GRA  Response from global rheumatology community to pandemic

 Gap in information  Better inform and guide patients  March 11, 2020 Twitter call-out  >400 members, including patient representatives  Multiple countries  Supported by >100 organizations

 American College of Rheumatology (ACR)  European League Against Rheumatism (EULAR)

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C19-GRA activities  Provider registry: 3,181 cases reported (as of 06/16)  Patient survey: 12,499 entries (702 patients with COVID-19) (as of 06/16)  Systematic literature reviews

 Use of anti-rheumatic drugs for treatment of COVID-19  Viral complications of anti-rheumatic medications  Advocacy

 Responsible use of HCQ in COVID-19  Drug shortages and impact on patients with lupus and RA  Proposals with ACR Confidential & Proprietary

What is a registry?  A collection of patient data  Enables the study of many people over a long period of time  Data can include information on the person, such as age and sex and related biological specimens, such as blood  Useful in examining effects of a disease in a group of people and in generating further research hypotheses  Established with patient consent and oversight of a review board

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Data analyzed and published from C19-GRA registry  Data include 600 patients from 40 countries  Published in Annals of the Rheumatic Diseases, online May 29, 2020

 “Characteristics associated with hospitalisation for COVID-19 in people with rheumatic disease: data from the COVID-19 Global Rheumatology Alliance physician-reported registry”

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Characteristics of rheumatic disease (RMD)patients in C19-GRA registry

Rheumatic Disease

Other 20%

RA 38%

Rheumatic Disease Activity

High disease activity 20%

Vasculitis 7%

AxSpa 8% PsA 12%

SLE 14%

Minimal/no disease activity 80%

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Characteristics of rheumatic disease (RMD) patients in C19-GRA registry

100 90

Died Men

< 50 years old

Not hospitalized

Women

50 + years old

Hospitalized

Survived

Age

Hospitalized Characteristics

Survival

Percent

70 60 50 40 30 20 10 0 Sex

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Characteristics associated with hospitalization in RMD patients  Duration of symptoms  2 weeks ≈ general population  General risk factors for hospitalization:

 Age > 65 years  High blood pressure

≈ General population

 Lung disease  Diabetes  Chronic kidney disease

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Characteristics associated with hospitalization in RMD patients

Rheumatoid arthritis Systemic lupus Psoriatic arthritis Spondyloarthritis Vasculitis Other

Not hospitalized N = 323 121 (37%) 37 (11%) 52 (16%) 32 (10%) 15 (5%) 66 (20%)

Hospitalized N = 277 104 (38%) 48 (17%) 22 (8%) 16 (6%) 24 (9%) 63(23%)

No single RMD associated with hospitalization

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Characteristics associated with hospitalization in RMD patients • Glucocorticoids Steroids such as prednisone, prednisolone

• Other medications: NSAIDS, oral anti-rheumatics, e.g., Plaquenil, methotrexate

• TNF-inhibitors:

 Moderate dose (>10mg) associated with increased risk of hospitalization

 Not associated with increased risk of hospitalization

 Decreased risk of hospitalization

e.g., Adalimumab, Etanercept, commonly used in RA

Numbers for other biologic agents such as rituximab, benlysta were too small to analyze Confidential & Proprietary

C19-GRA analysis of lupus and Plaquenil/HCQ • 80 patients with lupus and COVID-19 infection • No difference in hospitalization between those on Plaquenil and those not • No difference in maximum level of care required (supplemental O2, ICU)

Patients who took HCQ Patients who did as standard care not take HCQ 51 (64%) 29 (36%)

Lupus & COVID-19 patients Hospitalized patients 29 (57%)

16 (55%)

Total Patients 80 45

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Advocacy for patients and rigorous scientific inquiry

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C19-GRA data limitations and next steps  Risk of COVID-19 infection in lupus and other RMD patients cannot be assessed from these data

 Other ongoing studies (GRA patient registry, HSS cohort) might be better able to do so

 A few small studies report either similar or mildly increased risk  Continue to collect data

 Generate important information  Focus analysis on specific rheumatic diseases  Continue collaboration with ACR

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Use of Anti-rheumatic Medications for COVID-19

Limitations of therapeutic studies in COVID-19

Lack of control arm

Confounders Rigor and Transparency in research

•To really understand effect of medication, need to assess people not on the medication

•Characteristics or factors that might influence outcomes

•Haste to disseminate results

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ď&#x201A;§ Plaquenil/hydroxychloroquine (HCQ) ď&#x201A;§ Medication studies had several limitations

Number of studies

Outcome (objective)

Results

2 studies

Death

No benefit no harm

3 studies

Mechanical ventilation and death

No benefit no harm

1 study

Prevent development of infection

No benefit no harm

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Glucocorticoids (CG) - steroids  14+ studies comparing patients on and off GC  Important differences between each of them

 Timing of medication  Doses  Patients groups: demographics and severity/course of illness  Mixed results

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RECOVERY Trial of GC Information from press release; full data not yet available

 For patients on mechanical ventilation (intubated)

 1 death prevented by treating 8 patients

 For patients on supplemental oxygen

 1 death was prevented by treating 25 patients

 For patients not requiring oxygen

 No benefit observed

Final study results pending. No evidence that GC prevent worsening or death in patients with mild infection Confidential & Proprietary

Timing of medical intervention is crucial  What is driving the illness: virus or immune system  Different “arms” of immune system  Clinical symptoms and complications  Risks of weakening immune system (other infections)

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Other rheumatic disease medications under study

Tocilizumab

•RA, vasculitis, juvenile arthritis •Interest and limited studies showing some benefit •Larger randomized studies pending

Anakinra

•Juvenile arthritis, Still’s disease •2 studies (limited) showing a benefit in mortality •Larger randomized studies pending

Others

•Eculizumab, mavrilumab, IVIG, baricitinib, type I IFN blockers •Small studies, not definitive Confidential & Proprietary

https://rheum-covid.org/

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HSS Rheumatology Patients COVID-19 Registry Dr. Medha Barbhaiya

Goals of the HSS registry study  Investigate the role of immunomodulatory medication use and systemic rheumatic diseases on COVID-19 incidence and severity

 Medications can include Plaquenil/hydroxychloroquine, steroids, CellCept, Benlysta, other biologics, methotrexate, others

 Evaluate the impact of the COVID-19 pandemic on patients with systemic rheumatic diseases (SRDs)

 Lupus, RA, Scleroderma, Vasculitis, others

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Patient data collection survey  Secure, web-based survey created  Minimum of 54 questions  Five questionnaires

 1) COVID-19 exposure, symptoms, prevention and treatment  2) Rheumatic disease history and medication modifications  3) General medical history, environmental exposures (e.g., smoking and vaping), pregnancy history

 4) Social determinants of health (e.g., food insecurity, employment, socioeconomic status)

 5) Patient-Reported Outcomes (e.g., pain, sleep, fatigue, anxiety, depression)

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Qualifying rheumatology patients to participate in registry

Screened medical records of patients seen 4/1/18 â&#x20AC;&#x201C; 4/21/20 Excluded deceased, non-Englishspeaking, and pediatric patients 28,000 patients qualified for registry Confidential & Proprietary

Inviting patients to participate  Data collection period April 24, 2020 – May 26, 2020  Emails

 About 26,000 patients emailed  3 emails sent to request completion of survey  Telephone calls

 About 450 patients without email addresses contacted

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Survey responses

Survey Response

Number of Patients

Percent (%) of total recruited patients

Completion of any part of survey

8,400

Completion of at least the 7,000 first full questionnaire

Completion of entire survey

6,500

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Relevant Research Questions  What is the risk of developing COVID-19 or having severe COVID-19 in patients with rheumatic diseases and in those taking immunomodulatory medications?

• Lombardy, Italy • N=955 patients (>98% response rate) • Incidence of COVID-19 similar to general population • Arthritis and Rheumatology • Partners Healthcare System (Boston, MA) • Similar proportion of hospitalization and mortality, but higher intensive care admission and mechanical ventilation as general population • Small sample size (N=52) • Annals of Rheumatic Diseases

• Spanish BIOBADASER registry

• Similar risk of hospitalization and mortality as general population • Small sample size (N=41)

• Annals of Rheumatic Diseases

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Other Important Research Questions  How were immunomodulatory medications modified by our patients during the COVID19 pandemic?

 Are there particular disparities on the impact of the COVID-19 pandemic in patients with rheumatic diseases?

 How were pregnant women with rheumatic diseases affected by the COVID-19 pandemic?

 What is the psychosocial impact of COVID-19 on rheumatology patients?

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Psychosocial Impact of COVID-19 on Rheumatology Patients Jillian A. Rose, PhD

People at heightened risk for COVID-19  Older adults  Immuno-deficient people  People with underlying chronic health conditions

 Diabetes  High blood pressure  Obesity  Heart disease  People with inflammatory rheumatic conditions

 Underlying disease process  Medications used to treat their rheumatic disease Confidential & Proprietary

Disparities in burden of COVID-19 illness and death Death rates in New York City Race/ethnicity Black/African American Hispanic/Latino White Asian

Incidence per 100,000 people 92.3 74.3 45.2 34.5

Health disparities compounded by  Socioeconomic factors  Environmental conditions  Access to care  Underlying health conditions Confidential & Proprietary

Mental health and rheumatic diseases (RD) • Rheumatic illness can profoundly impact psychosocial wellbeing • Clinical depression and anxiety twice as prevalent as in general population

Depression & Anxiety

•Poorer health outcomes •Worse health-related QOL

Social & Peer Support

•Important to improve outcomes •Isolation/loneliness common in RD

COVID-19

•Raises anxiety •Worsens isolation/lowers support Confidential & Proprietary

HSS Department of Social Work Programs  Offers largest number of support and education programs for rheumatic patients and their loved ones in USA

 Focus on serving diverse communities nationally and internationally  Committed to highest quality of care  2019 programs met needs of 23,000 patients, family and community members

Psychosocial interventions

Support groups

Educational programs

Addressing Health Disparities

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Original research by HSS Social Work informs programming  Research shows that sound interventions include the patient’s voice  Peer-focused  Patient-centered  Patient participation

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New HSS research: psychosocial impact of COVID-19 Purpose

How information will be used

 Understand psychosocial impact of COVID-19 on rheumatic patient experience

 Review and enhance

 Self-reported physical health  Mental and emotional health  Access to health care and other social

 Medical care and research  Mental health care and interventions  Support and education programs  New and future programming

services

 Support and education needs

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New HSS research: psychosocial impact of COVID-19 How can you help?

Who do you talk to for questions?

 If you are diagnosed with a rheumatic condition and are at least 18 years of age, you can participate in this 15 – 20 minute survey.

 For questions or more information, please contact

 Anonymous  Confidential

 Jillian Rose, PhD, MPH, LCSW at rosej@hss.edu or 646.714.6673

 Melissa Flores, MPH, LCSW at

floresme@hss.edu or 646.797.8934

 Voluntary  Results will be shared in aggregate

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