Longitudinal Follow-up of Patients With Chronic Inflammatory Rheumatisms (CIRs) Vaccinated Against COVID-19 Compared to Patients Refusing Vaccination (COVID-RIC3)

To date, studies on SARS-CoV2and vaccines have been mostly from the general population not exposed to immunosuppressants. The efficacy and safety of COVID-19 vaccines need to be evaluated in these populations.

Study Overview

• Status: Completed
• Conditions: COVID-19; Rheumatic Diseases; SARS-CoV Infection
• Intervention / Treatment: Other: Biological samples

Detailed Description

Longitudinal, comparative, controlled, observational multicenter study based on a cohort of 1500 SARS-CoV-2 seronegative patients with CIRs from the COVID-RIC1 cohort: 750 accepting vaccination and 750 refusing vaccination matched on age (+/-10 years), gender, rheumatism and recruiting center. Schedule: 4 visits over a 12-month period.

An observational routine care study was initiated in 15 French hospitals to assess the SARS-CoV-2 seroprevalence in France in a population with CIRs. The project plans to screen 5000 CIRs patients. The COVID-RIC3 study will thus be proposed to these pre-screened subjects according to their agreement or refusal to be vaccinated against COVID-19 based on a question asked at the time of their inclusion in COVID-RIC1.

The efficacy and safety of the SARS-CoV2 vaccines as well as the vaccine-induced humoral immune responses and their maintenance over time in immunosuppressed patients with CIRs are essential to guide vaccine recommendations in these specific immunocompromised populations in terms of "boost" or booster.

• Study Type: Observational
• Enrollment (Actual): 397

Contacts and Locations

Study Locations

• France
  • Brest, France, 29200
    • CHU Brest
  • Clermont-Ferrand, France, 63000
    • CHU Clermont-Ferrand
  • Marseille, France, 13274
    • CHU Marseille
  • Nancy, France, 54511
    • CHU Nancy
  • Nantes, France, 44093
    • CHU Nantes
  • Nice, France, 06001
    • CHU Nice
  • Nîmes, France, 30029
    • CHU Nîmes
  • Paris, France, 75013
    • APHP La Pitié Salpêtrière
  • Paris, France, 75012
    • APHP Saint Antoine
  • Rouen, France, 76000
    • CHU Rouen
  • Toulouse, France, 31059
    • CHU Toulouse
  • Tours, France, 37170
    • CHU Tours
  • Occitanie
    • Montpellier, Occitanie, France, 34295
      • Centre Hospitalier Universitaire de Montpellier

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

1500 CIR patients with or without SARS-COV2 vaccine.

Description

Inclusion Criteria:

• Adult ≥ 18 years old,
• Chronic inflammatory arthritis: rheumatoid arthritis, psoriatic arthritis, axial SpA, diagnosed by a rheumatologist
• Having a negative serology for SARS-CoV-2 infection upon inclusion in COVID-RIC1.
• Under csDMARD (conventional synthetic Disease-modifying antirheumatic drug), biotherapy, JAK inhibitor or under symptomatic treatment such as NSAIDs or corticosteroids alone or in combination with a DMARD (Disease-modifying antirheumatic drug)
• Subject having signed a consent
• Affiliated with Social Security
• Having accepted or agreed to be vaccinated against COVID-19 (for vaccine group)
• Having refused to be vaccinated against COVID-19 (for non-vaccine group)

Exclusion Criteria:

• Adult patient under legal protection (guardian, curator)
• Patient vaccinated with an anti-SARS-CoV-2 vaccine before the serological test
• Refusal to be vaccinated (for vaccine group)
• Acceptance to be vaccinated (for non-vaccine group))
• Refusal to participate in the study
• Pregnancy and breast feeding

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Vaccinated; Seronegative Chronic Inflammatory Rheumatism (CIR) who accepted vaccination against SARS-CoV2	Other: Biological samples; Serum and plasma samples. At baseline, 3, 6 and 12 months
Non vaccinated; Seronegative Chronic Inflammatory Rheumatism (CIR) who refused vaccination against SARS-CoV2	Other: Biological samples; Serum and plasma samples. At baseline, 3, 6 and 12 months

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of documented COVID-19 infection in vaccinated chronic inflammatory Rheumatism patients	Proportion of documented COVID-19 infection according to Food and Drug Administration criteria in vaccinated chronic inflammatory Rheumatism patients	At 3 months of the 1st dose of vaccine SARS-COV-2
Proportion of documented COVID-19 infection in non vaccinated chronic inflammatory Rheumatism patients	Proportion of documented COVID-19 infection according to Food and Drug Administration criteria in non vaccinated chronic inflammatory Rheumatism patients	At 3 months of the 1st dose of vaccine SARS-COV-2

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of documented COVID-19 infection	Proportion of documented COVID-19 infection at 6 months between groups of vaccine and non vaccine patients	6 months from 1st vaccine dose
Proportion of documented COVID-19 infection	Proportion of documented COVID-19 infection at 12 months between groups of vaccine and non vaccine patients	12 months from 1st vaccine dose
occurrence of infections by type of treatment	occurrence of infections at 6 months by type of treatment	6 months from 1st vaccine dose
occurrence of infections by type of treatment	occurrence of infections at 12 months by type of treatment	12 months from 1st vaccine dose
occurrence of infections by type of vaccine	occurrence of infections at 3 months by type of vaccine	3 months from 1st vaccine dose
Proportion of patients who developed local or systemic reactions to the vaccine, in the vaccinated group at 3 months	Proportion of patients who developed local or systemic reactions to the vaccine, in the vaccinated group at 3 months	3 months from 1st vaccine dose
Proportion of patients who developed local or systemic reactions to the vaccine, in the vaccinated group at 6 months	Proportion of patients who developed local or systemic reactions to the vaccine, in the vaccinated group at 6 months	6 months from 1st vaccine dose
Proportion of patients who developed local or systemic reactions to the vaccine, in the vaccinated group at 12 months	Proportion of patients who developed local or systemic reactions to the vaccine, in the vaccinated group at 12 months	12 months from 1st vaccine dose
Proportion of patients who developed adverse events at 12 months	Proportion of patients who developed adverse events at 12 months	12 months from 1st vaccine dose
Proportion of patients with vaccine response	Proportion of patients with vaccine response (SARS-CoV-2 neutralizing antibody IgG and IgM titers) after vaccination against SARS-CoV2 in vaccine patients group	3 months from 1st vaccine dose
Proportion of patients with vaccine response	Proportion of patients with vaccine response (SARS-CoV-2 neutralizing antibody IgG and IgM titers) after vaccination against SARS-CoV2 in vaccine patients group	6 months from 1st vaccine dose
Proportion of responding patients	Proportion of responding patients with specific IgG in ELISA ≥ titer corresponding to the vaccine protection threshold and neutralizing IgG at 3 months of the first dose of COVID19 vaccine in vaccinated ICRs	3 months from 1st vaccine dose
Proportion of responding patients	Proportion of responding patients with specific IgG in ELISA ≥ titer corresponding to the vaccine protection threshold and neutralizing IgG at 3 months of the first dose of COVID19 vaccine in vaccinated ICRs	6 months from 1st vaccine dose
Proportion of responding patients	Proportion of responding patients with specific IgG in ELISA ≥ titer corresponding to the vaccine protection threshold and neutralizing IgG at 3 months of the first dose of COVID19 vaccine in vaccinated ICRs	12 months from 1st vaccine dose
compare the evolution of disease activity	compare the evolution of disease activity at 3 months in the two groups : change in formula DAS28- CRP (Disease Activity Score C-reactive Protein) between 0 and 3 months for patients with Rheumatoid Arthritis (RA) and patients with psoriatic arthritis. DAS28 < 2.6: Remission DAS28 >= 2.6 and <= 3.2:Low Disease Activity DAS28 > 3.2 and <= 5.1:Moderate Disease Activity DAS28 > 5.1: High Disease Activity	3 months from first vaccine dose
compare the evolution of disease activity	compare the evolution of disease activity at 6 months in the two groups : change in formula DAS28- CRP (Disease Activity Score C-reactive Protein) between 0 and 6 months for patients with Rheumatoid Arthritis (RA) and patients with psoriatic arthritis DAS28 < 2.6: Remission DAS28 >= 2.6 and <= 3.2:Low Disease Activity DAS28 > 3.2 and <= 5.1:Moderate Disease Activity DAS28 > 5.1: High Disease Activity	6 months from first vaccine dose
compare the evolution of disease activity	compare the evolution of disease activity at 12 months in the two groups : change in formula DAS28- CRP (Disease Activity Score C-reactive Protein) between 0 and 12 months for patients with Rheumatoid Arthritis (RA) and patients with psoriatic arthritis DAS28 < 2.6: Remission DAS28 >= 2.6 and <= 3.2:Low Disease Activity DAS28 > 3.2 and <= 5.1:Moderate Disease Activity DAS28 > 5.1: High Disease Activity	12 months from first vaccine dose
compare the evolution of disease activity	compare the evolution of disease activity at 3 months in the two groups : change in formula ASDAS-CRP (Ankylosing Spondylitis Disease Activity Score with C-reactive protein) between 0 and 6 months for patients with Ankylosing spondylitis (SpA) ASDAS < 1.3: Inactive disease ASDAS >= 1.3 and <= 2.1:Low Disease Activity ASDAS > 2.1 and <= 3.5:Moderate Disease Activity ASDAS > 3.5: High Disease Activity	3 months from first vaccine dose
compare the evolution of disease activity	compare the evolution of disease activity at 6 months in the two groups : change in formula ASDAS-CRP (Ankylosing Spondylitis Disease Activity Score with C-reactive protein) between 0 and 6 months for patients with Ankylosing spondylitis (SpA) ASDAS < 1.3: Inactive disease ASDAS >= 1.3 and <= 2.1:Low Disease Activity ASDAS > 2.1 and <= 3.5:Moderate Disease Activity ASDAS > 3.5: High Disease Activity	6 months from first vaccine dose
compare the evolution of disease activity	compare the evolution of disease activity at 12 months in the two groups : change in formula ASDAS-CRP (Ankylosing Spondylitis Disease Activity Score with C-reactive protein) between 0 and 12 months for patients with Ankylosing spondylitis (SpA) ASDAS < 1.3: Inactive disease ASDAS >= 1.3 and <= 2.1:Low Disease Activity ASDAS > 2.1 and <= 3.5:Moderate Disease Activity ASDAS > 3.5: High Disease Activity	12 months from first vaccine dose
Psychological impact scores: anxiety (GAD7 : General Anxiety Disorder-7)	The GAD-7 score is calculated by assigning scores of 0, 1, 2, and 3, to the response categories of 'not at all', 'several days', 'more than half the days', and 'nearly every day', respectively, and adding together the scores for the seven questions. Scores of 5, 10, and 15 are taken as the cut-off points for mild, moderate and severe anxiety, respectively.	3 months from first vaccine dose
Psychological impact scores: anxiety (GAD7 : General Anxiety Disorder-7)	The GAD-7 score is calculated by assigning scores of 0, 1, 2, and 3, to the response categories of 'not at all', 'several days', 'more than half the days', and 'nearly every day', respectively, and adding together the scores for the seven questions. Scores of 5, 10, and 15 are taken as the cut-off points for mild, moderate and severe anxiety, respectively.	6 months from first vaccine dose
Psychological impact scores: anxiety (GAD7 : General Anxiety Disorder-7)	The GAD-7 score is calculated by assigning scores of 0, 1, 2, and 3, to the response categories of 'not at all', 'several days', 'more than half the days', and 'nearly every day', respectively, and adding together the scores for the seven questions. Scores of 5, 10, and 15 are taken as the cut-off points for mild, moderate and severe anxiety, respectively.	12 months from first vaccine dose
Psychological impact scores: depression (HADS : Hospital Anxiety and Depression Scale)	The HADS is a self-administered 14-item scale. Each item is rated on a scale of 0 to 3. Borderline scores make it possible to distinguish: non-cases or asymptomatic ones (score ≤ 7); probable or borderline cases (score 8-10); clearly or clinically symptomatic cases (score ≥ 11).	3 months from first vaccine dose
Psychological impact scores: depression (HADS : Hospital Anxiety and Depression Scale)	The HADS is a self-administered 14-item scale. Each item is rated on a scale of 0 to 3. Borderline scores make it possible to distinguish: non-cases or asymptomatic ones (score ≤ 7); probable or borderline cases (score 8-10); clearly or clinically symptomatic cases (score ≥ 11).	6 months from first vaccine dose
Psychological impact scores: depression (HADS : Hospital Anxiety and Depression Scale)	The HADS is a self-administered 14-item scale. Each item is rated on a scale of 0 to 3. Borderline scores make it possible to distinguish: non-cases or asymptomatic ones (score ≤ 7); probable or borderline cases (score 8-10); clearly or clinically symptomatic cases (score ≥ 11).	12 months from first vaccine dose
Psychological impact scores: quality of life (EQ5D)	EQ-5D is an European quality of life scale. It is presents as follows: a first part with the questions called "EQ-5D descriptive system", supplemented by a visual analogue scale, called "EQ-5D VAS". It consists of a line of 20 cm, graduated from 0 to 100, where the patient must indicate how he assesses his current state of health, 0 being the worst state possible and 100 the best.	3 months from first vaccine dose
Psychological impact scores: quality of life (EQ5D)	EQ-5D is an European quality of life scale. It is presents as follows: a first part with the questions called "EQ-5D descriptive system", supplemented by a visual analogue scale, called "EQ-5D VAS". It consists of a line of 20 cm, graduated from 0 to 100, where the patient must indicate how he assesses his current state of health, 0 being the worst state possible and 100 the best.	6 months from first vaccine dose
Psychological impact scores: quality of life (EQ5D)	EQ-5D is an European quality of life scale. It is presents as follows: a first part with the questions called "EQ-5D descriptive system", supplemented by a visual analogue scale, called "EQ-5D VAS". It consists of a line of 20 cm, graduated from 0 to 100, where the patient must indicate how he assesses his current state of health, 0 being the worst state possible and 100 the best.	12 months from first vaccine dose

Collaborators and Investigators

• Sponsor: University Hospital, Montpellier

Study record dates

Study Major Dates

• Study Start (Actual): April 7, 2021
• Primary Completion (Actual): June 21, 2022
• Study Completion (Actual): June 27, 2023

Study Registration Dates

• First Submitted: March 31, 2021
• First Submitted That Met QC Criteria: April 2, 2021
• First Posted (Actual): April 5, 2021

Study Record Updates

• Last Update Posted (Actual): August 14, 2023
• Last Update Submitted That Met QC Criteria: August 11, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; Joint Diseases; Musculoskeletal Diseases; Connective Tissue Diseases; Arthritis; Bacterial Infections; Bacterial Infections and Mycoses; Streptococcal Infections; Gram-Positive Bacterial Infections; Severe Acute Respiratory Syndrome; COVID-19; Rheumatic Diseases; Collagen Diseases; Rheumatic Fever
• Other Study ID Numbers: RECHMPL21_0021

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No