UMIN-ICDS Clinical Trial

Public title

MASTARD-COVID: A Matched-Cohort Study of Treatment-requiring Autoimmune Rheumatic Diseases after COVID-19 Using Japanese Health Insurance Claims Data

Acronym

A Matched-Cohort Study of Treatment-requiring Autoimmune Rheumatic Diseases after COVID-19 in Japan Using Health Insurance Claims Data

Scientific Title

MASTARD-COVID: A Matched-Cohort Study of Treatment-requiring Autoimmune Rheumatic Diseases after COVID-19 Using Japanese Health Insurance Claims Data

Scientific Title:Acronym

MASTARD-COVID

Region

Japan

Condition

Coronavirus disease 2019
autoimmune inflammatory rheumatic diseases

Classification by specialty

Medicine in general	Clinical immunology	Infectious disease

Classification by malignancy

Others

Genomic information

NO

Narrative objectives1

Using the Japan Medical Data Center (JMDC) claims database derived from health insurance union-originated medical databases, COVID-19-infected and uninfected individuals were perfectly matched on a 1:1 basis based on adjustment factors. This study investigates the differential risk of developing AIIRD (Autoimmune Inflammatory Rheumatic Diseases) requiring disease-specific treatment.

Basic objectives2

Others

Basic objectives -Others

We calculate additional medical costs in patients who are eligible for AIIRD onset.

Trial characteristics_1

Confirmatory

Trial characteristics_2

Developmental phase

Not applicable

Primary outcomes

The primary outcome was defined as the incidence of AIIRD onset within one year during the study period.

Key secondary outcomes

Secondary outcomes were evaluated as follows:

1. The presence or absence of each outcome associated with hospitalization.
2. Total medical costs incurred after the onset of AIIRD within 12 months following the Index Month (IM) (in yen).
3. The prescription of AIIRD-specific medications.
4. The period from the IM to hospitalization following the onset of AIIRD (in months).

The Index Month is defined as the earliest month of COVID-19 diagnosis between July 2019 and August 2023.

Additionally, a sensitivity analysis was performed by excluding medications that could potentially be used for COVID-19 treatment (dexamethasone, tocilizumab, sarilumab, baricitinib) from the list of drugs used to determine AIIRD-specific prescriptions. The sensitivity analysis was conducted for the main outcome, which is the frequency distribution, and the exploratory outcome, which is the period from the month of COVID-19 diagnosis to hospitalization after the onset of AIIRD.

All of these analyses were conducted as post hoc analyses.

Study type

Observational

Basic design

Randomization

Randomization unit

Blinding

Control

Stratification

Dynamic allocation

Institution consideration

Blocking

Concealment

No. of arms

Purpose of intervention

Type of intervention

Interventions/Control_1

Interventions/Control_2

Interventions/Control_3

Interventions/Control_4

Interventions/Control_5

Interventions/Control_6

Interventions/Control_7

Interventions/Control_8

Interventions/Control_9

Interventions/Control_10

Age-lower limit

Not applicable

Age-upper limit

Not applicable

Gender

Male and Female

Key inclusion criteria

The study period spans from January 1, 2020, to August 31, 2022. We identified patients diagnosed with COVID-19, which is categorized under the International Classification of Diseases, Tenth Revision (ICD-10), as U07.1 (COVID-19, virus identified) and U07.2 (COVID-19, virus not identified). These groups form the basis of our exposed cohort. To establish a control group, we selected individuals from the same dataset who were neither diagnosed with COVID-19 nor with B34.2 (unspecified viral infection), matching them with the exposed group based on relevant criteria.

The exposed group (COVID-19 patients) includes individuals with a confirmed diagnosis coded either as U07.1 or U07.2 during the data period. Conversely, the control group (non-COVID-19 patients) consists of individuals who were not diagnosed with COVID-19 or B34.2 within the same timeframe. Additionally, the analysis will differentiate between groups based on the timing of COVID-19 infection, providing insights into the impact of infection waves and potentially differing strains of the virus.

Key exclusion criteria

Patients with AIIRD (Autoimmune/Inflammatory Rheumatic Diseases) diagnoses within the 6 months preceding COVID-19 infection will be excluded from the evaluation.

Target sample size

580000

Name of lead principal investigator

1st name	Ryuichi
Middle name	Minoda
Last name	Sada

Organization

Graduate School of Medicine, The University of Osaka

Division name

Department of Transformative Analysis for Human Specimen

Zip code

565-0871

Address

1-10, Yamadaoka, Suita, Osaka, Japan

TEL

+81-6-6105-6259

Email

sadao@cider.osaka-u.ac.jp

Name of contact person

1st name	Ryuichi
Middle name	Minoda
Last name	Sada

Organization

Graduate School of Medicine, The University of Osaka

Division name

Department of Transformative Analysis for Human Specimen

Zip code

565-0871

Address

1-10, Yamadaoka, Suita, Osaka, Japan

TEL

+81-6-6105-6259

Homepage URL

Email

sadao@cider.osaka-u.ac.jp

Institute

The University of Osaka

Institute

Department

Personal name

Ryuichi Minoda Sada

Organization

None.

Organization

Division

Category of Funding Organization

Other

Nationality of Funding Organization

Co-sponsor

Data Science Department, Shionogi & Co.

Name of secondary funder(s)

Organization

Department of Transformative Analysis for Human Specimen, Graduate School of Medicine, The University of Osaka

Address

1-10, Yamadaoka, Suita, Osaka, Japan

Tel

+81-6-6105-6259

Email

sadao@cider.osaka-u.ac.jp

Secondary IDs

NO

Study ID_1

Org. issuing International ID_1

Study ID_2

Org. issuing International ID_2

IND to MHLW

Institutions

大阪大学大学院医学系研究科（大阪大学）

Date of disclosure of the study information

2026

Year

02

Month

21

Day

URL releasing protocol

https://pmc.ncbi.nlm.nih.gov/articles/PMC11779304/

Publication of results

Partially published

URL related to results and publications

https://pmc.ncbi.nlm.nih.gov/articles/PMC11779304/

Number of participants that the trial has enrolled

1540996

Results

JMDC claims (Jul 2019-Aug 2023; N=13,432,790). Prior COVID-19: 2,955,248 (22.0%). Eligible COVID-19: 770,498 (1:1 matched controls 770,498; unmatched excluded 14,899). Matched analysis: 764,454/group. AIIRD incidence 0.21% vs 0.11% (RR 1.95, 95%CI 1.79-2.12). AIIRD-related hosp 0.037% vs 0.002% (RR 18.87, 95%CI 11.22-31.71). Sensitivity: exclude dexamethasone/tocilizumab/baricitinib/sarilumab: hosp 283->196; median 2.19->3.01 mo.

Results date posted

2026

Year

02

Month

21

Day

Results Delayed

Delay expected

Results Delay Reason

Submission is delayed due to repeated revisions to the content.

Date of the first journal publication of results

2025

Year

01

Month

29

Day

Baseline Characteristics

Baseline characteristics will be summarized for the final matched cohorts (COVID-19 vs non COVID-19 controls). Key variables include age category, sex, and baseline clinical risk status defined by the presence of at least one prespecified high-risk factor identified from claims records during the baseline period. Balance of baseline characteristics between the matched groups will be checked and described descriptively.

Participant flow

Participants will be identified from the JMDC claims database (July 2019-August 2023; total N=13,432,790). Individuals will be classified into those with a history of COVID-19 and those without, based on prespecified claims-based definitions. Among individuals with prior COVID-19 (2,955,248; 22.0%), eligibility criteria will be applied to define potential cases (n=785,397). Eligible cases without an appropriate match under the prespecified 1:1 matching algorithm will be excluded (n=14,899; 1.9% of eligible cases), leaving 770,498 individuals in the COVID-19 cohort (Group 1). Among individuals without prior COVID-19 (7,362,241; 54.8%), those meeting eligibility criteria will form the pool of potential controls (n=1,832,358). Using 1:1 matching to Group 1, 770,498 matched controls will be retained as the non-COVID-19 cohort (Group 2). The matched analysis population consists of 764,454 individuals per group, as prespecified.

Adverse events

None.

Outcome measures

Primary outcome: incident treatment-requiring autoimmune inflammatory rheumatic diseases (AIIRDs) during follow-up. AIIRD events will be identified using a prespecified claims-based algorithm that integrates diagnosis codes and prescription information to capture treatment-requiring disease and to reduce misclassification from rule-out diagnoses. Secondary outcomes: (1) AIIRD-related hospitalization, defined as an inpatient admission during which an AIIRD diagnosis meeting the prespecified outcome definition is recorded; and (2) disease-specific AIIRD incidence (e.g., rheumatoid arthritis, Sjogren's syndrome, spondyloarthropathy, systemic lupus erythematosus, idiopathic inflammatory myopathy, and ANCA-associated vasculitis), reported as comparative risk estimates between the COVID-19 cohort and matched controls. Sensitivity analysis: disease-specific incidence will be re-estimated after excluding four agents commonly used for acute COVID-19 management (dexamethasone, tocilizumab, baricitinib, sarilumab) from the prescription set used to define AIIRD events.

Plan to share IPD

No IPD sharing planned. JMDC is proprietary; access restricted. Only aggregated results will be reported; no record-level data shared.

IPD sharing Plan description

There is no plan to share individual participant data (IPD). The JMDC database is a third-party proprietary claims database, and data access is restricted by contractual and legal requirements. Only aggregated results will be reported in publications and presentations; no record-level data will be made publicly available.

Recruitment status

Main results already published

Date of protocol fixation

2024

Year

04

Month

09

Day

Date of IRB

2024

Year

04

Month

09

Day

Anticipated trial start date

2024

Year

04

Month

09

Day

Last follow-up date

2024

Year

04

Month

09

Day

Date of closure to data entry

2025

Year

12

Month

31

Day

Date trial data considered complete

2026

Year

03

Month

07

Day

Date analysis concluded

2026

Year

03

Month

31

Day

Other related information

This study is a secondary analysis using anonymized/de-identified data provided by JMDC, with no re-identification keys, intervention, specimen collection, or additional data collection from individuals; therefore, IRB review/approval was not required (outside the scope of ethical review requirements).
As this study does not involve prospective participant enrollment, but the registry system requires entries for "Date of IRB," "Date of first enrollment," and "Date of last enrollment," we entered the collaborative research agreement date (April 9, 2024) for administrative purposes. These dates do not represent an IRB approval date or an actual enrollment period.

Registered date

2026

Year

02

Month

21

Day

Last modified on

2026

Year

02

Month

21

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/icdr_e/ctr_view.cgi?recptno=R000061886