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Abstract Background Kawasaki disease has been described across the globe, although publications from Africa are limited. To our knowledge, there are no publications on Kawasaki disease from Kenya, which triggered this report. Methods A retrospective cross-sectional study was undertaken to identify in-patients with a discharge diagnosis of Kawasaki disease, over 2 different 5-year periods, at two pediatric hospitals in Nairobi, Kenya. We reviewed the medical records of all patients and report their clinical findings, diagnostic workup and treatment. In addition, we undertook a detailed review of the literature. Results Twenty-three patients with Kawasaki disease were identified, of those 12 (52.2%) had incomplete disease. The mean age was 2.3 years (SD+/-2.2) (range 0.3–10.3) with a male to female ratio of 1:1. The mean duration of fever at diagnosis was 8.3 days (SD+/-4.7) (range 2–20). Oral changes were the most common clinical feature and conjunctivitis the least common. Thrombocytosis at diagnosis was seen in 52% (12/23). Twenty-one patients (91.3%) were treated with intravenous immunoglobulin and all except 1 received aspirin. Baseline echocardiograms were performed in 95.7% (22/23) and found to be abnormal in 3 (13.6%). Follow-up data was limited. Our literature review identified 79 publications with documented cases of Kawasaki disease in children from 22 countries across the African continent with a total of 1115 patients including those from this report. Only 153 reported cases, or 13.7%, are from sub-Saharan Africa. Conclusions This is the first publication on Kawasaki disease from Kenya and one of the largest reports from sub-Saharan Africa. It is the first to have a complete review of the number of published cases from the African continent. Challenges in the diagnosis and management of Kawasaki disease in many African countries include disease awareness, infectious confounders, access and cost of intravenous immunoglobulin, access to pediatric echocardiography and follow-up. Increasing awareness and health care resources are important for improving outcomes of Kawasaki disease in Africa.

Background This multicenter incident cohort aimed to characterize how often early rheumatoid arthritis (ERA) patients self‐report episodic joint inflammation (palindromic rheumatism) preceding ERA diagnosis and which characteristics differentiate these patients from those without prior episodic symptoms. Methods Data were from patients with early confirmed or suspected RA (more than 6 weeks and less than 12 months) enrolled in the Canadian Early ArThritis CoHort (CATCH) between April 2017 to March 2018 who completed study case report forms assessing joint pain and swelling prior to ERA diagnosis. Chi‐square and t tests were used to compare characteristics of patients with and without self‐reported episodic joint inflammation prior to ERA diagnosis. Multivariable logistic regression was used to identify sociodemographic and clinical measures associated with past episodic joint inflammation around the time of ERA diagnosis. Results A total of 154 ERA patients were included; 66% were female, and mean (SD) age and RA symptom duration were 54 (15) years and 141 (118) days. Sixty‐five (42%) ERA patients reported a history of episodic joint pain and swelling, half of whom reported that these symptoms preceded ERA diagnosis by over 6 months. ERA patients with past episodic joint inflammation were more often female, had higher income, were seropositive, had more comorbidities, fewer swollen joints, and lower Clinical Disease Activity Index (CDAI) around the time of ERA diagnosis (P < 0.05). These associations remained significant in multivariable regression adjusting for other sociodemographic and RA clinical measures. Conclusion Almost half of ERA patients experienced episodic joint inflammation prior to ERA diagnosis. These patients were more often female, had higher income, and presented with milder disease activity at ERA diagnosis.

Objective Metabolic syndrome (MetS) prevalence in early rheumatoid arthritis (ERA) is conflicting. The impact of sex, including menopause, has not been described. We estimated the prevalence and factors associated with MetS in men and women with ERA. Methods A cross‐sectional study of the Canadian Early Arthritis Cohort (CATCH) was performed. Participants with baseline data to estimate key MetS components were included. Sex‐stratified logistic regression identified baseline variables associated with MetS. Results The sample included 1543 participants; 71% were female and the mean age was 54 (SD 15) years. MetS prevalence was higher in men 188 (42%) than women 288 (26%, P < 0.0001) and increased with age. Frequent MetS components in men were hypertension (62%), impaired glucose tolerance (IGT, 40%), obesity (36%), and low high‐density lipoprotein cholesterol (36%). Postmenopausal women had greater frequency of hypertension (65%), IGT (32%), and high triglycerides (21%) compared with premenopausal women (P < 0.001). In multivariate analysis, MetS was negatively associated with seropositivity and pulmonary disease in men. Increasing age was associated with MetS in women. In postmenopausal women, corticosteroid use was associated with MetS. Psychiatric comorbidity was associated with MetS in premenopausal women. MetS status was not explained by disease activity or core RA measures. Conclusion The characteristics and associations of MetS differed in men and women with ERA. Sex differences, including postmenopausal status, should be considered in comorbidity screening. With this knowledge, the interplay of MetS, sex, and RA therapeutic response on cardiovascular outcomes should be investigated.

Objective: Our objective was to characterize nonarticular pain (NAP) at early rheumatoid arthritis (RA) diagnosis, the evolution over the first year of treatment, associations with active RA inflammation, and the impact on remission., Methods: This real-world, longitudinal multicenter cohort study observed participants with active early RA (symptoms <1 year and Clinical Disease Activity Index [CDAI] >2.8) enrolled between January 2017 and January 2022 who completed a body pain diagram over 1 year. Participants were grouped by prespecified definitions of NAP: (1) none, (2) regional, or (3) widespread. Rheumatologists performed joint counts. Descriptive statistics summarized the frequency and evolution of NAP patterns over 1 year. Chi-square tests compared the proportions of tender and/or swollen joints by the presence of pain in each NAP section. Multiadjusted generalized estimating equations regression models estimated associations of NAP patterns with remission outcomes., Results: Participants (N = 392) were 70% female, with a mean ± SD age of 56 ± 14 years and mean ± SD symptoms duration of 5.1 ± 2.7 months. More than half reported NAP at baseline, with most (73%) presenting with regional NAP. Common patterns of regional NAP were axial (40%) and pain in upper quadrants (17%). A total of 43% of those with regional NAP persisted or worsened over 1 year, whereas 73% of those with widespread NAP resolved or improved. Joint inflammation was more frequently reported in areas with NAP versus areas without NAP. Regional and widespread NAP were associated with lower odds of reaching CDAI remission (adjusted odds ratio 0.42, 95% confidence interval 0.26-0.70 and adjusted odds ratio 0.30, 95% confidence interval 0.12-0.74), respectively., Conclusion: Regional NAP is common and persistent in early RA and impacts remission. RA activity may contribute to NAP. More attention to NAP in RA care is warranted., (© 2024 The Author(s). Arthritis & Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)

Objective: In the face of the ongoing circulation of SARS-CoV-2, the durability of neutralization post-COVID-19 vaccination in immune-mediated inflammatory disease (IMID) is a key issue, as are the effects of medications., Methods: Adults (n = 112) with inflammatory bowel disease, psoriasis/psoriatic arthritis, rheumatoid arthritis, spondylarthritis, and systemic lupus were recruited from participating Canadian medical centers from 2021 to 2023. We focused on log-transformed neutralization (lentivirus methods) as a continuous outcome, with separate models for wild-type and Omicron strains BA.1 and BA.5., Results: Compared with 30 to 120 days postvaccination, subsequent periods were associated with greater neutralization in unadjusted models for wild-type, BA.1, and BA.5 strains and against the BA.1 strain in adjusted models. Rituximab was associated with lower neutralization for the BA.1 strain in adjusted models, with a similar trend for BA.5. In methotrexate users, there were trends for less neutralization of BA.1 and BA.5 in all unadjusted models, whereas in adjusted models, there was significantly lower neutralization only for the wild type. Three or more doses and Omicron-specific vaccines were both independently associated with better neutralization ability for all three strains. A COVID-19 infection within six months before sampling was associated with higher neutralization of wild type and BA.1 in adjusted analyses. Anti-tumor necrosis factor agents were associated with lower neutralization ability for BA.5 in adjusted analyses., Conclusion: Neutralization responses in immunosuppressed individuals with IMID were durable over time and were augmented by more than three doses and Omicron-specific vaccines. Less neutralization was seen with certain medications. Our work clarifies the joint effects of vaccine history, infection, and medications on COVID-19 immunity., (© 2024 The Author(s). ACR Open Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)

Background/objective: In patients with rheumatoid arthritis (RA), high tender-swollen joint differences (TSJDs) have been associated with worse outcomes. A better understanding of the phenotype and impact of high TSJD on patient-reported outcomes (PROs) in early RA may lead to earlier personalized treatment targeting domains that are important to patients today. Our objectives were to evaluate the impact of TSJD on updated PROs in patients with early RA over 1 year and to determine differences in associations by joint size., Methods: This longitudinal cohort study followed patients with active, early RA enrolled in the Canadian Early Arthritis Cohort between 2016 and 2022, who completed clinical assessments and PROMIS-29 measures over 1 year. Twenty-eight joint counts were performed and TSJDs calculated. Adjusted associations between TSJD and PROMIS-29 scores were estimated using separate linear-mixed models. Separate analyses of large versus small-joint TJSDs were performed., Results: Patients with early RA (n = 547; 70% female; mean [SD] age, 56 [15] years; mean [SD] symptom duration, 5.3 [2.9] months) were evaluated. A 1-point increase in TSJD was significantly associated with worse PROMIS T-scores in all domains: physical function (adjusted regression coefficient, -0.27; 95% confidence interval [CI], -0.39, -0.15), social participation (adjusted regression coefficient, -0.34; 95% CI, -0.50, -0.19), pain interference (adjusted regression coefficient, 0.49; 95% CI, 0.35, 0.64), sleep problems (adjusted regression coefficient, 0.29; 95% CI, 0.16, 0.43), fatigue (adjusted regression coefficient, 0.34; 95% CI, 0.18, 0.50), anxiety (adjusted regression coefficient, 0.23; 95% CI, 0.08, 0.38), and depression (adjusted regression coefficient, 0.20; 95% CI, 0.06, 0.35). Large-joint TSJD was associated with markedly worse PROs compared with small-joint TSJD., Conclusions: Elevated TSJD is associated with worse PROs particularly pain interference, social participation, and fatigue. Patients with more tender than swollen joints, especially large joints, may benefit from earlier, targeted therapeutic interventions., Competing Interests: There is no financial support or other benefits from commercial sources for the work reported on in the manuscript or any other financial interests that any of the authors may have, which could create a potential conflict of interest or the appearance of a conflict of interest with regard to the work., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Objectives: Chronic inflammation promotes cardiovascular risk in rheumatoid arthritis (RA). Biological disease-modifying antirheumatic drugs (bDMARDs) improve disease activity and cardiovascular disease outcomes. We explored whether bDMARDs influence the impact of disease activity and inflammatory markers on long-term cardiovascular risk in RA., Methods: We studied 4370 participants without cardiovascular disease in a 10-country observational cohort of patients with RA. Endpoints were (1) major adverse cardiovascular events (MACE) encompassing myocardial infarction, stroke and cardiovascular death; and (2) any ischaemic cardiovascular events (iCVE) including MACE plus revascularisation, angina, transient ischaemic attack and peripheral arterial disease., Results: Over 26 534 patient-years, 239 MACE and 362 iCVE occurred. The interaction between 28-joint Disease Activity Score with C-reactive protein (DAS28-CRP) and bDMARD use was significant for MACE (p=0.017), suggesting the effect of DAS28-CRP on MACE risk differed among bDMARD users (n=515) and non-users (n=3855). DAS28-CRP (per unit increase) is associated with MACE risk in bDMARD non-users (HR 1.21 (95% CI 1.07 to 1.37)) but not users (HR 0.69 (95% CI 0.40 to 1.20)). The interaction between CRP (per log unit increase) and bDMARD use was also significant for MACE (p=0.011). CRP associated with MACE risk in bDMARD non-users (HR 1.16 (95% CI 1.04 to 1.30)), but not users (HR 0.65 (95% CI 0.36 to 1.17)). No interaction was observed between bDMARD use and DAS28-CRP (p=0.167) or CRP (p=0.237) for iCVE risk., Conclusions: RA activity and inflammatory markers associated with risk of MACE in bDMARD non-users but not users suggesting the possibility of biological-specific benefits locally on arterial wall independently of effects on systemic inflammation., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: Patients with early rheumatoid arthritis (RA) may present with more tender than swollen joints, which can persist. Elevated tender-swollen joint difference (TSJD) is often challenging, because there may be multiple causes and it may contribute to overestimating disease activity. Little is known about the phenotype and impact of TSJDs on patient function. Our objective was to evaluate the impact of TSJD on functional outcomes in early RA and to see whether associations vary by joint size., Methods: Data were from patients with active, early RA (≤12 months) enrolled in the Canadian Early Arthritis Cohort, who completed assessments of general function (Multidimensional Health Assessment Questionnaire [MDHAQ]), upper extremity (UE) function (Quality of Life in Neurological Disorders [Neuro-QoL] UE scale), and work/activity impairment (Work Productivity and Activity Impairment RA) over their first year of follow-up. A total of 28 joint counts were performed. TSJDs were calculated. Adjusted associations between TSJDs and functional outcomes were estimated in separate multivariable linear mixed effects models. Separate analyses were performed for large- versus small-joint TSJD., Results: Patients (N = 547) were 70% female, mean age 56 (SD 15) years, mean disease duration 5.3 (SD 2.9) months. At baseline, 287 (52%) had TSJD >0 (43% involved large joints and 34% small joints), decreasing to 32% at 12 months. A one-point increase in TSJD was significantly associated with worse function (MDHAQ: adjusted mean change 0.10, 95% confidence interval [CI] 0.08-0.13; Neuro-QoL UE function T score: adjusted mean change -0.59, 95% CI -0.76 to -0.43; and greater work impairment: adjusted mean change 1.95%, 95% CI 0.85%-3.05%). Higher large-joint TSJDs were associated with the worst functional outcomes., Conclusion: Having more tender than swollen joints is common in early RA and is associated with worse function, most notably when involving large joints. Early identification and targeted intervention strategies may be needed., (© 2024 The Authors. ACR Open Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)

Objective: To assess whether using ultrasound (US) in addition to clinical information versus only clinical information in a treat-to-target (T2T) strategy leads to more clinical remission and to less radiographic progression in RA., Methods: Patients with RA from the 2-year prospective BIODAM cohort were included. Clinical and US data (US7-score) were collected every 3 months and hands and feet radiographs every 6 months. At each visit, it was decided whether patients were treated according to the clinical definition of T2T with DAS44 remission as benchmark (T2T-DAS44). T2T-DAS44 was correctly applied if: (i) DAS44 remission had been achieved or (ii) if not, treatment was intensified. A T2T strategy also considering US data (T2T-DAS44-US) was correctly applied if: (i) both DAS44 and US remission (synovitis-score < 2, Doppler-score = 0) were present; or (ii) if not, treatment was intensified. The effect of T2T-DAS44-US on attaining clinical remission and on change in Sharp-van der Heijde score compared to T2T-DAS44 was analysed., Results: A total of 1016 visits of 128 patients were included. T2T-DAS44 was correctly followed in 24% of visits and T2T-DAS44-US in 41%. DAS44 < 1.6 was achieved in 39% of visits. Compared to T2T-DAS44, using the T2T-DAS44-US strategy resulted in a 41% lower likelihood of DAS44 remission [OR (95% CI): 0.59 (0.40;0.87)] and had no effect on radiographic progression [β(95% CI): 0.11 (- 0.16;0.39)] assessed at various intervals up to 12 months later., Conclusion: Our results do not suggest a benefit of using the US7-score in addition to clinical information as a T2T benchmark compared to clinical information alone. Key Points • Ultrasound has a valuable role in diagnostic evaluation of rheumatoid arthritis, but it is unclear whether adding ultrasound to the clinical assessment in a treat-to-target (T2T) strategy leads to more patients achieving remission and reduction in radiographic progression. • Our data from a real-world study demonstrated that adding information from ultrasound to the clinical assessment in a T2T strategy led to a lower rather than a higher likelihood of obtaining clinical remission as compared to using only clinical assessment. • Our data demonstrated that adding ultrasound data to a T2T strategy based only on clinical assessment did not offer additional protection against radiographic progression in patients with RA. • Adding US to a T2T strategy based on clinical assessment led to far more treatment intensifications (with consequences for costs and exposure to adverse events) without yielding a meaningful clinical benefit., (© 2024. The Author(s), under exclusive licence to International League of Associations for Rheumatology (ILAR).)

Background: Psychiatric comorbidity is common in inflammatory bowel disease (IBD) and can negatively affect disease outcomes. We explored the perceived need for mental health care among persons with IBD., Study: Persons with IBD completed self-report questionnaires, including the Hospital Anxiety and Depression Scale (HADS), and reported whether they wanted help with their mood. Each was also assessed using the Structured Clinical Interview for DSM-IV-TR Axis-I Disorders (SCIDs). We used logistic regression analyses to determine factors associated with the perceived need for mental health care., Results: Of 245 participants, 28% met the criteria for a past diagnosis of depression or anxiety disorder by SCID, and nearly 23% met the criteria for a current diagnosis of depression or anxiety disorder. One-third (n = 74) reported a perceived need for mental health care. Among those meeting criteria for a current SCID diagnosis of depression or anxiety, only 58% reported needing mental health care. Need for mental health care was reported by 79% of persons currently treated for either depression or 71% treated for anxiety. Persons with a perceived need for mental health care had higher mean HADS for depression and HADS for anxiety scores and also higher IBD symptom activity scores. Of those reporting no perceived need for mental health care, 13% had a current diagnosis of depression or anxiety disorder by SCID; even fewer had symptoms of depression or anxiety., Conclusions: Symptoms of depression or anxiety are more important than a formal diagnosis of depression or anxiety in predicting which persons with IBD will perceive a need for mental health care., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: Immune-mediated inflammatory diseases (IMID), such as multiple sclerosis (MS), inflammatory bowel disease (IBD) or rheumatoid arthritis (RA) have high rates of elevated anxiety symptoms. This can may worsen functioning and increase IMID disease burden. The rate of and factors associated with elevated anxiety symptoms may differ between males and females, which, in turn can affect diagnosis and disease management. We evaluated whether the frequency and factors associated with comorbid elevated anxiety symptoms in those with an IMID differed by sex., Methods: Participants with an IMID (MS, IBD or RA) completed two anxiety measures (HADS, GAD-7). We used logistic regression to investigate whether sex differences exist in the presence of comorbid elevated anxiety symptoms or in the endorsement of individual anxiety items in those with an IMID., Results: Of 656 participants, females with an IMID were more likely to have elevated anxiety symptoms compared to males (adjusted odds ratio [aOR] 2.05; 95%CI: 1.2, 3.6). Younger age, higher depressive symptoms and income were also associated with elevated anxiety symptoms in IMID. Lower income in males with an IMID, but not females, was associated with elevated anxiety symptoms (aOR: 4.8; 95%CI: 1.5, 15.6). No other factors demonstrated a sex difference. Males had nearly twice the odds of endorsing restlessness on the GAD-7 (OR = 1.8, 95%CI: 1.07, 3.15) compared to females., Discussion: We found evidence for sex differences in the factors associated with experiencing elevated anxiety symptoms in those with an IMID. These findings could be helpful to sensitize clinicians to monitor for comorbid anxiety symptoms in males with an IMID., Competing Interests: LG: consultant to Roche Canada (within last 36 months). RM receives research funding from: Canadian Institutes of Health Research, Research Manitoba, Multiple Sclerosis Society of Canada, Multiple Sclerosis Scientific Foundation, Crohn’s and Colitis Canada, National Multiple Sclerosis Society, Consortium of MS Centers, the Arthritis Society, US Department of Defense. She is supported by the Waugh Family Chair in Multiple Sclerosis. She is a co-investigator on a study funded in part by Biogen Idec and Roche (no funds to her or her institution). CB is supported in part by the Bingham Chair in Gastroenterology. He is on Advisory Boards for AbbVie Canada, Amgen Canada, Bristol Myers Squibb, Eli Lilly Canada, JAMP Pharmaceuticals, Janssen Canada, Pfizer Canada, Roche Canada, Sandoz Canada, Takeda Canada. He is a consultant for Mylan Pharmaceuticals and Takeda. He has received educational grants from AbbVie Canada, Pfizer Canada, Takeda Canada, Janssen Canada, and Bristol Myers Squibb Canada. He is on the speaker’s panel for AbbVie Canada, Janssen Canada, Pfizer Canada, and Takeda Canada. Received research funding from AbbVie Canada, Amgen Canada, Pfizer Canada, Sandoz Canada, and Takeda Canada. JF received research grant support from the Canadian Institutes of Health Research, the National Multiple Sclerosis Society, the Multiple Sclerosis Society of Canada, Crohn’s and Colitis Canada and Research Nova Scotia, and consultation and distribution royalties from MAPI Research Trust. All other authors report no disclosures related to this work. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Joyees, Marrie, Bernstein, Bolton, Fisk, Graff, Hitchon, Patten and Kowalec.)

Background: Differences in pain between subtypes of multiple sclerosis are understudied., Objective: To compare the prevalence of pain, and the association between pain and: (a) pain interference and (b) social participation in people with relapsing-remitting multiple sclerosis and progressive multiple sclerosis., Methods: Participants completed the McGill Pain Questionnaire Short-Form-2, Pain Effects Scale and Ability to Participate in Social Roles and Activities-V2.0 questionnaires. We tested the association between multiple sclerosis subtype, pain severity, and pain interference/social participation using quantile regression., Results: Of 231 participants (relapsing-remitting multiple sclerosis: 161, progressive multiple sclerosis: 70), 82.3% were women. The prevalence of pain was 95.2%, of more than mild pain was 38.1%, and of pain-related limitations was 87%; there were no differences between multiple sclerosis subtypes. Compared to participants with relapsing-remitting multiple sclerosis, those with progressive multiple sclerosis reported higher pain interference (mean (standard deviation) Pain Effects Scale; progressive multiple sclerosis: 15[6.0] vs relapsing-remitting multiple sclerosis: 13[5], p  = 0.039) and lower social participation (Ability to Participate in Social Roles and Activities T-scores 45[9.0] vs 48.3[8.9], p  = 0.011). However, on multivariable analysis accounting for age, physical disability, mood/anxiety and fatigue, multiple sclerosis subtype was not associated with differences in pain interference or social participation., Conclusions: Pain was nearly ubiquitous. Over one-third of individuals with relapsing-remitting multiple sclerosis and progressive multiple sclerosis reported pronounced pain, although this did not differ by multiple sclerosis subtype., Competing Interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: CNB is supported by the Bingham Chair in Gastroenterology. CNB has served on advisory Boards for AbbVie Canada, Amgen Canada, Bristol Myers Squibb Canada, JAMP Pharmaceuticals, Lilly Canada, Roche Canada, Janssen Canada, Sandoz Canada, Takeda Canada, and Pfizer Canada; Consultant for Mylan Pharmaceuticals and Takeda; Educational grants from Abbvie Canada, Pfizer Canada, Takeda Canada, and Janssen Canada. Speaker's panel for Abbvie Canada, Janssen Canada, Pfizer Canada, and Takeda Canada. Received research funding from Abbvie Canada, Amgen Canada, Sandoz Canada, Takeda Canada and Pfizer Canada. LAG has consulted for Roche Canada. She receives research funding from CIHR, the Multiple Sclerosis Society of Canada and Crohn's and Colitis Canada. JMB receives research funding from CIHR, Brain and Behavior Research Foundation, Crohn's and Colitis Canada and the MS Society of Canada. JDF receives research grant support from the Canadian Institutes of Health Research, the National Multiple Sclerosis Society, the Multiple Sclerosis Society of Canada, Crohn's and Colitis Canada, Research Nova Scotia; consultation and distribution royalties from MAPI Research Trust. CH receives research funding from CIHR, unrelated grant funding from Pfizer; Advisory board for Astra-Zeneca Canada for unrelated product, unrelated research funds from Research Manitoba, Health Sciences Center foundation, International League of Associations for Rheumatology, unrelated educational funds from the Royal College of Physicians and Surgeons of Canada. SBP receives research funding from CIHR, the MS Society of Canada, Roche, Biogen and the Government of Alberta. JJM has conducted trials for Biogen Idec and Roche, and receives research funding from the MS Society of Canada. RAM is a co-investigator on a study funded by Biogen Idec and Roche (no funds to her/her institution). Ruth Ann Marrie receives research funding from CIHR, Research Manitoba, Multiple Sclerosis Society of Canada, Multiple Sclerosis Scientific Foundation, Crohn's and Colitis Canada, National Multiple Sclerosis Society, CMSC, the Arthritis Society and the US Department of Defense, and is a co-investigator on studies receiving funding from Biogen Idec and Roche Canada. She holds the Waugh Family Chair in Multiple Sclerosis. DJ has no disclosures to report., (© The Author(s), 2023.)

Objective: To understand how people with chronic immune-mediated inflammatory diseases (IMIDs) trade off the benefits and risks of coronavirus disease 2019 (COVID-19) vaccine options., Methods: We conducted an online discrete-choice experiment in people with IMIDs to quantify the relative importance (RI) of attributes relevant to COVID-19 vaccination. Participants were recruited between May and August 2021 through patient groups and clinics in Canada, and completed 10 choices where they selected 1 of 2 hypothetical vaccine options or no vaccine. The RI of each attribute was estimated and heterogeneity was explored through latent class analysis., Results: The survey was completed by 551 people (89% female, mean age 46 yrs) with a range of IMIDs (inflammatory bowel disease [48%], rheumatoid arthritis [38%], systemic lupus erythematosus [16%]). Most had received 1 (94%) or 2 (64%) COVID-19 vaccinations. Across the ranges of levels considered, vaccine effectiveness was most important (RI = 66%), followed by disease flare (21%), rare but serious risks (9%), and number/timing of injections (4%). Patients would accept a risk of disease flare requiring a treatment change of ≤ 8.8% for a vaccine with a small absolute increase in effectiveness (10%). Of the 3 latent classes, the group with the greatest aversion to disease flare were more likely to be male and have lower incomes, but this group still valued effectiveness higher than other attributes., Conclusion: Patients perceived the benefits of COVID-19 vaccination to outweigh rare serious risks and disease flare. This supports COVID-19 vaccine strategies that maximize effectiveness, while recognizing the heterogeneity in preferences that exists., (Copyright © 2023 by the Journal of Rheumatology.)

Purpose: The Rheumatoid Arthritis Flare Questionnaire (RA-FQ) is a patient-reported measure of disease activity in RA. We estimated minimal and meaningful change from the perspective of RA patients, physicians, and using a disease activity index., Methods: Data were from 3- to 6-month visits of adults with early RA enrolled in the Canadian Early Arthritis Cohort. Participants completed the RA-FQ, the Patient Global Assessment of RA, and the Patient Global Change Impression at consecutive visits. Rheumatologists recorded joint counts and MD Global. Clinical Disease Activity Index (CDAI) scores were computed. We compared mean RA-FQ change across categories using patients, physicians, and CDAI anchors., Results: The 808 adults were mostly white (84%) women (71%) with a mean age of 55 and moderate-high disease activity (85%) at enrollment. At V2, 79% of patients classified their RA as changed; 59% were better and 20% were worse. Patients reporting they were a lot worse had a mean RA-FQ increase of 8.9 points, whereas those who were a lot better had a -6.0 decrease. Minimal worsening and improvement were associated with a mean 4.7 and - 1.8 change in RA-FQ, respectively, while patients rating their RA unchanged had stable scores. Physician and CDAI classified more patients as worse than patients, and minimal and meaningful RA-FQ thresholds differed by group., Conclusion: Thresholds to identify meaningful change vary by anchor used. These data offer new evidence demonstrating robust psychometric properties of the RA-FQ and offer guidance about improvement or worsening, supporting its use in RA care, research, and decision-making., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Objective: To develop group-based trajectories of depressive symptoms in immune-mediated inflammatory disease (IMID) to understand their evolution and identify any associated factors, with the overall goal of identifying those at highest risk of higher depressive symptom burden., Method: 922 participants had an IMID or anxiety/depression. The PHQ-9 was administered at four visits, and polygenic risk scores (PRS) for major depressive disorder, depressive symptoms, and body mass index (BMI) were generated. Group-based trajectory modelling of PHQ-9 scores estimated distinct trajectories. Regression tested whether specific factors were associated with the trajectories. Mediation analyses assessed whether IMID mediated the association between BMI PRS and trajectories., Results: Three trajectories were identified. Regression demonstrated those in Group 3 ('high symptoms') had significantly higher PRS for the three traits, compared to Group 1 ('minimal symptoms') (OR: 1.34-1.66, P < 0.01). Stratified analyses in the IMID subgroup revealed an increased effect for BMI PRS in Group 3 (OR: 2.31, P < 0.001), in contrast, BMI PRS was no longer associated in the non-IMID sample. No significant indirect effect of BMI PRS on depressive symptoms trajectories was identified via IMID., Conclusions: A significant association between polygenicity and PHQ-9 trajectories supports a role for genetic inheritance in the variability in depressive symptoms in IMID., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: Adults with rheumatoid arthritis (RA) are at a higher risk for infections, including influenza and related complications. We identified influenza vaccination coverage in adults newly diagnosed with RA and examined sociodemographic RA characteristics and attitudes associated with vaccination., Methods: We used data from patients enrolled in the Canadian Early Arthritis Cohort between September 2017 and February 2021. At enrollment, participants reported their vaccination status in the previous year and completed the Beliefs About Medicines Questionnaire (BMQ). Clinical data were obtained from medical records. Logistic regression was used to identify predictors of vaccination in the year after RA diagnosis., Results: The baseline analytic sample of 431 patients were mostly White (80%) women (67%) with a mean age of 56 (SD 14) years. Prediagnosis, influenza vaccine coverage was 38%, increasing to 46% post diagnosis in the longitudinal sample (n = 229). Participants with previous influenza vaccination (odds ratio [OR] 15.33; 95% confidence interval [CI] 6.37-36.90), on biologics or JAKs (OR 5.42; 95% CI 1.72-17.03), and with a higher change in BMQ Necessity-Concerns Differential scores (OR 1.08; 95% CI 1.02-1.15) had greater odds, whereas women (OR 0.32; 95% CI 0.14-0.71), participants with a non-White racial background (OR 0.13; 95% CI 0.04-0.51), and participants currently smoking (OR 0.09; 95% CI 0.02-0.37) had lower odds of influenza vaccine coverage., Conclusion: Influenza vaccination coverage in patients with early RA remains below national targets in adults living with a chronic condition. Discussing vaccine history and medication attitudes at initial clinic visits with new patients with RA may enhance vaccine acceptance and uptake., (© 2022 The Authors. ACR Open Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)

Background: We estimated COVID-19 vaccine effectiveness against SARS-CoV-2 infection and severe COVID-19 outcomes among individuals with immune-mediated inflammatory diseases in Ontario, Canada., Methods: In this population-based analysis, we used a test-negative design across four immune-mediated inflammatory disease population-based cohorts, comprising individuals with rheumatoid arthritis, ankylosing spondylitis, psoriasis, and inflammatory bowel disease. We identified all SARS-CoV-2 tests done in these populations between March 1 and Nov 22, 2021 (a period in which there was rapid uptake of vaccines, and the alpha [B.1.1.7] and delta [B.1.617.2] SARS-CoV-2 variants were predominantly circulating in Canada) and separately assessed outcomes of SARS-CoV-2 infection and severe COVID-19 outcomes (hospitalisation due to COVID-19 and death due to COVID-19) for each disease group. We used multivariable logistic regression to estimate the effectiveness of one, two, and three doses of mRNA-based COVID-19 vaccine (BNT162b2 [Pfizer-BioNTech], or mRNA-1273 [Moderna]) among individuals at the time of SARS-CoV-2 testing., Findings: Between March 1 and Nov 22, 2021, we identified 2127 (5·9%) test-positive cases among 36 145 individuals (26 476 [73·2%] were female and 9669 [26·8%] were male) with rheumatoid arthritis tested, 476 (6·1%) test-positive cases among 7863 individuals (4130 [52·5%] were female and 3733 [47·5%] were male) with ankylosing spondylitis tested, 3089 (6·5%) test-positive cases among 47 199 individuals (26 062 [55·2%] were female and 21 137 [44·8%] were male) with psoriasis tested, and 1702 (5·4%) test-positive cases among 31 311 individuals (17 716 [56·6%] were female and 13 595 [43·4%] were male) with inflammatory bowel disease tested. Adjusted vaccine effectiveness of two doses against infection was 83% (95% CI 80-86) in those with rheumatoid arthritis, 89% (83-93) among those with ankylosing spondylitis, 84% (81-86) among those with psoriasis, and 79% (74-82) among those with inflammatory bowel disease. After two vaccine doses, effectiveness against infection generally peaked 31-60 days after vaccination and waned gradually with each additional month. Vaccine effectiveness against severe outcomes after two doses was 92% (95% CI 88-95) in those with rheumatoid arthritis, 97% (83-99) among those with ankylosing spondylitis, 92% (86-95) among those with psoriasis, and 94% (88-97) among those with inflammatory bowel disease. Vaccine effectiveness after a third dose against infection was similar to or higher than after the second dose (ranging from 76% [47-89] to 96% [72-99]), although due to a paucity of events, estimates could not be calculated for some subgroups for severe outcomes., Interpretation: Two vaccine doses were found to be highly effective against both SARS-CoV-2 infection and severe COVID-19 outcomes in patients with rheumatoid arthritis, ankylosing spondylitis, psoriasis, and inflammatory bowel disease during the study period. Research is needed to determine the durability of effectiveness of three doses over time, particularly against emerging variants., Funding: Public Health Agency of Canada., Competing Interests: GGK has received honoraria for speaking or consultancy from AbbVie, Janssen, Pfizer, and Takeda; has received research support from Janssen, AbbVie, GlaxoSmithKline, Merck, Ferring, and Shire; has been a consultant for Gilead; and shares ownership of two patents (Treatment of inflammatory disorders, autoimmune disease, and PBC, UTI Limited Partnership, assignee. patent WO2019046959A1. PCT/CA2018/051098. Sept 7, 2018). EIB has acted as a legal consultant for Hoffman La-Roche and Peabody & Arnold, and consultant for McKesson Canada for matters unrelated to a medication used to treat inflammatory bowel disease or COVID-19 (ie, unrelated to the submitted work). LE reports grants from AbbVie, Novartis, UCB, Pfizer, and Eli Lilly. All other authors declare no competing interests., (© 2022 Elsevier Ltd. All rights reserved.)

Objective: Rheumatoid arthritis is a chronic inflammatory autoimmune disease that can lead to synovial damage, persistent joint pain, and functional disability. Our objective was to evaluate baseline synovial transcriptome from early inflammatory arthritis patients (EIA) and identify pretreatment biomarkers that could potentially provide insights into long-term functional outcomes of rheumatoid arthritis (RA)., Methods: Synovial biopsies from clinically inflamed knee joints were procured from either 17 EIA patients before initiation of disease modifying anti-rheumatic drug (DMARD) therapy (DMARD-naïve EIA) using the minimally invasive closed needle biopsy technique or advanced RA patients undergoing arthroplasty. Affymetrix Human Genome U133 Plus 2 microarray platform was used to profile the synovial transcriptome. The cohort was followed clinically for a median of 12.3 years, and patient data was collected at each visit. Short-term and long-term clinical outcomes were determined by assessing RA-associated clinical parameters Statistical adjustments were made to account for asynchronous clinical visits and duration of follow up., Results: Based on the transcriptomic analysis, we identified 5 differentially expressed genes (DEGs), including matrix metalloproteinase (MMP)-1 (fibroblast collagenase) and MMP-3 (stromelysin-1) in DMARD-naïve EIA patients, relative to advanced RA patients ( q < 0.05). Dichotomous expression of MMP-1 and MMP-3 mRNA and protein was confirmed by qPCR and immunohistochemistry respectively, based on which DMARD-naïve EIA subjects were classified as MMP-high or MMP-low. Hierarchical clustering of transcriptomic data identified 947 DEGs between MMP-high and MMP-low cohorts. Co-expression and IPA analysis of DEGs in the MMP-high cohort showed an enrichment of genes that participated in metabolic or biochemical functions and intracellular immune signaling were regulated through NF-κB and β-catenin complexes and correlated with markers of systemic inflammation. Analysis of short-term clinical outcomes in MMP-high cohort showed a significant reduction in the DAS-CRP scores relative to baseline (P <0.001), whereas area under the curve analyses of modified HAQ (mHAQ) scores correlated negatively with baseline MMP-1 ( R = -0.59, P = 0.03). Further, longitudinal mHAQ scores, number of swollen joints, number of DMARDs and median follow-up duration appeared to be higher in MMP-low cohort., Conclusion: Overall, our results indicate that the gene expression profiling of synovial biopsies obtained at the DMARD-naive stage in patients with EIA categorizes them into subsets with varying degrees of inflammation and can predict the future of long-term clinical outcome., Competing Interests: EH, RR, and PL are employed by Ampel BioSolutions, LLC. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Anaparti, Wiens, O'Neil, Hubbard, Robl, Smolik, Hitchon, Lipsky and El-Gabalawy.)

Objective: We assessed coronavirus disease 2019 (COVID-19) vaccine uptake among individuals with immune-mediated inflammatory diseases (IMIDs) and the Ontario general population., Methods: We studied all residents aged ≥ 16 years who were alive and enrolled in the Ontario Health Insurance Plan as of December 14, 2020, when vaccination commenced (n = 12,435,914). Individuals with rheumatoid arthritis (RA), ankylosing spondylitis (AS), psoriatic arthritis (PsA), psoriasis (PsO), and inflammatory bowel disease (IBD) were identified using established disease-specific case definitions applied to health administrative data. Vaccination status was extracted from the provincial COVaxON registry. Weekly cumulative proportions of first and second doses up until October 3, 2021, were expressed as the vaccinated percentage of each disease group, compared to the general Ontario population, and stratified by age., Results: By October 3, 2021, the cumulative percentage with at least 1 dose was 82.1% for the general population, 88.9% for those with RA, 87.4% for AS, 90.6% for PsA, 87.3% for PsO, and 87.0% for IBD. There was also a higher total cumulative percentage with 2 doses among IMIDs (83.8-88.2%) vs the general population (77.9%). The difference was also evident when stratifying by age. Individuals with IMIDs in the youngest age group initially had earlier uptake than the general population but remain the lowest age group with 2 doses (70.6% in the general population vs. 73.7-79.2% across IMID groups)., Conclusion: While implementation of COVID-19 vaccination programs has differed globally, these Canadian estimates are the first to reassuringly show higher COVID-19 vaccine uptake among individuals with IMIDs., (© 2022 by the Journal of Rheumatology.)

Objective: The aims of this study were (1) to compare grade 12 standardized test results of patients diagnosed with childhood-onset chronic rheumatic diseases (ChildCRD) and unaffected peers; and (2) to identify factors associated with test results of patients with ChildCRD and unaffected peers., Methods: This was a population-based retrospective cohort study. All patients with ChildCRD (juvenile arthritis and systemic autoimmune rheumatic diseases) from the only pediatric rheumatology center in Manitoba for birth cohorts January 1979 to December 1998 were linked to the provincial administrative databases containing records of healthcare use and education outcomes. Patients were matched by age, sex, and postal codes to their peers who did not have ChildCRD. The primary outcomes were the grade 12 Language Arts Achievement Index (LAI) and the Math Achievement Index (MAI) scores. ChildCRD, sociodemographic, and mental health factors were tested for their associations with LAI and MAI scores using multivariable linear regression., Results: Five hundred and forty-one patients with ChildCRD were matched to 2713 unaffected peers. Patients with ChildCRD had lower LAI and MAI scores compared to their peers. More patients with ChildCRD failed or did not take the language arts (51% vs 41%, P < 0.001) and math (61% vs 55%, P = 0.02) tests. On multivariable analysis, ChildCRD, lower socioeconomic status, younger maternal age at first childbirth, family income assistance, involvement with child welfare services, and mental health morbidities (between ChildCRD diagnosis and standardized testing), were associated with worse LAI and MAI results., Conclusion: This population-based study showed that patients with ChildCRD performed less well than their peers on grade 12 standardized testing, independent of sociodemographic and mental health comorbidities., (Copyright © 2022 by the Journal of Rheumatology.)

Background: Anti-citrullinated protein antibodies (ACPAs) are highly specific for rheumatoid arthritis (RA). In vivo, ACPAs target peptidyl-citrulline epitopes (cit-) in a variety of proteins (cit-prot-ACPAs) and derived peptides (cit-pept-ACPAs) generated via the peptidylarginine deiminase (PAD) isoenzymes. We aimed to identify a cell line with self-citrullination capacity, to describe its autoantigenic citrullinome, and to test it as a source of autocitrullinated proteins and peptides., Methods: Human cell lines were screened for cit-proteins by Western blot. PAD isoenzymes were identified by RT-PCR. Autocitrullination of ECV304 was optimized, and the ECV304 autocitrullinomes immunoprecipitated by sera from three RA patients were characterized by mass spectrometry. Cit-pept-ACPAs were detected using anti-CCP2 ELISA and cit-prot-ACPAs, by an auto-cit-prot-ECV304 ELISA. Sera from 177 RA patients, 59 non-RA rheumatic disease patients and 25 non-disease controls were tested., Results: Of the seven cell lines studied, only ECV304 simultaneously overexpressed PAD2 and PAD3 and its extracts reproducibly autocitrullinated self and non-self-proteins. Proteomic analysis of the cit-ECV304 products immunoprecipitated by RA sera, identified novel cit-targets: calreticulin, profilin 1, vinculin, new 14-3-3 protein family members, chaperones, and mitochondrial enzymes. The auto-cit-prot-ECV304 ELISA had a sensitivity of 50% and a specificity of 95% for RA diagnosis., Conclusions: ECV304 cells overexpress two of the PAD isoenzymes capable of citrullinating self-proteins. These autocitrullinated cells constitute a basic and clinical research tool that enable the detection of cit-prot-ACPAs with high diagnostic specificity and allow the identification of the specific cit-proteins targeted by individual RA sera., (© 2022. The Author(s).)

Objective: To determine whether childhood maltreatment is associated with immune-mediated inflammatory disorders (IMIDs; multiple sclerosis [MS], inflammatory bowel disease [IBD], and rheumatoid arthritis [RA]). We further aimed to determine the relationship between maltreatment and psychiatric comorbidity in IMIDs and whether these relationships differed across IMID., Methods: Six hundred eighty-one participants (MS, 232; IBD, 216; RA, 130; healthy controls, 103) completed a structured psychiatric interview to identify psychiatric disorders, and the Childhood Trauma Questionnaire to evaluate five types of maltreatment: emotional abuse, physical abuse, sexual abuse, emotional neglect, and physical neglect. We evaluated associations between maltreatment, IMID, and psychiatric comorbidity using multivariable logistic regression models., Results: The prevalence of having ≥1 maltreatment was similar across IMID but higher than in controls (MS, 63.8%; IBD, 61.6%; RA, 62.3%; healthy controls, 45.6%). Emotional abuse was associated with having an IMID (adjusted odds ratio [aOR] = 2.37; 1.15-4.89). In the sex-specific analysis, this association was only present in women. History of childhood maltreatment was associated with a lifetime diagnosis of a psychiatric disorder in the IMID cohort (OR = 2.24; 1.58-3.16), but this association did not differ across diseases. In those with IMID, total types of maltreatments (aOR = 1.36; 1.17-1.59) and emotional abuse (aOR = 2.64; 1.66-4.21) were associated with psychiatric comorbidity., Conclusions: Childhood maltreatment is more common in IMID than in a healthy population and is associated with psychiatric comorbidity. Given the high burden of psychiatric disorders in the IMID population, clinicians should be aware of the contribution of maltreatment and the potential need for trauma-informed care strategies., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Psychosomatic Society.)

Objective: To describe patterns of glucocorticoid use in a large real-world cohort with early rheumatoid arthritis (RA) and assess the impact on disease activity and treatment., Methods: Data are from adults with new RA (≤1 year) recruited to the Canadian Early Arthritis Cohort (CATCH) and are stratified on the basis of whether a person was prescribed oral glucocorticoids within 3 months of study entry. Disease activity was compared over 24 months. Mixed-effects logistic regression was used for adjusted odds ratios (aORs) of escalation to biologics separately for 12 and 24 months, with random effects terms to account for prescribing patterns clustering by study site., Results: Among 1891 persons, 30% received oral steroids. Users were older, were less often employed, and had shorter disease duration and higher disease activity. Disease activity improved over time, with early glucocorticoid users starting at higher levels of disease activity. Participants with early oral glucocorticoids were more likely to be on a biologic at 12 months (aOR = 2.4; 95% confidence interval [CI], 1.5-3.7) and 24 months (aOR = 1.9; 95% CI, 1.3-3.0). Despite Canadian clinical practice guidelines to limit corticosteroid use to short-term or 'bridge' therapy, 30% of patients who used oral glucocorticoids still used them 2 years later., Conclusion: Early steroids were prescribed sparingly in CATCH and were often indicative of more active baseline disease as well as the need for progression to biologics., (© 2021 The Authors. ACR Open Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)

Objective: In this study, we aimed to determine the lifetime prevalence of substance use disorder (SUD) in a Canadian rheumatoid arthritis (RA) cohort and factors associated with SUD in RA., Methods: Participants with RA (N = 154) were recruited via rheumatology clinics as part of a larger cohort study of psychiatric comorbidity in immune-mediated inflammatory diseases. SUD is defined as the uncontrolled use of a substance despite the harmful consequences of its use. To identify lifetime SUD, the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition was administered to participants. Participants' sociodemographic and RA clinical characteristics were also assessed. We examined factors associated with lifetime SUD using unadjusted and adjusted logistic regression modeling., Results: Twenty-three (14.9%) of 154 participants with RA met the criteria for a lifetime diagnosis of SUD. The majority of the participants were women, were White, had postsecondary education, and were on a disease-modifying antirheumatic drug. Factors associated with increased odds of SUD were male sex (adjusted odds ratio [aOR]: 3.63, 95% confidence interval [CI]: 1.03-12.73), younger age (aOR: 0.94, 95% CI: 0.90-0.98), and ever smoking (aOR: 6.44, 95% CI: 1.53-27.07)., Conclusion: We found that approximately 1 in 7 individuals with RA had a lifetime diagnosis of SUD, highlighting the importance of identifying and treating SUD in those with RA. In particular, the following factors were associated with higher odds of SUD: male sex, younger age, and smoking behaviors., (© 2021 The Authors. ACR Open Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)

Objective: To develop guidance on the use of coronavirus disease 2019 (COVID-19) vaccines in patients with autoimmune rheumatic diseases (ARD)., Methods: The Canadian Rheumatology Association (CRA) formed a multidisciplinary panel including rheumatologists, researchers, methodologists, vaccine experts, and patients. The panel used the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) approach. Outcomes were prioritized according to their importance for patients and clinicians. Evidence from the COVID-19 clinical trials was summarized. Indirect evidence for non-COVID-19 vaccines in ARD was also considered. The GRADE evidence-to-decision (EtD) framework was used to develop a recommendation for the use of the 4 COVID-19 vaccines approved in Canada as of March 25, 2021 (BNT162b2, mRNA-1273, ChAdOx1, and Ad26.COV2.S), over 4 virtual panel meetings., Results: The CRA guideline panel suggests using COVID-19 vaccination in persons with ARD. The panel unanimously agreed that for the majority of patients, the potential health benefits of vaccination outweigh the potential harms in people with ARDs. The recommendation was graded as conditional because of low or very low certainty of the evidence on the effects in the population of interest, primarily due to indirectness and imprecise effect estimates. The panel felt strongly that persons with autoimmune rheumatic diseases who meet local eligibility should not be required to take additional steps compared to people without ARDs to obtain their vaccination. Guidance on medications, implementation, monitoring of vaccine uptake, and research priorities are also provided., Conclusion: This recommendation will be updated over time as new evidence emerges, with the latest recommendation, evidence summaries, and EtD available on the CRA website., (© 2021 The Journal of Rheumatology.)