When Should I Get My Next COVID-19 Vaccine? Data From the Surveillance of Responses to COVID-19 Vaccines in Systemic Immune-Mediated Inflammatory Diseases (SUCCEED) Study.

OBJECTIVE: To determine how serologic responses to coronavirus disease 2019 (COVID-19) vaccination and infection in immune-mediated inflammatory disease (IMID) are affected by time since last vaccination and other factors. METHODS: Post-COVID-19 vaccination, data, and dried blood spots or sera were collected from adults with rheumatoid arthritis, inflammatory bowel disease, systemic lupus erythematosus, ankylosing spondylitis and spondylarthritis, and psoriasis and psoriatic arthritis. The first sample was collected at enrollment, then at 2 to 4 weeks and 3, 6, and 12 months after the latest vaccine dose. Multivariate generalized estimating equation regressions (including medications, demographics, and vaccination history) evaluated serologic response, based on log-transformed anti-receptor-binding domain (RBD) IgG titers; we also measured antinucleocapsid (anti-N) IgG. RESULTS: Positive associations for log-transformed anti-RBD titers were seen with female sex, number of doses, and self-reported COVID-19 infections in 2021 to 2023. Negative associations were seen with prednisone, anti-tumor necrosis factor agents, and rituximab. Over the 2021-2023 period, most (94%) of anti-N positivity was associated with a self-reported infection in the 3 months prior to testing. From March 2021 to February 2022, anti-N positivity was present in 5% to 15% of samples and was highest in the post-Omicron era, with antinucleocapsid positivity trending to 30% to 35% or higher as of March 2023. Anti-N positivity in IMID remained lower than Canada's general population seroprevalence (> 50% in 2022 and > 75% in 2023). Time since last vaccination was negatively associated with log-transformed anti-RBD titers, particularly after 210 days. CONCLUSION: Ours is the first pan-Canadian IMID assessment of how vaccine history and other factors affect serologic COVID-19 vaccine responses. These findings may help individuals personalize vaccination decisions, including consideration of additional vaccination when > 6 months has elapsed since last COVID-19 vaccination/infection.

Serologic phenotypes distinguish systemic lupus erythematosus patients developing interstitial lung disease and/or myositis.

OBJECTIVES: To determine if serologic phenotypes could be identified in systemic lupus erythematosus patients developing interstitial lung disease (ILD) and/or myositis. METHODS: Adult SLE patients (without myositis/ILD at baseline) had annual assessments and serum sampling between 2000 and 2017. New-onset ILD was identified using the SDI pulmonary fibrosis item. New-onset myositis was identified using the SLICC Damage Index muscle atrophy/weakness item, the SLEDAI-2K item for myositis, and annual creatinine kinase testing. Chart review confirmed ILD/myositis cases and randomly sampled SLE patients from baseline formed our sub-cohort (N = 72). Cases and sub-cohort were compared regarding myositis-related biomarkers at baseline and at a randomly selected follow-up between baseline and end of observation (date of ILD/myositis diagnosis or Dec. 31, 2017). Descriptive analyses and hazards ratios (HRs) were generated for ILD/myositis incidence, focusing on baseline serology and adjusting for sex, race/ethnicity, age at SLE diagnosis, and SLE duration. RESULTS: Fourteen SLE patients developed ILD (N = 9), myositis (N = 3), and/or both (N = 2). Thirteen of those (92.9%) developing ILD/myositis had at least one biomarker at baseline, versus 47 (65.3%) SLE patients who never developed myositis/ILD. The most common biomarkers in myositis/ILD were KL-6, anti-Ro52, and anti-Ku. Baseline biomarkers tended to remain positive in follow-up. In multivariate Cox regressions, SLE patients had higher risk of developing myositis/ILD with elevated baseline KL-6 (adjusted hazard ratio 3.66; 95% confidence interval 1.01, 13.3). When updating biomarkers over time, we also saw correlations between anti-Smith and ILD/myositis. CONCLUSIONS: Baseline myositis-related biomarkers were highly associated with ILD/myositis incidence. This is the first identification of biomarker phenotypes with ILD/myositis risk in SLE.

Clinical Significance of Raynaud Phenomenon in Systemic Lupus Erythematosus.

OBJECTIVE: There are limited reports of the clinical significance of Raynaud phenomenon (RP) in systemic lupus erythematosus (SLE), with some suggesting RP is associated with less severe lupus. Since most prior studies were small and/or focused on a specific race/ethnic demographic, it is unclear if those results are generalizable. We evaluated whether RP was associated with demographic and clinical factors in a large multiethnic SLE cohort. METHODS: We studied Montreal General Hospital SLE cohort patients who are followed with standardized annual assessments. We included patients with at least 1 visit across 2011-2018 and assessed demographic and clinical variables (using the 1997 American College of Rheumatology criteria and the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index) at their first visit. We present multivariate logistics regression analyses of cross-sectional associations between these variables and RP in SLE. RESULTS: Of 489 SLE patients, most were female (n = 445, 91%). Mean age at SLE diagnosis was 31.5 (standard deviation, 13.5) years, and 169 (34.6%) had RP. In our fully adjusted model, female sex (odds ratio [OR], 2.43; 95% confidence interval [CI], 1.07-6.03), White race/ethnicity (OR, 1.85; 95% CI, 1.10-3.17), neurological/neuropsychiatric manifestations (OR, 1.98; 95% CI, 1.10-3.56), and anti-RNP antibodies (OR, 3.03; 95% CI, 1.73-5.38) were positively associated with RP, whereas hemolytic anemia and cellular casts were negatively associated. CONCLUSIONS/DISCUSSION: Over one third of our large multiethnic North American SLE cohort had RP. This study confirmed associations between RP and a specific SLE phenotype.

Duration of Postvaccination Neutralizing Antibodies to SARS-CoV-2 and Medication Effects: Results from the Safety and Immunogenicity of COVID-19 Vaccination in Systemic Immune-Mediated Inflammatory Diseases Cohort Study.

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.

Retinal toxicity in a multinational inception cohort of patients with systemic lupus on hydroxychloroquine.

OBJECTIVE: To evaluate hydroxychloroquine (HCQ)-related retinal toxicity in the Systemic Lupus International Collaborating Clinics (SLICC) inception cohort. METHODS: Data were collected at annual study visits between 1999 and 2019. We followed patients with incident SLE from first visit on HCQ (time zero) up to time of retinal toxicity (outcome), death, loss-to-follow-up or end of study. Potential retinal toxicity was identified from SLICC Damage Index scores; cases were confirmed with chart review. Using cumulative HCQ duration as the time axis, we constructed univariate Cox regression models to assess if covariates (ie, HCQ daily dose/kg, sex, race/ethnicity, age at SLE onset, education, body mass index, renal damage, chloroquine use) were associated with HCQ-related retinal toxicity. RESULTS: We studied 1460 patients (89% female, 52% white). Retinal toxicity was confirmed in 11 patients (incidence 1.0 per 1000 person-years, 0.8% overall). Average cumulative time on HCQ in those with retinal toxicity was 7.4 (SD 3.2) years; the first case was detected 4 years after HCQ initiation. Risk of retinal toxicity was numerically higher in older patients at SLE diagnosis (univariate HR 1.05, 95% CI 1.01 to 1.09). CONCLUSIONS: This is the first assessment of HCQ and retinal disease in incident SLE. We did not see any cases of retinopathy within the first 4 years of HCQ. Cumulative HCQ may be associated with increased risk. Ophthalmology monitoring (and formal assessment of cases of potential toxicity, by a retinal specialist) remains important, especially in patients on HCQ for 10+ years, those needing higher doses and those of older age at SLE diagnosis.

Treatment patterns and control of hypertension in systemic lupus erythematosus (SLE): a cross-sectional study.

OBJECTIVE: Hypertension (HTN) is common in systemic lupus erythematosus (SLE), representing a key risk factor for cardiovascular and renal disease. We described HTN treatment patterns in SLE, evaluated uncontrolled HTN according to Canadian and American guidelines and identified factors associated with uncontrolled HTN. METHODS: We performed a cross-sectional study, identifying all McGill Lupus Clinic registry patients with an annual visit between January 2017 and May 2019 who were taking HTN medications. We excluded those taking medications only for another indication (eg, Raynaud's). We determined the frequency of uncontrolled HTN according to Canadian and American College of Cardiology/American Heart Association guidelines. Multivariate logistic regression (adjusted for age, sex and race/ethnicity) evaluated if uncontrolled HTN was more common with high body mass index (BMI), longer SLE duration, high disease activity, renal damage, multiple concomitant antihypertensives, prednisone and non-steroidal anti-inflammatory drugs. RESULTS: Of 442 patients with SLE, 108 were taking medications to treat HTN, and 38 took multiple medications concurrently. Angiotensin-receptor blockers were most common, followed by calcium channel blockers, diuretics, angiotensin-converting enzyme inhibitors and beta blockers. Among the 108 patients, 39.8% (n=43) had blood pressure (BP) >140/90 mm Hg, while 66.7% (n=72) had BP >130/80 mm Hg. In multivariate analyses, uncontrolled HTN (>130/80 mm Hg) was more likely in Caucasians (OR 2.72, 95% CI 1.12 to 6.78) and patients with higher BMI (OR 1.08, 95% CI 1.00 to 1.19). Patients with renal damage had better HTN control (OR 0.39, 95% CI 0.16 to 0.97). We could not draw definitive conclusions regarding other variables. CONCLUSION: Caucasians and patients with higher BMI had more uncontrolled HTN. The negative association with renal damage is reassuring, as controlled BP is key for renal protection.

Marital status and age of systemic lupus erythematous diagnosis: the potential for differences related to sex and gender.

OBJECTIVES: Chronic rheumatic diseases can challenge social and family relationships. We compared marital status in patients with systemic lupus erythematous (SLE) with their general population counterparts, stratified by sex and age of SLE onset. METHODS: We performed a cross-sectional analysis of a cohort of 382 patients with SLE at our centre (349 females, 33 males). We determined how many were married or living common-law at the time of last study visit. Patients were then divided into: SLE diagnosis before 18, between 18 and 30, between 31 and 44 and after 45 years of age. We then compared marital status among male and female patients with SLE, to Quebec age-specific marital statistics. RESULTS: Of 382 patients with SLE, 202 (52.9%) were married or living common-law, which was 9% lower than general population rates (95% CI 2% to 16%). One-third of women with paediatric-onset SLE were married or living common-law, which was 28% lower than their general population counterparts (95% CI 6% to 46%). Half of women diagnosed between age 18 and 30 were married or living common law, which was 14% less than general population rates (95% CI 4% to 25%). We could not establish significant differences for women diagnosed after age 30, or for males, versus their general population counterparts. CONCLUSIONS: Women diagnosed with SLE before age 30 were less likely to be married/living common-law, versus general population rates. This was not apparent for those diagnosed later in life. We did not clearly establish this effect in males, possibly due to power issues (vs a true effect of sex/gender). Additional studies (eg, focus groups) could elucidate reasons for our findings.