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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.
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Vacinas contra COVID-19 , COVID-19 , Humanos , Feminino , Masculino , COVID-19/prevenção & controle , COVID-19/imunologia , COVID-19/epidemiologia , Pessoa de Meia-Idade , Vacinas contra COVID-19/imunologia , Vacinas contra COVID-19/uso terapêutico , Adulto , Idoso , SARS-CoV-2/imunologia , Anticorpos Antivirais/sangue , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Vacinação , Lúpus Eritematoso Sistêmico/imunologia , Lúpus Eritematoso Sistêmico/sangue , Doenças Inflamatórias Intestinais/imunologia , Doenças Inflamatórias Intestinais/tratamento farmacológico , Doenças Inflamatórias Intestinais/sangueRESUMO
BACKGROUND: Thrombotic events, such as venous thromboembolism (VTE) are a major health complication linked to rheumatoid arthritis (RA). We performed a meta-analysis to evaluate the risk of VTE, including deep vein thrombosis (DVT) and pulmonary embolism (PE), in adults with RA compared to the general population. METHODS: MEDLINE and EMBASE databases were searched from inception to April 2022 to identify publications meeting the following criteria: (1) prospective and retrospective original data from cohort or case-control studies; (2) pre-specified RA definition; (3) clearly defined VTE outcomes; (4) reported risk estimate and 95% confidence intervals (95% CIs); (5) at least sex- and age-matched to comparison group; and (6) English language. Of 372 studies screened, 14 were included (602,760 RA patients, 123,076 VTE events) and their quality was assessed by an adaptation of the STROBE quality scoring scale. RESULTS: The pooled risk ratios of VTE, DVT and PE in patients with RA were 1.57 (95% CI 1.41-1.76), 1.58 (95% CI 1.26-1.97) and 1.57 (95% CI 1.30-1.88), respectively. The I2 value of 92%, 94% and 92% for VTE, DVT and PE analyses, suggesting considerable heterogeneity. There were no significant differences in risk estimates among the five subgroup analyses: quality score (P = 0.35, I2 = 0%); sex (P = 0.31, I2 = 1.7%); study year (P = 0.81, I2 = 0%); population source (P = 0.35, I2 = 0%); study design (P = 0.62, I2 = 0%). CONCLUSIONS: Results show that patients with RA are at a higher risk of VTE, DVT and PE compared to the general population.
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OBJECTIVE: To assess the risk of all-cause mortality and major adverse cardiovascular events (MACE) in patients with immune-mediated inflammatory diseases (IMIDs) and type 2 diabetes newly initiating glucagon-like peptide-1 receptor agonists (GLP-1-RAs) versus dipeptidyl peptidase-4 inhibitors (DPP-4is). METHODS: We performed a population-based cohort study using administrative health data from British Columbia. Patients with an IMID (i.e., rheumatoid arthritis, psoriatic disease, ankylosing spondylitis, inflammatory bowel disease, or a systemic autoimmune rheumatic disease) and type 2 diabetes who newly initiated a GLP-1-RA or DPP-4i between January 1, 2010, and December 31, 2021 were identified using ICD-9/10 codes. The primary outcome was all-cause mortality. Secondary outcomes included MACE and its components (i.e., cardiovascular death, myocardial infarction, and ischemic stroke). Cox proportional hazard regressions were used with propensity score overlap weighting. The analysis was repeated in age- and sex-matched adults without IMIDs. RESULTS: We identified 10,855 adults with IMIDs and type 2 diabetes who newly initiated a GLP-1-RA or DPP-4i. All-cause mortality rate was lower among initiators of GLP-1-RAs compared to initiators of DPP-4is, with a weighted hazard ratio (HR) of 0.48 (95% confidence interval [CI], 0.31-0.75) and rate difference (RD) of -9.4 (95% CI, -16.0 to -2.7) per 1000 person-years. Rate of MACE was also lower with GLP-1-RA exposure (HR 0.66 [0.50-0.88], RD -10.5 [-20.4 to -0.8]). Effect sizes were similar in adults without IMIDs. CONCLUSION: In patients with IMIDs and type 2 diabetes, GLP-1-RA exposure is associated with a lower risk of all-cause mortality and MACE compared to a cardioneutral active comparator.
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Doenças Cardiovasculares , Diabetes Mellitus Tipo 2 , Receptor do Peptídeo Semelhante ao Glucagon 1 , Humanos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/mortalidade , Feminino , Masculino , Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas , Pessoa de Meia-Idade , Idoso , Doenças Cardiovasculares/mortalidade , Inibidores da Dipeptidil Peptidase IV/uso terapêutico , Inibidores da Dipeptidil Peptidase IV/efeitos adversos , Adulto , Inflamação , Estudos de Coortes , Hipoglicemiantes/uso terapêutico , Hipoglicemiantes/efeitos adversos , Colúmbia Britânica/epidemiologia , Modelos de Riscos ProporcionaisRESUMO
OBJECTIVE: The study objective was to describe patterns of depression and anxiety health care use before and after diagnosis among patients with inflammatory arthritis (IA), namely, ankylosing spondylitis, psoriatic arthritis, and rheumatoid arthritis. METHODS: We used population-based linked administrative health data from British Columbia, Canada, to build a cohort of individuals (≥18 years) with incident IA and individuals without IA ("IA-free controls") matched on age and sex. We computed the proportion of individuals with IA and controls who had one or more depression or one or more anxiety health care encounters and the use of one or more antidepressants or one or more anxiolytics in each yearly interval five years before and after IA diagnosis. We used multivariable logistic regression models to evaluate the association between IA status and aforementioned depression and anxiety health care use outcomes in each yearly interval. RESULTS: A total of 80,238 individuals with IA (62.9% female; mean ± SD age 56.2 ± 16.7 years) and 80,238 IA-free controls (62.9% female; mean ± SD age 56.2 ± 16.6 years) were identified between January 1, 2001, and March 31, 2018. Individuals with IA had significantly increased odds of depression and anxiety health care encounters and dispensation of antidepressants and anxiolytics for each yearly interval before and after diagnosis. Adjusted odds ratios (ORs) were highest in the year immediately before (one or more depression visits: adjusted OR 1.61, 95% confidence interval [CI] 1.55-1.66; one or more anxiolytics: adjusted OR 1.71, 95% CI 1.66-1.77) or after (one or more antidepressants: adjusted OR 1.95, 95% CI 1.89-2.00) IA diagnosis. CONCLUSION: Findings suggest a role for depression and anxiety in characterizing the IA prodrome period and generate hypotheses regarding overlapping biopsychosocial processes that link IA and mental health comorbidities.
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Importance: Sodium-glucose cotransporter type 2 inhibitors (SGLT2i) are a revolutionary treatment for type 2 diabetes (T2D) with cardiovascular, kidney, and serum urate-lowering benefits. Objective: To compare risk of incident gout and rate of recurrent flares between patients with T2D initiating SGLT2i vs sulfonylurea, most common second-line glucose-lowering therapy, when added to metformin monotherapy. Design, Setting, and Participants: This sequential, propensity score-matched, new-user comparative effectiveness study using target trial emulation framework included adults with T2D receiving metformin monotherapy in a Canadian general population database from January 1, 2014, to June 30, 2022. Exposures: Initiation of SGLT2i vs sulfonylurea. Main Outcomes and Measures: The primary outcome was incident gout diagnosis, ascertained by emergency department (ED), hospital, outpatient, and medication dispensing records. Secondary outcomes were gout-primary hospitalizations and ED visits and major adverse cardiovascular events (MACE), as well as recurrent flare rates among prevalent gout patients. Heart failure (HF) hospitalization was assessed as positive control outcome and osteoarthritis encounters as negative control. For target trial emulations, we used Cox proportional hazards and Poisson regressions with 1:1 propensity score matching (primary analysis) and overlap weighting (sensitivity analysis). The analysis was conducted from September to December, 2023. Results: Among 34â¯604 propensity score matched adults with T2D initiating SGLT2i or sulfonylurea (20â¯816 [60%] male, mean [SD] age, 60 [12.4] years), incidence of gout was lower among SGLT2i initiators (4.27 events per 1000 person-years) than sulfonylurea initiators (6.91 events per 1000 person-years), with a hazard ratio (HR) of 0.62 (95% CI, 0.48-0.80) and a rate difference (RD) of -2.64 (95% CI, -3.99 to -1.29) per 1000 person-years. Associations persisted regardless of sex, age, or baseline diuretic use. SGLT2i use was also associated with fewer recurrent flares among gout patients (rate ratio, 0.67; 95% CI, 0.55-0.82; and RD, -20.9; 95% CI, -31.9 to -10.0 per 1000 person-years). HR and RD for MACE associated with SGLT2i use were 0.87 (95% CI, 0.77-0.98) and -3.58 (95% CI, -6.19 to -0.96) per 1000 person-years. For control outcomes, SGLT2i users had lower risk of HF (HR, 0.53; 95% CI, 0.38-0.76), as expected, with no difference in osteoarthritis (HR, 1.11; 95% CI, 0.94-1.34). Results were similar when applying propensity score overlap weighting. Conclusions: In this population-based cohort study, the gout and cardiovascular benefits associated with SGLT2i in these target trial emulations may guide selection of glucose-lowering therapy in patients with T2D, at risk for or already with gout.