Antibody and T cell responses to SARS-CoV-2 mRNA vaccines during maintenance therapy for immune-mediated inflammatory diseases

BackgroundLimited information is available on the impact of immunosuppressants on COVID-19 vaccination in patients with immune-mediated inflammatory diseases (IMID). MethodsThis observational cohort study examined the immunogenicity of SARS-CoV-2 mRNA vaccines in adult patients with inflammatory bowel disease, rheumatoid arthritis, ankylosing spondylitis, or psoriatic disease, with or without maintenance immunosuppressive therapies. Antibody and T cell responses to SARS-COV-2, including neutralization against SARS-CoV-2 variants were determined before and after 1 and 2 vaccine doses. ResultsWe prospectively followed 150 subjects, 26 healthy controls, 9 IMID patients on no treatment, 44 on anti-TNF, 16 on anti-TNF with methotrexate/azathioprine (MTX/AZA), 10 on anti-IL-23, 28 on anti-IL-12/23, 9 on anti-IL-17, and 8 on MTX/AZA. Antibody and T cell responses to SARS-CoV-2 were detected in all participants, increasing from dose 1 to dose 2 and declining 3 months later, with greater attrition in IMID patients compared to healthy controls. Antibody levels and neutralization efficacy against variants of concern were substantially lower in anti-TNF treated patients than in healthy controls and were undetectable against Omicron by 3 months after dose 2. ConclusionsOur findings support the need for a third dose of mRNA vaccine and for continued monitoring of immunity in these patient groups. FundingFunded by a donation from Juan and Stefania Speck and by Canadian Institutes of Health (CIHR) /COVID-Immunity Task Force (CITF) grants VR-1 172711 and VS1-175545 (T.H.W. and A.C.G); CIHR FDN-143250 (T.H.W.), GA2-177716 (V.C., A.C.G., T.W.), GA1-177703 (A.C.G.) and the CIHR rapid response network to SARS-CoV-2 variants, CoVaRR-Net (to A.C.G.).

Bone Mineral Density and Fracture Risk in Ankylosing Spondylitis: A Meta-Analysis.

We conducted a meta-analysis of studies to examine the risk of vertebral and non-vertebral fractures in patients with ankylosing spondylitis (AS). Additionally, we evaluated the risk factors of vertebral fractures in AS. Two authors independently searched Embase and Medline for studies that had assessed the risk of fractures in patients with AS. Twenty-two studies were eligible for the meta-analysis. Patients with AS had high frequency of vertebral fractures [OR (95% CI): 1.96 (1.52-2.51)]. Major risk factors for vertebral fractures in patients with AS include low BMD at the femoral neck and total hip, male gender, longer disease duration, higher BASDAI, higher BASRI, and possibly inflammatory bowel disease. The risk of non-vertebral fractures [OR (95% CI) 1.10 (1.04-1.15)] was 10% higher in AS patients than in controls. The risk of hip fractures in AS patients was not statistically significant [OR (95% CI) 1.17 (0.71-1.92)] in our pooled analysis. We found that patients with AS are at high risk of vertebral fractures. Male sex, duration of AS, mSASSS, BASRI, and low BMD at the hip and distal forearm were associated with the risk of vertebral fractures. Current evidence on the risk of hip fractures in patients with AS is inconsistent. Data about the effect of NSAIDs and TNF inhibitors on fracture risk in AS are limited.

Alterations of bone mineral density, bone microarchitecture and strength in patients with ankylosing spondylitis: a cross-sectional study using high-resolution peripheral quantitative computerized tomography and finite element analysis.

INTRODUCTION: Ankylosing spondylitis (AS) is an inflammatory disease associated with new bone formation and an increased risk of osteoporosis and fractures. The negative effects of AS on bone microarchitecture and strength are unclear. Thus, we conducted an observational study to analyze the effect of AS on bone microarchitecture and strength. METHODS: Patients with AS (n = 53) and non-AS subjects (n = 85) were recruited for the study. All subjects underwent clinical evaluation, DXA and high-resolution peripheral quantitative CT scans (HRpQCT). RESULTS: The AS patients were aged 44 ± 12 (mean ± standard deviation) years and had a median disease duration of 17 (interquartile range: 7-27) years. They were found to have lower cortical, trabecular and total vBMD at the distal radius and tibia than non-AS subjects on multivariable regression analysis. Cortical parameters such as cortical thickness and porosity, and bone strength parameters such bone stiffness and stress as estimated by finite element analysis (FEA) in AS patients were significantly worse than that of-non-AS subjects. Among patients with AS, male sex, mSASSS greater than zero and HLA-B27 negative status were associated with worse bone microarchitecture. CONCLUSIONS: Patients with AS have worse bone mineral density, microarchitecture and strength when compared to non-AS subjects. More research is needed to understand the mechanisms underlying bone pathology in AS and to assess the effect of treatments such as TNF inhibitors on bone quality and fracture risk.

Effect of vitamin D supplementation on glycemic control in patients with type 2 diabetes: a systematic review of interventional studies.

BACKGROUND: Diabetes and vitamin D deficiency are global epidemics. Researchers have long been exploring the role of potentially modifiable factors to manage type 2 diabetes. We conducted a systematic review of prospective studies and randomized controlled trials that involved vitamin D supplementation and specifically intended to study glycemic outcomes related to type 2 diabetes. METHODS: Two authors independently searched Medline and PubMed for longitudinal studies that had assessed the effect of vitamin D supplements on glycemic control, insulin resistance and beta-cell dysfunction in patients with diabetes. RESULTS: Seventeen randomized control trials and seven longitudinal studies with a minimum follow-up of one month were included. Results of the various short-term studies (follow up ≤ 3 months) suggested that vitamin D supplementation had a positive impact on glycemic control and metabolic parameters such as insulin resistance and beta cell dysfunction. However, the evidence was weak due to the low methodological quality of the studies. There was no significant effect on HbA1c, beta cell function and insulin resistance in the long-term studies (follow up > 3 months). There existed heterogeneity in the methodology of the studies, inclusion criteria, mode of supplementation of vitamin D and the duration of follow up. CONCLUSIONS: Current evidence based on randomized controlled trials and longitudinal studies do not support the notion that vitamin D supplementation can improve hyperglycemia, beta cell secretion or insulin sensitivity in patients with type 2 diabetes. Large-scale trials with proper study design, optimal vitamin D supplementation and longer follow up need to be conducted.