Background/Purpose : In light of the current COVID-19 pandemic, whether patients with rheumatic musculoskeletal disease (RMD) treated with conventional (cs) or biologic (b) disease-modifying drugs (DMARDs) exhibit an adequate immune response to the currently available SARS-CoV-2 vaccinations remains a major concern. There is an urgent need for more SARS-CoV-2 vaccine efficacy data to inform healthcare providers on the potential need for a booster vaccine. We established the ‘Detection of SARS-CoV-2 antibodies in Danish Inflammatory Rheumatic Outpatients’ study (DECODIR) in March 2021 in order to assess and compare the immunoglobulin G (IgG response) of the SARS-CoV-2 BNT162b2 vaccine (Pfizer, Groton, CT, USA/BioNTech, Mainz, Germany) and mRNA-1273 vaccine (Moderna, Cambridge, MA, USA) administered as part of the national vaccine roll out in patients with RMDs, irrespective of treatment. Patients’ SARS-CoV-2 IgG level was used as proxy to determine vaccination response. Methods: The study is a longitudinal prospective cohort study in which the SARS-CoV-2 antibody response was measured and compared at baseline and at six weeks following vaccination. The study population consisted of patients with rheumatoid arthritis (RA), spondyloarthropathies (SpA), or psoriatic arthritis (PsA) receiving their outpatient treatment at the Danish Hospital for Rheumatic Diseases, Sonderborg. Bloods, patient reported outcome measurements (PROMS), clinical data, and treatment information (cs/bDMARD) were collected at baseline/6 weeks and documented in the Danish DANBIO registry. Commercially available antibody tests (ThermoFisher, Waltham, MA, USA) were used, and SARS-CoV-2 IgG levels were reported in EliA U/mL. Sufficient IgG response was defined as ≥10 EliA U/mL (manufacturers cut-off). Associations between antibody response, age, gender, disease (RA/PsA/SpA), no treatment or cs/bDMARD treatment, and disease activity were tested using proportional odds regression and bootstrapped tests of medians. Results were reported using mean, median (IqR), and bootstrapped 95% confidence interval (CI) of the median. Results: A total of 243 patients were included. We observed a significant increase in IgG levels (median of <0.7 EliA U/mL at baseline versus 34.5 EliA U/mL at 6 weeks). Seventy-two patients (32%) had an insufficient IgG response. The median IgG level in patients treated with cs/bDMARD combination therapy was significantly lower compared to patients without any DMARD treatment (12 EliA U/mL vs. 92 EilA U/mL (p < 0.01)). Conclusion: Patients treated with a combination of cs/bDMARD are at significantly higher risk of an inadequate response to SARS-CoV-2 vaccines as measured by IgG level compared to patients without DMARD treatment. IgG SARS-CoV-2 are only part of the immune response, and further data are urgently needed. At present, our results may inform healthcare providers and policy makers on the decision for the need of a booster vaccine in this particular patient group.

Introduction: Obstetric antiphospholipid syndrome (OAPS) is an autoimmune disorder associated with pregnancy morbidity, including recurrent pregnancy loss, preeclampsia and fetal growth restriction. Despite standard of care (SoC) with low-dose aspirin (LDA) and low-molecular-weight heparin (LMWH), 20%–30% of pregnancies still result in adverse outcomes. The 2023 ACR/EULAR classification criteria have improved research standardisation, yet robust clinical evidence, including randomised controlled trials (RCTs), remains limited and current management largely relies on empirical practice and RCTs performed nearly two decades ago. Methods: In this mini-review, with a particular focus on refractory OAPS, we summarise the quality of evidence and methodological limitations underpinning current therapeutic strategies. This included existing SoC and potential adjuvant treatments, such as hydroxychloroquine (HCQ), corticosteroids, statins, intravenous immunoglobulin (IVIG) and biologics. Results: LDA and LMWH remain the cornerstone of OAPS care. Observational data suggest that HCQ may enhance live birth rates in refractory cases, while glucocorticoids offer limited benefit and pose maternal risks. Evidence for IVIG, statins, and biologics is sparse and primarily derived from small uncontrolled studies. With the exception of a few trials reported almost two decades ago, no RCTs have been conducted specifically in OAPS. Discussion: Improved management of OAPS requires higher-quality evidence. Trials in other high-risk pregnancy populations demonstrate that RCTs are feasible. Progress will depend on standardised pregnancy outcome measures, international collaboration with coordinated leadership and increased societal and regulatory recognition of the urgent need for research and funding. This mini-review synthesizes current knowledge on the treatment of refractory OAPS, identifies critical research gaps, and outlines key strategic elements needed to advance evidence-based care for this high-risk population.