Objectives To investigate whether MTX should be combined with an additional DMARD and bridging glucocorticoids as initial treatment for patients with early RA to induce an effective long-term response. Methods The Care in early RA study is a two-year investigator-initiated pragmatic multicentre randomized trial. Early RA patients, naïve to DMARDs and glucocorticoids, were stratified based on prognostic factors. High-risk patients were randomized to COBRA-Classic (n = 98): MTX, sulfasalazine, prednisone step-down from 60 mg; COBRA-Slim (n = 98): MTX, prednisone step-down from 30 mg; or COBRA-Avant-Garde (n = 93): MTX, leflunomide, prednisone step-down from 30 mg. Low-risk patients were randomized to COBRA-Slim (n = 43); or Tight Step Up (TSU) (n = 47): MTX without prednisone. Clinical/radiological outcomes at year 2, sustainability of response, safety and treatment adaptations were assessed. Results In the high-risk group 71/98 (72%) patients achieved a DAS28-CRP < 2.6 with COBRA-Slim compared with 64/98 (65%) with COBRA-Classic and 69/93 (74%) with COBRA-Avant-Garde (P = 1.00). Other clinical/radiological outcomes and sustainability of response were similar. COBRA-Slim treatment resulted in less therapy-related adverse events compared with COBRA-Classic (P = 0.02) or COBRA-Avant-Garde (P = 0.005). In the low-risk group, 29/43 (67%) patients on COBRA-Slim and 34/47 (72%) on TSU achieved a DAS28-CRP < 2.6 (P = 1.00). On COBRA-Slim, low-risk patients had lower longitudinal DAS28-CRP scores over 2 years, a lower need for glucocorticoid injections and a comparable safety profile compared with TSU. Conclusion All regimens combining DMARDs with glucocorticoids were effective for patients with early RA up to 2 years. The COBRA-Slim regimen, MTX monotherapy with glucocorticoid bridging, provided the best balance between efficacy and safety, irrespective of patients’ prognosis. Trial registration ClinicalTrials.gov, http://www.clinicaltrials.gov, NCT01172639.

This retrospective multi-center matched cohort study assessed the risk for severe COVID-19 (combination of severity indicators), intensive care unit (ICU) admission, and in-hospital mortality in hospitalized patients when infected with the Omicron variant compared to when infected with the Delta variant. The study is based on a causal framework using individually-linked data from national COVID-19 registries. The study population consisted of 954 COVID-19 patients (of which, 445 were infected with Omicron) above 18 years old admitted to a Belgian hospital during the autumn and winter season 2021–2022, and with available viral genomic data. Patients were matched based on the hospital, whereas other possible confounders (demographics, comorbidities, vaccination status, socio-economic status, and ICU occupancy) were adjusted for by using a multivariable logistic regression analysis. The estimated standardized risk for severe COVID-19 and ICU admission in hospitalized patients was significantly lower (RR = 0.63; 95% CI (0.30; 0.97) and RR = 0.56; 95% CI (0.14; 0.99), respectively) when infected with the Omicron variant, whereas in-hospital mortality was not significantly different according to the SARS-CoV-2 variant (RR = 0.78, 95% CI (0.28–1.29)). This study demonstrates the added value of integrated genomic and clinical surveillance to recognize the multifactorial nature of COVID-19 pathogenesis.

The objective of this study was to investigate the incidence and risk factors associated with COVID-19 vaccine breakthrough infections. We included all persons ≥18 years that had been fully vaccinated against COVID-19 for ≥14 days, between 1 February 2021 and 5 December 2021, in Belgium. The incidence of breakthrough infections (laboratory confirmed SARS-CoV-2-infections) was determined. Factors associated with breakthrough infections were analyzed using COX proportional hazard models. Among 8,062,600 fully vaccinated adults, we identified 373,070 breakthrough infections with an incidence of 11.2 (95%CI 11.2–11.3)/100 person years. Vaccination with Ad26.COV2.S (HR1.54, 95%CI 1.52–1.56) or ChAdOx1 (HR1.68, 95%CI 1.66–1.69) was associated with a higher risk of a breakthrough infection compared to BNT162b2, while mRNA-1273 was associated with a lower risk (HR0.68, 95%CI 0.67–0.69). A prior COVID-19-infection was protective against a breakthrough infection (HR0.23, 95%CI 0.23–0.24), as was an mRNA booster (HR0.44, 95%CI 0.43–0.45). During a breakthrough infection, those who had a prior COVID-19 infection were less likely to have COVID-19 symptoms of almost all types than naïve persons. We identified risk factors associated with breakthrough infections, such as vaccination with adenoviral-vector vaccines, which could help inform future decisions on booster vaccination strategies. A prior COVID-19 infection lowered the risk of breakthrough infections and of having symptoms, highlighting the protective effect of hybrid immunity.

ObjectivesTo identify and characterise a subgroup of patients with early rheumatoid arthritis (RA) reporting not feeling well 1 year after treatment initiation despite achieving optimal disease control according to current treatment standards.MethodsThis observational study included participants of the Care in early RA trial with a rapid and sustained response (DAS28CRP<2.6) from week 16 until year 1 after starting the first RA treatment. Feeling well was assessed at year 1, using five patient-reported outcomes (PROs): pain, fatigue, physical functioning, RA-related quality of life and sleep quality. K-means clustering assigned patients to a cluster based on these PROs. Cohen’s d effect size estimated cluster differences at treatment initiation and week 16, for the five clustering PROs, coping behaviour, illness perceptions and social support.ResultsAnalyses revealed three clusters. Of 140 patients, 77.9% were assigned to the ‘concordant to disease activity’ cluster, 9.3% to the ‘dominant fatigue’ cluster and 12.9% to the ‘dominant pain and fatigue’ cluster. Large differences in pain and fatigue reporting were found at week 16 when comparing the ‘concordant’ with the ‘dominant pain and fatigue’ or the ‘dominant fatigue’ cluster. Small differences in reporting were found for the other PROs. Illness perceptions and coping style also differed in the ‘concordant’ cluster.ConclusionsAlthough most patients reported PRO scores in concordance with their well-controlled disease activity, one in five persistent treatment responders reported not feeling well at year 1. These patients reported higher pain and fatigue, and different illness perceptions and coping strategies early in the disease course.