Project description:To construct a model of the antibody response to COVID-19 vaccination in patients with rheumatoid arthritis (RA), and to identify clinical factors affecting the antibody response. A total of 779 serum samples were obtained from 550 COVID-19-naïve RA patients who were vaccinated against COVID-19. Antibody titers for the receptor binding domain (anti-RBD) and nucleocapsid (anti-N) were measured. The time from vaccination, and the log-transformed anti-RBD titer, were modeled using a fractional polynomial method. Clinical factors affecting antibody responses were analyzed by a regression model using generalized estimating equation. The anti-RBD titer peaked at about 2 weeks post-vaccination and decreased exponentially to 36.5% of the peak value after 2 months. Compared with the first vaccination, the 3rd or 4th vaccinations shifted the peaks of anti-RBD antibody response curves significantly upward (by 28-fold [4-195] and 32-fold [4-234], respectively). However, there was no significant shift in the peak from the 3rd vaccination to the 4th vaccination (p = 0.64). Multivariable analysis showed that sulfasalazine increased the vaccine response (by 1.49-fold [1.13-1.97]), but abatacept or JAK inhibitor decreased the vaccine response (by 0.13-fold [0.04-0.43] and 0.44-fold [0.26-0.74], respectively). Age was associated with lower ln [anti-RBD] values (coefficient: - 0.03 [- 0.04 to - 0.02]). In conclusion, the anti-RBD response of RA patients peaked at 2 weeks after COVID-19 vaccination, and then decreased exponentially, with the maximum peak increase observed after the 3rd vaccination. The antibody response was affected by age and the medications used to treat RA.
Project description:ObjectiveRheumatoid factors (RFs) are a hallmark of rheumatoid arthritis but also arise in infections, including COVID-19. Moreover, infections, again including COVID-19, are associated with rheumatoid arthritis development, positioning RFs as a potential link between infection and rheumatoid arthritis. RFs traditionally have been thought to be relatively uniform in their reactivity across conditions apart from some increased reactivity in rheumatoid arthritis. Recently, however, IgG RFs that bind citrulline- and homocitrulline-containing IgG epitopes were identified in rheumatoid arthritis, but not other autoimmune diseases, whereas IgM RFs that bind specific native linear IgG epitopes were found uniquely post-COVID-19. The objective of this study was to determine if rheumatoid arthritis-associated RFs develop post-COVID-19 in order to provide new insights into post-infection immune tolerance loss.MethodsCOVID-19 convalescent, rheumatoid arthritis, and control sera (n=20) were used in enzyme-linked immunosorbent assay to evaluate IgG, IgM, and IgA binding to eight IgG1-derived peptides in their native, citrulline-containing, and homocitrulline-containing forms. Antibody levels were compared by Kruskal-Wallis test with Dunn's multiple comparisons test, and the number of participants with binding greater than all controls was compared by Fisher's exact test.ResultsIgG binding to seven of the eight IgG1-derived peptides was increased in a citrulline- or homocitrulline-specific manner only in rheumatoid arthritis. IgA binding was increased to five of eight IgG1-derived peptides in a citrulline- or homocitrulline-specific manner in rheumatoid arthritis and to one homocitrulline-containing peptide post-COVID-19. More post-COVID-19 participants than controls had elevated IgG or IgA binding to two IgG1-derived peptides in a homocitrulline-specific manner.ConclusionRheumatoid arthritis-associated RFs are primarily restricted to rheumatoid arthritis, but some individuals post-COVID-19 generate moderate levels of a few rheumatoid arthritis-associated RFs, especially of the IgA isotype and homocitrulline-reactive. These findings refine our understanding of RFs, provide novel insights into loss of immune tolerance post-infection, and reveal new possibilities for biomarker development in preclinical rheumatoid arthritis.
Project description:Baricitinib is a JAK1/2 inhibitor that was first approved for treating moderate to severe rheumatoid arthritis (RA) but that later showed considerable efficacy in the control of exaggerated inflammatory responses that occur in a wide range of diseases. There is a growing body of evidence, obtained from clinical trials and case reports, demonstrating clinical and paraclinical improvement in patients following administration of baricitinib including RA, systemic lupus erythematosus, psoriasis, atopic dermatitis, alopecia areata, interferon-mediated autoinflammatory diseases, graft-versus-host disease, diabetic kidney disease, and, recently, coronavirus disease-19. However, despite overall encouraging results, many adverse effects have been observed in baricitinib-treated patients, ranging from simple infections to increased risk of malignancies, particularly in long-term use. The significant efficacy of baricitinib, versus the probable adverse effects, urge further investigation before establishing it as a part of standard therapeutic protocols. Here, we have provided a review of the studies that have used baricitinib for treating various inflammatory disorders and summarized the advantages and disadvantages of its administration.
Project description:BackgroundSeveral retreatment strategies exist for rituximab in rheumatoid arthritis (RA). In some countries, reimbursement criteria require a loss of disease control for rituximab retreatment. Understanding the patients' and rheumatologists' perceptions regarding this retreatment strategy would be informative in identifying the optimal treatment administration schedule.ObjectivesThis study aimed to uncover patients' and rheumatologists' perceptions regarding retreatment strategies of rituximab.DesignQualitative study - semi-structured interviews.MethodsPatients with RA, treated with rituximab, and rheumatologists were invited to participate in a qualitative study consisting of individual, in-depth, semi-structured interviews. Interviews were analysed according to the Qualitative Analysis Guide of Leuven.ResultsA total of 16 patients and 13 rheumatologists were interviewed. Benefits (e.g. decreased risk of overtreatment, cost savings and long-lasting effectiveness of rituximab) and barriers (e.g. fluctuating disease activity, slow mode of action and increased glucocorticoid use) of on-flare retreatment were identified. To effectively treat on-flare, flares must first be identified timely. Both stakeholder groups acknowledged that patients are capable of recognizing flares. However, the patient's ability to discriminate between inflammatory and other types of pain was perceived as difficult. Furthermore, patients and rheumatologists stressed that patients must timely seek professional help in case of a flare, followed by a swift response from the rheumatologists. Remarkably, retreatment was approached in various ways among rheumatologists, and not always adhering strictly to the on-flare reimbursement criteria.ConclusionThis study revealed that both stakeholder groups perceived the heterogeneity in recognition of and reaction to a flare as important in influencing the effectiveness of the on-flare retreatment strategy. Moreover, this study identified the benefits and barriers of treating on-flare, which could be informative for daily practice decisions.
Project description:To investigate the incidence of COVID-19 hospitalisation in unvaccinated and vaccinated patients with rheumatoid arthritis (RA) compared with matched controls, and in patients with RA according to DMARD treatment. Danish nationwide matched cohort study from January to October 2021. Patients with RA were identified in the DANBIO register and matched 1:20 with individuals from the general population on age, sex, and vaccination status. Primary and secondary outcomes were COVID-19 hospitalisation (Danish National Patient Register) and first-time positive SARS-CoV2 PCR test (Danish COVID-19 Surveillance Register), respectively. Stratified by vaccination status, incidence rates (IRs) per 1000 person years (PY) and comorbidity-adjusted hazard ratios (aHRs) in cause-specific Cox models were calculated with 95% confidence intervals. In total, 28 447 unvaccinated patients and 568 940 comparators had Irs for COVID-19 hospitalisation of 10.4 (8.0-13.4) and 4.7 (4.3-5.1) per 1000 PY, respectively (aHR 1.88, 1.44-2.46). When fully vaccinated, corresponding Irs were 0.9 (0.5-1.6) and 0.5 (0.4-0.6) per 1000 PY (aHR 1.94, 1.03-3.66). Unvaccinated RA patients had an aHR of 1.22 (1.09-1.57) for testing positive for SARS-CoV2 and 1.09 (0.92-1.14) among vaccinated. Vaccinated rituximab-treated patients had increased crude IR of COVID-19 hospitalisation compared with conventional DMARD treated patients. The incidence of COVID-19 hospitalisation was increased for both unvaccinated and vaccinated patients with RA compared with controls. Importantly, the parallel decreasing risk for patients with RA suggests a comparable relative benefit of vaccination in most patients.
Project description:This study aimed to assess COVID-19 vaccination-related AEs in patients with rheumatoid arthritis (RA), in the COVID-19 Vaccination in Autoimmune Diseases (COVAD)-2 study. An online international cross-sectional survey captured self-reported data on COVID-19 vaccination-related adverse events (AEs) in people with RA, autoimmune diseases (AIDs; rheumatic [r] and non-rheumatic [nr]) and healthy controls (HCs). The survey was circulated by the COVAD study group, comprising 157 collaborators across 106 countries, from February to June 2022. Delayed AEs among RA were compared with other rAIDs, nrAIDs and HCs using multivariable binary regression. A total of 7203 participants were included (1423 [19.7%] RA, 2620 [36.4%] rAIDs, 426 [5.9%] nrAIDs, 2734 [38%] HCs), with 75% female. Compared to HCs, individuals with RA reported higher overall major AEs [OR 1.3 (1.0-1.7)], and an increased number of several minor AEs. Compared to nrAIDs, people with RA had several increased reported minor AEs including myalgia and joint pain. People with active RA had increased major AEs [OR 1.8 (1.1-3.0)] and hospitalisation [OR 4.1 (1.3 - 13.3)] compared to inactive RA. RA patients without autoimmune comorbidities had significantly fewer major and minor AEs than those with other rAIDs. A decreased incidence of hospitalisation was seen in patients taking methotrexate or TNF inhibitors compared to patients not taking these medications. COVID-19 vaccination is associated with minimal to no risks of delayed AEs in patients with RA compared to HCs, and fewer compared to other rAIDs. Active RA and presence of co-existing rAIDs were associated with an increased risk of delayed AEs.
Project description:BackgroundTo evaluate our hypotheses that, when rheumatoid arthritis (RA) flares postpartum, gene expression patterns are altered compared to (a) healthy women, (b) RA women whose disease activity is low or in remission postpartum, and (c) pre-pregnancy expression profiles.MethodsTwelve women with RA and five healthy women were included in this pilot study. RA disease activity and postpartum flare were assessed using the Clinical Disease Activity Index (CDAI). Total RNA from frozen whole blood was used for RNA sequencing. Differential gene expression within the same women (within-group) over time, i.e., postpartum vs. third trimester (T3) or pre-pregnancy (T0), were examined, using a significance threshold of q < 0.05 and fold-change ≥ 2.ResultsNine of the women with RA experienced a flare postpartum (RAFlare), while three had low disease activity or were in remission (RANoFlare) during that time frame. Numerous immune-related genes were differentially expressed postpartum (vs. T3) during a flare. Fold-changes in expression from T3 to postpartum were mostly comparable between the RAFlare and healthy groups. At 3 months postpartum, compared to healthy women, several genes were significantly differentially expressed only among the RAFlare women, and not among the RANoFlare women. Some of these genes were among those whose "normal" expression was significantly modulated postpartum, and the postpartum expression patterns were significantly altered during the RA flare. There were also some genes that were significantly differentially expressed in RAFlare compared to both healthy and RANoFlare women, even though their expression was not significantly modulated postpartum. Furthermore, while postpartum expression profiles were similar to those at pre-pregnancy among healthy women, significant differences were found between those time points among the RAFlare women.ConclusionsThe large majority of gene expression changes between T3 and 3 months postpartum among RA women who flared postpartum reflected normal postpartum changes also seen among healthy women. Nonetheless, during a postpartum flare, a set of immune-related genes showed dysregulated expression compared to healthy women and women with RA whose disease activity was low or in remission during the same time frame, while other genes demonstrated significant differences in expression compared to RA pre-pregnancy levels.