Dilemma of belimumab therapy (dis)continuation during pregnancy: Results of a retrospective study in eudravigilance.

INTRODUCTION: The first biologic authorized for systemic lupus erythematosus (SLE) up to this date, belimumab, is currently not recommended for use during pregnancy due to lack of data. Provided that the health of the child begins with the health of the mother, pregnant patients face the dilemma of cessation or continuation of belimumab. If belimumab is stopped, there will be a risk of SLE flare and its consequences for the mother and the foetus. Continuation is also not optimal because of the lack of knowledge on safety for use during pregnancy. AIM: To compare the reported foetal outcomes in SLE patients who stopped scheduled belimumab within the first trimester (group A) and those who continued scheduled belimumab during the first trimester or thereafter (group B). MATERIAL AND METHOD: All belimumab-exposed pregnancy-related reports were extracted from the EudraVigilance (EV) database until March 11th, 2021. After case review, repeated cases, uninformative reports, non-medical elective abortions and foetal chromosomal abnormalities were excluded. Included pregnancies were divided into two groups (group A and B, as described above). Foetal outcomes were divided into live birth or foetal death (due to miscarriage or stillbirth) and were compared between both groups. Furthermore, neonatal outcomes, such as reporting rates of preterm birth, low birth weight and major congenital malformations were compared. RESULTS: No statistical difference in foetal death was observed between group A and B (reported numbers (%) = 32 (46.4) and 11 (52.4), respectively). Odds ratio (OR, [95% Confidence Intervals (CIs)]) of foetal death in group B compared to group A was 1.27 [0.48, 3.32]. Reporting rates of preterm birth and low birth weight were higher - though not statistically different - in group A. CONCLUSION: The positive results of our study are supportive for the continuation of belimumab during pregnancy. Since the analysis is based on spontaneous reports/retrospective data, additional studies are needed to confirm the results.

Modern treatment approach results in low disease activity in 90% of pregnant rheumatoid arthritis patients: the PreCARA study.

OBJECTIVES: In patients with rheumatoid arthritis (RA), high disease activity impairs fertility outcomes and increases the risk of adverse pregnancy outcomes. The aim of this study was to determine the feasibility of a modern treatment approach, including treat-to-target (T2T) and the prescription of tumour necrosis factor (TNF) inhibitors, in patients with RA with a wish to conceive or who are pregnant. METHODS: Patients were derived from the Preconception Counseling in Active RA (PreCARA) cohort. Patients with a wish to conceive or who are pregnant were treated according to a modified T2T approach, in which the obvious restrictions of pregnancy were taken into account. Results of the PreCARA study were compared with results of the Pregnancy-induced Amelioration of Rheumatoid Arthritis (PARA) study, a historic reference cohort on RA during pregnancy. Patients in the PARA cohort were treated according to the standards of that time (2002-2010). Differences in disease activity over time between the two cohorts were tested using a linear mixed model. RESULTS: 309 patients with RA were included in the PreCARA study, 188 children were born. 47.3% of the patients used a TNF inhibitor at any time during pregnancy. Mean disease activity over time in the PreCARA cohort was lower than in the reference cohort (p<0.001). In the PreCARA cohort, 75.4% of the patients were in low disease activity (LDA) or remission before pregnancy increasing to 90.4% in the third trimester, whereas in the PARA cohort, these percentages were 33.2% and 47.3%, respectively. CONCLUSIONS: This first study on a modern treatment approach in pregnant patients with RA shows that LDA and remission are an attainable goal during pregnancy, with 90.4% of patients achieving this in the third trimester.

From patients with arthralgia, pre-RA and recently diagnosed RA: what is the current status of understanding RA pathogenesis?

It is believed that therapy for rheumatoid arthritis (RA) is the most effective and beneficial within a short time frame around RA diagnosis. This insight has caused a shift from research in patients with established RA to patients at risk of developing RA and recently diagnosed patients. It is important for improvement of RA therapy to understand when and what changes occur in patients developing RA. This is true for both seropositive and seronegative patients. Activation of the immune system as presented by autoantibodies, increased cytokine and chemokine production, and alterations within several immune cells occur during RA development. In this review we describe RA pathogenesis with a focus on knowledge obtained from patients with arthralgia, pre-RA and recently diagnosed RA. Connections are proposed between altered immune cells, cytokines and chemokines, and events like synovial hyperplasia, pain and bone damage.

Development of a clinical transition pathway for adolescents in the Netherlands.

AIMS: To explore how young people with juvenile-onset rheumatic and musculoskeletal diseases (jRMDs) and their parent(s) experience care during preparation for the upcoming transfer to adult services, and to develop a clinical transition pathway. METHOD: A survey was conducted with 32 young people aged between 14 and 20 years with jRMDs, and their parents ( n =33), treated at the department of paediatric rheumatology in a tertiary care children's hospital in the Netherlands. RESULTS: More than 30% of young people would have liked to discuss topics such as educational and vocational choices in a clinic, but did not get the opportunity. Preparation for transition was poor as was training in self-management skills. One third of parents had feelings of anxiety about the upcoming transfer. Results from the survey and evidence-based principles of transitional care were used to develop the clinical transition pathway. The pathway focuses on starting transition early, developing self-management skills, joint consultations and supporting parents in giving young people control of their clinical care. CONCLUSION: Care does not currently meet the needs of young people in the process of transition to adult rheumatology services. The clinical transition pathway developed as a result of the study is a tool that may improve this process.

How to study determinants related to medication adherence in newly diagnosed polyarthritis patients for the development of a prediction instrument.

INTRODUCTION: For patients with a chronic disease, the appropriate use of medication is the key to manage their illness. Adherence to medication is therefore important. Adherence can be divided into three parts: the initiation part, the execution phase, and the discontinuation part. Little is known about the determinants of the initiation part. For this reason, we describe the conduct of a stepwise procedure to study determinants of medication initiation for patients with a chronic disease. METHODS/DESIGN: The stepwise procedure comprises of eliciting a list of all potential determinants via literature review, interviewing patients, and consulting an expert panel. This is followed by embedding the determinants in a theoretical framework, developing a questionnaire, and choosing adherence measurement methods. The consecutive steps that we conducted for the development of a tool for the prediction of adherence in our study sample of early arthritis patients are described. DISCUSSION: Although we used a thorough procedure, there are still some pitfalls to take into account, such as the choice of theoretical framework. A strength of this study is that we use multiple adherence measurement methods and that we also take clinical outcomes into account.

Immunoglobulin G galactosylation and sialylation are associated with pregnancy-induced improvement of rheumatoid arthritis and the postpartum flare: results from a large prospective cohort study.

INTRODUCTION: Improvement of rheumatoid arthritis (RA) during pregnancy has been causatively associated with increased galactosylation of immunoglobulin G (IgG) N-glycans. Since previous studies were small, did not include the postpartum flare and did not study sialylation, these issues were addressed in the present study. METHODS: Serum from 148 RA cases and 32 healthy controls was collected at several time points before, during and after pregnancy. Improvement during pregnancy and postpartum flare were determined according to the European League Against Rheumatism (EULAR) response criteria. Galactosylation and sialylation of Immunoglobulin G (IgG) and the presence of bisecting N-acetylglucosamine (GlcNAc) were analyzed by matrix-assisted laser desorption/ionization - time of flight - mass spectrometry (MALDI-TOF-MS). RESULTS: IgG1 and IgG2 galactosylation of the cases and controls increased during pregnancy with a maximum in the third trimester. Galactosylation decreased directly postpartum. IgG galactosylation of controls was at a higher level than cases (P < 0.001 at all time points) and a similar pattern was observed for sialylation. Moreover, there was a good association between galactosylation and sialylation. The increase in galactosylation was significantly more pronounced for cases with improvement than cases without improvement during pregnancy. The reverse was true for deteriorators and non-deteriorators postpartum. The presence of bisecting GlcNAc was not significantly influenced by pregnancy or postpartum for cases and controls. CONCLUSIONS: This large cohort study demonstrates the association of changes in galactosylation with both pregnancy-induced improvement and postpartum flare in RA-patients, suggesting a role for changes in glycosylation in the pregnancy-induced improvement of RA.