Man, Y.A. de

Construct and criterion validity of several proposed DAS28-based rheumatoid arthritis flare criteria: An OMERACT cohort validation study (Article)

2012-11-23T00:00:00Z

Background: To describe rheumatoid arthritis (RA) worsening that leads to change or re-initiation of treatment, several Disease Activity Score 28 (DAS28)-based flare criteria have been described, but none validated. Methods: Six previously published DAS28-based flare criteria ((1) increase in DAS28 >1.2, or >0.6 if DAS28 >5.1; (2) increase in DAS28 >1.2, or >0.6 if DAS28 ≥3.2; (3) increase >0.6 or DAS28 >3.2; (4) increase in DAS28 >1.2; (5) DAS28 >3.2; (6) DAS28 >2.6) were tested against five hypotheses concerning criterion and construct validity: (1+2) Sensitivity and specificity >70% compared with patient's/physician's judgment; (3) difference in proportion with disease modifying anti-rheumatic drug/corticosteroid initiation/increase >0.2; (4) mean difference in C-reactive protein (CRP) >10 mg/l; and (5) no statistical difference in Short Form-36 Mental Health subscale change. Three different RA patient databases in which flare might occur were used. Sensitivity/specificity, Χ2and two-sample student t test analyses were done. Results: The analyses included 51, 147 and 744 RA patients, from the three databases. Criterion 2 fulfilled most hypotheses: 4 out of 5. Sensitivity and specificity varied between 63%-78% and 84%-92%. Construct validity was demonstrated with 23% more treatment change, higher mean CRP (11.4 mg/l) and depression scale change of -5. Criteria 3, 5 and 6 were more sensitive, criteria 1, 2 and 4 more specific. Conclusions: An increase in DAS28 >1.2 or >0.6 if DAS28 ≥3.2 appears most discriminating and valid by our predefined validation criteria. Considering the other criteria, sensitivity and specificity shown here might facilitate use in different settings. Copyright Article author (or their employer) 2012.

Women with rheumatoid arthritis negative for anti-cyclic citrullinated peptide and rheumatoid factor are more likely to improve during pregnancy, whereas in autoantibody-positive women autoantibody levels are not influenced by pregnancy (Article)

2010-02-01T00:00:00Z

Objectives: To determine whether changes in levels of anti-cyclic citrullinated peptide (anti-CCP) and rheumatoid factor (RF) are associated with the spontaneous improvement of rheumatoid arthritis (RA) during pregnancy and with the subsequent flare post partum. Methods: Disease activity scores from the Pregnancyinduced Amelioration of Rheumatoid Arthritis (PARA) study of 118 patients were available for analysis. Before conception (if applicable), at each trimester and at 6, 12 and 26 weeks post partum, levels of the autoantibodies anti-CCP, IgM-RF, IgG-RF and IgA-RF were determined. Responses in disease activity were classified according to European League Against Rheumatism (EULAR) response criteria during pregnancy and post partum, and associated with the presence or absence of autoantibodies. Results: The median levels of anti-CCP and all subclasses of RF during pregnancy were stable, whereas post partum the levels of anti-CCP, IgM-RF and IgA-RF declined. A significantly higher percentage of women without autoantibodies (negative for anti-CCP and RF) improved compared with women positive for either or both autoantibodies (75% vs 39%, p=0.01). The occurrence of a flare post partum was comparable between these groups. Conclusions: Improvement of disease activity of RA during pregnancy was not associated with changes in levels of autoantibodies during pregnancy, however, improvement may occur more frequently in the absence of anti-CCP and RF.

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 (Article)

2009-12-16T00:00:00Z

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.

Association of higher rheumatoid arthritis disease activity during pregnancy with lower birth weight: Results of a national prospective study (Article)

2009-11-01T00:00:00Z

Objective. To determine the outcome of pregnancy in women with rheumatoid arthritis (RA) in relation to disease activity and medication use during the pregnancy. Methods. In a prospective study, pregnant women with RA were evaluated before conception (when possible), during each trimester of the pregnancy, and postpartum. Clinical characteristics, disease activity, medication use, and pregnancy outcome were analyzed. To examine the independent influence of prednisone use and disease activity on birth weight, regression analyses were performed, with adjustments for gestational age of the child at delivery, the sex of the newborn, and the mother's smoking status, education level, parity, and use of an assisted reproduction technique. Kaplan-Meier curve analyses were performed to examine the association between medication use and gestational age at delivery. Results. Data from 152 Caucasian RA patients with singleton pregnancies were available. Both the mean ± SD birth weight (3,379 ± 564 gm) and the mean ± SD birth weight standard deviation score (SDS; +0.1 ± 1.1), which is the birth weight adjusted for the gestational age and sex of the newborn, were comparable with those in the general population. On multiple linear regression analyses of birth weight and birth weight SDS, both of which were adjusted for covariates, only disease activity was associated with lower birth weight (P = 0.025). The gestational age at delivery was significantly lower in women who were taking prednisone (38.8 versus 39.9 weeks; P = 0.001), and their delivery was more often premature (<37 weeks; P = 0.004). Conclusion. Pregnancy outcome in women with well-controlled RA is comparable with that in the general population. The effect of prednisone on birth weight is mediated by a lower gestational age at delivery, whereas a higher level of disease activity independently influences birth weight negatively, suggesting an immune-mediated mechanism.

Clinical Aspects of Pregnancy-induced Amelioration of Rheumatoid Arthritis: PARA-study (Doctoral Thesis)

2009-07-01T00:00:00Z

In this PhD thesis, embedded in the PARA (Pregnancy-induced Amelioration of Rheumatoid Arthritis) study, several clinical aspects of the spontaneously occurring pregnancy-induced improvement of rheumatoid arthritis (RA) are addressed. An overview is given of inflammatory rheumatic diseases and the current knowledge about their disease courses and treatment options during pregnancy and postpartum. This thesis focuses firstly on the description of tools to objectively measure the disease activity and functionality of RA before, during and after pregnancy. Associations with the disease course and patient’s characteristics are subsequently made. The influence on the pregnancy outcome of both disease activity and treatment of RA with prednisone, are assessed regarding pregnancy durations and birth weight. Postpartum however RA tends to flare again. The problems which patients with RA will encounter in parental function, while nursing their babies, are addressed.

Disease activity of rheumatoid arthritis during pregnancy: Results from a nationwide prospective study (Article)

2008-09-15T00:00:00Z

Objective. According to common knowledge and retrospective studies, approximately 75-90% of patients with rheumatoid arthritis (RA) will improve during pregnancy. Prospective data on disease activity during pregnancy are limited. Therefore, this study aimed to prospectively determine the disease activity during pregnancy in RA patients treated in an era of new treatment options. Methods. For 84 RA patients (American College of Rheumatology criteria), a Disease Activity Score in 28 joints (DAS28) and medication use were obtained, before conception if possible, at each trimester of pregnancy and at 6, 12, and 26 weeks postpartum. Improvement and deterioration were determined by assessing changes in DAS28 and by applying the DAS28-derived European League Against Rheumatism (EULAR) response criteria. Results. Disease activity decreased with statistical significance (P = 0.035) during pregnancy and increased postpartum. In patients with at least moderate disease activity in the first trimester (n = 52), at least 48% had a moderate response during pregnancy according to EULAR-defined response criteria. In patients with low disease activity in the first trimester (n = 32), disease activity was stable during pregnancy. Thirty-nine percent of patients had at least a moderate flare postpartum according to reversed EULAR response criteria. Less medication was used during pregnancy compared with before conception and compared with postpartum. Conclusion. This study demonstrates that patients achieve remission during pregnancy and deteriorate postpartum, although less frequently than previously described.

Measuring disease activity and functionality during pregnancy in patients with rheumatoid arthritis (Article)

2007-06-15T00:00:00Z

Objective. Pregnancy has a favorable effect on the course of rheumatoid arthritis (RA), although the magnitude of this effect is equivocal because RA assessment tools have never been validated in pregnancy. The goal of this study was to assess how pregnancy influences the scoring of the Disease Activity Score in 28 joints (DAS28) and the Health Assessment Questionnaire (HAQ), and how both scores perform in pregnant patients with RA. Methods. Thirty-two healthy women and 30 pregnant patients with RA were prospectively studied during pregnancy and at postpartum. At each trimester and postpartum the components of the DAS28 (global health [GH], erythrocyte sedimentation rate [ESR], and C-reactive protein level [CRP]) and HAQ scores were determined. Maximal influences of healthy pregnancy on each component of the DAS28 were calculated. The performances of different DAS28 scores and the HAQ were also determined in RA patients. Furthermore, variants of the HAQ were developed within the HAQ scoring rules. Results. The components of the DAS28 were influenced by healthy pregnancy, with average increases in DAS28 score of 0.22 (GH), 1.1 (ESR), and 0.25 (CRP). The DAS28 calculated with CRP (DAS28-CRP) and without GH performed the best in pregnant RA patients. In healthy pregnancy, the median HAQ increased to 0.50 in the third trimester and was reduced by the HAQ variants to 0.25. Conclusion. Pregnancy considerably influences the scoring of the DAS28 and HAQ. RA disease activity in pregnant patients should preferably be calculated with DAS28-CRP without GH. Even with HAQ variants, influences of pregnancy on the assessment of functionality cannot be precluded.

Mannose-binding lectin levels during pregnancy: A longitudinal study (Article)

2007-02-01T00:00:00Z

Background: Pregnancy is associated with changes in the immune system. Although previous studies have focussed mainly on adaptive immunity, there are indications that components of innate immunity, such as mannose-binding lectin (MBL), are associated with pregnancy outcome. Although this would suggest that pregnancy also involves adaptations in innate immunity, there are few studies in this area. Therefore, we aimed to determine whether MBL concentrations and the following steps in complement pathway activation are influenced by pregnancy. Methods: MBL and Ficolin-2 concentrations, MBL-MBL-associated serine protease (MASP) complex activity, MBL pathway activity and classical complement pathway activity were determined by enzyme-linked immunosorbent assay (ELISA) in sera from pregnant women (n = 32) during each trimester and post-partum. MBL genotyping was performed by PCR. Results: During pregnancy, MBL concentrations increased to 140% [interquartile range (IQR) 116-181%, P < 0.0001]. This increase was already present at 12 weeks of pregnancy and was most pronounced in the high-production AA-genotype. Directly Post-partum MBL concentrations dropped to 57% of baseline (IQR 44-66%, P < 0.0001). Variations in MBL levels were reflected by similar changes in the following steps of complement activation, r > 0.93 (P < 0.01). Ficolin-2 levels and classical complement pathway activity were not similarly influenced by pregnancy. Conclusions: Pregnancy and the post-partum period profoundly influence MBL serum concentration and MBL complement pathway activity.