Maternal and neonatal antibody levels on pertussis vaccination in pregnant women on immune-modulating therapy for rheumatic disease.

OBJECTIVES: While protection against pertussis following maternal tetanus-diphtheria-and-acellular-pertussis (Tdap) vaccination was demonstrated in healthy term-born infants, no evidence is available on Tdap vaccination in combination with immune-modulating therapy during pregnancy. In this pilot study, we explored whether treatment with tumour necrosis factor alpha inhibitors (TNFis) in pregnant patients with rheumatic disease interferes with Tdap vaccine responses and affects maternal anti-pertussis IgG antibody levels in newborns. METHODS: Patients were included by a rheumatologist during pregnancy in case they received maternal Tdap vaccination in the late-second or early-third trimester of pregnancy. Blood samples were obtained from mothers during the first pregnancy trimester, 3 months after delivery and from the umbilical cord. IgG antibody levels against Tdap-included antigens were measured using a bead-based multiplex immunoassay. Findings on patients exposed to TNFis were compared with those from TNFi-unexposed patients and with data from a historical comparator study among healthy Tdap vaccinated mother-infant pairs (n=53). RESULTS: 66 patients (46 exposed and 20 unexposed to TNFIs) were enrolled. No major differences in IgG antibody levels were observed between TNFi-exposed and unexposed mothers before maternal Tdap vaccination and 3 months after delivery. In cord sera, however, antibody levels against pertussis toxin were significantly lower after TNFi-treatment (35.94 IU/mL, 95% CI 20.68 to 62.45) compared with no TNFi-treatment of mothers with rheumatic disease (94.61 IU/mL, 95% CI 48.89 to 183.07) and lower compared with a cohort of healthy mothers (125.12 IU/mL, 95% CI 90.75 to 172.50). We observed similar differences for filamentous haemagglutinin, pertactin, tetanus toxoid and diphtheria toxoid. CONCLUSION: These preliminary data indicate no major differences in IgG antibody levels on maternal Tdap vaccination in pregnant women with or without immune-modulating treatment, although our findings suggest that TNFis during pregnancy induce lower maternal anti-pertussis-specific protective antibody levels in newborns.

Tumour necrosis factor inhibitor use during pregnancy is associated with increased birth weight of rheumatoid arthritis patients' offspring.

OBJECTIVES: To study pregnancy outcomes in a closely monitored, well-defined cohort of women with rheumatoid arthritis (RA). In particular, pregnancy outcomes of women that used a TNFi during pregnancy. METHODS: Patients were derived from a prospective study on pregnancy and RA (Preconception Counseling in Active RA study) and treated according to a treatment protocol aimed at minimal disease activity. Multivariate linear regression analysis was used to describe which variables influenced birth weight. RESULTS: 188 patients were included, 92 (48.9%) patients with RA used a TNFi during pregnancy. Disease Activity Score in 28 joints C reactive protein (DAS28CRP) was low at all time points during pregnancy (DAS28CRP in the third trimester: 2.17 (SD 0.73). TNFi use was not associated with an increase of adverse pregnancy outcomes such as low birth weight (<2500 g), (emergency) caesarian section, hypertensive disorders or congenital malformations. TNFi use resulted in less children born small-for-gestational age (p=0.05), however, did not increase the risk of large-for-gestational age (p=0.73). Mean birth weight was 173 g higher in women that used a TNFi during pregnancy (3.344 kg vs 3.171 kg, p=0.03). In the multivariate analysis, maternal age (ß -0.023, 95% CI -0.040 to -0.0065, p=0.007), TNFi use (ß 0.20, 95% CI 0.066, 0.34, p=0.004), diabetes mellitus (ß 0.37, 95% CI 0.12, 0.63, p=0.004) and gestational age (ß 0.18, 95% CI 0.15, 0.2, p<0.001) were statistically significant associated with birth weight. CONCLUSIONS: This is the first study to show that TNFi use during pregnancy is associated with increased birth weight of offspring of women with well-controlled RA. The underlying mechanism of TNF-inhibition on birth weight and the long-term consequences for the offspring should be explored in future research.

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.

Dual energy X-ray absorptiometry outcomes in male COPD patients after treatment with different glucocorticoid regimens.

STUDY OBJECTIVES: To compare bone mineral density (BMD) outcomes of patients who received continuous oral systemic glucocorticoids (GCs) with BMD outcomes of patients who received multiple GC courses, oral or IV. DESIGN: Cross-sectional study. PARTICIPANTS: Eighty-six white men with COPD selected from the outpatient clinic for pulmonary diseases. INTERVENTION: Data analysis from medical records, bone densitometry, and pulmonary function tests of consecutive selected patients. Inclusion period into the study was exactly 1 year. MEASUREMENTS AND RESULTS: Ten patients received oral prednisolone daily (group 1). Eleven patients were treated for several exacerbations with multiple systemic prednisolone courses, up to a period of 2 weeks per course, with a cumulative dose of > or = 1,000 mg (group 2). Likewise, 28 patients were treated with multiple systemic prednisolone courses, but with a cumulative dose < 1,000 mg (group 3). Thirty-seven patients were never treated with systemic prednisolone, and partly with inhaled corticosteroids (ICS) [group 4]. All groups were balanced for age and pack-years of smoking. In group 2, body mass index (BMI) and FEV(1) were lowest and hyperinflation was highest. The cumulative systemic prednisolone dose was highest in group 1, irrespective of the additional ICS treatments. Dual energy x-ray absorptiometry scanning of the lumbar spine, total hip, and femoral neck regions revealed a T score < or = 2.5 SD in 27 patients (31%), 31 patients (36%), and 34 patients (40%), respectively. BMD outcomes at any site were lower in patients receiving multiple systemic prednisolone courses > 1,000 mg, cumulatively (group 2), compared to the other groups, and these values were (mean +/- 1 SD) 0.759 +/- 0.238 g/cm(2), 0.683 +/- 0.115 g/cm(2), and 0.686 +/- 0.125 g/cm(2), respectively (p < 0.0001). Multivariate regression analysis revealed a correlation between the cumulative dose of prednisolone in group 2 and BMD of the lumbar spine (adjusted r = 0.48; p < 0.01). At the total hip and femoral neck regions, only a correlation between BMI and BMD was observed (adjusted r = 0.65 and 0.58, respectively; p < 0.0001 for both sites). CONCLUSIONS: Despite a far lower cumulative GC dose in comparison with patients treated with systemic corticosteroids continuously, after adjusting for BMI and lung function, osteoporosis of the lumbar spine was most frequent in patients receiving > 1,000 mg of prednisolone cumulatively, administered in multiple courses for the treatment of exacerbations of COPD.