Juvenile idiopathic arthritis patients with positive family history of autoimmune thyroid disease might benefit from serological screening: analysis of the international Pharmachild registry.

BACKGROUND: Little is known about the association between juvenile idiopathic arthritis (JIA) and autoimmune thyroid disease (AITD) and therefore there are no indications for AITD screening in this population, which is possible using standard blood tests. The objective of this study is to determine the prevalence and predictors of symptomatic AITD in JIA patients from the international Pharmachild registry. METHODS: Occurrence of AITD was determined from adverse event forms and comorbidity reports. Associated factors and independent predictors for AITD were determined using univariable and multivariable logistic regression analyses. RESULTS: The prevalence of AITD after a median observation period of 5.5 years was 1.1% (96/8965 patients). Patients who developed AITD were more often female (83.3% vs. 68.0%), RF positive (10.0% vs. 4.3%) and ANA positive (55.7% vs. 41.5%) than patients who did not. AITD patients were furthermore older at JIA onset (median 7.8 years vs. 5.3 years) and had more often polyarthritis (40.6% vs. 30.4%) and a family history of AITD (27.5% vs. 4.8%) compared to non-AITD patients. A family history of AITD (OR = 6.8, 95% CI: 4.1 - 11.1), female sex (OR = 2.2, 95% CI: 1.3 - 4.3), ANA positivity (OR = 2.0, 95% CI: 1.3 - 3.2) and older age at JIA onset (OR = 1.1, 95% CI: 1.1 - 1.2) were independent predictors of AITD on multivariable analysis. Based on our data, 16 female ANA positive JIA patients with a family history of AITD would have to be screened during ±5.5 years using standard blood tests to detect one case of AITD. CONCLUSIONS: This is the first study to report independent predictor variables for symptomatic AITD in JIA. Female ANA positive JIA patients with positive family history are at increased risk of developing AITD and thus might benefit from yearly serological screening.

Tofacitinib in juvenile idiopathic arthritis: a double-blind, placebo-controlled, withdrawal phase 3 randomised trial.

BACKGROUND: Tofacitinib is an oral Janus kinase inhibitor. This trial assessed the efficacy and safety of tofacitinib versus placebo in patients with polyarticular course juvenile idiopathic arthritis (JIA). METHODS: This double-blind, withdrawal phase 3 trial enrolled patients with polyarticular course JIA (extended oligoarthritis, rheumatoid factor-positive or rheumatoid factor-negative polyarthritis, or systemic JIA without active systemic features) aged 2 years to younger than 18 years, and was done at 64 centres of the Paediatric Rheumatology International Trials Organisation and Pediatric Rheumatology Collaborative Study Group networks in 14 countries. Patients with psoriatic arthritis or enthesitis-related arthritis were enrolled for exploratory endpoints. During part 1 of the study, patients received oral open-label tofacitinib (weight-based doses; 5 mg twice daily or lower) for 18 weeks. Patients achieving at least JIA/American College of Rheumatology 30 response were randomly assigned (1:1) using an Interactive Response Technology system to continue tofacitinib or switch to placebo in part 2 of the study for 26 weeks. The primary endpoint was JIA flare rate by week 44 in part 2 in patients with polyarticular course JIA; the intention-to-treat principle was applied. Safety was evaluated throughout part 1 and part 2 of the study in all patients who received one dose or more of study medication. This trial is registered with ClinicalTrials.gov, NCT02592434. FINDINGS: Between June 10, 2016, and May 16, 2019, of 225 patients enrolled, 184 (82%) patients had polyarticular course JIA, 20 (9%) had psoriatic arthritis, and 21 (9%) had enthesitis-related arthritis. 147 (65%) of 225 patients received concomitant methotrexate. In part 2, 142 patients with polyarticular course JIA were assigned to tofacitinib (n=72) or placebo (n=70). Flare rate by week 44 was significantly lower with tofacitinib (21 [29%] of 72 patients) than with placebo (37 [53%] of 70 patients; hazard ratio 0·46, 95% CI 0·27-0·79; p=0·0031). In part 2 of the study, adverse events occurred in 68 (77%) of 88 patients receiving tofacitinib and 63 (74%) of 85 in the placebo group. Serious adverse events occurred in one (1%) and two (2%), respectively. In the entire tofacitinib exposure period, 107 (48%) of 225 patients had infections or infestations. There were no deaths during this study. INTERPRETATION: The results of this pivotal trial show that tofacitinib is an effective treatment in patients with polyarticular course JIA. New oral therapies are particularly relevant for children and adolescents, who might prefer to avoid injections. FUNDING: Pfizer.

The effect of low alcohol consumption during pregnancy on the lipid peroxidation-antioxidant defense system of women, their alcohol-exposed infants, and growth, health, and developmental outcomes.

BACKGROUND: Few studies have examined the effects of low-dose alcohol consumption on the "lipid peroxidation-antioxidant defense" (LPO-AOD) system of mothers and infants, and on infant growth and development. This study examined effects of alcohol consumption on the LPO-AOD system of pregnant women and newborns and infant development. METHODS: A total of 209 pregnant women were recruited for this prospective study at the first prenatal visit and followed until delivery: 112 consumed alcohol and 97 reported no alcohol use during pregnancy. Infants were evaluated at birth, and at 6 and 12 months of age. The study controlled for the confounding effect of maternal smoking. RESULTS: Biomarkers of lipid peroxidation, for example, thiobarbituric acid reactants, were higher and the activity of the antioxidant defense system was lower in drinkers and their infants. Higher rates of pathological conditions and slower postnatal growth were observed among infants who were prenatally exposed to alcohol. Low-dose alcohol use and tobacco smoking were associated with lower postnatal infant growth trajectories, resulting in restricted growth at 6 and 12 months among infants born to mothers who drank or smoked during pregnancy. Alcohol had a broad effect on the infant and maternal LPO-AOD system, while the effect of smoking was limited in this study to maternal glutathione peroxidase. CONCLUSIONS: Small amounts of alcohol consumed during pregnancy are associated with dysfunction of the LPO-AOD system and development of oxidative stress in women and their children. Identification and preventive interventions are needed for pregnant women who use alcohol in any amount.

Lipid peroxidation and antioxidant protection in girls with type 1 diabetes mellitus during reproductive system development.

BACKGROUND AND OBJECTIVE: Type 1 diabetes mellitus (T1D) is found worldwide and is regarded as one of the main risks to human health. The objective of this study was to determine the state of lipid peroxidation (LPO) and antioxidant protection in girls with T1D type considering the stages of reproductive system development. MATERIALS AND METHODS: This study enrolled 56 young girls with T1D and 60 healthy girls (control) matched by age. The study population was divided into 3 age groups: prepubertal, adolescent, and juvenile. The state of LPO and antioxidant system was assessed using the coefficient of oxidative stress that represented the ratio of LPO products to general antioxidative blood activity. Spectrophotometric and fluorometric methods were applied. RESULTS: The results of our study showed increased conjugated diene (CD) and thiobarbituric acid reactant (TBAR) concentrations as well as a decreased reduced glutathione level in prepubertal girls with T1D. Adolescent girls with T1D had a significantly greater CD level and juvenile girls with T1D had a significantly greater TBAR level and lower α-tocopherol concentration than girls in the control group. The greatest coefficient of oxidative stress (1.16) was observed in the prepubertal period. CONCLUSIONS: The prepubertal period is characterized by the most severe state of lipid peroxidation process-antioxidant protection.

Antioxidant status in peri- and postmenopausal women.

Menopause is a risk factor for oxidative stress. The aim of our study is to assess antioxidant system parameters (α-tocopherol, retinol, reduced glutathione, total antioxidant activity) in peri- and postmenopausal women. The antioxidant defense activity by estimation of total antioxidant activity, α-tocopherol, retinol, oxidized and reduced glutathione levels was studied in women of reproductive age (n=37), in perimenopausal (n=41) and postmenopausal women (n=41). In our study we used spectrofluorofotometer methods. Statistical analysis was performed by non-parametric tests with p<0.05 as the level of significance. The results of our study showed the decrease of α-tocopherol and retinol concentrations and the increase of oxidized glutathione level in blood serum both in perimenopausal and postmenopausal women, the total antioxidant activity of blood serum was decreased in postmenopausal women only. The results of our study demonstrate that decrease of antioxidant defense system resources depends on the menopausal phase.