Higher 25-hydroxyvitamin D level is associated with increased risk for Behçet's disease.

BACKGROUND & AIM: Previous studies showed a vitamin D deficiency in patients with Behçet's disease, suggesting potential benefits of vitamin D supplementation in the prevention and treatment of Behçet's disease. Interpretation of these studies may be limited by reverse causality or confounding bias. We aim to determine the causal association between serum 25-hydroxyvitamin D [25(OH)D] and the risk of Behçet's disease by Mendelian randomization. METHODS: An allele score formed by four variants (rs2282679, rs10741657, rs12785878 and rs6013897) that were associated with serum 25(OH)D level, was examined using data of genome-wide association study (GWAS) on 999 Behçet's disease and 4417 healthy individuals of Chinese ancestry and validated using data of GWAS on 1215 Behçet's disease and 1278 controls of Turkish ancestry. The primary outcome was the risk of Behçet's disease, evaluated by an inverse variance weighted average of the associations with genetically determined 25(OH)D levels. RESULTS: The inverse variance weighted estimate showed that genetically increased 25(OH)D level was associated with a higher risk of Behçet's disease. In the Chinese cohort, the odds ratio for Behçet's disease in one standard deviation increase of natural log-transformed 25(OH)D level was 3.82 (95% CI: 1.27-11.42). Data from Turkish cohort confirmed the association with Behçet's disease (OR, 95% CI: 4.18, 1.15-15.12). In overall combination of Chinese and Turkish cohorts, the odds ratio for Behçet's disease per standard deviation increase of natural log-transformed 25(OH)D level was estimated to be 3.96 (95% CI: 1.72-9.13; P = 0.001). No significant evidence of pleiotropy and heterogeneity was detected. CONCLUSIONS: On the basis of evidence in 7909 human beings, this study provides the newest indication that a lifelong higher 25(OH)D level is associated with an increased risk of Behçet's disease. Special attention should be paid to the potential harm of long-term or high-dose use of vitamin D supplements in clinical practice.

The efficacy and safety of total glucosides of peony in the treatment of primary Sjögren's syndrome: a multi-center, randomized, double-blinded, placebo-controlled clinical trial.

To evaluate the efficacy and safety of total glucosides of peony (TGP) in adults with primary Sjögren's syndrome (pSS). A multi-center, randomized, double-blinded, placebo-controlled study was conducted between March 2012 and July 2014 at ten Chinese hospitals. In total, 320 pSS patients-classified according to the 2002 American-European Consensus Group Criteria-were randomized (2:1 ratio) to receive TGP(600 mg, tid) in the TGP group or placebo for 24 weeks in the placebo group. Study personnel, investigators, and patients were blinded to the treatment grouping. The primary endpoint was the improvement of EULAR Sjögren's Syndrome Patient Reported Index (ESSPRI) at week 24. The secondary endpoints were dry eyes/mouth/skin/nose/throat/vagina visual analogue scale (VAS), pain and discomfort VAS, fatigue VAS, mental discomfort VAS, patient global assessment (PGA), EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI), Schirmer's test, basal/stimulated salivary flow-rate values, and erythrocyte sedimentation rate (ESR). All adverse events were recorded during the trial period. ESSPRI improved more in the TGP than the placebo group (p < 0.001). Dry eyes/throat/vagina VAS, fatigue VAS, mental discomfort VAS, PGA, Schirmer's test, and ESR also improved more in the TGP group than in the placebo group (all p < 0.05). Stimulated salivary flow-rate values increased in the TGP group at week 12 but not at week 24. Adverse events in TGP group were 10.9%. TGP can alleviate some dryness symptoms as well as disease activity in pSS patients over 24 weeks. TGP was well tolerated by study subjects. TGP seems to be an effective and safe treatment for pSS.

Correction to: the efficacy and safety of total glucosides of peony in the treatment of primary Sjögren's syndrome: a multi-center, randomized, double-blinded, placebo-controlled clinical trial.

The authors regret that the Fig. 1 in the original version of this article contained an error. In the left column, 211 cases in the TGP group should be followed up for 8 weeks before 12 weeks. The correct figure presented in this article.

Folate Supplementation for Methotrexate Therapy in Patients With Rheumatoid Arthritis: A Systematic Review.

OBJECTIVE: To review the evidence for benefits and harms of folate (folic acid or folinic acid) supplementation on methotrexate (MTX) treatment for rheumatoid arthritis (RA), to assess whether or not folate supplementation would reduce MTX toxicity or reduce MTX benefits, and to decide whether a higher MTX dosage is essential. METHODS: We performed a sensitive search strategy and searched systematically the Medline, Embase, Web of Science and Cochrane Library databases from inception to 2 June 2016. Abstracts from major rheumatology meetings and major trial registers were also searched to retrieve all randomized controlled trials that interested us. RESULTS: Seven studies with 709 patients were included. No significant heterogeneity was found between these trials. For RA patients treated with MTX, those supplied with folate were less likely to have elevated transaminase (odds ratio [OR] 0.15; 95% confidence interval [95% CI] 0.10, 0.23 [p < 0.00001]) and gastrointestinal side-effects such as nausea and vomiting (OR 0.71; 95% CI 0.51, 0.99 [p = 0.04]). Folate appeared to promote compliance to MTX as it reduced patient withdrawal compared to placebo (OR 0.29; 95% CI 0.21, 0.42 [p < 0.00001]). There was no statistical difference for mouth sores between folate and placebo (OR 0.83; 95% CI 0.57, 1.22 [p = 0.35]). As the markers of disease activity in those trials were not consistent, it was impossible to decide whether folate supplementation reduced MTX efficacy. Besides, we compared high-dose folate (≥25 mg per week) and low-dose folate (≤10 mg per week) on MTX efficacy, finding no statistical difference (OR 2.07; 95% CI 0.81, 5.30 [p = 0.13]), nor on MTX toxicity (OR 1.56; 95% CI 0.80,3.04 [p = 0.19]). CONCLUSION: Folate supplementation can reduce the incidence of hepatotoxicity and gastrointestinal side-effects of MTX in patients with RA. It can also reduce patient withdrawal from MTX treatment. Although it tended to reduce mouth sores, it had no statistical significance. No significant difference was found between high-dose folate and low-dose folate on MTX efficacy or toxicity.

High prevalence of hypovitaminosis D of patients with autoimmune rheumatic diseases in China.

We aimed to determine the prevalence of hypovitaminosis D in patients with autoimmune rheumatic diseases (ARDs) in China and its association with demographic characteristics of the patients. We recruited 384 patients in this cross-sectional study including 121 cases of systemic lupus erythematosus (SLE), 131 rheumatoid arthritis (RA), 102 spondyloarthritis (SpA) and 30 other ARDs. For each patient, demographic information was collected and serum concentration of 25OHD3 was measured by electrochemiluminescence immunoassay (ECLIA). The multivariate logistic regression model was used to investigate the association between vitamin D deficiency and patient characteristics. The mean serum vitamin D level of the 384 patients was 18.91 (8.12) ng/mL, and the median age was 37.33 (12.01) yrs. Among these patients, 222 (57.81%) and 127 (33.07%) were found to be vitamin D deficiency and insufficiency, respectively. From the disease perspective, the percentages of insufficiency and deficiency were as follow: 97.52% and 84.30% in SLE, 87.02% and 48.85% in RA, 88.24% and 40.20% in SpA, 90.89% and 57.81% in other ARDs patients. The causative factors for vitamin D deficiency included SLE per se (OR 12.54, P < 0.001) and high body mass index (BMI) (OR 1.88, P < 0.001). However, the seniors were less likely to have vitamin D deficiency (OR 0.95, P = 0.005). No correlation was disclosed between vitamin D deficiency and gender or disease duration. Hypovitaminosis D is highly prevalent among autoimmune rheumatic diseases population in China. The SLE per se and the obesity are the risk factors for vitamin D deficiency. Clinicians are advised to supplement vitamin D in these patients.