Multivariate analysis of the effects of demographic and clinical variables and treatment strategy on total costs over 4 years.

<p>The reported Rate Ratios describe the variations in costs expressed as a multiplicative factor for patients presenting the associated characteristic compared to those who did not, all other things being equal.</p><p>MCMC = Markov Chain Monte Carlo; CI = Confidence Intervalle; HAQ = Health Assessment Questionnaire; RA = Rheumatoid Arthritis; ICC = Intraclass Correlation Coefficient.</p>1<p>Median and range for all 24 imputed datasets.</p

Disease activity per period among matched groups of FYB and LYB users.

<p>* 37 FYB users and 37 LYB users were matched for clinical and sociodemographic baseline characteristics using a logistic regression propensity score. ** Low disease activity is defined as DAS-28≤3.2.</p

Multivariate analysis of the effects of demographic and clinical variables and treatment strategy on other health resource use costs over 4 years.

<p>The reported Rate Ratios describe the variations in costs expressed as a multiplicative factor for patients presenting the associated characteristic compared to those who did not, all other things being equal.</p><p>MCMC = Markov Chain Monte Carlo; CI = Confidence Intervalle; HAQ = Health Assessment Questionnaire; RA = Rheumatoid Arthritis; ICC = Intraclass Correlation Coefficient.</p>1<p>Median and range for all 24 imputed datasets<b>.</b></p

Mean costs per period according to treatment strategy.

<p>(A) Mean total costs according to treatment strategy; (B) Mean other health resource use costs according to treatment strategy.</p

Baseline patient characteristics.

<p>Values are mean values (SD) or number of patients (%).</p>1<p>Eular Guideline: 1st rheumatologist visit after RA onset <45 days; ESR = Erythrocyte sedimentation rate, CRP = C-Reactive Protein, DAS-28 = Disease Activity Score 28, HAQ = Health Assessment Questionnaire, ACR = American College of Rheumatology, VAS = Visual analogue scale, EULAR = European League Against Rheumatism, DMARD = Disease-modifying antirheumatic drug, ACPA = anti-citrullinated protein antibody.</p

Annual costs over the 4-year follow-up by resource component.

1<p>Physician visit costs used were the following: 28.27€ for rheumatologists, 28.61€ for internists, 22.13€ for general practitioners and 30.56€ for orthopaedist surgeons.</p>2<p>Health professional consultation costs used were the following: 11.30 € for nurses, 16.32 € for physiotherapists, 40.82 € for psychologists and 14.90 € for occupational therapists.</p>3<p>Lab test costs used were the following: 173.80 € for inclusion biologic investigations, 28.86 € for monthly biologic tests and 42.63 € for annual biologic tests.</p>4<p>Imaging and other devices costs included the following: 19.95 to 39.95 € for X-ray depending on the number of X-rays (19.95 € for the 1st X-ray, 39.95 € for the 2nd, 21.28 € for the 3rd, 20.00 € for the 4th), 69.00 € for MRI, 25.27 € for CT-scanner, 96.00 € for gastric endoscopy and 204.18 € for colonoscopy.</p>5<p>Transportation costs were calculated on the basis of a reimbursement fee of 1.17 € per km.</p>6<p>Inpatient costs were based on DRG tariffs.</p><p>DMARD = Disease-modifying antirheumatic drugs.</p

Additional file 1 of Sensitive B-cell receptor repertoire analysis shows repopulation correlates with clinical response to rituximab in rheumatoid arthritis

Supplementary Material 1

Humoral immune response to TNF.

<p>Patients were treated with 2 doses (days 0 and 28) or 3 doses (days 0, 7, and 28) of placebo or 90, 180, or 360 µg TNF-K. Anti-TNF antibody titers were determined by enzyme-linked immunosorbent assay. (A) GMTs. (B) Percent of patients in each treatment group with detectable anti-TNF antibodies (titer ≥200) up to month 3 (at study day 38, 56, or 84), at month 6, at month 12, or at any time up to month 12 (i.e., antibody responders).</p

Study design.

<p>In the first stage, 8 patients were randomized 3∶1 to receive 90 µg TNF-K or placebo, in the second, 16 patients were randomized 3∶1 to receive 180 µg TNF-K or placebo, and in the third, 17 patients were randomized 3∶1 to receive 360 µg TNF-K or placebo. In each stage, patients were also randomized 1∶1 to receive 2 doses (day 0, 28) or 3 doses (day 0, 7, 28) (arrows). For stages 1 and 2, after 3 patients had been enrolled and no safety issues had been reported for at least 7 days, enrolment in the subsequent stage started in parallel. One patient randomized to receive 3 doses of 360 µg TNF-K withdrew consent prior to treatment. The principal analysis portion of the study continued up to day 84, and the follow-up portion continued up to month 12.</p

CD4⁺ T-cell DNA methylation changes during pregnancy significantly correlate with disease-associated methylation changes in autoimmune diseases

Epigenetics may play a central, yet unexplored, role in the profound changes that the maternal immune system undergoes during pregnancy and could be involved in the pregnancy-induced modulation of several autoimmune diseases. We investigated changes in the methylome in isolated circulating CD4+ T-cells in non-pregnant and pregnant women, during the 1st and 2nd trimester, using the Illumina Infinium Human Methylation 450K array, and explored how these changes were related to autoimmune diseases that are known to be affected during pregnancy. Pregnancy was associated with several hundreds of methylation differences, particularly during the 2nd trimester. A network-based modular approach identified several genes, e.g., CD28, FYN, VAV1 and pathways related to T-cell signalling and activation, highlighting T-cell regulation as a central component of the observed methylation alterations. The identified pregnancy module was significantly enriched for disease-associated methylation changes related to multiple sclerosis, rheumatoid arthritis and systemic lupus erythematosus. A negative correlation between pregnancy-associated methylation changes and disease-associated changes was found for multiple sclerosis and rheumatoid arthritis, diseases that are known to improve during pregnancy whereas a positive correlation was found for systemic lupus erythematosus, a disease that instead worsens during pregnancy. Thus, the directionality of the observed changes is in line with the previously observed effect of pregnancy on disease activity. Our systems medicine approach supports the importance of the methylome in immune regulation of T-cells during pregnancy. Our findings highlight the relevance of using pregnancy as a model for understanding and identifying disease-related mechanisms involved in the modulation of autoimmune diseases. Abbreviations: BMIQ: beta-mixture quantile dilation; DMGs: differentially methylated genes; DMPs: differentially methylated probes; FE: fold enrichment; FDR: false discovery rate; GO: gene ontology; GWAS: genome-wide association studies; MDS: multidimensional scaling; MS: multiple sclerosis; PBMC: peripheral blood mononuclear cells; PBS: phosphate buffered saline; PPI; protein-protein interaction; RA: rheumatoid arthritis; SD: standard deviation; SLE: systemic lupus erythematosus; SNP: single nucleotide polymorphism; TH: CD4+ T helper cell; VIStA: diVIsive Shuffling Approach.</p