ObjectivesTo identify serious infection (SI) risk by aetiology and site in patients with rheumatoid arthritis (RA) compared with those with non-inflammatory rheumatic and musculoskeletal diseases (NIRMD).MethodsPatients participating in FORWARD from 2001 to 2016 were assessed for SIs; defined by infections requiring hospitalisation, intravenous antibiotics or followed by death. SIs were categorised by aetiology and site. SI risk was assessed through Cox proportional hazards models. Best models were selected using machine learning Least Absolute Shrinkage and Selection Operator (LASSO) methodology.ResultsAmong 20 361 patients with RA and 6176 patients with NIRMD, 1600 and 276 first SIs were identified, respectively. Incidence of SIs was higher in RA compared with NIRMD (IRR = 1.5; 95% CI 1.2 to 1.5). The risk persisted after adjusting using the LASSO model (HR 1.7; 95% CI 1.5 to 1.8), but attenuated when additionally adjusted for glucocorticoid use (HR 1.3; 95% CI 1.2 to 1.5). SI risk was significantly higher in RA versus NIRMD for bacterial infections as well as for respiratory, skin, bone, joint, bloodstream infections and sepsis irrespective of glucocorticoid use. Compared with NIRMD, SI risk was significantly increased in patients with RA who were in moderate and high disease activity but was similar to those in low disease activity/remission (p trend < 0.001).ConclusionsThe risk of all SIs, particularly bacterial, respiratory, bloodstream, sepsis, skin, bone and joint infections are significantly increased in patients with RA compared with patients with NIRMD. This infection risk appears to be greatest in those with higher RA disease activity.

In RA, incidence of DM is increased. Hydroxychloroquine and abatacept were associated with decreased risk of DM, and glucocorticoids and statins with increased risk.

ObjectiveTo examine the fracture risk with use of disease-modifying antirheumatic drugs (DMARDs), statins, proton pump inhibitors (PPIs), opioids, non-opioid analgesics and psychotropic medications in a US-wide observational rheumatoid arthritis (RA) cohort.MethodsPatients with RA without prior fracture from 2001 through 2017 in FORWARD, a longitudinal observational registry, were assessed for osteoporosis-related site fractures (vertebra, hip, forearm and humerus). DMARD exposure was assessed in four mutually exclusive groups: (1) methotrexate monotherapy-reference, (2) tumour necrosis factor-α inhibitors (TNFi), (3) non-TNFi biologics and (4) others. Non-DMARDs and glucocorticoids were classified as current/ever use and based on treatment duration. Fracture Risk Assessment Tool (FRAX) scores estimating for 10-year major osteoporotic fractures were calculated. Cox proportional hazard models stratified by FRAX were used to adjust for confounders.ResultsDuring median (IQR) 3.0 (1.5–6.0) years of follow-up in 11 412 patients, 914 fractures were observed. The adjusted models showed a significant fracture risk increase with use of any dose glucocorticoids ≥3 months (HR (95% CI) for <7.5 mg/day 1.26 (1.07 to 1.48) and for ≥7.5 mg/day 1.57 (1.27 to 1.94)), opioids (for weak: 1.37 (1.18 to 1.59); strong: 1.53 (1.24 to 1.88)) and selective serotonin reuptake inhibitors (SSRIs) (1.37 (1.15 to 1.63)). Fracture risk with opioids increased within 1 month of use (1.66 (1.36 to 2.04)) and with SSRIs >3 months of use (1.25 (1.01 to 1.55)). Statins (0.77 (0.62 to 0.96)) and TNFi (0.72 (0.54 to 0.97)) were associated with reduction in vertebral fracture risk only. PPIs and other psychotropic medications were not associated with increased fracture risk.ConclusionUse of opioids, SSRIs and glucocorticoids were associated with increased risk of any fracture in patients with RA, whereas statins and TNFi were associated with decreased vertebral fractures.

Objective To examine the comparative effects of biologic disease-modifying antirheumatic drugs (bDMARDs) and tofacitinib against conventional synthetic (cs) DMARDs on incident cardiovascular disease (CVD) in patients with rheumatoid arthritis (RA). Methods RA patients with ≥1-year participation in FORWARD from 1998 through 2017 were assessed for incident composite CVD events (myocardial infarction, stroke, heart failure and CVD-related death validated from hospital/death records). DMARDs were categorized into 7 mutually exclusive groups: (1) csDMARDs-referent (2) TNFi (3) Abatacept (4) Rituximab (5) Tocilizumab (6) Anakinra (7) Tofacitinib. Glucocorticoids were assessed using a weighted cumulative exposure (WCE) model which combines information about duration, intensity, and timing of exposure into a summary measure by using the weighted sum of past oral doses (prednisolone equivalent). Cox proportional hazard models were used to adjust for confounders. Results During median (IQR) 4.0 (1.7-8.0) years of follow-up, 1,801 CVD events were identified in 18,754 RA patients. The adjusted model showed CVD risk reduction with TNFi (HR 0.82 [95% CI 0.72-0.94]) and abatacept (HR 0.50 [95% CI 0.30-0.83]) compared to csDMARDs. While higher glucocorticoid exposure as WCE was associated with CVD risk increase (HR 1.15 [95% CI 1.11-1.19]), methotrexate use was associated with CVD risk reduction (use vs. non-use: HR 0.82 [95% CI 0.74-0.90] and high-dose[>15mg/week] vs. lowdose[≤ 15mg/week]: HR 0.83 [95% CI 0.70-0.99]). Conclusion Abatacept and TNFi were associated with decreased risk of CVD compared to csDMARDs. Minimizing glucocorticoid use and optimizing MTX dose may improve CV outcomes in patients with RA.

Th1/Th17-type T-cell responses are upregulated in Behcet’s disease (BD). However, signaling pathways associated with this aberrant immune response are not clarified. Whole-genome microarray profiling was performed with human U133 (Plus 2.0) chips using mRNA of isolated CD14+ monocytes and CD4+ T-cells from PBMC in patients with BD (n=9) and healthy controls (HC) (n=9). Flow cytometric analysis of unstimulated (US) and stimulated (PHA) STAT3 and pSTAT3 expressions of PBMCs were also analysed (BD and HC, both n=26). JAK1 was observed to be upregulated in both CD14+ monocytes (1.95 fold) and CD4+ T-lymphocytes (1.40 fold) of BD patients. Using canonical pathway enrichment analysis, JAK/STAT signaling was identified as activated in both CD14+ monocytes (p= 9.55E-03) and in CD4+ lymphocytes (p= 8.13E-04) in BD. Interferon signaling was also prominent among upregulated genes in CD14+ monocytes (p= 5.62E-05). Glucocorticoid receptor signaling and IL-6 signaling were among the most enriched pathways in differentially expressed genes in CD14+ monocytes (p= 2.45E-09, and 1.00E-06, respectively). Basal unstimulated total STAT3 expression was significantly higher in BD (1.2 vs 3.45, p<0.05). The JAK1/STAT3 signaling pathway is activated in BD, possibly through the activation of Th1/Th17-type cytokines such as IL-2, IFNγ, IL-6, IL-17 and IL-23.

ObjectiveThe objective of this study is to examine the risk of serious infections (SIs) associated with biological disease‐modifying antirheumatic drugs (bDMARDs) compared with conventional synthetic disease‐modifying antirheumatic drugs (csDMARDs) in patients with rheumatoid arthritis (RA).MethodsWe studied patients with RA who initiated bDMARDs or csDMARDs from 2001 to 2016 in FORWARD–The National Databank for Rheumatic Diseases. Disease‐modifying antirheumatic drugs (DMARDs) were categorized into three groups: (1) csDMARDs (bDMARD‐naïve; reference), (2) tumor necrosis factor α inhibitors (TNFis), and (3) non‐TNFi biologics (abatacept, rituximab, tocilizumab, and anakinra). SIs were defined as those requiring intravenous antibiotics or hospitalization or those resulting in death. We calculated the propensity score (PS), which reflected the probability of receiving a specific DMARD group, and estimated the hazard ratio (HR) (with the 95% confidence interval [CI]) for SI from multivariable Cox models, adjusting for PS and time‐varying confounders.ResultsA total of 694 (5.9%) first SIs were identified in 11 623 patients with RA during 27 552 patient‐years of follow‐up. The SI incidence rate per 1000 patient‐years was 22.4 (95% CI 19.2‐26.1) for csDMARDs, 26.9 (95% CI 24.5‐29.6) for TNFis, and 23.3 (95% CI 19.0‐28.5) for non‐TNFi bDMARDs. Adjusted HRs for SIs were 1.33 (95% CI 1.05‐1.68) for TNFis and 1.48 (95% CI 1.02‐2.16) for non‐TNFi bDMARDs, compared with csDMARDs. The SI risk with non‐TNFi bDMARDs versus TNFis was not different. Other risk factors for SI were older age, higher comorbidity burden (particularly pulmonary disease), higher weighted cumulative prednisone dose, disability and disease activity, and number of prior csDMARD failures.Conclusion TNFis and non‐TNFi bDMARDs were associated with an increased SI risk compared with csDMARDs in RA, even after accounting for risk‐associated patient characteristics.

The use of 2D STE can be helpful in the detection of impairment in RV and RA functions in SSc patients with normal PAP.

Background To assess the risks of malignancies, infections and autoimmune diseases in patients with rheumatoid arthritis (RA) treated with abatacept compared with other biologic (b) disease-modifying antirheumatic drugs (DMARDs) or conventional synthetic (cs)DMARDs, in a US-wide observational RA cohort Methods Data were reviewed from patients (≥ 18 years) with RA who were registered with FORWARD, the National Databank for Rheumatic Diseases, and who initiated abatacept, other bDMARDs or csDMARDs between 2005 and 2015. Patients who switched treatment during the study could be allocated to more than one group. The incidence rates (IRs) by treatment were calculated for malignancies, hospitalized infections and autoimmune diseases identified by six monthly questionnaires and medical records. The hazard ratios (HRs) (95% confidence intervals [CIs]) for all outcomes with abatacept compared with other bDMARDs or csDMARDs were determined using marginal structural models adjusted for clinical confounders. Results In the study sample, 1496 initiated abatacept, 3490 initiated another bDMARD and 1520 initiated a csDMARD. The risk of malignancies with abatacept was not statistically significant versus other bDMARDs (HR [95% CI)] 1.89 [0.93, 3.84]) or versus csDMARDs (HR [95% CI] 0.93 [0.20, 4.27]). Patients receiving abatacept versus other bDMARDs were at a lower risk of hospitalized infections (HR [95% CI] 0.37 [0.18, 0.75]); the risk versus csDMARDs was lower with wide CIs (HR [95% CI] 0.31 [0.09, 1.05]). The relative risks for psoriasis were similar between treatment groups (HR [95% CI] 1.46 [0.76, 2.81] and HR [95% CI] 2.05 [0.59, 7.16] for abatacept versus other bDMARDs and versus csDMARDS, respectively). The IR (95% CI) of severe infusion/injection reactions was lower with abatacept compared with other bDMARDs (1.57 [1.11, 2.17] vs 2.31 [1.87, 2.82] per 100 patient-years, respectively). Conclusions In this analysis, abatacept was well tolerated and did not result in an overall increased risk of malignancies, infections or autoimmune diseases compared with other bDMARDs or csDMARDs. Electronic supplementary material The online version of this article (10.1186/s13075-019-1921-z) contains supplementary material, which is available to authorized users.