Basic science232. Certolizumab pegol prevents pro-inflammatory alterations in endothelial cell function

Background: Cardiovascular disease is a major comorbidity of rheumatoid arthritis (RA) and a leading cause of death. Chronic systemic inflammation involving tumour necrosis factor alpha (TNF) could contribute to endothelial activation and atherogenesis. A number of anti-TNF therapies are in current use for the treatment of RA, including certolizumab pegol (CZP), (Cimzia ®; UCB, Belgium). Anti-TNF therapy has been associated with reduced clinical cardiovascular disease risk and ameliorated vascular function in RA patients. However, the specific effects of TNF inhibitors on endothelial cell function are largely unknown. Our aim was to investigate the mechanisms underpinning CZP effects on TNF-activated human endothelial cells. Methods: Human aortic endothelial cells (HAoECs) were cultured in vitro and exposed to a) TNF alone, b) TNF plus CZP, or c) neither agent. Microarray analysis was used to examine the transcriptional profile of cells treated for 6 hrs and quantitative polymerase chain reaction (qPCR) analysed gene expression at 1, 3, 6 and 24 hrs. NF-κB localization and IκB degradation were investigated using immunocytochemistry, high content analysis and western blotting. Flow cytometry was conducted to detect microparticle release from HAoECs. Results: Transcriptional profiling revealed that while TNF alone had strong effects on endothelial gene expression, TNF and CZP in combination produced a global gene expression pattern similar to untreated control. The two most highly up-regulated genes in response to TNF treatment were adhesion molecules E-selectin and VCAM-1 (q 0.2 compared to control; p > 0.05 compared to TNF alone). The NF-κB pathway was confirmed as a downstream target of TNF-induced HAoEC activation, via nuclear translocation of NF-κB and degradation of IκB, effects which were abolished by treatment with CZP. In addition, flow cytometry detected an increased production of endothelial microparticles in TNF-activated HAoECs, which was prevented by treatment with CZP. Conclusions: We have found at a cellular level that a clinically available TNF inhibitor, CZP reduces the expression of adhesion molecule expression, and prevents TNF-induced activation of the NF-κB pathway. Furthermore, CZP prevents the production of microparticles by activated endothelial cells. This could be central to the prevention of inflammatory environments underlying these conditions and measurement of microparticles has potential as a novel prognostic marker for future cardiovascular events in this patient group. Disclosure statement: Y.A. received a research grant from UCB. I.B. received a research grant from UCB. S.H. received a research grant from UCB. All other authors have declared no conflicts of interes

Prescribing patterns and safety of biologics in immune-mediated rheumatic diseases: Karnataka biologics cohort study group experience

Introduction: Biologics are widely used in Autoimmune rheumatologic diseases (AIRDs), however the need to capture real life data which monitors indications, adverse reactions cannot be over emphasized. Methods: This is a cross-sectional ambidirectional multi-center study conducted over 8 months from January 2016 to August 2016, across 12 tertiary care rheumatology centers in Karnataka, India conducted by members of the Karnataka Rheumatology Association. Results: The most common biologic prescribed is tumour necrosis factor antagonist etanercept. Commonest indication for biologics being Spondyloarthropathy group of disorders. The most common cause for stopping biologics is clinical improvement. Only 4.8% of patents discontinued biologics due to ADRs. Conclusion: The prescribing patterns, mode of use, prebiologics screening methods, and adverse event profile are similar across centres. Pre-screening for latent tuberculosis (TB) is consistent across centres, and TB prophylaxis appears to be effective in preventing its reactivation

Impaired mobility drives disability in psoriatic arthritis – An observational study from Karnataka Psoriatic Arthritis Cohort (KPsAC)

Introduction: Psoriatic arthritis (PsA) is a chronic inflammatory disease with significant functional impairment. Health Assessment Questionnaire-Disability Index (HAQ-DI) is a reliable and validated outcome measure for a variety of arthritides including PsA. Objective: The objective of this study was to assess the disability as an outcome measure in PsA using the Indian version of HAQ (I-HAQ). Methods: The I-HAQ was administered to PsA patients diagnosed as per the Classification Criteria for PsA. The I-HAQ comprises 12 questions (nine basic and three advanced activities of daily living (ADLs), on the standard HAQ format) relevant to the Indian population. Results: In the 549 participants, the mean I-HAQ was 0.31 (0.45) and 48.2% had mild-to-moderate disability (I-HAQ>0–1). Female gender, older age, higher skin, joint scores, and Disease Activity Index for PsA were associated with some disability (I-HAQ>0). Symmetric polyarthritis (0.34) and spondyloarthritis (0.32) had a significantly higher disability compared to other subsets. Analyzing the individual questions of I-HAQ, squatting in the toilet or sitting cross-legged on the floor (r = 0.78), walking 3 km (r = 0.77), and climbing a flight of stairs (r = 0.74) correlated maximally to the total I-HAQ. ADL which was affected most frequently was “climbing a flight of stairs.” I-HAQ was significantly lower in patients who had been on disease-modifying antirheumatic drugs for 6 months or more (P = 0.0001). Conclusions: The Indian version of HAQ-DI could be efficiently employed to assess outcomes in our cohort. Nearly half of the cohort had mild-to-moderate disability suggesting a high burden of inflammation. Higher joint activity scores are strongly associated with disability