Fahd Adeeb

A comparative study of renal dysfunction in patients with inflammatory arthropathies: strong association with cardiovascular diseases and not with anti‐rheumatic therapies, inflammatory markers or duration of arthritis

Aims:  The aim of this study was to investigate the prevalence of chronic kidney disease (CKD) among comparable patients with rheumatoid arthritis (RA) and seronegative inflammatory arthritis, and to explore any predictive factors for renal impairment.

Early- and late-stage morphea subtypes with deep tissue involvement is treatable with Abatacept (Orencia)

OBJECTIVES This case series explores the potential efficacy of Abatacept in patients presenting with morphea subtypes and deep tissue involvement. METHODS Three patients with established morphea subtypes and deep tissue involvement and with no contraindication to Abatacept were included in this prospective open-label study. The index patient was exceptionally severely affected with a mean Modified Rodnan Skin Score (MRSS) of 38/51. At baseline, whole-body MRI and skin biopsy were performed which confirmed classical deposition of dense fibrous tissue in the appropriate layer of the skin. MRSS was performed independently by three clinicians and VAS scores (10cm) were measured at baseline for Patient Global Disease Activity (PGDA), Patient Global Pain (PGP), Patient Day Pain (PDP), Patient Night Pain (PNP), and Physician Global Disease Activity (PhGDA). Patients 2 and 3 were similarly screened at baseline except for MRI. Patients were commenced on Abatacept as per body weight (10mg/kg) given intravenously with concomitant tapering dose of oral prednisolone. All three were re-assessed at 6 months and the index case was further re-assessed at 18 months. RESULTS All patients tolerated the Abatacept well and showed dramatic improvement. The index patients clinical signs and symptoms, whole-body MRI, and mean Modified Rodnan Skin Score improved dramatically from baseline by 37% at 6 months and by 74% at 18 months. There were no clinically significant adverse outcomes noted. CONCLUSION We present three cases, one with exceptionally severe disease, which demonstrated excellent clinical response to Abatacept. Abatacept is a promising option for the treatment of severe or resistant morphea, especially in those with deep tissue involvement.

Temporal trends in hyperuricaemia in the Irish health system from 2006-2014: A cohort study.

Background Elevated serum uric acid (sUA) concentrations are common in the general population and are associated with chronic metabolic conditions and adverse clinical outcomes. We evaluated secular trends in the burden of hyperuricaemia from 2006–2014 within the Irish health system. Methods Data from the National Kidney Disease Surveillance Programme was used to determine the prevalence of elevated sUA in adults, age > 18 years, within the Irish health system. Hyperuricaemia was defined as sUA > 416.4 μmol/L in men and > 339.06 μmol/L in women, and prevalence was calculated as the proportion of patients per year with mean sUA levels above sex-specific thresholds. Temporal trends in prevalence were compared from 2006 to 2014 while general estimating equations (GEE) explored variation across calendar years expressed as odds ratios (OR) and 95% Confidence intervals (CI). Results From 2006 to 2014, prevalence of hyperuricaemia increased from 19.7% to 25.0% in men and from 20.5% to 24.1% in women, P<0.001. The corresponding sUA concentrations increased significantly from 314.6 (93.9) in 2006 to 325.6 (96.2) in 2014, P<0.001. Age-specific prevalence increased in all groups from 2006 to 2014, and the magnitude of increase was similar for each age category. Adjusting for baseline demographic characteristics and illness indicators, the likelihood of hyperuricemia was greatest for patients in 2014; OR 1.45 (1.26–1.65) for men and OR 1.47 (1.29–1.67) in women vs 2006 (referent). Factors associated with hyperuricaemia included: worsening kidney function, elevated white cell count, raised serum phosphate and calcium levels, elevated total protein and higher haemoglobin concentrations, all P<0.001. Conclusions The burden of hyperuricaemia is substantial in the Irish health system and has increased in frequency over the past decade. Advancing age, poorer kidney function, measures of nutrition and inflammation, and regional variation all contribute to increasing prevalence, but these do not fully explain emerging trends.

High Vitamin D Levels May Downregulate Inflammation in Patients with Behçet’s Disease

Vitamin D plays a significant role in the immune system modulation and may confer a protective role in autoimmune diseases. We conducted a case-control study to compare 25(OH)D levels in patients with BD who were managed at a regional rheumatology programme in the midwest region of Ireland compared to matched controls. Healthy controls were selected from the Irish health system and matched in 1 : 5 ratio for age, sex, and the month of the year. 25(OH)D levels <20 nmol/L were classified as deficient while levels between 20 and 40 nmol/L were classified as insufficient. Differences between groups were assessed using Mann–Whitney test and associations between cases and controls were expressed as odds ratios and 95% confidence intervals. Nineteen patients with BD were compared with 95 controls matched by age, sex, and month of blood draw. 25(OH)D levels were significantly higher in patients in BD than in matched controls (median values: 45 nmol/L versus 22 nmol/L, p < 0.005) and tended to be lower in patients with active disease than in those without (median values: 35 nmol/L (IQR: 22.75–47.25 nm/L) versus 50 nmol/L (IQR: 35–67 nmol/L), p = 0.11). Compared to controls, patients with BD were significantly less likely to have 25(OH)D deficiency or insufficiency (OR: 0.09, 95% CI: 0.03–0.28, p < 0.001). Our findings suggest a possible role for 25(OH)D in modifying the inflammatory response in BD and uncover a potential opportunity to assess whether correction of Vit D deficiency confers protective benefits.

The real-world use of different anti-tumor necrosis factor agents in a Northern European population of patients with Behçet's disease

Objective The aim of this study was to evaluate prescription practices, treatment responses, and serious adverse events of anti-tumor necrosis factor (anti-TNF) therapies in Behçets disease (BD). Material and Methods Patients with BD satisfying the International Study Group for Behçets Disease or the International Criteria for Behçets Disease criteria were recruited from a regional rheumatology program. The choice of anti-TNF, treatment response, and adverse events were specified. Response to treatment was evaluated by the detection of new, worsening, or improving clinical features, and management was benchmarked against current The European League against Rheumatism recommendations published in 2008. Results Out of the total of 22 patients, 18 (81.9%) received anti-TNF therapies, resulting in 14 (77.8%) complete and 4 (22.2%) partial remissions. Eleven (61.1%) patients switched to a second anti-TNF, seven patients (38.9%) required three different anti-TNFs, and one required a fourth anti-TNF to achieve remission. Two patients required retrials before their disease was controlled. Anti-TNF therapy included infliximab (IFX): n=15, 83.3%; adalimumab (ADA): n=9, 50%; golimumab: n=6, 33.3%; etanercept: n=5, 27.8%; and certolizumab pegol: n=2, 11.1%. Secondary failure was observed with IFX (4/15; 26.7%) and ADA (2/9; 22.2%), and these (100%) were manifested after at least 2 years of treatment. Five patients with potentially life-threatening laryngeal involvement received anti-TNFs successfully halting disease progression. Five allergic reactions were encountered, and five serious infections were documented involving three patients aged ≥ 50 years, all with the use of IFX. Conclusion Anti-TNF therapy induced a clinical response in 100% patients and achieved complete remission in 78% patients. It provides an effective alternative option for first-line therapy in severe BD where many conventional immunosuppressive therapies fail. Patients with BD who do not respond to one or more anti-TNFs because of intolerance, ineffectiveness, or secondary failure might benefit from switching to another drug from this group or even a retrial of a previously administered anti-TNF because unsatisfactory results with one biologic is not predictive of response to another anti-TNF. For those with potentially life-threatening destructive laryngeal manifestation, anti-TNF as a first choice may be considered.

SAT0689 Prevalence of and temporal trends in hyperuricaemia among adult patients with chronic kidney disease in ireland

Background An increasing body of evidence links hyperuricaemia with the development of several metabolic disorders and major cardiovascular outcomes. A better understanding of the burden and variation of hyperuricemia within the health system is important in order to identify high-risk groups and facilitate early intervention with effective management strategies. Objectives The aim of this study was to describe the prevalence of hyperuricaemia, and period trends within the Irish Health System among patients with chronic kidney disease (CKD). Methods 136,325 adult CKD patients aged 18 and above with valid measurements of serum uric acid and creatinine levels were identified between 2006 and 2014 from the laboratory systems within the Irish health system. Hyperuricaemia was defined as serum uric acid ≥420μmol/L in men and ≥360μmol/L in women. Estimated glomerular filtration rates were determined using the Chronic Kidney Disease-Epidemiology Collaboration (CKD-EPI) equation and patients were classified by CKD stage according to the Kidney Disease Improving Global Outcomes (KDIGO) staging system. Age- and sex-specific prevalence of hyperuricemia estimates with 95% confidence intervals were determined for each group and across calendar years. Comparisons among groups and across years were conducted using chi-square and multivariate logistic regression was used to explore associations using adjusted odds ratios (AOR) and 95% Confidence Intervals (CI). Results Patients with hyperuricaemia were noted to be older [58.2 (18.5) vs. 51.2 (17.4) years]. The prevalence of hyperuricaemia increased progressively between 2006 and 2014 from 20.3% (19.5, 21.0) to 26.5% (25.8, 27.2%) in men and from 17.9% (17.2, 18.6) to 20.4% (19.8, 21.0) in women, p<0.001. Age-specific prevalence increased significantly over time for all age groups (18–39, 40–59, 60–79, and ≥80 years) for men and women, p<0.001. Prevalence was significantly higher with more advanced CKD stage: 15.1% (14.5, 15.6) in Stage 1 CKD compared to 43.0% (34.8, 51.1) in Stage 5 CKD, p<0.001. However, rates fell significantly for those Stage 4 and 5 CKD respectively (Figure1). In multi-variable models, the adjusted likelihood of hyperuricaemia increased with each successive year (Figure 2). Conclusions The prevalence of hyperuricaemia is substantial in the Irish health system and has increased in frequency over the past decade. Although the burden was highest among patients with more advanced CKD, an encouraging decline in prevalence was observed in recent years. Greater management of gout and hyperuricaemia from increasing utilization of urate-lowering therapies may be responsible for this trend. Disclosure of Interest None declared

Knitting the threads of silk through time: Behçet’s disease—past, present, and future

Behçets disease (BD) is a chronic relapsing vasculitis that affects vessels of all types and sizes with a broad spectrum of phenotypic heterogeneity and complex immunopathogenesis. Efforts by the scientific community to resolve the unmet needs of BD and gaps in our knowledge have been hampered by considerable challenges that primarily relate to the rare nature of the disease in many parts of the world and its heterogeneity. Controversies remain in many aspects of the disease including the diagnostic criteria, immunopathogenesis and biomarker discovery, geographical variation, and therapeutic considerations. In this review, we highlight recent advances in our scientific understanding of BD, shed new insights into diagnostic and treatment strategies, and discuss residual gaps in our knowledge that will serve as the basis for current and future research.

03.08 High vitamin d levels may downregulate inflammation in behçet’s disease patients

Background Vitamin D has been shown to be directly or indirectly involved in the regulation of proliferation, differentiation, and function of immune cells. Many studies have revealed higher levels of Vitamin D deficiency among patients with autoimmune diseases compared to controls. Aim Aim of the study was to evaluate the serum 25-hydroxyvitamin D (25(OH)D) levels in Behçet’s disease (BD) patients in the midwest region of Ireland, and to correlate with its disease activity. Methods All BD patients attending our rheumatology service and satisfying the ISGBD/ICBD criteria were included in the study and compared in a 1:5 ratio with samples taken from controls matched for age, gender- and the month of the year. Exclusion criteria included other rheumatological or bone/skeletal diseases, a history of chronic kidney disease or other chronic systemic diseases, malignancies, limited physical activity, and if on vitamin D supplementation or medications that could have affected vitamin D metabolism including calcium supplements, cytotoxic drugs, anticonvulsants, bisphosphonates and thyroxine but not glucocorticoids and disease-modifying anti-rheumatic drugs. The total serum 25(OH)D was measured by using competitive chemiluminescence immunoassays (DiaSorin, Dietzenbach, Germany). Levels<20 ng/ml were defined as deficient, between 20–40 ng/ml as insufficient. Results 19 Caucasian BD patients were included in the study (5 male, 14 female, median age of 37.5 years (interquartile range (IQR), 24.3–51.2 years). The median 25(OH)D of BD patients and controls were 45 ng/ml (IQR,33–65 ng/ml) and 22 ng/ml (IQR, 15–31 ng/ml) respectively. The median 25(OH)D was relatively lower in active BD patients in comparison to inactive patients: 35 ng/ml (IQR, 22.75–47.25 ng/ml) compared to 50 ng/ml (IQR, 35–67 ng/ml). Overall, none of the patients had Vit D deficiency, however 6 patients had Vit D insufficiency. Conclusion In contrast to many previous studies in other BD cohorts and other autoimmune diseases our study suggests the mean 25(OH)D levels was significantly higher in this BD group. In patients with active disease however serum levels were relatively low compared to the inactive group which is in concordance with the literature. Our findings suggest vitamin D may be a potential suppressor of inflammation in BD, however larger studies are needed to support this thesis and to conclusively understand its role in the inflammatory pathway.

07.03 Behçet’s disease and hla-b51 in ireland

Background Behçet’s disease (BD) is a type of vasculitis with distinctive clinical manifestations and multifactorial immunopathogenesis. Association of HLA-B51 (which belongs to the HLA-B5/B35 cross-reacting group) is well recognised as the strongest genetic susceptibility gene so far in BD. Aim The aim of this study is to determine the association of HLA-B51 in our BD cohort in the Midwest region of Ireland. Methods Patients meeting the ISGBD or the ICBD criteria for BD were identified from our institutional database. Medical charts and electronic data were reviewed retrospectively to document the HLA antigen profile of the patients (which were carried out by a same recognised lab in London using Gen-Probe Lifecodes HLA-SSO Typing kits based on Luminex xMAP technology). Results 22 patients of Irish descent were identified satisfying the diagnosis for BD, and among them 19 patients (6 males, 13 females) were HLA typed. The HLA-B51 antigen was found in only one of the 19 patients (5.3%) with a higher frequency HLA-B*08, B*44 (6 patients each; 31.6%), B*35, B*57 (5 patients each; 26.3%), B*15 (4 patients; 21%) and B*27 (3 patients; 15.8%). We found no association between HLA-B*51 and our Irish cohort of BD patients compared to control. Conclusion The overall frequency of HLA-B51 is not increased in our BD cohort. We acknowledge that the study is subject to several limitations including small sample size. Further study of a larger patient population is needed, which may include combination of BD cohorts throughout the country, which will be important to substantiate, support or refute this finding.

AB0903 Behcet's Disease in The Midwest Region of Ireland: Patient Access and Response To Anti-TNF Biologics

Background Current literature shows promising data for efficacy of anti-tumor necrosis factor (anti-TNF) biological therapy in Behcets disease (BD) patients. Objectives The aim was to investigate a cohort of BD patients in Midwest Region of Ireland, current prescription practice for anti TNF biologics in this cohort, patient response & the risk of serious infections or other serious side effects. Methods All BD patients attending our rheumatology service & satisfying the ISGBD or ICBD criteria were included in the study. Response was evaluated on patients new/worsening clinical features & improvement/resolution of clinical symptoms. Management was benchmarked against current European League Against Rheumatism (EULAR) guidelines published in 2009. Serious infection was defined as the requirement for intravenous antimicrobial therapy and hospitalization. Results From a cohort of 22 patients, 18 (81.9%) received anti-TNF (6 males, 12 females) with mean age 38.9 years. 14 patients (77.8%) achieved complete remission & 4 patients (22.2%) achieved low disease activity on anti-TNF. Among this 3 patients (16.7%) were successfully switched to a different agent due to secondary failure, 6 patients (33.3%) needed 3 different anti-TNFs and one patient required a fourth anti-TNF therapy to achieve remission. Indications to start anti-TNF among our cohort include severe mucocutaneous lesions with significant impact to quality of life (15/18), ocular manifestations (7/18), destructive laryngeal disease (5/18), vascular manifestations (3/18) & resistance or intolerance to conventional treatments (8/18). Anti-TNF was extremely effective in suppressing the mucocutaneous oral & laryngeal manifestations, significantly improving patients quality of life. However resistant genital ulcers was often a difficult symptom to control with 3 patients achieving partial remission.5 allergic reactions were encountered, all with administration of infliximab. 5 serious infections were documented involving 3 patients (16.7%) and all in patients aged 50 years or above. No other serious side effects were noted. Conclusions Anti TNF-α biological therapy is an important alternative option for first line therapy in severe BD as many conventional treatments failed to maintain clinical remission and prevention of life-threatening complications. Response rates to anti-TNF-α therapy were excellent and treatment was well tolerated but should be used with caution in patients age 50 or above. BD patients who fail one anti TNF-α due to intolerance, ineffectiveness or secondary failure may still benefit from switching to another drug from this group or even re-trial of a previously administered anti-TNF. References P.P. Sfikakis, N. Marcomichelakis, E. Alpsoy et al. Anti-TNF therapy in the management of Behçets disease-review and basis for recommendations. Rheumatology (Oxford), 46 (2007), pp. 736–741 Hatemi G, Silman A, Bang D et al. Management of Behçet disease: a systematic literature review for the European League Against Rheumatism evidence-based recommendations for the management of Behçet disease. Ann Rheum Dis 68(10): 1528–1534 Fitzgerald CW, Adeeb F, Timon CV, Shine NP, Fraser AD, Hughes JP. Significant laryngeal destruction in a northern European cohort of Behçets disease patients. Clin Exp Rheumatol. 2015 Nov-Dec;33(6 Suppl 94):S123–8. Disclosure of Interest None declared