Physical activity but not sedentary activity is reduced in primary Sjögren's syndrome.

The aim of the study was to evaluate the levels of physical activity in individuals with primary Sjögren's syndrome (PSS) and its relationship to the clinical features of PSS. To this cross-sectional study, self-reported levels of physical activity from 273 PSS patients were measured using the International Physical Activity Questionnaire-short form (IPAQ-SF) and were compared with healthy controls matched for age, sex and body mass index. Fatigue and other clinical aspects of PSS including disease status, dryness, daytime sleepiness, dysautonomia, anxiety and depression were assessed using validated tools. Individuals with PSS had significantly reduced levels of physical activity [median (interquartile range, IQR) 1572 (594-3158) versus 3708 (1732-8255) metabolic equivalent of task (MET) × min/week, p < 0.001], but similar levels of sedentary activity [median (IQR) min 300 (135-375) versus 343 (223-433) (MET) × min/week, p = 0.532] compared to healthy individuals. Differences in physical activity between PSS and controls increased at moderate [median (IQR) 0 (0-480) versus 1560 (570-3900) MET × min/week, p < 0.001] and vigorous intensities [median (IQR) 0 (0-480) versus 480 (0-1920) MET × min/week, p < 0.001]. Correlation analysis revealed a significant association between physical activity and fatigue, orthostatic intolerance, depressive symptoms and quality of life. Sedentary activity did not correlate with fatigue. Stepwise linear regression analysis identified symptoms of depression and daytime sleepiness as independent predictors of levels of physical activity. Physical activity is reduced in people with PSS and is associated with symptoms of depression and daytime sleepiness. Sedentary activity is not increased in PSS. Clinical care teams should explore the clinical utility of targeting low levels of physical activity in PSS.

Real-world evidence for secukinumab in UK patients with psoriatic arthritis or radiographic axial spondyloarthritis: interim 2-year analysis from SERENA.

Objectives: The aim was to evaluate retention rates for secukinumab in patients with active PsA or radiographic axial spondyloarthritis (r-axSpA) treated in routine UK clinical practice. Methods: SERENA (CAIN457A3403) is an ongoing, non-interventional, international study of patients with moderate-to-severe chronic plaque psoriasis, active PsA or active r-axSpA, who had received secukinumab for ≥16 weeks before enrolment. The primary objective of this interim analysis was to assess treatment retention rates in patients with PsA or r-axSpA who were enrolled and followed for ≥2 years at centres in the UK. The safety analysis set includes all patients who received at least one dose of secukinumab. The target population set includes all patients who fulfilled the patient selection criteria. Results: The safety set comprised 189 patients (PsA, n = 81; r-axSpA, n = 108), and the target population set comprised 183 patients (PsA, n = 78; r-axSpA, n = 105). In the safety set, 107 patients (45 of 81 with PsA and 62 of 108 with r-axSpA) had previously received a biologic agent. Retention rates were similar between patients with PsA and r-axSpA after 1 year (PsA 91.0%, 95% CI: 84.0, 98.0; r-axSpA 89.2%, 95% CI: 82.7, 95.7) and 2 years (PsA 77.6%, 95% CI: 67.6, 87.7; r-axSpA 76.2%, 95% CI: 67.4, 85.0) of observation. Overall, 17.5% of patients (33 of 189) experienced at least one treatment-related adverse event, and 12.7% of patients (24 of 189) discontinued secukinumab because of adverse events. Conclusion: This analysis of real-world data from the UK demonstrates high retention rates for secukinumab over 2 years in patients with PsA or r-axSpA, with a favourable safety profile.

Subjective and Objective Measures of Dryness Symptoms in Primary Sjögren's Syndrome: Capturing the Discrepancy.

OBJECTIVE: To develop a novel method for capturing the discrepancy between objective tests and subjective dryness symptoms (a sensitivity scale) and to explore predictors of dryness sensitivity. METHODS: Archive data from the UK Primary Sjögren's Syndrome Registry (n = 688) were used. Patients were classified on a scale from -5 (stoical) to +5 (sensitive) depending on the degree of discrepancy between their objective and subjective symptoms classes. Sensitivity scores were correlated with demographic variables, disease-related factors, and symptoms of pain, fatigue, anxiety, and depression. RESULTS: Patients were on average relatively stoical for both types of dryness symptoms (mean ± SD ocular dryness -0.42 ± 2.2 and -1.24 ± 1.6 oral dryness). Twenty-seven percent of patients were classified as sensitive to ocular dryness and 9% to oral dryness. Hierarchical regression analyses identified the strongest predictor of ocular dryness sensitivity to be self-reported pain and that of oral dryness sensitivity to be self-reported fatigue. CONCLUSION: Ocular and oral dryness sensitivity can be classified on a continuous scale. The 2 symptom types are predicted by different variables. A large number of factors remain to be explored that may impact symptom sensitivity in primary Sjögren's syndrome, and the proposed method could be used to identify relatively sensitive and stoical patients for future studies.

The prevention and treatment of glucocorticoid-induced osteoporosis in clinical practice.

Glucocorticoids are associated with increased risk of bone loss and fracture. This study compared the prescribing of bone protective agents by rheumatologists in clinical practice with the standards recommended in the 1998 UK Consensus guidelines. All glucocorticoid users who attended rheumatology outpatients during a four-week period were eligible. Notes were audited according to a predefined proforma. Among the 1290 rheumatology outpatients seen in the study period, 189 (15%) were taking glucocorticoids. 63% of glucocorticoid patients were taking calcium and 46% vitamin D. In total, 124 (71%) of the 175 patients available for review were at high risk of osteoporotic fracture, of whom 76 (61%) were taking appropriate prophylaxis. In 26 (15%) patients, insufficient information was available to be able to quantify the risk of fracture. The study showed that the audit standard was not met in 39% of cases. A better strategy for the monitoring of clinical risk factors is therefore required.

Intra-articular injection and driving advice: a survey of UK rheumatologists' current practice.

OBJECTIVE: To determine the current practice of UK rheumatologists regarding driving advice and intra-articular injection. A secondary objective was to clarify legal advice on driving after intra-articular injection. METHODS: A link to an online questionnaire was sent out via the British Society of Rheumatology (BSR) monthly e-newsletter to all BSR members in January 2010. In addition, we contacted the Medical Defence union (MDU), Medical Protection Society (MPS), Driving and Vehicle Licensing Agency (DVLA) and insurance companies for statements regarding legal advice. RESULTS: A total of 134 responses were obtained. These were collected on a web-based database. The majority of forms returned were from consultant rheumatologists. Fifty-six per cent of respondents said that they routinely asked patients about driving prior to joint injection. Seventy-six respondents (57%) considered driving to be an issue when injecting joints. If a patient had driven to clinic, 30% of respondents said that they would inject as normal, 28% opting to inject but ask the patient to wait following injection. Only 12% (16 respondents) said that they would not undertake an injection if the patient was driving. Sixty-one (46%) respondents did not run an injection clinic. Of those who did (71 respondents) 55% pre-warned patients not to drive. CONCLUSION: There is no clear consensus among rheumatologists as to practice regarding driving following an intra-articular injection. Medico-legally, there is no absolute bar to driving following an intra-articular injection, and guidance points to clinicians' own judgement as to the safety of driving.

The natural history of ankylosing spondylitis as defined by radiological progression.

OBJECTIVE: Radiological status is an important objective endpoint in the assessment of ankylosing spondylitis (AS). We investigated the disease development of AS using radiological change. METHODS: The existing radiographs (n = 2,284) of 571 AS patients attending the Royal National Hospital for Rheumatic Diseases were scored retrospectively using the Bath Ankylosing Spondylitis Radiology Index. (1) Progression of disease was initially examined cross sectionally. Univariate analysis was used to examine factors associated with joint involvement. (2) Progression of disease was then examined longitudinally for patients with films at time of symptom onset. (3) Rate of progression of radiological change was calculated using longitudinal data of 2 sets of radiographs taken 10 years apart (patient number = 54). The results from this were used to extrapolate backwards to age at first radiological change. RESULTS: (1) Progression to cervical spine disease was a function of: disease duration, severity of hip and lumbar involvement, and a history of iritis (p < 0.001). Lumbar involvement was associated with disease duration, age now, and severity of cervical and hip involvement (p < 0.001). Hip involvement was a marker for cervical disease and associated with disease duration (p < 0.001). (2) Longitudinal analysis revealed marked variation among patients with a slow general rate of progression. (3) The progression of AS over any 10 year period is linear [first 10 years = 30% (SD 0.3) of potential change, 10-20 yrs = 40% (SD 0.3) change, 20-30 yrs = 35% (SD 0.4) change (p = 0.5)]. Backward extrapolation suggests that the approximate time of first radiological change is at the age of 8 years. CONCLUSION. (1) AS is a linearly progressive disease with about 35% change every 10 years. Spinal involvement is largely an expression of disease duration while the hips become involved in about 25% of individuals and may predict a more severe outcome for the cervical spine. (2) Backward extrapolation shows that the disease process may start as young as 8 years of age. However, the time interval between the disease trigger and radiological change remains unknown.

Predictors of longterm outcome in ankylosing spondylitis.

OBJECTIVE: To determine predictors of longterm outcome in ankylosing spondylitis (AS). METHODS: Data were collected retrospectively on constitutional and environmental factors that may predict outcome in AS in 311 patients (252 men, 81%). Univariate statistics and multivariable linear regression analyses were used to identify factors correlated with disease outcome, which was defined in terms of radiological (Bath AS Radiology Index, BASRI) and functional status (Bath AS Functional Index, BASFI). RESULTS: Disease duration, sex, and iritis are independently associated with BASRI and account for 23% (p < 0.001) of variation in radiological scores (BASRI-t), a measure that includes the hip joint in the score. Radiological hip involvement is significantly associated with higher scores of spinal radiological change (BASRI-s) (p < 0.001). Cigarette smoking, radiological status, and Bath AS Disease Activity Index score (BASDAI) are independently associated with and account for 50% of variability in functional status (p < 0.001). CONCLUSION: Much of the variability in disease severity in AS remains unexplained. All but one of the factors associated with outcome in this study are inherent. This suggests that genetic factors have a greater influence than environmental factors on radiological progression and disability in AS. It may, however, be possible to improve longterm functional outcome in AS by targeting high risk individuals early in the disease course with more aggressive management strategies and encouraging smoking cessation in all patients with AS.

Investigation of susceptibility loci identified in the UK rheumatoid arthritis whole-genome scan in a further series of 217 UK affected sibling pairs.

OBJECTIVE: A previous whole-genome scan (WGS) of 182 UK rheumatoid arthritis (RA) affected sibling pair (ASP) families suggested linkage to HLA and 11 other chromosome regions. Replication of such findings in an independent cohort can help to distinguish true linkages from false-positive linkages. Since RA is a heterogeneous disease, some loci may be linked only in subsets of patients. Thus, the aim of this study was to investigate in an additional set of RA ASP families linkage to regions showing deviation in expected allele-sharing ratios in the UK WGS and to perform subset analysis on the combined cohort. METHODS: Twenty loci were investigated for linkage in 217 Caucasian UK RA ASPs. Stratification analysis was performed on the combined cohort of 377 RA ASP families to account for sex, RA severity, and the shared epitope (SE). RESULTS: None of the regions of linkage identified in the initial WGS achieved statistical significance in the second cohort. In contrast, after stratification analysis, 14 regions showed nominal evidence of linkage (logarithm of odds score >0.8) in one or more subgroups. In particular, the strength of evidence for linkage to chromosome 16p was increased in subsets of ASPs with younger age at disease onset (LOD score 2.38) and for linkage to chromosome 6q in female-female ASPs (LOD score 2.31) and in ASPs in which both siblings had 2 copies of the SE (LOD score 3.03). CONCLUSION: These results support the evidence for heterogeneity of RA. This information will inform the future design of association-based investigations as the search for disease genes in the linked regions begins.

Whole-genome linkage analysis of rheumatoid arthritis susceptibility loci in 252 affected sibling pairs in the United Kingdom.

OBJECTIVE: To undertake a systematic whole-genome screen to identify regions exhibiting genetic linkage to rheumatoid arthritis (RA). METHODS: Two hundred fifty-two RA-affected sibling pairs from 182 UK families were genotyped using 365 highly informative microsatellite markers. Microsatellite genotyping was performed using fluorescent polymerase chain reaction primers and semiautomated DNA sequencing technology. Linkage analysis was undertaken using MAPMAKER/SIBS for single-point and multipoint analysis. RESULTS: Significant linkage (maximum logarithm of odds score 4.7 [P = 0.000003] at marker D6S276, 1 cM from HLA-DRB1) was identified around the major histocompatibility complex (MHC) region on chromosome 6. Suggestive linkage (P < 7.4 x 10(-4)) was identified on chromosome 6q by single- and multipoint analysis. Ten other sites of nominal linkage (P < 0.05) were identified on chromosomes 3p, 4q, 7p, 2 regions of 10q, 2 regions of 14q, 16p, 21q, and Xq by single-point analysis and on 3 sites (1q, 14q, and 14q) by multipoint analysis. CONCLUSION: Linkage to the MHC region was confirmed. Eleven non-HLA regions demonstrated evidence of suggestive or nominal linkage, but none reached the genome-wide threshold for significant linkage (P = 2.2 x 10(-5)). Results of previous genome screens have suggested that 6 of these regions may be involved in RA susceptibility.