Scoring inflammatory activity of the spine by magnetic resonance imaging in ankylosing spondylitis: a multireader experiment

OBJECTIVE: Magnetic resonance imaging (MRI) of the spine is increasingly important in the assessment of inflammatory activity in clinical trials with patients with ankylosing spondylitis (AS). We investigated feasibility, inter-reader reliability, sensitivity to change, and discriminatory ability of 3 different scoring methods for MRI activity and change in activity of the spine in patients with AS. METHODS: Thirty sets of spinal MRI at baseline and after 24 weeks of followup, derived from a randomized clinical trial comparing a tumor necrosis factor (TNF)-blocking drug (n = 20) with placebo (n = 10) and selected to cover a wide range of activity at baseline and change in activity, were presented electronically in a partial latin-square design to 9 experienced readers from different countries (Europe, Canada). Readers scored each set of MRI 3 times, using 3 different methods including the Ankylosing Spondylitis spine Magnetic Resonance Imaging-activity [ASspiMRI-a, grading activity (0-6) per vertebral unit in 23 units]; the Berlin modification of the ASspiMRI-a; and the Spondyloarthritis Research Consortium of Canada (SPARCC) scoring system, which scores the 6 vertebral units considered by the reader as the most abnormal, with additional scores for "depth" and "intensity." Both the order of the methods used by each reader and the timepoints (before/after treatment) were randomized. Feasibility of each scoring system was evaluated by measuring the mean time needed to score each set of MRI, and inter-reader reliability was evaluated by smallest detectable change (SDC) and by intraclass correlation coefficients (ICC) for all readers together and for all possible reader pairs separately. Sensitivity to change was investigated by calculating Guyatt's effect size on change scores. Discriminatory ability was assessed using Z-scores (Mann-Whitney test) comparing change in score between patients treated with TNF-blocking drug and placebo. RESULTS: The mean time to score one set of MRI was shortest for the Berlin method. SDC was lowest for the Berlin method and highest for SPARCC. Overall inter-reader ICC per method were between 0.49 and 0.77 for scoring activity status, and between 0.46 and 0.72 for scoring activity change. ICC for all possible reader pairs showed much more fluctuation per method, with lowest observed values of about 0.05 (very low agreement) and highest observed values over 0.90 (excellent agreement). In general, ICC for SPARCC were consistently higher than for other systems. Sensitivity to change differed per reader, and was more consistent with SPARCC than with the other methods, but was in general excellent for all 3 methods. Discrimination between groups (TNF-blocker vs placebo) assessed by Z-scores was good and comparable among methods. CONCLUSION: This experiment demonstrates the feasibility of multiple-reader MRI scoring exercises for method comparison, provides evidence for the feasibility, reliability, sensitivity to change, and discriminatory capacity of all 3 tested scoring systems to be used in assessing spinal activity on MRI in patients with AS in clinical trials. On the basis of these results it is not possible to prioritize one of the 3 methods.     

The Natural Course of Radiographic Progression in Ankylosing Spondylitis: Differences Between Genders and Appearance of Characteristic Radiographic Features

Our study set out to analyze the radiographic progression of ankylosing spondylitis (AS) patients based on gender differences. A total of 146 AS patients were retrospectively blindly analyzed in at least 2 time points within 6 years using the modified Stokes AS Spine Score. The mean follow-up time was 3.8 ± 1.7 years, and 114 patients (78%) were male. The overall progression was similar between genders. Females showed higher progression in the cervical spine, and males in the lumbar spine. More females showed new cervical syndesmophytes, and more males showed new lumbar syndesmophytes. More females showed slow radiographic progression, and more males showed fast radiographic progression, while moderate progression was similar for both genders. Dorsal syndesmophytes showed no impact in the prediction of future progression. Female AS patients showed more cervical structural lesions, but male patients overall showed more rapid progress, leading us to conclude that dorsal vertebral edges do not add in depiction of radiographic deterioration in AS patients.     

Anxiety is associated with hormonal and metabolic profile in women with polycystic ovarian syndrome

Background Increased prevalence of psychological morbidities, including anxiety, depression and eating disorders, has been reported in women with polycystic ovary syndrome (PCOS) in comparison with normal ovulating, nonhyperandrogenemic women. Aim of the study To investigate the relationship between the degree of anxiety, depression and eating disorders via self‐reported symptoms and the severity of hormonal and metabolic aberrations in women with PCOS. For this purpose, the PCOS cohort was subdivided into three subgroups according to the degree of anxiety. Methods One hundred and thirty women with PCOS of similar age and BMI were studied. In each subject, hormonal and metabolic status as well as psychological profile was assessed with the use of specific questionnaires. Specifically, anxiety (trait and state) was assessed with the use of STAI‐T and STAI‐S, while depression and eating disorders were evaluated with the use of the Beck Depression Inventory and the Eating Attitudes test, respectively. Results The subgroups did not differ in age and BMI. Subjects with the highest STAI‐S compared with those with the lowest STAI‐S displayed significantly higher the homeostasis assessment model‐insulin resistance (HOMA‐IR) and free androgen index values (P < 0·05), respectively. Regarding trait anxiety, assessed by STAI‐T, HOMA‐IR values were significantly elevated (P < 0·05) in the subgroup with the higher STAI‐T score compared with the HOMA‐IR in the group with the lower STAI‐T score. Conclusions In women with PCOS, the degree of anxiety, state and trait (STAI‐S, STAI‐T) appears to vary in a pattern similar to that of hyperandrogenemia and insulin resistance, independently of age and BMI. The pathophysiological mechanisms underlying the association of psychological morbidities with androgen excess and insulin resistance in PCOS remain to be elucidated.     

Is there a need for weekend face-to-face inpatient assessments by hospital specialist palliative care services? Evaluation of an out-of-hours service

There is an increasing demand for hospital specialist palliative care services to be made more accessible outside of normal working hours. However, it has been argued that extended service provision could be misused and that specialist telephone advisory services are an adequate response to this demand. A 'routine' Saturday face-to-face visiting service was introduced into a hospital palliative care team and the service was evaluated to determine whether it was being utilised appropriately. A retrospective notes review of out-of-hours assessments was undertaken. Anonymised data relating to the nature of the interaction with the palliative care team and the outcome of the consultation were entered into an electronic database. A random sample of routine weekday interactions was also evaluated. A total of 336 Saturday and 93 weekday assessments were analysed. Most of the Saturday assessments resulted in a significant change in management (57%) or were undertaken on patients close to death (10%). There were 39/336 (12%) new referrals assessed on Saturdays. There were few differences between the nature of the Saturday and the weekday service and no evidence of 'inappropriate' referrals. We found clear evidence of the need for a specialist out-of-hours face-to-face inpatient visiting service for hospital palliative care.     

Do patients with non‐radiographic axial spondylarthritis differ from patients with ankylosing spondylitis?

Objective

Patients with axial spondylarthritis (SpA) who have structural changes in the sacroiliac joints and/or the spine have been classified as having ankylosing spondylitis (AS), while those without such changes are now classified as having nonradiographic axial SpA (nr‐axSpA). The differentiating features are incompletely understood.

Methods

Data from 100 consecutive patients with axial SpA not treated with tumor necrosis factor antagonists were compared clinically and with laboratory parameters, spinal radiographs, and magnetic resonance imaging (MRI) of the spine. Standardized clinical assessment tools were used to assess health status.

Results

AS was diagnosed in 56 patients and nr‐axSpA in 44 patients. Signs of inflammation were significantly higher in patients with AS than in patients with nr‐axSpA, with a median C‐reactive protein level of 8.0 versus 3.8 mg/liter, a median Ankylosing Spondylitis Disease Activity Score of 2.2 versus 2.8, respectively, and a median amount of spinal inflammatory lesions on MRI of 2.0 versus 0.0, respectively. Significant differences between these 2 groups were seen in sex (76.8% male AS patients versus 31.8% male nr‐axSpA patients). Clinical variables did not differ between patients with AS and nr‐axSpA (Bath Ankylosing Spondylitis Disease Activity Index, Bath Ankylosing Spondylitis Functional Index, Ankylosing Spondylitis Quality of Life questionnaire, Short Form 36 health survey).

Conclusion

Patients with nr‐axSpA were characterized by the low proportion of male patients and the low burden of inflammation compared to patients with AS. While both groups did not differ regarding health status, disease activity, and physical function, they did differ in signs of inflammation; all were higher in patients with AS. Since many patients with nr‐axSpA had not developed structural changes after years of symptoms, we propose that those patients should not be regarded as having preradiographic AS but rather as having nr‐axSpA.     

The early disease stage in axial spondylarthritis: Results from the german spondyloarthritis inception cohort

Objective

Ankylosing spondylitis (AS) is diagnosed late, because radiographs of the sacroiliac joints often do not show definite sacroiliitis at the time of disease onset. The aim of this study was to investigate whether patients without definite radiographically defined sacroiliitis, referred to as nonradiographic axial spondylarthritis (SpA), are different from patients with AS with regard to clinical manifestations and disease activity measures. Moreover, we sought to identify determinants of the development of radiographic sacroiliitis.

Methods

In a cross‐sectional analysis of 462 patients, we compared 226 patients with nonradiographic axial SpA (symptom duration ≤5 years) and 236 patients with AS (symptom duration ≤10 years) who are participants in the German Spondyloarthritis Inception Cohort. Radiographs of the sacroiliac joints and the spine were assessed by 2 readers in a blinded manner. Logistic regression analysis was applied to identify parameters associated with structural damage.

Results

The 2 groups did not differ in the frequency of HLA–B27 positivity, inflammatory back pain, arthritis, enthesitis, and uveitis and had similar levels of disease activity, using measures such as the Bath Ankylosing Spondylitis Disease Activity Index. In both groups, HLA–B27 positivity determined the age at disease onset. Male sex (adjusted odds ratio [OR] 2.38, 95% confidence interval [95% CI] 1.19–4.73 [P = 0.014]) and an elevated C‐reactive protein (CRP) level (adjusted OR 1.85, 95% CI 0.96–3.56 [P = 0.066]) were associated with radiographic sacroiliitis. In patients with AS, male sex and an elevated CRP level were also associated with the presence of syndesmophytes.

Conclusion

Clinical manifestations and disease activity measures are highly comparable between patients with early nonradiographic axial SpA and those with early AS, suggesting that these 2 entities are part of the same disease. Male sex and an elevated CRP level are associated with structural damage on radiographs, whereas HLA–B27 positivity determines the age at disease onset.

     

Anaemia is associated with higher disease activity in axial spondyloarthritis but is not an independent predictor of spinal radiographic progression: data from the Swiss Clinical Quality Management Registry

Objective

As anaemia represents a biomarker for increased radiographic damage in rheumatoid arthritis, we aimed to investigate whether it independently predicts spinal radiographic progression in axial spondyloarthritis (axSpA).

Methods

AxSpA patients with available haemoglobin levels from the prospective Swiss Clinical Quality Management Registry were included for comparison of patients with and without anaemia. Spinal radiographic progression was assessed according to the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS) in patients with ankylosing spondylitis (AS) if ≥ 2 sets of spinal radiographs were available every 2 years. The relationship between anaemia and progression (defined as an increase ≥ 2 mSASSS units in 2 years) was analysed with generalized estimating equation models after adjustment for the Ankylosing Spondylitis Disease Activity Score (ASDAS) and potential confounding, as well as after multiple imputations of missing values.

Results

A total of 212/2522 axSpA patients presented with anaemia (9%). Anaemic patients had higher clinical disease activity, higher acute phase reactants and more severe impairments in physical function, mobility and quality of life. In the subgroup of patients with AS (N = 433), a comparable mSASSS progression was found in anaemic and non-anaemic patients (OR 0.69, 95% CI 0.25 to 1.96, p = 0.49). Age, male sex, baseline radiographic damage and ASDAS were associated with enhanced progression. The results were confirmed in complete case analyses and with progression defined as the formation of ≥ 1 syndesmophyte in 2 years.

Conclusion

Although anaemia was associated with higher disease activity in axSpA, it did not additionally contribute to the prediction of spinal radiographic progression.