Louise Hamilton

Services for people with ankylosing spondylitis in the UK—a survey of rheumatologists and patients

OBJECTIVE . To investigate the services offered to patients with AS in the UK in 2010. METHODS Two thousand non-health-care professional members of the National Ankylosing Spondylitis Society (NASS) were sent a questionnaire asking about their experiences surrounding diagnosis, treatment and access to therapies (response rate 40%). A separate questionnaire was sent to a consultant rheumatologist in every acute NHS trust in the UK, asking about services offered to patients with AS (response rate 68%). RESULTS Overall, there was a mean diagnostic delay of 8.57 years. Almost one-third (32.2%) of patients were not reviewed in secondary care. Non-attendance was associated with increasing age and longer disease duration. Twenty per cent of patients were taking anti-TNF drugs, but 18.8% of departments reported that their ability to give anti-TNF therapy was restricted (64% reported primary-care trust rationing and 14% lack of staff). Almost all rheumatology departments had access to MRI, but 70.9% still used X-ray radiographs as their first-line investigation. A minority (5.6%) of patients reported they had never seen a physiotherapist, but less than one-third could self-refer for treatment during a flare. CONCLUSION This is the first study to explore the services available to people with AS in the UK. Almost one-third of patients are not seen in rheumatology departments and therefore may be under-treated. For those who are seen, access to anti-TNF drugs and other therapies remains an issue.

The prevalence of inflammatory back pain in a UK primary care population

OBJECTIVE Inflammatory back pain (IBP) is the earliest and most common symptom of axial SpA. However, there is very little information about the prevalence of IBP in the UK. In this cross-sectional cohort study we examined the prevalence of IBP in a UK primary care population using three published IBP criteria. METHODS Potential participants aged 18-80 years were identified from the records of a large general practice in Norfolk, UK, with 17 177 patients. Read codes were used to identify those who had consulted their general practitioner on at least one occasion with back pain. A self-completed screening questionnaire was sent to a sample of 978 patients, enquiring about symptoms of IBP and extra-spinal manifestations of SpA. Questionnaire responses were used to determine whether patients met the Assessment of SpondyloArthritis international Society (ASAS), Calin and Berlin IBP criteria. RESULTS Five hundred and five completed questionnaires were returned (response rate 51.6%). The median age of respondents was 60 years [interquartile range (IQR) 48-67] and 44.8% were male. The minimum prevalence of IBP among patients with at least one previous consultation for back pain was 7.7% (95% CI 6.2, 9.5) using the ASAS criteria, 13.5% (11.5, 15.8) using the Calin criteria and 15.4% (13.3, 17.8) using the Berlin criteria. There was no significant difference in prevalence between men and women, and between different age groups. Extrapolated to the practice population as a whole, the minimum prevalence of IBP in a UK primary care population is 1.7-3.4%. CONCLUSION The prevalence of IBP varies significantly depending on the criteria used for classification.

Is Etanercept 25 mg Once Weekly as Effective as 50 mg at Maintaining Response in Patients with Ankylosing Spondylitis? A Randomized Control Trial.

Objective. To investigate, in a pilot randomized controlled trial, whether etanercept (ETN) 25 mg once weekly is effective at maintaining a clinical response in patients with ankylosing spondylitis (AS) who have responded to the standard 50 mg dose. Methods. Adults with AS not responding to conventional therapies were prescribed ETN 50 mg once weekly for 6 months. Responders as defined by the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) were randomly assigned to taper to 25 mg once weekly or continue on 50 mg and followed for a further 6 months. The primary outcome measure was maintenance of a 50% reduction in the BASDAI or fall in BASDAI by ≥ 2 units and a ≥ 2-unit reduction in BASDAI spinal pain as measured on a 10-point visual analog scale at 6 months postrandomization. Results. Of 89 patients assessed for eligibility, 59 were enrolled; 47 (80%) had sufficient clinical response and were eligible for randomization, 24 were assigned to continue receiving ETN 50 mg, and 23 to taper to 25 mg. After 6 months, 20 (83%) of the 50 mg arm maintained clinical response compared with 12 (52%) of the 25 mg arm (a difference of −31%, 95% CI −58% – −5%). Conclusion. Although this pilot study demonstrates that treatment with ETN 25 mg was less effective at maintaining treatment response in the stepdown phase, 52% of participants maintained treatment response. Future research should address which patients are suitable for tapering.

Validation of a patient self-reported screening questionnaire for axial spondyloarthropathy in a UK Population.

Study Design. Cross-sectional cohort study. Objective. The aim of this study was to develop and validate a patient-completed screening questionnaire for axial spondyloarthropathy for use in the United Kingdom. Summary of Background Data. Axial spondyloarthropathy (axial SpA) can be difficult to diagnose in the early stages of disease, leading to diagnostic delay and morbidity. Existing population screening tools lack sensitivity or have not been validated in the UK population. Methods. Questionnaires were sent to 295 patients with definite ankylosing spondylitis (meeting modified New York criteria), nonradiographical axial SpA (sacroiliitis on magnetic resonance imaging), or mechanical back pain. Responses from 190 patients were analyzed. Binary logistic regression was used to develop a model differentiating inflammatory from mechanical pain. Results. The final model (male sex, onset of symptoms by age 33 years, no radiation of pain, pain gets better as day goes on, pain increases with rest, and personal history of iritis) correctly classified 86% of cases with Nagelkerke R2 = 0.486. A numerical score (with 1 point assigned for each feature present) was calculated and receiver operating characteristic curve was constructed, with area under the curve of 0.911 (95% confidence interval: 0.87–0.96). A score of ≥3/6 had sensitivity of 75.6% and specificity of 87.9% for inflammation. Conclusion. We have developed a model that differentiates patients with ankylosing spondylitis/axial SpA from those with mechanical spinal disease and can be used as a self-completed screening tool.

BSR and BHPR guideline for the treatment of axial spondyloarthritis (including ankylosing spondylitis) with biologics

Axial SpA (axSpA) is a chronic inflammatory condition predominantly involving the spine and sacroiliac joints (SIJ), with or without extra-spinal manifestations including peripheral arthritis, enthesitis, iritis, psoriasis and IBD. Individuals with axSpA experience significant pain, stiffness and lack of function, which translates into important health care costs and increased mortality. AxSpA can be classified into two subgroups: radiographic axSpA, commonly referred to as AS, and non-radiographic axSpA (nr-axSpA). The primary difference between these two subgroups is the presence or absence of defined structural changes in the SIJ as detected on plain radiography. A diagnosis of AS can be made according to the modified New York criteria when radiographs show at least grade 2 sacroiliitis bilaterally or grade 3 unilaterally, in the presence of appropriate clinical symptoms [1]. In contrast, SIJ radiographs may be completely normal in nr-axSpA. The radiographic changes of AS may take 8 10 years to manifest, with a progression rate from nr-axSpA to AS of 12% every 2 years [2], although some patients with nr-axSpA never develop AS. Disease progression is predicted most strongly

Delayed presentation of Wegener’s granulomatosis with pancreatic involvement

Dear Sir, We would like to report an unusual case of Wegener’s granulomatosis. A 78 year old woman was first seen in rheumatology clinic in 2001 with arthralgia and raised inflammatory markers. Her rheumatoid factor was elevated at 120 IU/mL (normal < 20 IU/mL), but there was no synovitis to find on clinical examination. Five months later, after mentioning a short-lived purpuric rash on her legs, she was found to be c-ANCA positive, with PR3 > 100 u/mL (positive > 9 u/mL). She denied respiratory or ENT symptoms, and remained systemically well over the next 6 months before being discharged. A chest radiograph at this stage was normal. The patient returned to clinic in January 2008, after her primary care doctor rechecked her serology and found the PR3 level had risen further to 4030 u/mL. She admitted to occasional arthralgia, not intrusive enough to warrant even simple analgesia, but again there were no clinical features of Wegener’s granulomatosis and she was discharged. The patient was then admitted acutely in April 2009 with a 3–4 week history of night sweats, fatigue and weight loss. She had flitting arthralgia, and a blocked nose, but no respiratory symptoms and no nasal crusting or epistaxis. She denied abdominal pain. Urinalysis revealed 2 + blood and 2 + protein, and a chest radiograph showed right lower lobe consolidation. ANCA was again positive with PR3 > 600 u/mL. A CT scan of the thorax showed multiple soft tissue masses in both lungs, some showing early cavitation, with a bulky mass in the tail of the pancreas (Fig. 1, left image). No abnormality was seen in the liver or spleen. A CT scan of the sinuses showed only mild thickening of the left maxillary mucosa. The patient underwent an ultrasoundguided biopsy of a right-sided lung mass. Histology was consistent with Wegener’s granulomatosis, with foci of necrosis together with granulomatous palisading. The patient was treated with oral steroids, and six cycles of intravenous cyclophosphamide. She is now asymptomatic on 5 mg prednisolone daily with a Birmingham Vasculitis Activity Score (BVAS) of 0. A repeat CT scan 2 months after treatment showed complete resolution of the masses in the pancreas (Fig. 1, right image) and chest. Her PR3 level remains > 600 u/mL. Wegener’s granulomatosis is an ANCA-associated vasculitis (AAV) characterised by necrotising granulomata. It most commonly involves the upper airways and the respiratory tract, though a fifth of patients have renal disease at presentation and 70% will eventually develop glomerulonephritis. Gastro-intestinal involvement is rare. The aetiology of Wegener’s granulomatosis is still not understood, but anti-neutrophil cytoplasmic antibodies (ANCA), along with T cells, are thought to play a key role in mediating tissue damage. Although this patient remains well on low-dose prednisolone it is important to note that glucocorticoids alone do not constitute remission-maintenance therapy. CARI and EULAR guidelines recommend remission induction with steroids and either cyclophosphamide (for generalised or severe disease) or methotrexate (in patients with no organ-threatening disease), followed by remission maintenance with a combination of tapering steroids and a steroid-sparing agent (azathioprine, leflunomide or methotrexate). This case is unusual in two respects. Firstly, the patient was systemically well for 8 years, with a high PR3 level, before developing features of Wegener’s granulomatosis. ANCA directed against PR3 (a serine protease) are thought to be directly involved in the development of focal necrosis in Wegener’s, although evidence for a pathogenic role is limited to in vitro studies, and the correlation between rising ANCA titres and clinical relapse is controversial. It is unusual therefore to find such a high PR3 level, for a sustained period of time, in a patient without clinical features of Wegener’s granulomatosis. There are reports of patients developing pulmonary manifestations (and consequently being diagnosed with International Journal of Rheumatic Diseases 2011; 14: e54–e55

Teaching knee joint aspiration to medical students—an effective training with long-term benefits

The objective of this study was to assess the effectiveness of undergraduate training in knee aspiration and to determine the impact this had on subsequent postgraduate clinical practice. This paper is a cohort study of undergraduate training with a cross-sectional questionnaire study of postgraduate practice. The study was held at the University of Cambridge and NHS hospitals in the Eastern Region Postgraduate Deanery (England). The main outcome measures are the undergraduate competence in practical skills in a simulated setting and the differences in postgraduate practice with or without prior undergraduate training in knee aspiration. Implementing an undergraduate training programme in knee aspiration resulted in student competence in this skill. Undergraduate teaching of knee aspiration also improved postgraduate clinical practice, significantly increasing trainee doctor confidence and also increasing the frequency with which knee aspiration was undertaken. Postgraduate reinforcement of learning was identified as an additional requirement. Undergraduate teaching of knee aspiration not only results in competent performance in end of course assessments but also improves postgraduate confidence that potentially translates into improved clinical practice.

Tumour necrosis factor inhibitor survival and predictors of response in axial spondyloarthritis—findings from a United Kingdom cohort

Objectives To analyse long-term survival and efficacy of TNFi, reasons for switching or discontinuing, baseline predictors of response and remission in axial spondyloarthritis (axSpA) patients in a UK cohort. Methods All patients with a physician-verified diagnosis of axSpA attending two specialist centres who fulfilled the eligibility criteria for TNFi were included. Routinely recorded patient data were reviewed retrospectively. Initial TNFi was recorded as the index drug. Results Six hundred and fifty-one patients (94% AS) were included; adalimumab (n = 332), etanercept (n = 205), infliximab (n = 51), golimumab (n = 40) and certolizumab pegol (n = 23) were index TNFi. The mean (s.d.) duration from symptom onset to time of diagnosis was 8.6 (8.7) years and mean (s.d.) duration from diagnosis to TNFi initiation was 12.6 (11.5) years. A total of 224 (34.4%) stopped index TNFi, and 105/224 switched to a second TNFi. Median drug survival for index and second TNFi were 10.2 years (95% CI: 8.8, 11.6 years) and 5.5 years (95% CI: 2.7, 8.3 years), respectively (P < 0.05). Survival rates were not influenced by choice of TNFi. HLA-B27 predicted BASDAI50 and/or two or more point reduction within 6 months and long-term drug survival (P < 0.05). Low disease activity was predicted by non-smoking and low baseline BASDAI (P < 0.05). Conclusion We have observed good TNFi survival rates in axSpA patients treated in a real-life setting. This is best for first TNFi and not influenced by drug choice.

Comment on: Tumour necrosis factor inhibitor survival and predictors of response in axial spondyloarthritis — findings from a United Kingdom cohort: Reply

SIR, We read with interest the report by Yahya et al. [1] on tumour necrosis factor inhibitor (TNFi) survival and predictors of response in axial spondyloarthritis (axSpA) patients treated in a real-life setting in the UK, where no sex differences were identified impacting these outcomes. Data over the last decade suggest sex-attributable differences in disease features, clinical outcomes and treatment response in axSpA, with a longer diagnostic delay [2], older age at disease onset [3] and higher number of affected first-degree relatives [4] in females. These findings suggest that a higher genetic load is needed in order to develop the disease in females than in males [5]. Furthermore, women appear to have a higher burden of disease [3], reduced response to TNFi [6, 7] and higher switching rate [8]. Characterization of these differences is essential for a better understanding of the disease trajectory in order to deliver optimal personalized medical management. Here, we report our experience from a single tertiary centre in a large teaching hospital, exploring the role of sex in treatment response, drug survival and switching rate in a cohort of biologic-treated axSpA patients. As part of service development and to comply with mandatory audit according to National Health Service governance systems, we conducted a retrospective evaluation of anonymized data using the Leeds Spondyloarthritis Service database. Subjects were eligible if they had a physician-verified diagnosis of radiographic axSpA fulfilling the modified New York criteria (mNYC) for AS and if they received the first TNFi between 1999 and 2017. Exclusion criteria included being prescribed the first TNFi for a diagnosis other than AS, not having TNFi as the first biological (switch to another biological class was allowed), having a follow-up <12 months or participating in the placebo arm of a clinical trial. In compliance with National Institute for Health and Care Excellence guidance, all subjects had a BASDAI 4 at initiation of the first TNFi. Information on disease characteristics, patient-reported outcomes for disease activity (BASDAI), function (BASFI) and pain (visual analog scale) were available at baseline. Treatment response was evaluated by the improvement of 50% in BASDAI (BASDAI50) after 3–6 months (first evaluation) and 1–1.5 years (second evaluation) of treatment. Kaplan–Meier curves were calculated to describe drug survival, and the log-rank test was used to test for differences between the sexes. Discontinuation was classified as attributable to non-response, intolerance (including adverse events) or other reasons (patient decision, death, finished a trial), and the frequency of switching between biologicals was calculated by sex for each drug. All statistical analyses were done in SPSS software (SPSS Statistics, version 21). Data from 280 patients (75 females and 205 males) were available for analysis (Supplementary Table S1, available at Rheumatology Advances in Practice online). Significant differences between the sexes were observed, with females having a higher prevalence of IBD at the baseline (21.3 vs 9.8%; P1⁄4 0.010) and family history of SpA (61.4 vs 41.8%; P1⁄4 0.013) than males. No other sex differences were observed with regard to age at diagnosis, disease onset, delay in diagnosis, symptom duration, patient-reported outcomes or baseline CRP. At the first evaluation, more females reached BASDAI50, but this was not sustained at the second evaluation (Supplementary Tables S2 and S3, available at Rheumatology Advances in Practice online). In contrast to the findings of Yahya et al. [1], females showed a significantly shorter drug survival for the first drug compared with males (median, 34.4 vs 91.6 months; P < 0.001), but this difference was not significant for the total number of biological drugs (Fig. 1). More females than males discontinued treatment owing to intolerance (Supplementary Figure S1, available at Rheumatology Advances in Practice online), which includes adverse events (81.3 vs 48.6%). A total of 40.4% of patients switched to a second drug, with more females than males (53.3 vs 35.6%) mainly because of non-response. Our cohort comprises solely AS patients, with a switching rate similar to the DANBIO registry [8] but higher than that reported by Yahya et al. [1], probably reflecting locally agreed commissioning pathways. There are a number of limitations to our report, such as the retrospective design, small sample size and missing BASDAI data, which lead to a low statistical power; however, these data provide one of the longest observational reports to date, with some patients being followed up for 19 years. In conclusion, in our cohort there was no difference in disease burden between sexes at the time of TNFi initiation, although females had a higher prevalence of IBD and more relatives with SpA, as shown by other groups. Although no sex difference in treatment response was seen, a higher switching rate and shorter drug survival of the first TNFi was seen in females compared with L E T T E R

FRI0427 The Prevalence of Axial Spondyloarthritis in Patients Presenting with Acute Anterior Uveitis

Background Estimates for the prevalence of axial spondyloarthritis (axSpA) in patients presenting with acute anterior uveitis (AAU) range from 11–28%. However, to date no studies have classified patients according to the MRI-based Assessment of Spondyloarthritis International Society (ASAS) criteria. Objectives To determine the prevalence of axSpA in patients presenting with AAU and identify new “undiagnosed” cases using contemporary MRI-based classification criteria. Methods Consecutive adult patients presenting to a university teaching hospital between February 2014 and March 2015 with a diagnosis of non-traumatic, non-infective AAU were invited to participate. Patients with a pre-existing diagnosis of axial SpA or another underlying cause of AAU (e.g. sarcoidosis) were not evaluated further. Patients who reported chronic back pain commencing before age 45 were evaluated clinically by an experienced rheumatologist and investigated with laboratory tests and magnetic resonance imaging (MRI). Those patients newly diagnosed with axSpA were classified according to ASAS criteria and the burden of disease recorded. Results Two hundred and forty-one of 366 patients responded; 57 had a pre-existing diagnosis of axSpA, 77 others fulfilled the study eligibility criteria and 73 (95%) completed the study. Sixteen patients (22%) were diagnosed with axSpA according to the ASAS definition of a positive MRI (12 sacroiliac, 4 spinal). Including those with a previous diagnosis, the minimum prevalence of axSpA in patients presenting with AAU was 19.9%; of these 22% were previously undiagnosed. The median age of “new” axSpA patients was 54 (IQR 41.5 – 58) and 8 (50%) were female. Nine patients (56%) were HLA-B27 positive; 31.3% had a raised CRP. The median duration of back pain was 20.5 years (IQR 17–30.25), and median number of episodes of AAU prior to the diagnosis of axSpA was 3 (IQR 1–7). The median duration of back pain at the time of first episode of uveitis was 15.5 years (IQR 8.5–20.5). Amongst the undiagnosed cases, 6.3% of patients had a pre-existing diagnosis of psoriasis, 18.8% inflammatory bowel disease, 12.5% peripheral inflammatory arthritis and 6.3% a family history of axSpA. The mean BASDAI was 3.17 (SD 1.50), spinal pain visual analogue scale 4.31 (SD 2.02), BASMI 1.63 (SD 1.36), BASFI 2.74 (SD 2.20) and BAS-G 4.70 (SD 1.45). Conclusions This is the first study to use MRI in order to classify patients with AAU and chronic back pain. At least one fifth of patients presenting to secondary care with AAU have an underlying diagnosis of axSpA. There was a significant hidden burden of disease in that 22% of axSpA patients were previously undiagnosed despite having a long duration of symptoms. Patients presenting with AAU should be screened for chronic back pain and referred to a rheumatologist; this represents an opportunity to shorten the diagnostic delay. Acknowledgement This study was funded by AbbVie Ltd. Disclosure of Interest M. Sykes Grant/research support from: AbbVie Ltd, L. Hamilton: None declared, C. Jones: None declared, K. Gaffney Grant/research support from: AbbVie Ltd, MSD, Pfizer, Speakers bureau: AbbVie Ltd, MSD, Pfizer, Novartis, UCB