Drug-survival profiling of second-line biologic therapy in rheumatoid arthritis: Choice of another tumour necrosis factor inhibitor or a biologic of different mode of action?

OBJECTIVES: To assess the best choice of second-line therapy between tumour necrosis factor-inhibitor (TNFi) and biologics of different-mode-of-action (BDMA-rituximab/tocilizumab/abatacept) in rheumatoid arthritis (RA) by evaluating drug-survival following discontinuation of the first-line TNFi. METHODS: This retrospective drug-survival study was performed across two different hospitals by conventional-statistics and machine-learning approach. RESULTS: From a total of 435 patients, 213 (48.9%; TNFi = 122, BDMA = 91) discontinued their second-line biologic {median drug-survival: TNFi, 27 months [95% confidence interval (95%CI) 22-32] vs BDMA, 37 months (95%CI 32-52)}. As a second-line biologic, BDMA was likely to reduce the risk of treatment-discontinuation [hazard-ratio (HR) 0.63, 95%CI 0.48-0.83] compared to TNFi, but only in seropositive-patients (HR 0.52, 95%CI 0.38-0.73), not in seronegative-RA. Drug-survival benefit of BDMA over TNFi was not observed if the seropositive-patients were previously exposed to monoclonal-TNFi (HR 0.77, 95%CI 0.49-1.22) versus soluble-TNFi (etanercept/biosimilars) or if the first-line TNFi was terminated within 23.9 months of initiation (HR 0.97, 95%CI 0.56-1.68). CONCLUSIONS: BDMA, as a second-line biologic, is more likely to be sustained in seropositive-patients, particularly without prior exposure to monoclonal-TNFi. The drug-survival benefit of BDMA was not observed in seronegative-patients or if the first-line TNFi was stopped within 2 years.

The JAK inhibitor baricitinib inhibits oncostatin M induction of proinflammatory mediators in ex-vivo synovial derived cells.

OBJECTIVES: To investigate the ex vivo effect of the JAK1/2 inhibitor baricitinib on expression of pro-inflammatory mediators in rheumatoid arthritis (RA) fibroblast like synoviocytes (FLS) stimulated with TNFα, IL-1ß and oncostatin M (OSM), and in RA synovial membrane cells (SMCs). METHODS: RA and osteoarthritis (OA) SMCs, were isolated from arthroplasty specimens of RA (n=8) and OA (n=8) patients, respectively, using enzymatic digestion followed by cell propagation to obtain RA (n=5) and OA (n=3) FLS. Normal FLS and normal human foreskin fibroblasts (HSF) were purchased from commercial sources. Fibroblasts were stimulated with cytokines with or without baricitinib. RA SMCs were cultured in the presence of baricitinib without stimulation. JAK/STAT activation and levels of mRNA and proteins of the various inflammatory cytokines (IL-6, IL-8, MCP-1, RANTES and IP-10) were determined by qPCR, ELISA and MSD. RESULTS: Baricitinib inhibited OSM-induced JAK signalling in RA synovial fibroblasts and effectively suppressed subsequent expression of the proinflammatory mediators IL-6, MCP-1 and IP-10. However, baricitinib was not effective in altering levels of spontaneously released TNFα, IL-6 and IL-8 in RA SMC. Although both TNFα and IL-1ß signal independently of the JAK/STAT pathway, in HSF, but not in RA FLS, baricitinib significantly inhibited TNFα- and IL-1ß-induced MCP-1 and IP-10 protein levels in a dose dependent manner. Furthermore, baricitinib did not inhibit TNFα- and IL-1ß-induced expression of IL-6, IL-8 and MCP-1 in RA FLS. CONCLUSIONS: These findings are consistent with known signalling pathways employed by OSM, TNFα and IL-1ß, but our data suggest that in HSF, baricitinib may have anti-inflammatory effects via downstream modulation of cytokines and chemokines produced in response to TNFα or IL-1ß.

Effect of rituximab on a salivary gland ultrasound score in primary Sjögren's syndrome: results of the TRACTISS randomised double-blind multicentre substudy.

OBJECTIVES: To compare the effects of rituximab versus placebo on salivary gland ultrasound (SGUS) in primary Sjögren's syndrome (PSS) in a multicentre, multiobserver phase III trial substudy. METHODS: Subjects consenting to SGUS were randomised to rituximab or placebo given at weeks 0, 2, 24 and 26, and scanned at baseline and weeks 16 and 48. Sonographers completed a 0-11 total ultrasound score (TUS) comprising domains of echogenicity, homogeneity, glandular definition, glands involved and hypoechoic foci size. Baseline-adjusted TUS values were analysed over time, modelling change from baseline at each time point. For each TUS domain, we fitted a repeated-measures logistic regression model to model the odds of a response in the rituximab arm (≥1-point improvement) as a function of the baseline score, age category, disease duration and time point. RESULTS: 52 patients (n=26 rituximab and n=26 placebo) from nine centres completed baseline and one or more follow-up visits. Estimated between-group differences (rituximab-placebo) in baseline-adjusted TUS were -1.2 (95% CI -2.1 to -0.3; P=0.0099) and -1.2 (95% CI -2.0 to -0.5; P=0.0023) at weeks 16 and 48. Glandular definition improved in the rituximab arm with an OR of 6.8 (95% CI 1.1 to 43.0; P=0.043) at week 16 and 10.3 (95% CI 1.0 to 105.9; P=0.050) at week 48. CONCLUSIONS: We demonstrated statistically significant improvement in TUS after rituximab compared with placebo. This encourages further research into both B cell depletion therapies in PSS and SGUS as an imaging biomarker. TRIAL REGISTRATION NUMBER: 65360827, 2010-021430-64; Results.

Genetic diagnostic profiling in axial spondyloarthritis: a real world study.

OBJECTIVES: Spondyloarthritis (SpA) is often diagnosed late in the course of the disease and improved methods for early diagnosis are required. We have tested the ability of genetic profiling to diagnose axial SpA (axSpA) as a whole group, or ankylosing spondylitis (AS) alone, in a cohort of chronic back pain patients. METHODS: 282 patients were recruited from centres in the United Kingdom, Germany, Taiwan, Canada, Columbia and Turkey as part of the ASAS classification criteria for axSpA study (ASAS cohort). Subjects were classified according to the ASAS axSpA criteria, and the modified New York Criteria for AS. Patients were genotyped for ~200,000 immune-mediated disease SNPs using the Illumina Immunochip. RESULTS: We first established the predictive accuracy of genetic data comparing 9,638 healthy controls and 4,428 AS cases from the homogenous International Genetics of AS (IGAS) Consortium Immunochip study which showed excellent predictive power (AUC=0.91). Genetic risk scores had lower predictive power (AUC=0.83) comparing ASAS cohort axSpA cases meeting the ASAS imaging criteria with IGAS controls. Comparing genetic risk scores showed moderate discriminatory capacity between IGAS AS and ASAS imaging positive cases (AUC 0.67±0.05), indicating that significant differences in genetic makeup exist between the cohorts. CONCLUSIONS: In a clinical setting of referred back pain patients suspected to have axial SpA we were unable to use genetic data to construct a predictive model better than that based on existing clinical data. Potential confounding factors include significant heterogeneity in the ASAS cohort, possibly reflecting the disease heterogeneity of axSpA, or differences between centres in ascertainment or classification performance.

Predictive validity of the ASAS classification criteria for axial and peripheral spondyloarthritis after follow-up in the ASAS cohort: a final analysis.

OBJECTIVE: To establish the predictive validity of the Assessment of SpondyloArthritis international Society (ASAS) spondyloarthritis (SpA) classification criteria. METHODS: 22 centres (N=909 patients) from the initial 29 ASAS centres (N=975) participated in the ASAS-cohort follow-up study. Patients had either chronic (>3 months) back pain of unknown origin and age of onset below 45 years (N=658) or peripheral arthritis and/or enthesitis and/or dactylitis (N=251). At follow-up, information was obtained at a clinic visit or by telephone. The positive predictive value (PPV) of the baseline classification by the ASAS criteria was calculated using rheumatologist's diagnosis at follow-up as external standard. RESULTS: In total, 564 patients were assessed at follow-up (345 visits; 219 telephone) with a mean follow-up of 4.4 years (range: 1.9; 6.8) and 70.2% received a SpA diagnosis by the rheumatologist. 335 patients fulfilled the axial SpA (axSpA) or peripheral SpA (pSpA) criteria at baseline and of these, 309 were diagnosed SpA after follow-up (PPV SpA criteria: 92.2%). The PPV of the axSpA and pSpA criteria was 93.3% and 89.5%, respectively. The PPV for the 'clinical arm only' was 88.0% and for the 'clinical arm'±'imaging arm' 96.0%, for the 'imaging arm only' 86.2% and for the 'imaging arm'+/-'clinical arm' 94.7%. A series of sensitivity analyses yielded similar results (range: 85.1-98.2%). CONCLUSIONS: The PPV of the axSpA and pSpA criteria to forecast an expert's diagnosis of 'SpA' after more than 4 years is excellent. The 'imaging arm' and 'clinical arm' of the axSpA criteria have similar predictive validity and are truly complementary.

Comparison between the intermalleolar distance measured on the couch and on the floor in axial spondyloarthritis.

The aim of this study was to assess whether axial spondyloarthritis (axial SpA) patients' supine position on the couch (OC) or on the floor (OF) affects intermalleolar distance (IMD) measurement and its Bath Ankylosing Spondylitis Metrology Index (BASMI) scoring, using all three versions of BASMI index. OC- and OF-IMDs were obtained for 43 axial SpA patients (M:F = 19:24). Age, gender, height, weight, body mass index (BMI), disease type and disease duration were also collected. Statistical analyses and correlations were performed as appropriate. Mean IMD measurements obtained with individuals in the two distinct measuring positions were not significantly different in the patients studied. Furthermore, there was a significant correlation between OC-IMD and OF-IMD values. There was no significant relationship between IMD and patient age, gender, height, weight, BMI, or disease duration. However, looking at disease type, IMDs of patients with ankylosing spondylitis (AS) were ~30 % greater than those with psoriatic arthritis (PsA) in our study population (p < 0.05). There were no significant differences between the measured patient characteristics that accounted for the greater IMDs of those diagnosed with AS. IMD measurements and resultant BASMI scores were the same whether the patient was positioned OC or OF in our axial SpA cohort. Unexpectedly, IMD measurements were significantly greater (~30 %) in AS patients than in axial PsA patients.

The development of candidate composite disease activity and responder indices for psoriatic arthritis (GRACE project).

OBJECTIVE: To develop new composite disease activity indices for psoriatic arthritis (PsA). METHODS: Data from routine clinic visits at multiple centres were collected in a systematic manner. Data included all domains identified as important in randomised controlled trials in PsA. Decisions to change treatment were used as surrogates for high disease activity. New indices were developed by multiple linear regression (psoriatic arthritis disease activity score: PASDAS) and empirically, utilising physician-defined cut-offs for disease activity (arithmetic mean of desirability functions: AMDF). These were compared with existing composite measures: Composite Psoriatic arthritis Disease Activity Index (CPDAI), Disease Activity for PSoriatic Arthritis (DAPSA), and Disease Activity Score for rheumatoid arthritis (DAS28). RESULTS: 161/503 (32%) subjects had treatment changes. Although all measures performed well, compared with existing indices, PASDAS was better able to discriminate between high and low disease activity (area under receiver operating curves (ROC)) curve with 95% CI: PASDAS 0.773 (0.723, 0.822); AMDF 0.730 (0.680, 0.780); CPDAI 0.719 (0.668, 0.770); DAPSA 0.710 (0.654, 0.766); DAS28 0.736 (0.680, 0.792). All measures were able to discriminate between disease activity states in patients with oligoarthritis, although area under the receiver operating curves (AUC) were generally smaller. In patients with severe skin disease (psoriasis area and severity index>10) both nonparametric and AUC curve statistics were nonsignificant for all measures. CONCLUSIONS: Two new composite measures to assess disease activity in PsA have been developed. Further testing in other datasets, including comparison with existing measures, is required to validate these instruments.

Medical students' attitude towards rheumatology training at foundation years' level in the UK and rationale behind the students' choice: results from a national survey.

The aims are to assess whether medical students are interested in rheumatology as a training post during post-medical-school and prior to specialty training that is covered by foundation years (FY) training in the UK, to determine the time spent in the undergraduate training in rheumatology and whether the desire for musculoskeletal (MsK) medicine training (rheumatology and orthopaedics taken together) is enhanced during FY training and to analyse the rationale behind their choice for rheumatology alone or combined with orthopaedics. An online questionnaire was distributed to all 31 UK medical schools, addressed to fourth-, fifth- and sixth-year medical students. The questionnaire was completed by 256 students from 11 of 31 medical schools existed in the UK in 2009. Most respondents (n = 156; 60.9 %) received 3 weeks (96 h) exposure to rheumatology, whilst one-fifth (n = 53; 20.7 %) had received no exposure in rheumatology. A total of 122 students of the 256 that responded (47.6 %) would like to do rheumatology as part of their training and 116 (45.3 %) would like to have more posts available in rheumatology. However, when asked to choose 6 specialties, out of 21, which would be most useful for post-university training, rheumatology was amongst the bottom three, attracting only 9.4 % of respondent students. A total of 68 of 256 (26.5 %) students, however, expressed a desire for MsK medicine: 44/256 (17.1 %) for orthopaedics and 24/256 (9.4 %) for rheumatology. From a total of 49 of 256 (19.1 %) open-ended responses obtained, 25 (51 %) were from those medical students willing to have exposure in MsK medicine: 15 of 44 (34 %) willing to have orthopaedics and 10 of 24 (41.6 %) willing to have rheumatology. Analysis of the responses revealed that it is mostly the specialty choice that guides towards specialty training. One in five of the medical students responded to had received (actual or perceived) no exposure to rheumatology during their undergraduate years. Career choice that derived mostly from undergraduate exposure is the driving force behind medical students' choice for foundation year training.

Clinical overlap between fibromyalgia tender points and enthesitis sites in patients with spondyloarthritis who present with inflammatory back pain.

OBJECTIVES: To assess the extent of coexistence of inflammatory back pain (IBP) with fibromyalgia (FM) features in patients with spondyloarthritis (SpA), and to assess the degree of overlap of FM tender points (TeP) and enthesitis sites (ES) in patients with SpA. METHODS: We evaluated 61 consecutive patients who presented with IBP. Anterior and posterior anatomic diagrams were used as an aid to record assessments of TeP typically seen in FM and ES. RESULTS: Of the patients assessed (n=61), 60 patients (97.9%) fulfilled criteria for IBP (male: female=17:43 (28.3%:71.7%); mean age=47.9 years (SD=11.5) and were included in the analysis. Of those who returned the questionnaire (n=47 (78.3%), 76.6% had onset of symptoms at ≤40 years (mean age=33.5±12.5 years), 87.2% had back pain of ≥3 months duration, 91.5% had morning stiffness (mean duration=70±66 minutes), and 60% showed improvement of pain with exercise. Eating disorders were reported by 21.3% of subjects, and stress was identified as a disease trigger by 40.4% of the respondents. Other symptoms related to FM were reported by 68.1% of the interviewed subjects. Of the 60 patients assessed, 18 (30%) fulfilled the clinical criteria for FM (at least 11 out of 18 TeP). Using regression analysis, a significant correlation was identified between FM TeP and ES. CONCLUSIONS: One third of patients with IBP fulfilled the criteria for FM. There is a significant degree of overlap between FM TeP and ES in patients with IBP.

Early spondyloarthritis in multiracial society: differences between gender, race, and disease subgroups with regard to first symptom at presentation, main problem that the disease is causing to patients, and employment status.

To determine whether the first presenting symptoms, the main problem that the disease is causing to patients, and the employment status at presentation of patients with early spondyloarthritis (SpA) in a multicultural/multiracial patient cohort are different between gender, race, and disease subgroups of the SpA spectrum (ankylosing spondylitis, enteropathic arthritis, psoriatic arthritis, or undifferentiated arthritis). All patients above the age of 16 years, with disease duration of less than 3 years since symptom onset, seen in clinic between 2004 and 2008 with spondyloarthritis (SpAs) were assessed regarding their first presenting symptom, the main problem caused by the disease, and their employment status. In addition, clinical parameters such as the degree of disease activity (measured by BASDAI, ESR, and CRP), functional ability (measured by BASFI), night pain, sleep disturbance, well-being over past week, and over past 6 months prior to assessment (measured by a 10 cm VAS; 0 = good health, 10 = worst possible) were obtained. Statistical analysis with Pearson's χ(2) test compared and correlated two groups, and one-way analysis of variance (ANOVA) was used when more than two groups were compared and correlated. A total of 96 patients [(male:female = 33:63; (34.4:65.6%), (mean age 43.8 ± (SD) 13.9)] with early SpA were assessed. They were of multiethnic background representing Caucasians (n = 52; 54.2%), Asians (n = 33; 34.4%), and Africans (n = 10; 10.4%) mixed race (n = 1; 1%). The disease spectrum consisted of ankylosing spondylitis (AS) (n = 12; 12.7%), enteropathic arthritis or SpA associated with inflammatory bowel disease (IBD) (n = 9; 9.4%), psoriatic arthritis (PsA) (n = 47; 49%), undifferentiated spondyloarthritis (USpA) (n = 27; 28.2%), reactive arthritis (n = 1;1%), and juvenile SpA (n = 1;1%). Back pain stated as the first presenting symptom by 45 patients (46.8%) (followed by knee pain) and joint pains as the main problem by 49 patients (51.7%), while 47 patients of 93 who replied on the employment section (50.5%) were working. The total group had BASDAI score of 5.91 (±2.1), ESR of 19.65 (±19.4) mmHg/h, CRP of 8.10 (±9.2) mmol/L, BASFI score of 4.51 (±2.57), night pain of 5.26 (±3.2), sleep disturbance of 5.24 (±3.03) well-being over past week of 5.9 (±2.7), and well-being over past 6 months of 6.4 (±2.5). Most patients had PsA at presentation. Comparisons between genders showed significantly more women to have knee pain as first presenting symptom than men. No differences between races found in the first presenting symptom, main problem caused to patients by disease, and employment, but Africans have significantly more sleep disturbance than other races. Comparisons between disease subgroups showed patients with AS to have significantly more back pain and hip pain as first presenting symptom and patients with IBD to have more joint pain as main problem caused by the disease.

Development of a structured on-site nursing program for training nurse specialists in rheumatology.

There is currently no structured system for nurses or allied health professionals to undertake further training to become a nurse specialist (NSp) or nurse practitioner (NP) in rheumatology on-site, while working in a district general hospital setting. These shortcomings have prompted us to develop a structured pathway that could be followed by staff nurses who wish to become NSp in rheumatology. The proposed pathway aims to assist the nurses or therapists (physiotherapists, psychologists, occupational therapist, podiatrists, etc.) to develop a sound knowledge based on the rationale, safety, and high quality clinical care when monitoring of patients taking disease-modifying anti-rheumatic drugs (DMARDs) to ensure they acquire skills enabling them to provide safe, evidence-based effective patient-centered care. Near the end of the pathway, the trainee would be expected to have an understanding of the particularities of chronic arthritis conditions as well as screening, assessment, and monitoring of patients receiving DMARDs and biological agents. Tests for competencies are included and certification may be considered.

The treatment of rheumatoid arthritis during pregnancy.

There are a wide variety of medications available to treat patients with rheumatoid arthritis, many of which are considered unsafe during pregnancy. It is important to tailor a treatment regimen that stabilises the woman's disease prior to conception, using medications that are safe to continue throughout pregnancy and the post-partum period. Drugs that may be safely used during pregnancy include NSAIDs, corticosteroids, plus several DMARDs, including sulfasalazine and hydroxychloroquine. Drugs recommended to be stopped before pregnancy include methotrexate and leflunomide, plus the biologics: anti-TNF agents, rituximab and abatacept.

Methotrexate for rheumatoid arthritis patients who are on hemodialysis.

Methotrexate (MTX) can be toxic to patients suffering from end stage renal disease (ESRD) on hemodialysis even at low doses. This increase in toxicity is more notable in terms of bone marrow suppression in the form of pancytopenia. Many methods of elimination including dialysis itself have been proven ineffective, and alternate treatments with anti-TNF alpha blockers can be considered.

Spondyloarthritis in African Populations Compared to Europeans Living in the United Kingdom.

BACKGROUND: With the aim to study Spondyloarthritis in patients originating from Africa and compare the disease with the way it is manifested in Europeans, data was analysed from 62 African patients and compared with 56 Europeans living in the same geographical area (north East London, United Kingdom) and treated under the same health system (NHS). Data analysed were demographic, social and clinical characteristics. RESULTS: Comparisons showed differences in prevalence of psoriasis (more in Caucasians), uveitis (more in Africans), smoking (more in Europeans), and significantly fewer patients of African origin declared family history of SpA. African patients have less disease activity (but not significantly better measured by BASDAI), and statistically significant better functional ability (BASFI) compared to Europeans. No difference has been noted in gender distribution, age of disease onset, disease duration, delay in diagnosis, disease associations with IBD, night pain, or overall wellbeing. CONCLUSIONS: SpA is different in Africans in that it shows to be milder in terms of disease activity and functional ability with more uveitis less psoriasis and less family history of SpAs.

Clinical application of the CASPAR criteria for psoriatic arthritis compared to other existing criteria.

OBJECTIVES: Psoriatic arthritis (PsA) has been defined as a systemic, chronic, inflammatory arthritis, usually seronegative for rheumatoid factor (RF), associated with cutaneous psoriasis. The exact prevalence of PsA is unknown and its estimation has been difficult, partly due to the lack of a widely accepted classification criteria. Agreed and validated criteria will facilitate comparison between centres and different countries in the areas of epidemiology, outcome studies and therapeutic trials. A number of classification criteria have been published by Moll & Wright (M & W), Bennett's, Vasey and Espinoza (V & E), Fournié's, European Spondyloarthropathy Study Group (ESSG), McGonagle, Gladman and most recently, the CASPAR Study Group. In this paper, we present an audit aiming to assess which of these criteria performs better in clinical practice. METHODS: Sixty-nine (69) patients with evidence of PsA were seen in the clinic as regular outpatients and were assessed as to whether they fulfil any of the 6 existing criteria for PsA: M & W, Bennett's, V & E, Fournié's, ESSG and CASPAR criteria. All items included in the 6 sets of criteria were recorded for each patient based on interview, clinical examination and scrutiny of clinical medical records. By comparing the criteria between themselves as well as the items used in each one of them we tried to assess which one of the criteria was performing best. RESULTS: A total of 69 patients (M/F=24/45; mean age 46.4 years (+/-20.3), and delay in diagnosis of 3.4 years (+/-4.1) was assessed. From those, 9 patients did not fulfil any criteria and excluded from the analysis. From the remaining 60 patients [M/F=21/39; (age 48+/-15.3)], 21 patients (35%) fulfilled all 6 sets of criteria. The remaining 39 patients (M/F=41/59 %; age 47+/-14.9) were further analysed with regards to the feature that did not enable concordance. From those 39 patients, Bennett's criteria were positive in only 4/39 (10.2%), M & W criteria were positive in 12/39 (30.7%), ESSG criteria in 17/39 (43.5%), V & E criteria were positive in 18/39 (46.1%), Fournié's criteria were positive in 31/39 (79.4%) and CASPAR criteria in 35/39 (89.7%). By including family history of psoriasis in the criteria, 11/39 patients (28.2%), who did not fulfil M & W or V & E due to lack of family history of psoriasis as item, met the CASPAR criteria. In addition, some patients who did not fulfil the M & W criteria, since RF positive (7/39; 17.9%), were able to satisfy the CASPAR criteria. CONCLUSIONS: Family history of psoriasis is the main advantage of the new CASPAR Criteria over M & W and V & E. In addition, using the CASPAR criteria, it is possible to make a diagnosis of PsA in a patient who develops inflammatory articular disease even if with RF positive and polyarticular symmetrical arthritis. It is also important to have these classification criteria for the development of recommendations for the optimal treatment of patients with PsA. We believe that the CASPAR criteria, which are simple and easy to use, have high potential to be introduced as the universal classification criteria for PsA. However, further study of the validation of these new criteria is required.

The Semantics of 'Hip Pain' and its Impact on Clinical Practice in Patient-Reported Outcome Measures (PROMs) of Disease: Results from a Clinical and Radiological Evaluation Cohort.

INTRODUCTION: The item 'hip pain' is widely used in questionnaires related to Spondyloarthritis and/or Ankylosing spondylitis (AS), either in clinics with patients being physically present or remotely, as the hip joint is known to affect AS in particular. Patients in clinics often claim to have hip pain. However, by stating "hip" they are referring to variable structures located in the hip region not necessarily related to hip joint itself. OBJECTIVE: To assess which structure(s) patients mean when referring to hip pain. METHODS: A diagram used as a proforma for patients to indicate the site of 'hip pain' following a detailed history and examination was used. Radiological imaging was utilised for those patients with multiple sites or clinically unclear causes of "hip" pain. RESULTS: From 54 patients 7 different anatomical sites described which were: Trochanter, (27.2%), hip joint (20.8%), iliac crests (anterior superior [6.9%], posterior superior [8.3%], and anterior inferior [4.1%]), lumbar spine (8.3%), sacroiliac joint (6.9%). More than 1 sites in the same patient: (17.5%). Diagnoses were: Trochanteric bursitis (27%), osteoarthritis of hip and spine, (25%), enthesitis (22%), sacroiliitis (6.7%), synovitis (5%), fibromyalgia (3.4%), and hip dislocation (1.6%). More than 1 diagnosis in same patient: 9.3%. CONCLUSION: 'hip pain' as an item used in questionnaires must be interpreted with caution.

CNS Vasculitis in Anti-Synthetase Syndrome.

A 52-year-old woman known to have anti-synthetase syndrome (ASS) with positive anti-alanyl-tRNA synthetase antibody (anti-PL 12) for 4 years presented with headache and progressive deterioration of cognitive functions manifested predominantly by episodes of confusion and dyslexia. Clinical, laboratory and radiological evaluation as well as response to treatment was indicative of vasculitis of the central nervous system (CNS). CNS vasculitis is one of the rare manifestations of inflammatory myositis and no case has been reported to suggest CNS vasculitis in ASS.

Safety of Ixekizumab in Patients With Psoriatic Arthritis: Results From a Pooled Analysis of Three Clinical Trials.

OBJECTIVE: To evaluate ixekizumab safety in adults with psoriatic arthritis (PsA). METHODS: Safety data from 2 integrated data sets are presented: 1) 24-week, double-blind, placebo-controlled period of SPIRIT-P1 and SPIRIT-P2; and 2) all ixekizumab-treated patients of SPIRIT-P1 and SPIRIT-P2 plus SPIRIT-P3 open-label period. We report adverse event (AE) frequency and exposure-adjusted incidence rates per 100 patient-years at 12-week intervals to week 96. RESULTS: The placebo-controlled period had 678 patients (safety population): 224 placebo, 229 ixekizumab every 4 weeks, and 225 ixekizumab every 2 weeks. Overall, 1,118 patients received ixekizumab (total exposure 1,373.4 patient-years). In the placebo-controlled period, the frequencies of ixekizumab-treated patients experiencing ≥1 treatment-emergent AE (TEAE) and those experiencing serious AEs were 68.1% (56.7% placebo) and 4.4% (2.7% placebo), respectively. Injection site reactions (ISRs) were very common (21.4% ixekizumab [4.5% placebo]), with ISR discontinuation rates of 1.1% (ixekizumab) and 0.4% (placebo). Through week 96, the incidence rates of ISRs decreased with increasing ixekizumab exposure. The frequencies of AEs of special interest were 32.8% (ixekizumab) and 27.7% (placebo); for serious infections, the frequencies were 1.3% and 0%, respectively; Candida infections, 2.6% and 0.4%; confirmed major adverse cardiac events, 0% and 0%; malignancy, 0.4% and 0%; hypersensitivities, 5.3% and 1.8%; and depression-related, 1.8% and 1.3%. The frequency of Crohn's disease and ulcerative colitis (investigator-reported) was 0% in both groups, and the frequencies of sponsor-determined inflammatory bowel disease were 0.2% in the ixekizumab group and 0% in the placebo group. Overall, no active tuberculosis, invasive Candida infections, anaphylaxis, or suicide/self-injury behaviors were reported. CONCLUSION: The PsA ixekizumab safety integrated data set reached 1,373.4 patient-years total exposure. Ixekizumab-treated patients had higher rates of overall TEAEs, serious infections, mucocutaneous Candida, hypersensitivities (non-anaphylactic), and ISRs than placebo-treated patients. No unexpected safety outcomes were reported.