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Objectives: Granulocyte-macrophage colony-stimulating factor (GM-CSF) is implicated in pathogenesis of giant cell arteritis. We evaluated the efficacy of the GM-CSF receptor antagonist mavrilimumab in maintaining disease remission.Methods: This phase 2, double-blind, placebo-controlled trial enrolled patients with biopsy-confirmed or imaging-confirmed giant cell arteritis in 50 centres (North America, Europe, Australia). Active disease within 6 weeks of baseline was required for inclusion. Patients in glucocorticoid-induced remission were randomly assigned (3:2 ratio) to mavrilimumab 150 mg or placebo injected subcutaneously every 2 weeks. Both groups received a 26-week prednisone taper. The primary outcome was time to adjudicated flare by week 26. A prespecified secondary efficacy outcome was sustained remission at week 26 by Kaplan-Meier estimation. Safety was also assessed.Results: Of 42 mavrilimumab recipients, flare occurred in 19% (n=8). Of 28 placebo recipients, flare occurred in 46% (n=13). Median time to flare (primary outcome) was 25.1 weeks in the placebo group, but the median was not reached in the mavrilimumab group (HR 0.38; 95% CI 0.15 to 0.92; p=0.026). Sustained remission at week 26 was 83% for mavrilimumab and 50% for placebo recipients (p=0.0038). Adverse events occurred in 78.6% (n=33) of mavrilimumab and 89.3% (n=25) of placebo recipients. No deaths or vision loss occurred in either group.Conclusions: Mavrilimumab plus 26 weeks of prednisone was superior to placebo plus 26 weeks of prednisone for time to flare by week 26 and sustained remission in patients with giant cell arteritis. Longer treatment is needed to determine response durability and quantify the glucocorticoid-sparing potential of mavrilimumab.Trial Registration Number: ClinicalTrials.gov number: NCT03827018, Europe (EUdraCT number: 2018-001003-36), and Australia (CT-2018-CTN-01 865-1). [ABSTRACT FROM AUTHOR]

Objectives: Ultrasound of temporal and axillary arteries may reveal vessel wall inflammation in patients with giant cell arteritis (GCA). We developed a ultrasound scoring system to quantify the extent of vascular inflammation and investigated its diagnostic accuracy and association with clinical factors in GCA.Methods: This is a prospective study including 89 patients suspected of having GCA, of whom 58 had a confirmed clinical diagnosis of GCA after 6 months follow-up. All patients underwent bilateral ultrasound examination of the three temporal artery (TA) segments and axillary arteries, prior to TA biopsy. The extent of vascular inflammation was quantified by (1) counting the number of TA segments and axillary arteries with a halo and (2) calculating a composite Halo Score that also incorporated the thickness of each halo.Results: Halo counts and Halo Scores showed moderate diagnostic accuracy for a clinical diagnosis of GCA. They correlated positively with systemic inflammation. When compared with the halo count, the Halo Score correlated better with C-reactive protein (CRP) levels and allowed to firmly establish the diagnosis of GCA in more patients. Higher halo counts and Halo Scores were associated with a higher risk of ocular ischaemia. They allowed to identify subgroups of patients with low risk (≤5%) and high risk of ocular ischaemia (>30%).Conclusions: Ultrasound halo scoring allows to quantify the extent of vascular inflammation in GCA. Extensive vascular inflammation on ultrasound may provide strong diagnostic confirmation and associates with ocular ischaemia in GCA. [ABSTRACT FROM AUTHOR]

Background: Since the publication of the European League Against Rheumatism (EULAR) recommendations for the management of large vessel vasculitis (LVV) in 2009, several relevant randomised clinical trials and cohort analyses have been published, which have the potential to change clinical care and therefore supporting the need to update the original recommendations.Methods: Using EULAR standardised operating procedures for EULAR-endorsed recommendations, the EULAR task force undertook a systematic literature review and sought opinion from 20 experts from 13 countries. We modified existing recommendations and created new recommendations.Results: Three overarching principles and 10 recommendations were formulated. We recommend that a suspected diagnosis of LVV should be confirmed by imaging or histology. High dose glucocorticoid therapy (40-60 mg/day prednisone-equivalent) should be initiated immediately for induction of remission in active giant cell arteritis (GCA) or Takayasu arteritis (TAK). We recommend adjunctive therapy in selected patients with GCA (refractory or relapsing disease, presence of an increased risk for glucocorticoid-related adverse events or complications) using tocilizumab. Methotrexate may be used as an alternative. Non-biological glucocorticoid-sparing agents should be given in combination with glucocorticoids in all patients with TAK and biological agents may be used in refractory or relapsing patients. We no longer recommend the routine use of antiplatelet or anticoagulant therapy for treatment of LVV unless it is indicated for other reasons.Conclusions: We have updated the recommendations for the management of LVV to facilitate the translation of current scientific evidence and expert opinion into better management and improved outcome of patients in clinical practice. [ABSTRACT FROM AUTHOR]

Giant cell arteritis (GCA) represents the most common form of primary systemic vasculitis and is frequently associated with comorbidities related to the disease itself or induced by the treatment. Systematically collected data on disease course, treatment and outcomes of GCA remain scarce. The aim of this EULAR Task Force was to identify a core set of items which can easily be collected by experienced clinicians, in order to facilitate collaborative research into the course and outcomes of GCA. A multidisciplinary EULAR task force group of 20 experts including rheumatologists, internists, epidemiologists and patient representatives was assembled. During a 1-day meeting, breakout groups discussed items from a previously compiled collection of parameters describing GCA status and disease course. Feedback from breakout groups was further discussed. Final consensus was achieved by means of several rounds of email discussions after the meeting. A three-round Delphi survey was conducted to determine a core set of parameters including the level of agreement. 117 parameters were regarded as relevant. Potential items were subdivided into the following categories: General, demographics, GCA-related signs and symptoms, other medical conditions and treatment. Possible instruments and assessment intervals were proposed for documentation of each item. To facilitate implementation of the recommendations in clinical care and clinical research, a minimum core set of 50 parameters was agreed. This proposed core set intends to ensure that relevant items from different GCA registries and databases can be compared for the dual purposes of facilitating clinical research and improving clinical care. [ABSTRACT FROM AUTHOR]

To develop evidence-based recommendations for the use of imaging modalities in primary large vessel vasculitis (LVV) including giant cell arteritis (GCA) and Takayasu arteritis (TAK). European League Against Rheumatism (EULAR) standardised operating procedures were followed. A systematic literature review was conducted to retrieve data on the role of imaging modalities including ultrasound, MRI, CT and [18F]-fluorodeoxyglucose positron emission tomography (PET) in LVV. Based on evidence and expert opinion, the task force consisting of 20 physicians, healthcare professionals and patients from 10 EULAR countries developed recommendations, with consensus obtained through voting. The final level of agreement was voted anonymously. A total of 12 recommendations have been formulated. The task force recommends an early imaging test in patients with suspected LVV, with ultrasound and MRI being the first choices in GCA and TAK, respectively. CT or PET may be used alternatively. In case the diagnosis is still in question after clinical examination and imaging, additional investigations including temporal artery biopsy and/or additional imaging are required. In patients with a suspected flare, imaging might help to better assess disease activity. The frequency and choice of imaging modalities for long-term monitoring of structural damage remains an individual decision; close monitoring for aortic aneurysms should be conducted in patients at risk for this complication. All imaging should be performed by a trained specialist using appropriate operational procedures and settings. These are the first EULAR recommendations providing up-to-date guidance for the role of imaging in the diagnosis and monitoring of patients with (suspected) LVV. [ABSTRACT FROM AUTHOR]

Introduction Acute gout occurs in people with chronic kidney disease, who are commonly older people with comorbidities such as hypertension, heart disease and diabetes. Potentially harmful treatments are administered to these vulnerable patients due to a lack of clear evidence. Newly available treatment that targets a key inflammatory pathway in acute gout attacks provides an opportunity to undertake the first-ever trial specifically looking treating people with kidney disease. This paper describes the protocol for a feasibility randomised controlled trial (RCT) comparing anakinra, a novel interleukin-1 antagonist versus steroids in people with chronic kidney disease (ASGARD). Methods and analysis ASGARD is a two-parallel group double-blind, double-dummy multicentre RCT comparing anakinra 100 mg, an interleukin-1 antagonist, subcutaneous for 5 days against intramuscular methylprednisolone 120 mg. The primary objective is to assess the feasibility of the trial design and procedures for a definitive RCT. The specific aims are: (1) test recruitment and retention rates and willingness to be randomised; (2) test eligibility criteria; (3) collect and analyse outcome data to inform sample and power calculations for a trial of efficacy; (4) collect economic data to inform a future economic evaluation estimating costs of treatment and (5) assess capacity of the project to scale up to a national multicentre trial. We will also gather qualitative insights from participants. It aims to recruit 32 patients with a 1:1 randomisation. Information from this feasibility study will help design a definitive trial and provide general information in designing acute gout studies. Ethics and dissemination The London-Central Ethics Committee approved the protocol. The results will be disseminated in peer-reviewed journals and at scientific conferences. Trial registration number EudraCT No. 2015-001787-19, NCT/Clinicalstrials.gov No. NCT02578394, pre-results, WHO Universal Trials Reference No. U1111-1175-1977. NIHR Grant PB-PG-0614-34090. [ABSTRACT FROM AUTHOR]

There is convincing evidence for the known and unambiguously accepted beneficial effects of glucocorticoids at low dosages. However, the implementation of existing recommendations and guidelines on the management of glucocorticoid therapy in rheumatic diseases is lagging behind. As a first step to improve implementation, we aimed at defining conditions under which long-term glucocorticoid therapy may have an acceptably low level of harm. A multidisciplinary European League Against Rheumatism task force group of experts including patients with rheumatic diseases was assembled. After a systematic literature search, breakout groups critically reviewed the evidence on the four most worrisome adverse effects of glucocorticoid therapy (osteoporosis, hyperglycaemia/diabetes mellitus, cardiovascular diseases and infections) and presented their results to the other group members following a structured questionnaire for final discussion and consensus finding. Robust evidence on the risk of harm of long-term glucocorticoid therapy was often lacking since relevant study results were often either missing, contradictory or carried a high risk of bias. The group agreed that the risk of harm is low for the majority of patients at long-term dosages of ≤5 mg prednisone equivalent per day, whereas at dosages of >10 mg/day the risk of harm is elevated. At dosages between >5 and ≤10 mg/day, patient-specific characteristics (protective and risk factors) determine the risk of harm. The level of harm of glucocorticoids depends on both dose and patient-specific parameters. General and glucocorticoid-associated risk factors and protective factors such as a healthy lifestyle should be taken into account when evaluating the actual and future risk. [ABSTRACT FROM AUTHOR]

Objectives To evaluate the risk of aortic aneurysm in patients with giant cell arteritis (GCA) compared with age-, gender- and location-matched controls. Methods A UK General Practice Research Database (GPRD) parallel cohort study of 6999 patients with GCA and 41 994 controls, matched on location, age and gender, was carried out. A competing risk model using aortic aneurysm as the primary outcome and non-aorticaneurysm- related death as the competing risk was used to determine the relative risk (subhazard ratio) between non-GCA and GCA subjects, after adjustment for cardiovascular risk factors. Results Comparing the GCA cohort with the non-GCA cohort, the adjusted subhazard ratio (95% CI) for aortic aneurysm was 1.92 (1.52 to 2.41). Significant predictors of aortic aneurysm were being an ex-smoker (2.64 (2.03 to 3.43)) or a current smoker (3.37 (2.61 to 4.37)), previously taking antihypertensive drugs (1.57 (1.23 to 2.01)) and a history of diabetes (0.32 (0.19 to 0.56)) or cardiovascular disease (1.98 (1.50 to 2.63)). In a multivariate model of the GCA cohort, male gender (2.10 (1.38 to 3.19)), ex-smoker (2.20 (1.22 to 3.98)), current smoker (3.79 (2.20 to 6.53)), previous antihypertensive drugs (1.62 (1.00 to 2.61)) and diabetes (0.19 (0.05 to 0.77)) were significant predictors of aortic aneurysm. Conclusions Patients with GCA have a twofold increased risk of aortic aneurysm, and this should be considered within the range of other risk factors including male gender, age and smoking. A separate screening programme is not indicated. The protective effect of diabetes in the development of aortic aneurysms in patients with GCA is also demonstrated. [ABSTRACT FROM AUTHOR]

Objectives The aim of this 12-week Phase IIb study was to assess the efficacy and safety of olokizumab (OKZ), a humanised anti-IL6 monoclonal antibody, in patients with rheumatoid arthritis (RA) with moderate-to-severe disease activity who had previously failed tumour necrosis factor (TNF) inhibitor therapy. The dose-exposure-response relationship for OKZ was also investigated. Methods Patients were randomised to one of nine treatment arms receiving placebo (PBO) or OKZ (60, 120 or 240 mg) every 4 weeks (Q4W) or every 2 weeks (Q2W), or 8 mg/kg tocilizumab (TCZ) Q4W. The primary endpoint was change from baseline in DAS28(C-reactive protein, CRP) at Week 12. Secondary efficacy endpoints were American College of Rheumatology 20 (ACR20), ACR50 and ACR70 response rates at Week 12. Exploratory analyses included comparisons of OKZ efficacy with TCZ. Results Across 221 randomised patients, OKZ treatment produced significantly greater reductions in DAS28(CRP) from baseline levels at Week 12, compared to PBO (p<0.001), at all the OKZ doses tested (60 mg OKZ p=0.0001, 120 and 240 mg OKZ p<0.0001). Additionally, ACR20 and ACR50 responses were numerically higher for OKZ than PBO (ACR20: PBO=17.1-29.9%, OKZ=32.5-60.7%; ACR50: PBO=1.3-4.9%, OKZ=11.5-33.2%). OKZ treatment, at several doses, demonstrated similar efficacy to TCZ across multiple endpoints. Most adverse events were mild or moderate and comparable between OKZ and TCZ treatment groups. Pharmacokinetic/ pharmacodynamic modelling demonstrated a shallow dose/exposure response relationship in terms of percentage of patients with DAS28(CRP) <2.6. Conclusions OKZ produced significantly greater reductions in DAS28(CRP) from baseline at Week 12 compared with PBO. Reported AEs were consistent with the safety pro le expected of this class of drug, with no new safety signals identified. Trial register number: NCT01242488. [ABSTRACT FROM AUTHOR]

Objectives To evaluate the efficacy and safety of subcutaneous golimumab as add-on therapy in patients with active rheumatoid arthritis (RA) despite diseasemodifying antirheumatic drug (DMARD) treatment. To evaluate an intravenous plus subcutaneous (IV+SC) golimumab strategy in patients who had not attained remission. Methods GO-MORE was an open-label, multinational, prospective study in patients with active RA in typical clinical practice settings. In part 1, patients received addon monthly 50-mg subcutaneous golimumab for 6 months. The percentage of patients with good/ moderate European League Against Rheumatism (EULAR) 28-joint disease activity score (DAS28)--erythrocyte sedimentation rate (ESR) response was compared in patient subgroups with various concurrent or previous DMARD treatments. In part 2, patients with EULAR responses but not remission were randomly assigned to receive IV+SC or subcutaneous golimumab to month 12; DAS28--ESR remission was measured. Results 3366 patients were enrolled. At baseline of part 1, 3280 efficacy-evaluable patients had mean disease duration of 7.6 years and mean DAS28--ESR of 5.97 (SD=1.095). At month 6, 82.1% achieved good/moderate EULAR responses and 23.9% attained remission. When EULAR responses were analysed by the number of previously failed DMARD or the concomitant methotrexate dose, DMARD type, or corticosteroid use, no statistically significant differences were observed. Part 2 patients (N=490) who received IV+SC or subcutaneous golimumab achieved similar remission rates (///25%). Adverse events were consistent with previous reports of golimumab and other tumour necrosis antagonists in this population. Conclusions Add-on monthly subcutaneous golimumab resulted in good/moderate EULAR response in most patients; 25% achieved remission after 6 more months of golimumab, but an IV+SC regimen provided no additional efficacy over the subcutaneous regimen. [ABSTRACT FROM AUTHOR]

The objective of this study was to develop EULAR/ ACR classification criteria for polymyalgia rheumatica (PMR). Candidate criteria were evaluated in a 6-month prospective cohort study of 125 patients with new onset PMR and 169 non-PMR comparison subjects with conditions mimicking PMR. A scoring algorithm was developed based on morning stiffness >45 minutes (2 points), hip painlimited range of motion (1 point), absence of RF and or ACPA (2 points), and absence of peripheral joint pain (1 point). A score ≥4 had 68% sensitivity and 78% specificity for discriminating all comparison subjects from PMR. The specificity was higher (88%) for discriminating shoulder conditions from PMR and lower (65%) for discriminating RA from PMR. Adding ultrasound, a score ≥5 had increased sensitivity to 66% and specificity to 81%. According to these provisional classification criteria, patients ≥50 years old presenting with bilateral shoulder pain, not better explained by an alternative pathology, can be classified as having PMR in the presence of morning stiffness >45 minutes, elevated CRP and or ESR and new hip pain. These criteria are not meant for diagnostic purposes. [ABSTRACT FROM AUTHOR]

Objective To compare current definitions of remission and relapse in polymyalgia rheumatica (PMR) with items resulting from a Delphi-based expert consensus. Methods Relevant studies including definitions of PMR remission and relapse were identified by literature search in PubMed. The questionnaire used for the Delphi survey included clinical (n=33), laboratory (n=54) and imaging (n=7) parameters retrieved from a literature search. Each item was assessed for importance and availability/practicability, and limits were considered for metric parameters. Consensus was defined by an agreement rate of ≥80%. Results Out of 6031 articles screened, definitions of PMR remission and relapse were available in 18 and 34 studies, respectively. Parameters used to define remission and/or relapse included history and clinical assessment of pain and synovitis, constitutional symptoms, morning stiffness (MS), physician's global assessment, headache, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), blood count, fibrinogen and/or corticosteroid therapy. In the Delphi exercise a consensus was obtained on the following parameters deemed essential for definitions of remission and relapse: patient's pain assessment, MS, ESR, CRP, shoulder and hip pain on clinical examination, limitation of upper limb elevation, and assessment of corticosteroid dose required to control symptoms. Conclusions Assessment of patient's pain, MS, ESR, CRP, shoulder pain/limitation on clinical examination and corticosteroid dose are considered to be important in current available definitions of PMR remission and relapse and the present expert consensus. The high relevance of clinical assessment of hips was unique to this study and may improve specificity and sensitivity of definitions for remission and relapse in PMR. [ABSTRACT FROM PUBLISHER]

The article offers information on giant cell arteritis that affects large and medium sized arteries, largely branches of the external carotid artery. The symptoms are generally caused by local ischaemia due to endovascular damage and cytokine mediated systemic illness. There is considerable overlap with polymyalgia rheumatica. Acute blindness can occurs in up to 20 percent of patients with giant cell arteriti. Erythrocyte sedimentation rate and C reactive protein are normal in only four percent of cases but may be mildly raised in a fifth of cases. INSETS: LEARNING POINTS;CASE SCENARIO;HOW COMMON IS IT?.

Objectives: To report on fatigue in patients from the United Kingdom primary Sjögren's syndrome (pSS) registry identifying factors associated with fatigue and robust to assignable causes such as comorbidities and medications associated with drowsiness., Methods: From our cohort (n = 608), we identified those with comorbidities associated with fatigue, and those taking medications associated with drowsiness. We constructed dummy variables, permitting the contribution of these potentially assignable causes of fatigue to be assessed. Using multiple regression analysis, we modelled the relationship between Profile of Fatigue and Discomfort physical and mental fatigue scores and potentially related variables., Results: Pain, depression and daytime sleepiness scores were closely associated with both physical and mental fatigue (all p ≤ 0.0001). In addition, dryness was strongly associated with physical fatigue (p ≤ 0.0001). These effects were observed even after adjustment for comorbidities associated with fatigue or medications associated with drowsiness., Conclusions: These findings support further research and clinical interventions targeting pain, dryness, depression and sleep to improve fatigue in patients with pSS.This finding is robust to both the effect of other comorbidities associated with fatigue and medications associated with drowsiness., Competing Interests: Competing interests: SJB has provided consultancy services in the area of Sjögren’s syndrome for the following companies: Celgene, Eli Lilly, Glenmark, GSK, Medimmune, Novartis, Ono, Pfizer, Takeda, UCB. PE has undertaken clinical trials and provided expert advice to Pfizer, MSD, Abbvie, BMS, UCB, Roche, Novartis, Samsung, Sandoz and Lilly. WFN has undertaken clinical trials and provided consultancy or expert advice in the area of Sjögren’s syndrome to the following companies: GlaxoSmithKline, MedImmune, Novartis, UCB, Abbvie, Roche, Eli Lilly, Takeda, Resolves Therapeutics, and Nascient.

Objectives: To define the elementary ultrasound (US) lesions in giant cell arteritis (GCA) and to evaluate the reliability of the assessment of US lesions according to these definitions in a web-based reliability exercise., Methods: Potential definitions of normal and abnormal US findings of temporal and extracranial large arteries were retrieved by a systematic literature review. As a subsequent step, a structured Delphi exercise was conducted involving an expert panel of the Outcome Measures in Rheumatology (OMERACT) US Large Vessel Vasculitis Group to agree definitions of normal US appearance and key elementary US lesions of vasculitis of temporal and extracranial large arteries. The reliability of these definitions on normal and abnormal blood vessels was tested on 150 still images and videos in a web-based reliability exercise., Results: Twenty-four experts participated in both Delphi rounds. From originally 25 statements, nine definitions were obtained for normal appearance, vasculitis and arteriosclerosis of cranial and extracranial vessels. The 'halo' and 'compression' signs were the key US lesions in GCA. The reliability of the definitions for normal temporal and axillary arteries, the 'halo' sign and the 'compression' sign was excellent with inter-rater agreements of 91-99% and mean kappa values of 0.83-0.98 for both inter-rater and intra-rater reliabilities of all 25 experts., Conclusions: The 'halo' and the 'compression' signs are regarded as the most important US abnormalities for GCA. The inter-rater and intra-rater agreement of the new OMERACT definitions for US lesions in GCA was excellent., Competing Interests: Competing interests: None declared.

Objective: To assess the efficacy and safety of modified-release (MR) versus immediate-release (IR) prednisone in newly diagnosed glucocorticoid (GC)-naïve patients with polymyalgia rheumatica (PMR)., Methods: Patients were randomised to double-blind MR prednisone (taken at approximately 22:00) or IR prednisone (taken in the morning), 15 mg/day for 4 weeks. The primary end point was complete response rate (≥70% reduction in PMR visual analogue scale, duration of morning stiffness and C reactive protein (CRP) (or CRP <2× upper limit of normal (ULN))) at week 4. Non-inferiority was decided if the lower 95% confidence limit (MR vs IR prednisone) was above -15%. 400 patients were planned but only 62 were enrolled due to difficulties in recruiting GC-naïve patients with PMR with CRP ≥2×ULN., Results: The percentage of complete responders at week 4 was numerically greater for MR prednisone (53.8%) than for IR prednisone (40.9%). Non-inferiority of MR versus IR prednisone was not proven in the primary analysis on the per protocol population (N=48; treatment difference: 12.22%; 95% CI -15.82% to 40.25%). However, sensitivity analysis on the full analysis population showed an evident trend favouring MR prednisone (N=62; treatment difference: 15.56%; 95% CI -9.16% to 40.28%). Adverse events were generally mild and transient with no unexpected safety observations., Conclusions: The study showed a clear trend for favourable short-term efficacy of MR prednisone versus IR prednisone in early treatment of PMR. Further studies are warranted., Trial Registration Number: EudraCT number 2011-002353-57; Results., Competing Interests: Competing interests: MC received grant/research support from Horizon Pharma, is a consultant for Mundipharma International and is on the speaker’s bureau for Mundipharma International. MH is an employee of Mundipharma Research GmbH & Co. KG. SL is an employee of Mundipharma Research GmbH & Co. KG. BD received grant/research support from NAPP Pharmaceuticals, and is a consultant for Servier, Roche, Merck, GSK & Mundipharma. FB received grant/research support from Horizon Pharma, is a consultant for Mundipharma International and Horizon Pharma, and is on the speaker’s bureau for Mundipharma International and Horizon Pharma.

Objectives: This article reports relationships between serum cytokine levels and patient-reported levels of fatigue, in the chronic immunological condition primary Sjögren's syndrome (pSS)., Methods: Blood levels of 24 cytokines were measured in 159 patients with pSS from the United Kingdom Primary Sjögren's Syndrome Registry and 28 healthy non-fatigued controls. Differences between cytokines in cases and controls were evaluated using Wilcoxon test. Patient-reported scores for fatigue were evaluated, classified according to severity and compared with cytokine levels using analysis of variance. Logistic regression was used to determine the most important predictors of fatigue levels., Results: 14 cytokines were significantly higher in patients with pSS (n=159) compared to non-fatigued healthy controls (n=28). While serum levels were elevated in patients with pSS compared to healthy controls, unexpectedly, the levels of 4 proinflammatory cytokines-interferon-γ-induced protein-10 (IP-10) (p=0.019), tumour necrosis factor-α (p=0.046), lymphotoxin-α (p=0.034) and interferon-γ (IFN-γ) (p=0.022)-were inversely related to patient-reported levels of fatigue. A regression model predicting fatigue levels in pSS based on cytokine levels, disease-specific and clinical parameters, as well as anxiety, pain and depression, revealed IP-10, IFN-γ (both inversely), pain and depression (both positively) as the most important predictors of fatigue. This model correctly predicts fatigue levels with reasonable (67%) accuracy., Conclusions: Cytokines, pain and depression appear to be the most powerful predictors of fatigue in pSS. Our data challenge the notion that proinflammatory cytokines directly mediate fatigue in chronic immunological conditions. Instead, we hypothesise that mechanisms regulating inflammatory responses may be important.

Giant cell arteritis (GCA) is a chronic systemic vasculitis affecting large-sized and medium-sized vessels. Glucocorticoids are currently the mainstay of treatment for GCA and associated large vessel vasculitis (LVV) but are associated with frequent adverse events. Methotrexate has only demonstrated a modest benefit while anti-TNF biological agents (infliximab and etanercept) have been inefficacious. Elevated levels of interleukin-6 (IL-6), a proinflammatory cytokine, has been associated with GCA. Tocilizumab (TCZ), a humanised antihuman IL-6 receptor antibody, has been used successfully in several reports as a treatment for GCA and LVV. We report the potentially long-term successful use of TCZ in 8 cases of refractory LVV. All of our patients achieved a good clinical response to TCZ and C reactive protein reduced from an average of 70.3 to 2.5. In all cases, the glucocorticoid dose was reduced, from an average of 24.6 mg prednisolone prior to TCZ treatment to 4.7 mg, indicating that TCZ may enable a reduction in glucocorticoid-associated adverse events. However, regular TCZ administration was needed for disease control in most cases. TCZ was discontinued in one case due to the development of an empyema indicating the need for careful monitoring of infection when using this treatment.