Subscribe: Rheumatology - current issue
http://rheumatology.oxfordjournals.org/rss/current.xml
Added By: Feedage Forager Feedage Grade B rated
Language: English
Tags:
arthritis  cells  clinical  disease  gca  mtx  patient  patients  prevalence  response  study  tocilizumab  trials  years 
Rate this Feed
Rate this feedRate this feedRate this feedRate this feedRate this feed
Rate this feed 1 starRate this feed 2 starRate this feed 3 starRate this feed 4 starRate this feed 5 star

Comments (0)

Feed Details and Statistics Feed Statistics
Preview: Rheumatology - current issue

Rheumatology Current Issue





Published: Fri, 15 Dec 2017 00:00:00 GMT

Last Build Date: Fri, 15 Dec 2017 07:50:00 GMT

 



Guidelines for the management of systemic lupus erythematosus: great synthesis of evidence and eminence with limited focus on patient's needs

Fri, 15 Dec 2017 00:00:00 GMT

Progress in medicine is mostly based on evidence from international collaborations and trials, which are especially needed in infrequent diseases, such as SLE. In addition to EULAR recommendations, national guidelines for the management of SLE are needed to optimize management consistent with current evidence and specific national practices. British experts publish in this issue of Rheumatology an excellent composition based on evidence-based medicine (including literature until June 2015) and eminent experiences providing comprehensive recommendations covering diagnosis, assessment, monitoring and treatment of SLE [1].






Biosimilars Forum Applauds Food and Drug Administration on New Educational Program Promoting Safety and Effectiveness of Biosimilars

Tue, 14 Nov 2017 00:00:00 GMT

Washington, D.C. (October 24, 2017) – The Biosimilars Forum issued the following statement on the Food and Drug Administration (FDA)’s new educational program promoting the safe and effective use of biosimilars.



Patient acceptable symptom state in scleroderma: results from the tocilizumab compared with placebo trial in active diffuse cutaneous systemic sclerosis

Wed, 25 Oct 2017 00:00:00 GMT

Abstract
Objectives
Patient acceptable symptom state (PASS) as an absolute state of well-being has shown promise as an outcome measure in many rheumatologic conditions. We aimed to assess whether PASS may be effective in active diffuse cutaneous SSc differentiating active from placebo.
Methods
Data from the phase 2 Safety and Efficacy of Subcutaneous Tocilizumab in Adults with Systemic Sclerosis (faSScinate) trial were used, which compared tocilizumab (TCZ) vs placebo over 48 weeks followed by an open-label TCZ period to 96 weeks. Three different types of PASS questions were evaluated at weeks 8, 24, 48 and 96, including if a current state would be acceptable over time as a yes vs no response and Likert scales about how acceptable a current state is if remaining over time. Additional outcomes assessed included modified Rodnan skin score, HAQ disability index (HAQ-DI), physician and patient global assessments on a visual analogue scale, CRP and ESR.
Results
The placebo group consisted of 44 patients and the TCZ group had 43 patients. At baseline, 33% achieved a PASS for all three PASS questions, with the proportion increasing to 69, 71 and 78%, respectively, at 96 weeks. Changes in PASS scores showed a moderately negative correlation with HAQ-DI and patient and physician global assessments visual analogue scales, which indicates expected improvements as PASS improved. The PASS question, ‘Considering all of the ways your scleroderma has affected you, how acceptable would you rate your level of symptoms?’ showed significant correlations with patient-reported outcomes and differentiating placebo vs TCZ at 48 weeks (P = 0.023).
Conclusion
PASS may be used as a patient-centred outcome in SSc, especially as a 7-point Likert scale. Further validation is required to determine the utility as an outcome measure in trials and clinical practice.



Prevalence and predictors of tumour necrosis factor inhibitor persistence in psoriatic arthritis

Wed, 25 Oct 2017 00:00:00 GMT

Abstract
Objectives
To evaluate TNF-α inhibitor (TNFi) persistence when used as first- or second-line biologic therapy for the management of PsA, and to determine baseline clinical and laboratory parameters associated with TNFi persistence.
Methods
A retrospective single-centre cohort study was performed on all patients with PsA initiated on TNFi therapy between 2003 and 2015. Demographic, clinical and laboratory characteristics were compared with TNFi persistence, using Kaplan–Meier survival and Cox proportional hazards models.
Results
One hundred and eighty-eight patients with PsA were prescribed TNFi therapy as first-line biologic therapy over a period of 635 person-years [46% male, mean (s.d.) age 47.3 (11.4) years; median (interquartile range) disease duration 11 (7–16) years]. At 12 months of follow-up 79% of patients persisted with TNFi therapy, and 73% at 24 months. Of those discontinuing TNFi, 35% stopped due to primary inefficacy, 22% secondary inefficacy and 43% adverse events. Multivariable analysis identified female sex (hazard ratio (HR) 2.57; 95% CI: 1.26, 5.24; P = 0.01) and the presence of metabolic syndrome-related co-morbidities (HR = 2.65, 95% CI: 1.24, 5.69; P = 0.01) as predictors of lower persistence. Of 32 cases treated with a second TNFi, persistence at 12 months was 56%. TNFi persistence was 2-fold less likely in these 32 cases compared with first-line TNFi users (HR = 2.02, 95% CI: 1.20, 3.42; P = 0.01).
Conclusion
Patients with PsA who are female and have metabolic syndrome-related co-morbidities have lower TNFi persistence. Although persistence was lower in patients who had switched to a second TNFi, a substantial proportion of these cases responded, advocating switching to a second TNFi as a valid therapeutic strategy.



Autoantibodies to the survival of motor neuron complex in a patient with necrotizing autoimmune myopathy

Mon, 23 Oct 2017 00:00:00 GMT

Rheumatology key message
  • Autoantibodies to the survival motor neuron complex may be a biomarker of necrotizing autoimmune myopathy.



Serious infusion-related reaction after rituximab, abatacept and tocilizumab in rheumatoid arthritis: prospective registry data

Mon, 23 Oct 2017 00:00:00 GMT

Abstract
Objective
The aim was to evaluate the incidence of serious infusion-related reactions (SIRRs) in RA treated by non-TNF-targeted biologics.
Methods
We analysed data from three independent prospective registers, namely autoimmunity and rituximab, Orencia (abatacept) and RA (ORA) and Registry RoAcTEmra (tocilizumab), promoted by the French Society of Rheumatology and including patients with RA. SIRRs were defined by an occurrence during or within 24 h of an infusion and requiring discontinuation of treatment. Characteristics of patients with SIRRs were extracted from the electronic database.
Results
Among the 4145 patients, SIRRs occurred in 100 patients: 56 patients with the rituximab cohort (2.8% or 0.7/100 patient-years), 15 with the abatacept cohort (1.5% or 0.6/100 patient-years) and 29 with tocilizumab (1.9% or 1/100 patient-years). No fatal SIRR occurred. A previous mild infusion reaction to non-TNF-targeted biologics was observed in a quarter of patients with SIRRs. After pooled multivariate analysis, positive anti-CCP was associated with a higher risk of SIRR (odds ratio = 2.5; 95% CI: 1.01, 6.17). Absence of concomitant treatment with a synthetic DMARD tended to be associated with a higher risk of SIRR (odds ratio = 1.67; 95% CI: 1.00, 2.86).
Conclusion
In daily practice, SIRRs are slightly more frequent than in clinical trials and rarely life threatening. In common practice, serological status (anti-CCP positivity) and absence of concomitant treatment with a synthetic DMARD increase the risk of SIRR.



Development of a national audit tool for juvenile idiopathic arthritis: a BSPAR project funded by the Health Care Quality Improvement Partnership

Mon, 23 Oct 2017 00:00:00 GMT

Abstract
Objective
Timely access to holistic multidisciplinary care is the core principle underpinning management of juvenile idiopathic arthritis (JIA). Data collected in national clinical audit programmes fundamentally aim to improve health outcomes of disease, ensuring clinical care is equitable, safe and patient-centred. The aim of this study was to develop a tool for national audit of JIA in the UK.
Methods
A staged and consultative methodology was used across a broad group of relevant stakeholders to develop a national audit tool, with reference to pre-existing standards of care for JIA. The tool comprises key service delivery quality measures assessed against two aspects of impact, namely disease-related outcome measures and patient/carer reported outcome and experience measures.
Results
Eleven service-related quality measures were identified, including those that map to current standards for commissioning of JIA clinical services in the UK. The three-variable Juvenile Arthritis Disease Activity Score and presence/absence of sacro-iliitis in patients with enthesitis-related arthritis were identified as the primary disease-related outcome measures, with presence/absence of uveitis a secondary outcome. Novel patient/carer reported outcomes and patient/carer reported experience measures were developed and face validity confirmed by relevant patient/carer groups.
Conclusion
A tool for national audit of JIA has been developed with the aim of benchmarking current clinical practice and setting future standards and targets for improvement. Staged implementation of this national audit tool should facilitate investigation of variability in levels of care and drive quality improvement. This will require engagement from patients and carers, clinical teams and commissioners of JIA services.



Blockade of GM-CSF pathway induced sustained suppression of myeloid and T cell activities in rheumatoid arthritis

Mon, 23 Oct 2017 00:00:00 GMT

Abstract
Objectives
Targeting the granulocyte-macrophage colony-stimulating factor (GM-CSF) pathway holds great potential in the treatment of inflammatory diseases. Mavrilimumab, a human monoclonal GM-CSF receptor-α antibody, has demonstrated clinical efficacy in RA. Our current study aimed to elucidate mechanisms of action and identify peripheral biomarkers associated with therapeutic responses of GM-CSF antagonism in RA.
Methods
A 24-week placebo (PBO)-controlled trial was conducted in 305 RA patients who received mavrilimumab (30, 100 or 150 mg) or PBO once every 2 weeks. Serum biomarkers and whole blood gene expression profiles were measured by protein immunoassay and whole genome microarray.
Results
Mavrilimumab treatment induced significant down-regulation of type IV collagen formation marker (P4NP 7S), macrophage-derived chemokine (CCL22), IL-2 receptor α and IL-6 compared with PBO. Both early and sustained reduction of P4NP 7S was associated with clinical response to 150 mg mavrilimumab treatment. Gene expression analyses demonstrated reduced expression of transcripts enriched in macrophage and IL-22/IL-17 signalling pathways after GM-CSF blockade therapy. Myeloid and T cell-associated transcripts were suppressed in mavrilimumab-treated ACR20 responders but not non-responders. While CCL22 and IL-6 down-regulation may reflect a direct effect of GM-CSFR blockade on the production of pro-inflammatory mediators by myeloid cells, the suppression of IL-2 receptor α and IL-17/IL-22 associated transcripts suggests an indirect suppressive effect of mavrilimumab on T cell activation.
Conclusion
Our results demonstrated association of peripheral biomarker changes with therapeutic response to mavrilimumab in RA patients. The sustained efficacy of mavrilimumab in RA may result from both direct effects on myeloid cells and indirect effects on T cell activation after GM-CSFR blockade.



The effect of hydroxychloroquine on haemostasis, complement, inflammation and angiogenesis in patients with antiphospholipid antibodies

Tue, 17 Oct 2017 00:00:00 GMT

Abstract
Objectives
HCQ has been described as having a beneficial effect in patients with APS but its mechanism of action is unclear. We hypothesized that HCQ may have effects on subnormal angiogenesis, inflammation and haemostatic biomarkers seen in APS. The aim of our study was to assess laboratory markers [annexin A5 (AnxA5) anticoagulant activity, tissue factor (TF) levels, thromboelastography (TEG), CRP, Bb, C3a and VEGF] in HCQ-naïve patients with aPL at baseline and after commencing HCQ.
Methods
Twenty-two patients with aPL [20 female, 2 male, median age 55 (range 18–70) years] had blood taken pre- and 3 months after starting HCQ 200 mg daily.
Results
Soluble TF levels were significantly reduced comparing baseline and 3 months after HCQ commencement [401.8 (152.8) vs 300.9 (108) pg/ml (P = 0.010)]. No significant changes were found in the following [reported as pre- and post-HCQ commencement, mean (s.d.)]: AnxA5 anticoagulant ratio [187.1 (29.5) vs 193 (31) (P = 0.157)], anti-domain1 β2 glycoprotein1 IgG activity [1.8 (2) vs 1.2 (1.4) μg/ml (P = 0.105)], complement C3a-des-Arg [147.8 (84.5) vs 154.4 (88.1) ng/ml (P = 0.905)], complement Bb [1.3 (0.7) vs 1.1 (0.7) μg/ml (P = 0.422)], VEGF [68.8 (40) vs 59.4 (19.6) pg/ml (P = 0.454)] and CRP [7 (3.5) vs 7 (3.9) μg/ml (P = 0.917)]. TEG results including TEG reaction time, achievement of clot firmness, TEG maximum amplitude and TEG percentage lysis 30 and 60 min after maximum amplitude showed no significant difference.
Conclusion
HCQ significantly reduced soluble TF levels in patients with aPL. No significant change was observed in AnxA5 activity, anti-domain 1 IgG activity, TEG, CRP, complement Bb and C3a-des-Arg, and VEGF. Further studies of a larger patient cohort are needed.



Clinical trial parameters that influence outcomes in lupus trials that use the systemic lupus erythematosus responder index

Tue, 17 Oct 2017 00:00:00 GMT

Abstract
Objective
The SLE Responder Index (SRI) is a composite endpoint used in SLE trials. This investigation examined the clinical trial elements that drive response measured by the SRI.
Methods
Analyses are based on data from two phase 3 trials (n = 2262) that evaluated the impact of an anti-B-cell activating factor antibody on disease activity using SRI-5 as the primary endpoint (ClinicalTrials.gov NCT01196091 and NCT01205438).
Results
The SRI-5 response rate at week 52 for all patients was 32.8%. Non-response due to a lack of SLEDAI improvement, concomitant medication non-compliance or dropout was 31, 16.5 and 19.1%, respectively. Non-response due to deterioration in BILAG or Physician’s Global Assessment after SLEDAI improvement, concomitant medication compliance and trial completion was 0.5%. Disease activity in three SLEDAI organ systems was highly prevalent at baseline: mucocutaneous, 90.6%; musculoskeletal, 82.9%; and immunologic, 71.6%. Disease activity in each of the other organ systems was <11% of patients. Four clinical manifestations were highly prevalent at baseline: arthritis, 82.6%; rash, 69.2%; alopecia, 58.2%; and mucosal ulcer, 32.5%. The combined prevalence of renal, vascular and CNS disease at baseline was 17.6%; these patients had high SRI-5 response rates. Adjustments to corticosteroids were allowed during the first 24 weeks. Increases in corticosteroids above 2.5 mg/day were observed in 16.2% of placebo patients over the first 24 weeks after randomization.
Conclusion
The primary drivers of SRI-5 response were SLEDAI improvement, concomitant medication adherence and trial completion. Arthritis, rash, alopecia and mucosal ulcer were the most prevalent clinical manifestations at baseline. Corticosteroid increases and rare, highly weighted disease manifestations in SLEDAI can confound the SRI signal.



The proposed role of ultrasound in the management of giant cell arteritis in routine clinical practice

Mon, 16 Oct 2017 00:00:00 GMT

Abstract
Objective
To develop and explore a protocol for using colour duplex sonography (CDS) in the routine care of GCA.
Methods
We tested CDS of temporal arteries and axillary arteries (AXs) on consecutive patients with suspected or established GCA, between July 2014 and September 2016.
Results
We assessed 293 patients [age 72 (10), female/male 196/97], of whom 118 had clinically confirmed GCA. Seventy-three percent of patients had already received high-dose glucocorticoids (GCs) for 17 (33) days. Among new referrals with <7 days of GC treatment (n = 55), the sensitivity of CDS was 63.3% (95% CI: 44%, 80%), specificity 100% (95% CI: 83%, 100%), positive predictive value 100% and negative predictive value 64.5% (95% CI: 53%, 74%). Sensitivity rose to 81.8% in patients with jaw claudication and high inflammatory markers. During the observation period, the rate of temporal artery biopsies decreased from 72 (42%) to 36 (25%) (P = 0.002). CDS was positive in 21% of 89 follow-up scans in asymptomatic individuals, compared with 37% in patients experiencing clinical flares. Over time, the number of halos reduced; only new or flaring patients showed a halo in four or more sites. The diameter of axillary halos reduced from referral [1.6 (0.4) mm] to follow-up [1.4 (0.2) mm, P = 0.01] or flares [1.4 (0.2) mm, P = 0.02].
Conclusion
CDS provides high positive predictive value for diagnosing GCA and allows for a significant reduction in temporal artery biopsies. We explored the role of CDS in detecting flares and demonstrated a relationship to the extent of the distribution of halos, but not to their size.



Familial Mediterranean fever mutations are hypermorphic mutations that specifically decrease the activation threshold of the Pyrin inflammasome

Thu, 12 Oct 2017 00:00:00 GMT

Abstract
Objectives
FMF is the most frequent autoinflammatory disease and is associated in most patients with bi-allelic MEFV mutations. MEFV encodes Pyrin, an inflammasome sensor activated following RhoGTPase inhibition. The functional consequences of MEFV mutations on the ability of Pyrin variants to act as inflammasome sensors are largely unknown. The aim of this study was to assess whether MEFV mutations affect the ability of Pyrin to detect RhoGTPase inhibition and other inflammasome stimuli.
Methods
IL-1β and IL-18 released by monocytes from healthy donors (HDs) and FMF patients were measured upon specific engagement of the Pyrin, NLRP3 and NLRC4 inflammasomes. Cell death kinetics following Pyrin activation was monitored in real time.
Results
Monocytes from FMF patients secreted significantly more IL-1β and IL-18 and died significantly faster than HD monocytes in response to low concentrations of Clostridium difficile toxin B (TcdB), a Pyrin-activating stimulus. Monocytes from patients bearing two MEFV exon 10 pathogenic variants displayed an increased Pyrin inflammasome response compared with monocytes from patients with a single exon 10 pathogenic variant indicating a gene-dosage effect. Using a short priming step, the response of monocytes from FMF patients to NLRP3- and NLRC4-activating stimuli was normal indicating that MEFV mutations trigger a specific hypersensitivity of monocytes to low doses of a Pyrin-engaging stimulus.
Conclusion
Contrary to the NLRP3 mutations described in cryopyrin-associated periodic syndrome, FMF-associated MEFV mutations do not lead to a constitutive activation of Pyrin. Rather, FMF-associated mutations are hypermorphic mutations that specifically decrease the activation threshold of the Pyrin inflammasome without affecting other canonical inflammasomes.



Decreased incidence of gout in diabetic patients using pioglitazone

Tue, 10 Oct 2017 00:00:00 GMT

Abstract
Objective
The incidence and prevalence of gout are increasing, but the management is poor. Considering the increased prevalence of gout in the diabetic population, this study evaluated the effects of pioglitazone, an insulin resistance inhibitor, on the incidence of gout in the diabetic population.
Methods
We used data from the National Health Insurance program in Taiwan. The pioglitazone cohort contained 30 100 patients and each patient was age and sex matched with three non-pioglitazone users who were randomly selected from the diabetic population. Cox proportional hazards regression analysis was conducted to estimate the effects of pioglitazone on the incidence of gout in the diabetic population.
Results
The incidence of gout was significantly lower in pioglitazone users than in non-pioglitazone users [adjusted hazard ratio (aHR) 0.81 (95% CI 0.78, 0.85)]. The HR for the incidence of gout was lower in both male [aHR 0.80 (95% CI 0.75, 0.85)] and female [aHR 0.83 (95% CI 0.78, 0.88)] pioglitazone users than in non-pioglitazone users. An analysis of three age groups (<40, 40–59 and ⩾60 years) revealed that the HRs of both the 40–59 years [aHR 0.78 (95% CI 0.73, 0.83)] and the ⩾60 years [aHR 0.85 (95% CI 0.80, 0.91)] age groups were significantly lower among pioglitazone users than non-pioglitazone users.
Conclusion
Compared with the non-pioglitazone users, the incidence of gout in the diabetic population using pioglitazone was less.



IgG4-related disease presenting with raised serum IgG2—real timeline of IgG4-RD?

Mon, 09 Oct 2017 00:00:00 GMT

Rheumatology key message
  • Elevation of serum IgG2 may be a precursor to classical IgG4-related disease



Work productivity in systemic sclerosis, its economic burden and association with health-related quality of life

Mon, 09 Oct 2017 00:00:00 GMT

Abstract
Objective
To evaluate work productivity and its economic burden in SSc patients.
Methods
Consecutive SSc patients enrolled in the Australian Scleroderma Cohort Study were mailed questionnaires assessing employment (Workers’ Productivity and Activity Impairment Questionnaire and a custom-made questionnaire) and health-related quality of life (HRQoL) (36-item Short Form Health Survey and Patient-Reported Outcomes Measurement Information System 29). Linear regression methods were used to determine factors associated with work productivity.
Results
Among 476 patients submitting responses, 55.2% <65 years of age were employed. Unemployed patients were older at the time of survey completion (57.1 vs 53.7 years; P < 0.001) and had longer disease duration from first SSc clinical manifestation (16.2 vs 14.9 years; P = 0.01) than employed patients. The mean age at unemployment onset was 13.2 years below the average Australian retirement age. Of those working in the week prior to completing the survey, 16.0% reported missing work (absenteeism) due to their SSc, accounting for 32.9% of their working week. Reduced productivity while at work (presenteeism) accounted for 22% of their working week. Annual costs per patient as a consequence of unemployment and reduced productivity equated to a total of AUD$67 595.40. Factors independently associated with reduced work productivity were presence of synovitis and sicca symptoms, while tertiary education protected against work impairment. Patients with low HRQoL scores also had low work productivity.
Conclusion
SSc is associated with considerable unemployment and reduced productivity, which in turn is associated with a substantial economic burden and poor HRQoL. Raising awareness and identifying modifiable factors are possible ways of reducing this burden.



Tapering versus steady-state methotrexate in combination with tocilizumab for rheumatoid arthritis: a randomized, double-blind trial

Mon, 09 Oct 2017 00:00:00 GMT

Abstract
Objective
To explore whether tocilizumab + tapering MTX has comparable efficacy and safety vs tocilizumab + stable MTX in adult RA patients with inadequate response to MTX.
Methods
This randomized, placebo-controlled non-inferiority study involved patients with severe active RA [28-joint DAS (DAS28) >5.1] who had initiated tocilizumab + MTX at the study start. Patients received open-label tocilizumab (8 mg/kg i.v. every 4 weeks) and open-label MTX. At week 24, patients achieving good/moderate EULAR response were randomized to group A (double-blind MTX taper) or group B (double-blind MTX maintenance); both arms continued open-label tocilizumab. Primary analysis was the proportion of patients maintaining good/moderate EULAR response from week 24 to 60.
Results
The study stopped early due to low recruitment, although the predetermined non-inferiority criteria were still met; 427 patients were enrolled to the open-label phase at week 0. At week 24, EULAR good/moderate response was achieved in 272 individuals (64.4%) who were randomized, 136 in each arm (36% withdrew/were not eligible). Additionally, 45.0% achieved DAS28 ⩽3.2, 33.5% achieved remission (DAS28 <2.6) and 64.2% had a DAS28 change ⩾1.2. After week 24 randomization, the proportion of patients maintaining good/moderate EULAR response to week 60 was significantly greater for MTX taper vs stable MTX (76.5 vs 65.4%; P = 0.036), and since the lower limit of the 95% CI was >0.9, the pre-determined criteria for non-inferiority was fulfilled despite reduced recruitment. Safety analysis revealed no unexpected tocilizumab safety signals.
Conclusions
Tapering MTX in patients with RA receiving tocilizumab was non-inferior to continuing stable MTX in maintaining a good/moderate EULAR response. There were no unexpected safety signals; tocilizumab and MTX therapy was generally well tolerated in both groups.Trial registration number: EudraCT 2011-005260-20



The British Society for Rheumatology guideline for the management of systemic lupus erythematosus in adults: Executive Summary

Fri, 06 Oct 2017 00:00:00 GMT

lupusdiagnosisassessmentmonitoringmanagementimmunosuppressantstreatmentefficacynon-biologicsbiologics



The British Society for Rheumatology guideline for the management of systemic lupus erythematosus in adults

Fri, 06 Oct 2017 00:00:00 GMT

lupusdiagnosisassessmentmonitoringmanagementimmunosuppressantstreatmentefficacynon-biologicsbiologics



Interleukin-6 flags infection in tocilizumab-treated giant cell arteritis

Fri, 08 Sep 2017 00:00:00 GMT

Rheumatology key message
  • High IL-6 levels during tocilizumab therapy may flag masked infections with suppressed CRP.



Increased expression of interleukin-22 in patients with giant cell arteritis

Thu, 07 Sep 2017 00:00:00 GMT

Abstract
Objectives
GCA is characterized by arterial remodelling driven by inflammation. IL-22 is an attractive cytokine which acts at the crosstalk between immune and stromal cells. We hypothesized that IL-22 might be induced in GCA and might be involved in disease pathogenesis.
Methods
Patients subjected to temporal artery biopsies (TABs) naïve from therapy were enrolled: 27 biopsy-proven GCA, 8 biopsy-negative GCA, 21 biopsy-negative non-GCA patients. Expression of IL-22 was determined in TABs by immunohystochemistry, in plasma by ELISA, in peripheral blood mononuclear cells by real-time PCR and flow cytometry. Effects of IL-22 on viability and gene expression of primary cultures obtained from TABs were also evaluated.
Results
Inflamed TABs from GCA patients showed a higher expression of IL-22 and IL-22 specific receptor subunit (IL-22R1) than non-inflamed TABs. IL-22 was expressed in infiltrating immune cells and spindle shaped cells, IL-22R1 was expressed in endothelial cells. Patients with biopsy-proven GCA showed increased levels of IL-22 in plasma than patients with biopsy-negative GCA, without GCA and healthy subjects. Peripheral blood mononuclear cells from GCA patients expressed higher IL-22 transcript than healthy subjects. After stimulation in vitro with phorbol 12-myristate 13-acetate and ionomycin, the frequencies of Th22 and IL-22+ CD4+ lymphocytes were similar between patients with and without GCA. Treatment with IL-22 of primary cultures obtained from TABs increased cell viability under stress conditions and expression of B-cell activating factor.
Conclusion
IL-22 is increased in patients with GCA and affects viability and gene expression of arterial cells, supporting a potential role in disease pathogenesis.



Pragmatic trials in osteoarthritis—Are we ready?

Tue, 01 Aug 2017 00:00:00 GMT

Analysing delivery in clinical care



Toward cellular biomarkers for rheumatoid arthritis

Thu, 27 Jul 2017 00:00:00 GMT

Biomarkers in RA



Central nervous system vasculitis presenting as an ischaemic stroke in a young woman with systemic sclerosis

Wed, 12 Jul 2017 00:00:00 GMT

A 29-year-old woman with diffuse cutaneous SSc for 7 years presented with the acute onset of right hemiparesis. She had a regular pulse of 90/min and blood pressure 126/84 mmHg. Power in the right arm and leg was initially 4/5 but rapidly worsened to 3/5 in the leg with a positive Babinski sign.



Uncommon local reaction at the injection site of subcutaneous methotrexate

Tue, 11 Jul 2017 00:00:00 GMT

A 66-year-old man with a long-standing history of seronegative knee arthritis treated with subcutaneous MTX (15mg/week) presented with an asymptomatic erythematous plaque with crusting and scaling at the left side of the abdomen, corresponding to the last injection site (Fig. 1A). The patient explained similar local reactions had healed without scars appearing with the last injections, when the accumulated dose was 1.425 g. He self-administered the drug and was instructed in MTX self-injection several times, but the injection technique was not verified. Histopathological and microbiological studies of the plaque were unremarkable (Fig. 1B). Subcutaneous MTX was discontinued and switched to oral administration. One week later, the lesion had almost healed without scarring (Fig. 1C). No new skin lesions appeared after 1 year of follow-up.



Magnetic resonance imaging versus ultrasonography for the diagnosis of synovitis in rheumatoid arthritis

Tue, 04 Jul 2017 00:00:00 GMT

Comparing MRI and US for synovitis diagnosis



Can epidemiological studies uncover the origin of Behçet’s disease?

Sun, 25 Jun 2017 00:00:00 GMT

The origin of Behçet’s disease



Chronic recurrent multifocal osteomyelitis in children and adults: current understanding and areas for development

Thu, 06 Apr 2017 00:00:00 GMT

Abstract
Since the first descriptions of chronic recurrent multifocal osteomyelitis in the 1970s, there have been numerous case reports in the literature; both unusual case reports and case series from all over the world. Our understanding of the pathogenesis has significantly changed, with it now being regarded as an autoinflammatory condition. Treatment options have also expanded, but little progress has been made in developing the evidence for treatments. Advancing gene studies have provided a mouse model, but the quest for a single gene to match the phenotype has been elusive. Early cohorts of patients have grown up into adults, allowing prospective data to inform the expected outcomes.



The problem in differentiation between psoriatic-related polyenthesitis and fibromyalgia

Wed, 05 Apr 2017 00:00:00 GMT

Abstract
The recognition of the primacy of enthesitis in animal models of spondyloarthritis and the prevalence of clinically occult enthesopathy in psoriatic subjects and of persistent joint pain in PsA subjects who have ostensibly good reduction of joint swelling under biological therapy has highlighted the potential impact of polyenthesitis in psoriatic disease. In daily practice, the formal demonstration of enthesitis is challenging for the following reasons: the relatively avascular nature of enthesis, often leading to the absence of overt clinical inflammatory signs; the frequent lack of elevation of inflammatory markers; and finally, the limitations of current imaging techniques to provide supportive evidence for inflammation in these areas. Consequently, enthesitis may present as widespread pain indistinguishable from FM or may emerge as the dominant feature after successful biological therapy for suppression of synovitis. The unmet needs in the differentiation between FM and enthesitis in psoriatic disease patients are highlighted and critically evaluated in this article.



Musculoskeletal manifestations of Ebola virus

Tue, 04 Apr 2017 00:00:00 GMT

Abstract
The 2014 West African Ebola virus disease outbreak shocked the world as it swept through the region leaving Guinea, Liberia and Sierra Leone struggling to gain control. As the largest Ebola virus disease outbreak to date, there are more survivors in its wake than ever before, with a spectrum of health problems requiring management. Here we review various musculoskeletal manifestations of the virus that can occur both during and after the infection, and consider possible pathogenesis.



Differential effects of biological DMARDs on peripheral immune cell phenotypes in patients with rheumatoid arthritis

Mon, 27 Mar 2017 00:00:00 GMT

Abstract
Objective
The aim of this study was to assess the therapeutic effects of biological DMARDs (bDMARDs) on the diversity of immune cell phenotypes in peripheral blood of patients with RA.
Methods
Peripheral immune cell phenotypes were determined in 108 RA patients who were non-responsive to conventional DMARDs and 33 healthy control subjects by eight-colour flow cytometry. We also examined the correlation between the phenotypes and clinical findings and assessed the effects of 24-week treatment with bDMARDs.
Results
The proportions of T follicular helper (Tfh) cells, IgD CD27 double negative B cells and plasmacytoid dendritic cells (pDCs) were higher in patients with active RA than in healthy control. The percentages of memory T cells, Th17 and Tfh cells correlated with autoantibody titres, whereas that of plasmablasts correlated with disease activity scores. Treatment with TNF inhibitors reduced the proportion of pDCs, while tocilizumab reduced the proportion of double-negative B cells but increased naïve and activated Treg cells. Abatacept treatment resulted in marked decrease in the proportion of activated Tfh but slightly reduced Th17 and Treg cells. The proportion of Tfh cells was an independent and significant predictor of the response to abatacept therapy.
Conclusion
Molecular targeted therapies induced different changes in different immune cell phenotypes. Among the phenotypes, Tfh cells seem a potential target for abatacept. Immunophenotypic analysis might be useful for prediction of the response to bDMARDs.



Evaluating the design and reporting of pragmatic trials in osteoarthritis research

Fri, 24 Mar 2017 00:00:00 GMT

Abstract
Objectives
Among the challenges in health research is translating interventions from controlled experimental settings to clinical and community settings where chronic disease is managed daily. Pragmatic trials offer a method for testing interventions in real-world settings but are seldom used in OA research. The aim of this study was to evaluate the literature on pragmatic trials in OA research up to August 2016 in order to identify strengths and weaknesses in the design and reporting of these trials.
Methods
We used established guidelines to assess the degree to which 61 OA studies complied with pragmatic trial design and reporting. We assessed design according to the pragmatic–explanatory continuum indicator summary and reporting according to the pragmatic trials extension of the CONsolidated Standards of Reporting Trials guidelines.
Results
None of the pragmatic trials met all 11 criteria evaluated and most of the trials met between 5 and 8 of the criteria. Criteria most often unmet pertained to practitioner expertise (by requiring specialists) and criteria most often met pertained to primary outcome analysis (by using intention-to-treat analysis).
Conclusion
Our results suggest a lack of highly pragmatic trials in OA research. We identify this as a point of opportunity to improve research translation, since optimizing the design and reporting of pragmatic trials can facilitate implementation of evidence-based interventions for OA care.



Rheumatological complications of beta-thalassaemia: an overview

Wed, 22 Mar 2017 00:00:00 GMT

Abstract
Beta-thalassaemia, an autosomal recessive haemoglobinopathy, ranks among the most frequent monogenetic diseases globally. The severe form of the disease, beta-thalassaemia major, is accompanied by progressive involvement of multiple organ systems as a result of the disease pathophysiology as well as iron overload from blood transfusions on a regular basis. Some of the manifestations might also be caused by medications used to manage iron overload. The purpose of this review is to highlight the rheumatological complications of beta-thalassaemia, which include musculoskeletal manifestations, such as arthritis and arthropathies, joint effusions, osteoporosis, bone fractures and myalgias, in addition to CTDs, such as pseudoxanthoma elasticum. Rheumatologists are strongly encouraged to take part in a multidisciplinary approach to the management of this debilitating disease.



Diagnostic test accuracy of ultrasound for synovitis in rheumatoid arthritis: systematic review and meta-analysis

Fri, 03 Mar 2017 00:00:00 GMT

Abstract
Objective
To evaluate diagnostic test accuracy of US compared with MRI for the detection of synovitis in RA patients.
Methods
A systematic literature search was performed in the PubMed, EMBASE, Cochrane Library and Web of Science Core Collection databases. Studies evaluating the diagnostic test accuracy of US for synovitis detected by MRI as the reference standard for wrist, MCP, PIP and knee joints were included. To assess the overall accuracy, we calculated the diagnostic odds ratio using a DerSimonian–Laird random effects model and the area under the curve (AUC) for the hierarchical summary receiver operating characteristics using Holling’s proportional hazards models. The summary estimate of the sensitivity and specificity were obtained using the bivariate model.
Results
Fourteen of 601 identified articles were included in the review. The diagnostic odds ratio was 11.6 (95% CI 5.6, 24; I2 = 0%), 28 (95% CI 12, 66; I2 = 11%), 23 (95% CI 6.5, 84; I2 = 19%) and 5.3 (95% CI 0.60, 48; I2 = 0%) and the AUC was 0.81, 0.91, 0.91 and 0.61 for wrist, MCP, PIP and knee joints, respectively. The summary estimates of sensitivity and specificity were 0.73 (95% CI 0.51, 0.87)/0.78 (95% CI 0.46, 0.94), 0.64 (95% CI 0.43, 0.81)/0.93 (95% CI 0.88, 0.97), 0.71 (95% CI 0.33, 0.93)/0.94 (95% CI 0.89, 0.97) and 0.91 (95% CI 0.56, 0.99)/0.60 (95% CI 0.20, 0.90) for wrist, MCP, PIP and knee joints, respectively.
Conclusion
US is a valid and reproducible technique for detecting synovitis in the wrist and finger joints. It may be considered for routine use as part of the standard diagnostic tools in RA.



Exploring the variability in Behçet’s disease prevalence: a meta-analytical approach

Fri, 17 Feb 2017 00:00:00 GMT

Abstract
Background
Surveys of Behçet’s disease (BD) have shown substantial geographic variations in prevalence, but some of these differences may result from methodological inconsistencies. This meta-analysis explored the effect of geographic location and study methodology on the prevalence of BD.
Methods
We systematically searched the literature in electronic databases and by handsearching to identify population-based prevalence surveys of BD. Studies were eligible if they provided an original population-based prevalence estimate for BD with the number of prevalent cases identified in the study area. Pooled prevalence proportions across all studies were computed by using random effects models based on a Poisson normal distribution. Pre-defined subgroup analyses and meta-regression were used to investigate the effect of covariates on the prevalence proportions.
Results
We included 45 reports published from 1974 to 2015 and covering worldwide areas. The pooled estimates of prevalence proportions (expressed as cases/100 000 inhabitants) were 10.3 (95% CI 6.1, 17.7) for all studies and 119.8 (59.8, 239.9) for Turkey, 31.8 (12.9, 78.4) for the Middle East, 4.5 (2.2, 9.4) for Asia and 3.3 (2.1, 5.2) for Europe. Subgroup analyses showed a strikingly greater prevalence for studies with a sample survey design than a census design [82.5 (95% CI 47.3, 143.9) vs 3.6 (2.6, 5.1)]. Metaregression identified study design as an independent covariate significantly affecting BD prevalence proportions.
Conclusions
Differences in BD prevalence proportions likely reflect a combination of true geographic variation and methodological artefacts. In particular, use of a sample or census study design may strongly affect the estimated prevalence.



The funding lottery for potentially life-threatening rare diseases

Sat, 04 Feb 2017 00:00:00 GMT

It’s not fair, my disease is rare