Patients with early inflammatory arthritis who fulfil the 2010 American College of Rheumatology–European League Against Rheumatism classification criteria for rheumatoid arthritis have increased mortality compared with those who do not: results from the Norfolk Arthritis Register

BackgroundMortality is increased in rheumatoid arthritis compared with the general population. Most studies have used the 1987 American College Rheumatology criteria to define rheumatoid arthritis when investigating mortality. The aims of this study were to examine whether, in a cohort of patients with early inflammatory polyarthritis, the 2010 American College of Rheumatology–European League Against Rheumatism classification criteria for rheumatoid arthritis identify those with decreased survival; and if so to identify which components of the criteria are the strongest predictors of mortality.MethodsAdults with two or more swollen joints for 4 or more weeks were recruited to the Norfolk Arthritis Register (NOAR) between 1990 and 2009. Patients included in this analysis had symptom duration of at least 2 years and had not received any disease modifying therapy at initial assessment. Data on the components of the 2010 criteria, along with demographic details, were obtained at baseline-visit through a nurse-administered questionnaire and joint examination. Bloods samples were taken for C-reactive protein (CRP), rheumatoid factor (RF), and anti-citrullinated protein antibody (ACPA) estimation. All patients registered with NOAR are flagged with the UK Office for National Statistics (ONS) which provides mortality data. Survival analyses were performed with Cox proportional hazards models in univariate analyses, then adjusted for age and sex. A multivariable model was then developed including all components of the 2010 criteria as well as baseline smoking status, age, and gender.Findings1671 patients had complete data for analysis, with 20 488 person-years of follow-up. 1092 (65%) patients were female and there were 471 deaths reported by the ONS by Dec 31, 2011. 905 (54%) patients fulfilled the 2010 criteria at baseline, and they had a significantly increased risk of death compared with patients in NOAR who did not fulfil the 2010 criteria, both in univariate analyses and in the age-adjusted and sex-adjusted model (adjusted hazard ratio (HR) 1·39 [95% CI 1·15–1·68]). The multivariable model identified high titre RF, ACPA (or both) positivity (more than three times the upper limit of normal) and raised CRP as significant predictors of mortality (HR 1·64 [95% CI 1·31–1·97] and 1·25 [95% CI 1·02–1·52], respectively).InterpretationPatients presenting with early inflammatory polyarthritis who fulfil the 2010 criteria have significantly increased mortality compared with those who do not. The components of the 2010 criteria that seem to be important predictors of mortality are high titre RF or ACPA positivity, and abnormal CRP at baseline.FundingArthritis Research UK.     

The effect of methotrexate and anti-tumor necrosis factor therapy on the risk of lymphoma in rheumatoid arthritis in 19,562 patients during 89,710 person-years of observation

OBJECTIVE: To ascertain the relationship between anti-tumor necrosis factor (anti-TNF) therapy, methotrexate (MTX), and the risk of lymphoma in patients with rheumatoid arthritis (RA). This report updates our previous report during 29,314 person-years of followup. METHODS: Participants in the National Data Bank for Rheumatic Diseases (NDB) longitudinal study of long-term outcomes of RA completed semiannual questionnaires from 1998 through 2005, during 89,710 person-years of followup. Lymphoma reports were validated by medical records. The association between lymphoma and treatment was investigated using conditional logistic regression, adjusted for severity and demographic covariates. RESULTS: Of the 19,591 participants, 55.3% received biologic agents and 68.0% received MTX while enrolled in the NDB. The lymphoma incidence rate was 105.9 (95% confidence interval [95% CI] 86.6-129.5) per 100,000 person-years of exposure. Compared with the SEER (Surveillance, Epidemiology, and End-Results) lymphoma database, the standardized incidence ratio was 1.8 (95% CI 1.5-2.2). The odds ratio (OR) for lymphoma in patients who received anti-TNF therapy compared with patients who did not receive anti-TNF therapy was 1.0 (95% CI 0.6-1.8 [P = 0.875]). The OR for lymphoma in patients who received anti-TNF plus MTX therapy compared with patients who received MTX treatment alone was 1.1 (95% CI 0.6-2.0 [P = 0.710]). Infliximab and etanercept considered individually also were not associated with a risk of lymphoma. CONCLUSION: In a study of lymphoma in 19,591 RA patients over 89,710 person-years of followup, which included exposure to anti-TNF therapy in 10,815 patients, we did not observe evidence for an increase in the incidence of lymphoma among patients who received anti-TNF therapy.     

Cardiovascular Risk in Rheumatoid Arthritis: Comparing TNF-α Blockade with Nonbiologic DMARDs

Background

Elevated tumor necrosis factor (TNF)-α likely contributes to the excess cardiovascular risk observed in rheumatoid arthritis. We compared the cardiovascular risk in rheumatoid arthritis patients starting a TNF-α blocking agent versus a nonbiologic disease-modifying antirheumatic drug (nbDMARD).

Methods

Subjects with rheumatoid arthritis participating in several different US insurance programs between 1998 and 2007 who received methotrexate were eligible. Those who added a TNF-α blocking agent were compared with subjects who added a nbDMARD in Cox regression models stratified by propensity score decile and adjusted for oral glucocorticoid dosage. We examined the composite cardiovascular end point of myocardial infarction, stroke, or coronary re-vascularization after 6 months.

Results

We compared 8656 new users of a nbDMARD with 11,587 new users of a TNF-α blocking agent with similar baseline covariates. Incidence rates per 100 person-years for the composite cardiovascular end point were 3.05 (95% confidence interval [CI], 2.54-3.65) for nbDMARDs and 2.52 (95% CI, 2.12-2.98) for TNF-α blocking agents. The hazard ratio (HR) for the TNF-α blocking agent compared with nbDMARD carrying the first exposure forward was 0.80 (95%, CI 0.62-1.04), while the HR for the as-treated analysis was 0.71 (95% CI, 0.52-0.97). The potential cardiovascular benefit of TNF-α blocking agents was strongest among individuals ≥65 years of age (HR 0.52; 95% CI, 0.34 -0.77; P for interaction = 0.075).

Conclusion

Among subjects with rheumatoid arthritis, TNF-α blocking agents may be associated with a reduced risk of cardiovascular events compared with an nbDMARD. Randomized controlled clinical trials should be considered to test this hypothesis.     

Cerebrovascular accidents in Ebstein’s anomaly

Introduction: Mechanisms and risk factors for cerebrovascular accidents (CVAs) in Ebstein’s anomaly (EA) are not well understood; hence, we aimed to clarify these in a large cohort of EA patients.
Methods: Patients with a confirmed diagnosis of EA were retrospectively reviewed. Baseline characteristics were compared between patients with and without a prior history of CVA using logistic regression modeling. Cox regression analysis was used to identify predictors of CVA following initial evaluation. CVA incidence from birth and following tricuspid valve surgery were estimated using the Kaplan‐Meier method.
Results: Nine hundred sixty‐eight patients (median age 21.1 years, 41.5% male) were included, in which, 87 patients (9.0%) had a history of CVA (54 strokes, 33 transient ischemic attacks; 5 associated with brain abscesses) prior to their initial evaluation. The odds of atrial septal defect/patent foramen ovale (odds ratio [OR] 4.91; 95% CI 2.60‐21.22; p = .0002) and migraines/headaches (OR 2.38; 95% CI 1.40‐4.04; p = .0013) but not atrial arrhythmias (OR 0.75; 95% CI 0.44‐1.30; p = .31) were sig‐ nificantly higher among patients with prior CVA following multivariable adjustment. Seventeen patients experienced CVA following initial evaluation; no examined vari‐ ables including atrial arrhythmias (HR 2.38; 0.91‐6.19; p = .076) were predictive of CVA risk. The 10‐year, 50‐year, and 70‐year incidences of CVA were 1.4%, 15.9%, and 23.5%, respectively, with paradoxical embolism heavily implicated.
Conclusion: Patients with EA are at substantive risk for CVA. Histories of migraines/ headaches and interatrial shunts should prompt concern for paradoxical embolic CVAs. This has significant implications for all patients with atrial‐level shunting.     

Problems encountered during anti-tumour necrosis factor therapy

Worldwide, over 400,000 patients have been treated with tumour necrosis factor (TNF)-alpha antagonists for indications that include rheumatoid arthritis, juvenile rheumatoid arthritis, inflammatory bowel disease, psoriatic arthritis and ankylosing spondylitis. Since their approval, concerns regarding safety have been raised. There is a risk of re-activation of granulomatous diseases, especially tuberculosis, and measures should be taken for detection and treatment of latent tuberculosis infections. Preliminary data suggest that anti-TNF therapy may be safe in chronic hepatitis C. However, TNF-alpha antagonists have resulted in re-activation of chronic hepatitis B if not given concurrently with antiviral therapy. Solid tumours do not appear to be increased with anti-TNF therapy. Variable rates of increased lymphoma risk have been described with anti-TNF therapy compared with the general population, although no increased risk was found compared with a rheumatoid arthritis population. Large phase II and III trials with TNF-alpha antagonists in advanced heart failure have shown trends towards a worse prognosis, and should therefore be avoided in this population. Both etanercept and infliximab are associated with the formation of autoantibodies, and these autoantibodies are rarely associated with any specific clinical syndrome. Rare cases of aplastic anaemia, pancytopenia, vasculitis and demyelination have been described with anti-TNF therapy. This chapter will discuss the safety profile and adverse events of the three commercially available TNF-alpha antagonists: etanercept, infliximab and adalimumab. The data presented in this review have been collected from published data, individual case reports or series, package inserts, the Food and Drug Administration postmarketing adverse events surveillance system, and abstracts from the American College of Rheumatology and European Congress of Rheumatology meetings for 2005.     

Infliximab and brucellosis: not the usual suspects,this time

Abstract

Tumor necrosis factor (TNF) plays an important role in the host defense mechanism, and anti-TNF antibody therapies may increase the risk of serious infections. We herein report a case of 57-year-old male with rheumatoid arthritis who developed brucellosis during treatment with infliximab in combination with methotrexate and a low-dose steroid. Brucellosis should be kept in mind, particularly in endemic areas, in patients receiving anti-TNF therapy. Clinicians should be aware of brucellosis symptoms and ways of contamination and should warn their patients. Early diagnosis and rapid treatment may prevent a possible poor course of the disease in immunocompromised patients.     

Heart failure and anti tumor necrosis factor-alpha in systemic chronic inflammatory diseases

Tumor necrosis factor alpha (TNF-alpha) antagonists have emerged as an effective therapy for patients with diseases as Crohn's disease, rheumatoid arthritis, and other chronic systemic inflammatory diseases. In the last years, there has been a growing interest in the role that inflammatory cytokines, which sustain the pathogenesis of these diseases, plays in regulating cardiac structure and function, particularly in the progression of chronic heart failure.In fact there is an increase of anti-TNF alpha levels in advanced heart failure but the treatment with anti-TNF alpha has been shown to worsen the prognosis of heart failure in randomized controlled trials.Patients with rheumatoid arthritis have an increased risk for cardiovascular disease and anti-TNF alpha therapy seems to be beneficial on the risk of cardiovascular disease. In Crohn's disease the increased risk of cardiovascular disease is controversial and therefore it is impossible to demonstrate an effect in reduction of the risk; however, heart failure in patients treated with anti-TNF alpha, despite in a small proportion, has been observed.On the basis of this observation, anti-TNF alpha therapy is contraindicated in patients with Crohn's disease and III–IV New York Heart Association heart failure class.     

A rare complication of cerebral venous thrombosis during simple percutaneous coronary intervention: A case report

Rationale:Cerebrovascular accidents (CVAs) after percutaneous coronary intervention (PCI), although rare, are associated with high in-hospital morbidity and mortality rates. Cerebral venous thrombosis (CVT) is an uncommon cause of CVAs compared with arterial disease but is associated with favorable outcomes in most cases. We present a rare case of CVT following a simple PCI procedure with stent implantation, which has not been previously reported in the literature.Patient concerns:A 78-year-old woman with hypertension, hyperlipidemia, and coronary artery disease received simple PCI with stent implantation. After PCI, she developed a throbbing headache with nausea and vomiting, with her blood pressure increasing to 190/100 mmHg. Drowsiness, disorientation, and neck stiffness were noted. Neurological complication due to the PCI procedure was highly suspected.Diagnosis:Noncontrast brain computed tomography was performed along with emergency neurological consultation, and the patient was diagnosed as having acute CVT.Interventions:The patient was treated with anti-intracranial pressure therapy and anticoagulation therapy through low-molecular-weight heparin and was subsequently treated with warfarin.Outcomes:After treatment, the patient''s symptoms and signs gradually subsided, and her clinical condition improved. She was discharged with full recovery thereafter.Lessons:A case of acute CVT, a rare, and atypical manifestation of venous thromboembolism and CVA, complicated simple PCI with stent implantation. During PCI, identifying patients with a high risk of a CVA is critical, and special care should be taken to prevent this devastating complication.     

Prediction model for rheumatoid arthritis: modelling 46 genetic risk variants with smoking

Background Improved characterisation of the risk factors for rheumatoid arthritis raises the possibility that they could be combined to identify individuals at high risk of disease in whom preventive strategies can be evaluated. Our aim was to develop a prediction model capable of identifying such individuals with sufficient accuracy to enable the assessment of preventive treatments.MethodsOur prediction model combines odds ratios for 15 HLA-DRB1 alleles, 31 non-HLA single nucleotide polymorphisms (SNPs), and smoking status to classify an individual's risk of seropositive rheumatoid arthritis. Our novel modelling technique employs confidence intervals to classify disease risks using a computer-simulated population. We developed several models (HLA, HLA-10/20/31 SNP, HLA-smoking models) to evaluate the impact of different factors on prediction. The ability of each model to discriminate between rheumatoid arthritis and controls was evaluated in two European cohorts: the Wellcome Trust Case Control Consortium (WTCCC: 1542 cases, 1226 controls) and the UK Rheumatoid Arthritis Genetics Consortium (UKRAG: 2623 cases, 1503 controls).Findings HLA-DRB1 alleles conferred most prediction: the WTCCC HLA-only model classified 50% antibodies to citrullinated protein antigens (ACPA)-positive rheumatoid arthritis versus 17% controls as high risk and 60% controls versus 25% ACPA-positive rheumatoid arthritis as reduced risk. Adding smoking information improved prediction (p=0·00033); SNPs provided no significant benefits. The highest area under the curve was 0·81 (95% CI 0·78–0·85). Only a minority had substantially elevated risks of rheumatoid arthritis: 6·9% ACPA-positive cases and 0·31% controls in WTCCC had an odds ratio for rheumatoid arthritis of more than 20 when evaluated with the HLA-31 SNP model.InterpretationCombined information on HLA-DRB1 alleles and smoking provides informative risk prediction for rheumatoid arthritis. Since only a minority of individuals are at substantially elevated risks, modelling may be best focused in a-priori high-risk groups such as those with family histories of rheumatoid arthritis. Further work is needed to define risk factors with large effect sizes for incorporation within our modelling framework.FundingArthritis Research UK.     

Subclinical synovitis measured by ultrasound in rheumatoid arthritis patients with clinical remission induced by synthetic and biological modifying disease drugs

BackgroundRheumatoid arthritis (RA) patients with disease in clinical remission might show subclinical synovitis, which can be related to the progress of structural joint damage.ObjectiveTo determine and compare the degree of synovial inflammation by ultrasound (US) in patients with RA in clinical remission, treated with DMARD or combination therapy with DMARD and anti-TNF.MethodsHospital-based cross-sectional study of 58 patients with RA in sustained remission for at least 6 months by DAS28 <2.6, who attended the Rheumatology Service at the Hospital Universitario de Caracas. Patients underwent clinical, functional, and laboratory assessments. Ultrasound was performed in hands measuring synovial effusion, synovial hypertrophy and power Doppler signal; using a semiquantitative 4-point scale of 0 = none to 3 = severe. Chi-square and t-test were used to compare the clinical, functional, laboratory and US assessments between the DMARD (N = 37) and combination therapy with DMARD and anti-TNF (N = 21) groups. A p-value <0.05 was considered statistically significant.ResultsOut of 58 patients, 25.9% had remission by US and 74.1% had synovial effusion or hypertrophy or positive power Doppler signal. Non-significant differences in US synovitis between the two groups were found.ConclusionsPersistent US activity was evident in a high percentage of rheumatoid arthritis patients in clinical remission by DAS28. No differences in subclinical synovitis measured by US were found between patients with DMARD and anti-TNF-induced clinical remission.     

Early rheumatoid arthritis and resolving fibroblasts segregate according to Dickkopf related protein 1 expression

BackgroundDickkopf related protein 1 (DKK1) has been proposed as the master regulator of joint remodelling. This Wnt signalling pathway inhibitor is involved in osteoblast growth and differentiation. In rheumatoid arthritis, increased DKK1 plasma levels correlate with inflammation and bone erosions. Furthermore, patients with rheumatoid arthritis who carry genetic variants in the DKK1 gene have higher serum DKK1 levels and more progressive joint destruction, suggesting a fundamental role for DKK1 in rheumatoid arthritis. In the diseased joint, synovial fibroblasts are key mediators of bone and cartilage destruction via secretion of matrix metalloproteinases and regulation of monocyte to osteoclast differentiation. In this study we analysed whether DKK1 secretion might contribute to this effect. We hypothesised that synovial fibroblasts from patients with early rheumatoid arthritis would be characterised by high DKK1 expression compared with those from patients with resolving arthritis.MethodsSynovial tissue samples were obtained by ultrasound-guided biopsy from patients with early synovitis within 12 weeks of symptom onset. 12 patients developed rheumatoid arthritis (according to 1987 American College of Rheumatology criteria) and eight had self-limiting disease within 18 months’ follow-up. Synovial fibroblasts were cultured and expanded to passage three with established methods. mRNA expression was quantified with real-time quantitative PCR. DKK1 levels were measured in the supernatants of cultured cells with a commercial ELISA kit (R&D systems). The methylation status of the DKK1 gene promoter was assessed with methylated DNA immunoprecipitation assays.FindingsExpression of DKK1 mRNA was significantly higher in synovial fibroblasts from patients with early rheumatoid arthritis than in those with resolving arthritis (2^?dCt relative to glyceraldehyde 3-phosphate dehydrogenase 0·024 vs 0·009, p<0·005). Differential expression was confirmed at the protein level (median 23·2 ng/mL [IQR 11·1–48·5] vs 6·6 ng/mL [4·2–23·6]; p=0·07). Expression levels of DKK1 mRNA or protein did not correlate with disease duration, or with clinical indices. Analysis of DKK1 promoter methylation showed a trend towards promoter hypomethylation in samples from early rheumatoid arthritis compared with resolving samples (1·04-fold enrichment vs 1·52-fold enrichment, not significant). Further samples are being analysed to increase the power of the study.InterpretationDKK1 is an inhibitor of the Wnt signalling pathway that promotes cell invasion and a pro-destruction imbalance of osteoblast and osteoclast activity. Our data suggest that expression of DKK1 by fibroblasts cultured from treatment-naive patients discriminates between persistent and resolving disease, and occurs early in the disease process in rheumatoid arthritis. This difference in gene expression might be under epigenetic control at the level of DNA methylation. Current studies are focusing on validating these findings.FundingWellcome Trust.     

Cardiovascular risk in patients with psoriasis,psoriatic arthritis,and rheumatoid arthritis: a prospective study of data from the Secure Anonymised Information Linkage databank

BackgroundThe increased risk of cardiovascular disease in individuals with rheumatoid arthritis, psoriatic arthritis, and psoriasis is well known. However, the precise cardiovascular risk in psoriasis and psoriatic arthritis is less understood, particularly the relative contribution of traditional cardiovascular risk factors, such as obesity, smoking, and systemic inflammation as measured by C-reactive protein and erythrocyte sedimentation rate. The objective of this study was to compare the incidence of major adverse cardiac events (MACE) among patients with rheumatoid arthritis, psoriatic arthritis, and psoriasis with population controls adjusting for traditional cardiovascular risk factors, systemic inflammation, and disease-modifying anti-rheumatic drug (DMARD) treatment to better define cardiovascular risk in patients with these conditions.MethodsThe study used linked, routinely collected Welsh health data from 1999 to 2013 available from the Secure Anonymised Information Linkage (SAIL) databank, which includes datasets from general practice (GP), hospitals, and rheumatology clinics. Incidence and first occurrence of a MACE was investigated in individuals who were present in the GP system and positive for Read codes for rheumatoid arthritis (n=8650), psoriatic arthritis (2128), psoriasis (24 630), and controls without codes for the conditions investigated (1 187 706). We controlled for traditional cardiovascular risk factors, such as age, sex, smoking, body-mass index, comorbidities (hyperlipidaemia, diabetes, and hypertension), and medication (non-steroidal anti-inflammatory drugs, DMARDs, and steroids). We used a Cox proportional hazard model with the st command in Stata (version 13).FindingsWhen controlling for traditional risk factors, cardiovascular risk was significantly increased for individuals with rheumatoid arthritis (number of MACE events 548, hazard ratio 1·2, 95% CI 1·0–1·3; p=0·038) and psoriasis (879, 1·1, 1·0–1·3; p=0·025), but not for those with psoriatic arthritis (43, 1·0, 0·7–1·5; p=0·887). No interaction between DMARDs and MACE occurrence was observed.InterpretationThere is an increased incidence of cardiovascular disease for patients with rheumatoid arthritis and psoriasis, but not for those with psoriatic arthritis. This finding demonstrates the varying mediators of cardiovascular risk across these conditions and highlights the importance of cardiovascular risk reduction strategies, especially for patients with rheumatoid arthritis and psoriasis, who may benefit from closer monitoring to help reduce the incidence of MACE.FundingSupported by a Pfizer Inflammation Competitive Research Programme grant. The funder had no involvement in the study.     

Biological Disease-Modifying Antirheumatic Drugs and Osteoporotic Fracture Risk in Patients with Rheumatoid Arthritis: A Danish Cohort Study

ObjectivesClinical trials have shown a beneficial effect from biological disease-modifying antirheumatic drugs (bDMARDs) on hand or axial bone loss in patients with rheumatoid arthritis; however, it is unclear if this translates to a reduced fracture risk. We investigated the effect of bDMARDs on osteoporotic fracture risk compared to no biological treatment in rheumatoid arthritis.MethodsA cohort of patients with rheumatoid arthritis aged 18+ from DANBIO was linked to population-based health registries in Denmark (2006-2016). Adopting a prevalent new-user design, we matched bDMARD users to bDMARD-naïve patients using time-conditional propensity scores. The risk of incident osteoporotic fractures (including hip, vertebrae, humerus, and forearm) was estimated among the matched patients by Cox proportional hazards models.ResultsOut of 24,678 patients with rheumatoid arthritis, 4265 bDMARD users were matched to the same number of bDMARD-naïve patients (mean age 56.2 years, 74% female). During follow-up, 229 osteoporotic fractures occurred among bDMARD users and 205 fractures among bDMARD-naïve patients (incidence rates 12.1 and 13.0 per 1000 person-years, respectively). The use of bDMARDs was not associated with a reduced risk of osteoporotic fractures among patients with rheumatoid arthritis (hazard ratio 0.97, 95% confidence interval 0.78-1.20), compared with no biological treatment. The risk estimates were similar for all osteoporotic fracture sites.ConclusionWe found no independent beneficial effect from using bDMARDs on reducing the risk of osteoporotic fractures in patients with rheumatoid arthritis.     

Anti-TNFα treatment decreases the previously increased serum Indian Hedgehog levels in patients with ankylosing spondylitis and affects the expression of functional Hedgehog pathway target genes

ObjectiveIndian Hedgehog (Ihh) is the ligand that activates the Hedgehog pathway (HH) in the skeleton—the main controller of endochondral ossification. We aimed at assessing serum levels of Ihh in patients with ankylosing spondylitis (AS) and the effect of serum from patients with AS on HH pathway activation.MethodsSerum Ihh levels were measured in 59 patients with AS, 70 patients with rheumatoid arthritis (RA), and 53 healthy subjects. The effect of serum from patients with AS on HH pathway activation was evaluated using an osteoblast-like cell line model.ResultsPatients with AS not on anti-TNFα treatment had significantly higher Ihh levels compared to patients with RA not on anti-TNFα treatment (mean ± SEM of OD: 0.370 ± 0.025 vs. 0.279 ± 0.026 for patients with AS and RA, respectively, p = 0.027) and healthy subjects (p = 0.031). Patients with AS on anti-TNFα treatment had significantly lower Ihh levels compared to patients with AS not on such treatment (p = 0.028). Patients with RA on anti-TNF treatment had higher levels of Ihh compared to patients not on such treatment (p = 0.013). PTHrP levels were similar in patients with RA, AS, and healthy subjects and were not affected by anti-TNFα treatment. We next assessed HH pathway activation in Saos2 cells following incubation with serum from AS patients prior to and following anti-TNF treatment. The HH pathway was downregulated following treatment.ConclusionsIhh levels are increased in patients with AS and decrease following anti-TNFα treatment; this finding may have pathogenic and clinical implications.     

The Rheumatoid Arthritis and Falls (RAF) study: a prospective study of fall risk factors in adults with rheumatoid arthritis

BackgroundRheumatoid arthritis is linked to an increased risk of falls resulting in osteoporotic fractures, which may involve lower limb joints, leading to impaired mobility, impaired balance, and postural instability. This study aimed to investigate the association between potential risk factors and falls in community dwelling adults with rheumatoid arthritis.MethodsAdults with rheumatoid arthritis were recruited from four outpatient clinics in the northwest of England and followed for 1 year after clinical assessment, using monthly falls calendars and telephone calls. Outcome measures included fall occurrence, reason for fall, type and severity of injuries, fractures, fall location, lie-times, use of health services, and functional ability. Risk factors for falls included lower limb muscle strength, postural stability, number of swollen and tender joints, functional status, history of falling, fear of falling, pain, fatigue, and medication. Data on demographics, vision, co-morbidities, history of surgery, fractures, and joint replacements were also recorded.Findings559 adults with rheumatoid arthritis (386 women, 173 men, aged 18–88 years) had baseline measurements taken. 535 (96%) participants completed 1-year follow-up. Univariate logistic regression showed that falls risk was independent of age and gender. Multivariate logistic regression revealed that a history of multiple falls in the previous 12 months was the most significant predictive risk factor (odds ratio 5·3 [95% CI 2·3–12·3], p=0<0·001). The most significant modifiable risk factors were swollen and tender lower limb joints (odds ratio 1·7 [95% CI 1·1–2·7], p=0·03), psychotropic medication (1·8 [1·1–3·1], p=0·03), and fatigue (1·13 [1·02–1·2], p=0·01).InterpretationAdults of all ages with rheumatoid arthritis are at high risk of falls. In clinical practice, patients with rheumatoid arthritis at high risk of falls can be identified by asking whether they have fallen in the past year. The management of swollen and tender lower limb joints, fatigue, and consideration of psychotropic medicines may be the most effective strategy to reduce falls in this group of patients.FundingArthritis Research UK.     

Actualización de las guías del tratamiento farmacológico de la artritis reumatoide del Colegio Mexicano de Reumatología 2018

Therapeutic advances in rheumatoid arthritis require periodic review of treatment guidelines.ObjectiveTo update the Mexican College of Rheumatology guidelines on the pharmacological treatment of rheumatoid arthritis.MethodBoard certified rheumatologists from different health institutions and regions of the country participated. Work teams were formed that reviewed the previous guidelines, elaborated new questions, reviewed the literature, and scored the evidence that was presented and discussed in plenary session. The conclusions were presented to infectologists, gynaecologists and patients. Recommendations were based on levels of evidence according to GRADE methodology.ResultsUpdated recommendations on the use of available medications for rheumatoid arthritis treatment in Mexico up to 2017 are presented. The importance of adequate and sustained control of the disease is emphasized and relevant safety aspects are described. Bioethical conflicts are included, and government action is invited to strengthen correct treatment of the disease.ConclusionsThe updated recommendations of the Mexican College of Rheumatology on the pharmacological treatment of rheumatoid arthritis incorporate the best available information to be used in the Mexican health care system.     

Efficacy of rituximab in resistant palindromic rheumatism: first report in literature

Clinical Rheumatology - Rituximab (RTX) provides significant clinical benefits in active rheumatoid arthritis (RA) patients with inadequate response to DMARDs and anti-TNF. There is no data...     

Minimum Effective Dosages of Anti-TNF in Rheumatoid Arthritis: A Cross-sectional Study

AimsTo evaluate the modified dosages of anti-TNF in controlling disease activity in rheumatoid arthritis (RA) measured by DAS28-ESR.Patients and methodsCross-sectional study: RA patients treated with etanercept (ETN), adalimumab (ADA) or infliximab (IFX), at standard or modified doses. Main variables: dosage, concomitant disease modifying drugs (DMARDs), DAS28-ESR.Results195 RA patients included (79% women, mean age 58.1 years): ETN=81, ADA=56, IFX=58. Mean disease duration and time to first biological treatment was higher in IFX group (P=.01). Patients distribution by dosage: standard: ETN (72.8%), ADA (69.6%), IFX (27.6%); escalated: IFX (69%), ADA (5.4%), ETN (0%); reduced: ETN (27.1%), ADA (25%), IFX (3.4%). Concomitant DMARDs use was lower in ETN (58.2%) than ADA (66.07%) and IFX (79.31%). Higher proportion of responders (DAS28 ≤3.2) in ADA (65.3%) and ETN (61.7%) than IFX (48.3%).ConclusionsRA clinical control can be preserved with modified anti-TNF dosages. Controlled prospective studies should be performed to define when therapy can be tailored and for which patients.