Frailty in rheumatoid arthritis: A systematic review and meta-analysis

ObjectiveRheumatoid arthritis (RA) may cause damage to multiple organs and may further restrict the patient's physical, psychological and social functions. This meta-analysis aimed to explore the prevalence of frailty and prefrailty and the influential factors in RA patients.MethodsPubMed, Web of Science, Cochrane, Embase, and CNKI were searched to identify related articles. Articles published before July 23rd, 2021 that assessed frailty in patients with RA qualified for the systematic review and meta-analysis. A quality appraisal of the studies was performed using the Agency for Healthcare Research and Quality and Newcastle–Ottawa Scales. The pooled results were displayed as odds ratios or standardized mean differences (ORs/SMDs) and 95% confidence intervals (CIs).ResultsThe article search generated 2273 articles, of which 16 satisfied the inclusion criteria and were merged in the final review. A total of 8556 RA patients were finally included. The pooled prevalence of frailty in the patients with RA was 33.5% (95% CI: 25.2–41.7%), and the pooled prevalence of prefrailty was 39.9% (95% CI: 29.4–50.3%). Subgroup analyses showed that frailty was more prevalent in females (24.7%) than in males (19.1%). The prevalence of prefrailty in females was similar to that in males among the RA patients. Frailty in RA was associated with the female sex (OR: 1.47, 95% CI: 1.04–2.07) and disease activity (OR: 1.47, 95% CI: 1.03–2.09).ConclusionFrailty is prevalent in RA patients. Female gender and disease activity are associated with the prevalence of frailty in RA patients.     

Effect of biologics on fatigue in psoriatic arthritis: A systematic literature review with meta-analysis

Objectives

Fatigue is a significant issue in psoriatic arthritis. The objective was to assess the effect of biological disease modifying antirheumatic drugs and apremilast on fatigue in psoriatic arthritis randomised controlled trials and to compare this effect with the effect in the same trials, on pain, through a systematic literature review and meta-analysis.

Rheumatoid arthritis risk in periodontitis patients: A systematic review and meta-analysis

ObjectiveMany clinical studies have been carried out to investigate the relationship between periodontitis and rheumatoid arthritis (RA). Owing to limited evidence and inconsistent findings among these studies, it is unclear whether periodontitis would increase the risk for RA. This meta-analysis was performed to evaluate whether periodontitis represents a risk factor for RA.MethodsPubMed, Cochrane Library, Embase, Web of Science, and Wanfang were searched for eligible studies that compared periodontitis patients with controls. A pooled odds ratio (OR) and 95% confidence interval (CI) were calculated to assess the association between periodontitis and RA.ResultsThirteen studies including a total of 706611 periodontitis patients and 349983 control subjects were included. The pooled OR of RA risk between periodontitis and controls was (OR: 1.69; 95% CI: 1.31–2.17; P < 0.0001), indicating that the patients in periodontitis group had a 69% greater risk for RA than people in control group. When stratified by disease type, the pooled results showed periodontitis represents a risk factor for incident RA (OR = 1.70, 95%CI: 0.75–3.85, P < 0.001) and mixed RA (OR = 1.61, 95%CI: 1.26–2.06; P < 0.001). When stratified by disease duration, the pooled results showed periodontitis represents a risk factor for RA disease duration > 5 years (OR = 2.88, 95%CI: 0.66–12.62, P = 0.018), disease duration < 5 years (OR = 2.59, 95%CI: 0.83–8.11, P < 0.001), mixed disease duration (OR = 1.53; 95%CI: 1.05–2.22, P < 0.001).ConclusionOur meta-analysis revealed an increased risk of RA in patients with periodontitis compared to healthy controls. Moreover, when stratified by disease type, there was a higher risk between incident RA and periodontitis. When stratified by disease duration, the patients with periodontitis might be more closely associated with the RA patients with disease duration >5 years.     

Hand bone mass in rheumatoid arthritis: A review of the literature

Rheumatoid arthritis (RA) is a common chronic inflammatory disease and periarticular osteoporosis or osteopenia of the inflamed hand joints is an early feature of RA. Quantitative measurement of hand bone loss may be an outcome measure for the detection of joint destruction and disease progression in early RA. This systematic review examines the published literature reporting hand bone mass in patients with RA, particularly those using the dual X-ray absorptiometry (DXA) methods. The majority of the studies reported that hand bone loss is associated with disease activity, functional status and radiological progression in early RA. Quantitative measurement of hand bone mineral density by DXA may be a useful and practical outcome measure in RA and may be predictive for radiographic progression or functional status in patients with early RA.     

Cognitive impairment in patients with rheumatoid arthritis: A systematic review and meta-analysis

ObjectiveAn increasing number of studies have demonstrated cognitive impairment in patients with rheumatoid arthritis (RA). The literature indicates many factors play an important role in this clinical problem, such as the severity of depressive symptoms and the treatment used. The aim of this study was to systematically review studies comparing cognitive functioning between healthy participants and RA patients and to determine both the severity and potential moderators of cognitive impairment.MethodsFor this purpose, 16 studies that fulfilled all selection criteria were carefully selected. Altogether, 921 patients with RA (812 women and 109 men) and 700 controls participated in these studies. Due to the inability to perform a network meta-analysis, it was decided to determine the effect sizes for studies which used the same measurement methods.ResultsThe analysis demonstrated greater impairment of cognitive functioning in patients with RA than in healthy controls, with effect sizes ranging from small to large, depending on the assessment method used in the study.ConclusionsThe study pinpoints potential biases, lack of replication, and inconsistencies in reporting data as possible confounding factors and suggests further recommendations for assessment methods, research directions and clinical implications.Clinical trial registrationNot applicable.     

骨质疏松与类风湿关节炎

类风湿关节炎和骨质疏松在我国都属于常见病和多发病,而二者之间又有着非常重要的联系。但是目前临床上还没有一个广泛应用的药物可以同时对两者都产生很好的治疗效果。为了进一步了解骨质疏松和类风湿关节炎的关系,将来能够找到更好的治疗药物,笔者从流行病学、发病机制以及治疗方法等方面分别进行了论述。     

Rheumatoid factor and response to TNF antagonists in rheumatoid arthritis: Systematic review and meta-analysis of observational studies

ObjectiveTo systematically analyze literature with the aim of examining whether rheumatoid factor (RF) is a predictor of response to tumor necrosis factor (TNF) antagonists in rheumatoid arthritis (RA).MethodsA systematic review and meta-analysis of observational studies were conducted. All studies on the association of baseline RF (titer and/or status) and response to any TNF antagonists, or with enough information to estimate this association were included. Qualitative analysis and meta-analysis using random-effects approach by type of outcome response and RF test was performed. Risk of publication bias was also evaluated.ResultsThe systematic review included 18 studies of 4163 identified articles, involving 5703 patients with homogeneous baseline characteristics. The most common outcome to assess response was European League Against Rheumatism (EULAR) response criteria, normally merging good and moderate categories as response. The weighted mean difference (WMD) of baseline IgM RF titer in meta-analysis was higher in the non-responders group [−101.58 (95% CI −156.58,−46.59) I² = 0.0]. Combined odds ratios (ORs) of positive IgM RF, positive IgA RF, and positive IgG RF to achieve good/moderate response were 1.08 (0.80, 1.47), I² = 40.9%; 0.83 (0.39, 1.73), I² = 39.8%, and 1.30 (0.48, 3.51), I² = 62.9%, respectively. We did not find an association between a positive IgM RF and EULAR good response or remission.ConclusionsThis meta-analysis does not support baseline IgM RF titer as a predictor of response to TNF antagonists in RA. However, this conclusion is hampered by high heterogeneity in the studies included in this meta-analysis.     

Epstein-Barr virus and rheumatoid arthritis

Rheumatoid arthritis (RA) is one of the most common autoimmune diseases, with a 0.5% worldwide prevalence. The cause of RA remains unknown, however both genetic and environmental factors may contribute to its development. Among these is the Epstein-Barr virus (EBV). Here, we discuss several aspects of the close relationship between EBV and RA. Patients with RA have impaired control of EBV infection. Indeed, they have high titres of antibodies against EBV antigens. Their peripheral blood T lymphocytes are less efficient at controlling the outgrowth of EBV-infected B cells. RA patients have more EBV-infected B cells than normal controls, leading to a 10-fold systemic EBV overload. Post-transplant lymphoproliferative disorder (PTLPD) is a polyclonal EBV-positive B lymphocyte proliferation, which can evolve into an EBV-positive B cell lymphoma. RA patients also have an increased risk of developing EBV-associated lymphoproliferative disorder (LPD). Hence the need to monitor EBV load when treating RA patients with immunosuppressors. EBV, a widespread virus, highly recognized by antibodies but never eliminated, is an ideal candidate to trigger chronic immune complex disease. Anti-EBV antibody responses should be considered as one of the chronic autoantibody responses linked to the development of RA, in the same way as anti-citrullinated protein antibodies.     

Ultrasonography of shoulders in spondyloarthritis and rheumatoid arthritis: A case-control study

IntroductionShoulders are often involved in spondyloarthritis (SpA) and rheumatoid arthritis (RA). The diagnosis of peripheral SpA and its differential diagnosis with RA could be challenging. A recent ultrasound study showed that ultrasonography (US) of the hands might differentiate psoriatic arthritis to RA. The aim of the study was to compare different US features in SpA, RA and healthy controls.MethodsA total of 38 SpA and 43 RA patients with clinical involvement of shoulders were included and compared to 33 controls. One blinded rheumatologist performed US examinations. The following items were assessed: gleno-humeral effusion, long-head biceps tendon tenosynovitis, subacromial and subdeltoid bursitis, acromio clavicular (AC) synovitis and humeral bone erosion.ResultsThirty-eight SpA (mean age: 49.9 ± 15.4 years, 58% of male), 43 RA patients (52.9 ± 16.6 years, 26% of male) and 33 controls (55.2 ± 16.9 years, 42% of male) were assessed. In comparison to RA, SpA patients had higher frequency of AC synovitis (66% vs 5%, P < 0.0001) but lower prevalence of subacromial and subdeltoid bursitis (39% vs 67%, P = 0.015), gleno-humeral effusion (5% vs 28%, P = 0.008) and humeral bone erosion (10% vs 56%, P < 0.0001). Unilateral abnormalities were found more frequently in SpA patients than in RA (64% vs 26%, P < 0.0001).ConclusionOur results suggest that AC synovitis is highly evocative of SpA in patients with inflammatory painful shoulders. Thus, US might help to diagnose SpA and to differentiate with RA.     

Bronchiectasis in rheumatoid arthritis. A clinical appraisial

Bronchiectasis is defined as irreversibly damaged and dilated bronchi and is one of the most common pulmonary manifestations in patients with rheumatoid arthritis (RA). The model of RA-associated autoimmunity induced in some individuals by chronic bacterial infection in bronchiectasis is becoming increasingly acceptable, although a genetic predisposition to RA-associated bronchiectasis has also been demonstrated. Bronchiectasis should be suspected in RA patients with chronic cough and sputum production or frequent respiratory infections and the diagnosis must be confirmed by thoracic high-resolution computed tomography. Management of patients with RA-associated bronchiectasis includes a multimodal treatment approach. Similar to all patients with non-cystic fibrosis bronchiectasis, patients with RA-associated bronchiectasis benefit from a pulmonary rehabilitation program, including an exercise/muscle strengthening program and an education program with a specific session on airway clearance techniques. Prophylactic antibiotics are recommended for patients with frequent (3 or more infective exacerbations per year) or severe infections requiring hospitalization/intravenous antibiotics and inhaled corticosteroids and long-acting β2-agonists should be used in patients with non-cystic fibrosis bronchiectasis and associated airway hyper-responsiveness. In patients with RA-associated bronchiectasis the use of immunomodulatory drugs has to be carefully considered, as they are essential to control disease activity, despite being associated with an increased infectious risk. Pneumococcal and influenza vaccines are advised to all patients with RA-associated bronchiectasis in order to reduce the risk of infection. Patients with RA-associated bronchiectasis have a poorer prognosis than those with either RA or bronchiectasis alone and require regular follow-up, under the joint care of a rheumatologist and a pulmonologist.     

Low-power laser therapy in rheumatoid arthritis

Thirty-five patients suffering from rheumatoid arthritis were allocated at random to treatment with either a low-power laser (3.58 J cm^–2, continuous wave 820 nm) or a placebo in a 4-week, double-blind study. Eight finger joints (2nd–5th metacarpo- and proximal interphalangeal joints) of the most affected hand were treated. In the laser group the grip strength and finger flexibility improved, the swelling of the joints declined, the morning stiffness and pain decreased. The sedimentation rate and the number of leukocytes showed a fall with a significant trend. In the placebo group there were no changes in these parameters except for the registration of pain, where a significant, less than with the laser, effect was observed. Thus, low-power laser therapy, at the chosen wavelength and energy dose, appears to be effective against the classical complaints from rheumatoid arthritis.     

Response to interleukin-6 receptor antagonists in patients with rheumatoid arthritis is independent of the number of prior used TNF inhibitors: A systematic review and metaanalysis

ObjectiveTo investigate whether early response to tocilizumab (TCZ) and sarilumab (SAR) therapy in patients with active rheumatoid arthritis (RA) is influenced by previous use of biologic agents.MethodsWe performed a systematic literature review and a meta-analysis of original studies that analyzed the effectiveness of TCZ or SRL in subgroups of RA patients, including biologic-naïve patients versus those with inadequate response to at least one biologic DMARD (bDMARD), and patients with failure to 1 versus ≥ 2 bDMARDs.ResultsThe study selection process finally included 17 articles corresponding to 14 studies, including 7 randomized controlled trials (RCTs). Although the existing literature that compared the response in biologic-naïve patients versus those with inadequate response to at least one bDMARD showed conflicting results, meta-analysis of 6 published studies revealed a significantly higher likelihood of remission (RR = 1.3; 95% CI: 1.2–1.5) and low activity disease (RR = 1.3; 95% CI: 1.2–1.4) in the biologic-naïve group at week 24. However, differences between groups were not clinically meaningful in all studies and not always maintained after 6 to 12 months of treatment. In addition, data from RCT RADIATE and TARGET suggest that the response to IL-6 pathway inhibitors seems to be similar, regardless of the number of tumor necrosis factor inhibitors (TNFis) previously tested.ConclusionDisease activity was more rapidly reduced in the early stages of treatment in biologic-naïve patients. However, near similar efficacy can be expected in patients who experienced a failure of at least one bDMARD (mainly TNFis) beyond the first 6 to 12 months of treatment, suggesting that the response occurs independently of the number of prior TNFis.     

抗CCP抗体在类风湿性关节炎诊断中的应用进展

目前类风湿关节炎的诊断检查有炎性标志物（包括血沉和C反应蛋白）检测,免疫复合物和补体检测,关节滑液检测以及自身抗体检测。这些指标经常伴随类风湿关节炎的活动而改变,早期诊断主要依靠的是自身抗体检测。抗环瓜氨酸肽（ cyclic citrullinated peptide,CCP）抗体是一种抗角蛋白抗体,在类风湿性关节炎的敏感度和特异度较类风湿因子高。发病一年内,类风湿性关节炎患者大部分血清中可检测到抗CCP抗体的存在,同时抗CCP抗体阳性也可以用来预测严重破坏的类风湿性关节炎。因此,抗CCP抗体对于类风湿性关节炎的早期诊断及预后评估是极有帮助的。本文综述了近年来抗CCP抗体对于诊断类风湿关节炎的应用进展。     

老年类风湿性关节炎治疗进展

老年类风湿性关节炎患者在选择NSAIDs药物时,需评估老年患者的危险因素。目前研究热点多集中于生物制剂治疗,老年患者使用生物制剂时应更多关注其感染的风险。传统中医药方案疗效确切,尤以雷公藤为突出,应开展大型关于中西医治疗老年类风湿性关节炎临床试验精确用药策略。老年患者更易合并心血管疾病、间质性肺病等共存病,治疗共存病同时也可控制类风湿本身疾病活动。老年类风湿性关节炎与其他年龄发病类风湿性关节炎一致,也需要"达标治疗",以疾病完全缓解及降低疾病活动度为目标,但由于老年类风湿性关节炎的发病及临床特点及治疗策略与其他年龄发病类风湿性关节炎不同,因此其达标治疗理念可能也会有所不同,目前临床试验多将老年患者排除在外,导致相应循证数据缺乏。因此需开展针对老年患者的临床研究,为临床治疗方案提供依据和指导。     

Controversies in rheumatoid arthritis glucocorticoid therapy

Despite therapeutic innovations in the past 20 years, glucocorticoids (GC) are still widely used for the symptomatic treatment of rheumatoid arthritis (RA). Studies have demonstrated the clinical and structural efficacy of moderate doses (i.e. 30–60 mg/d) GC in addition to disease modifying anti-rheumatic drug (DMARD) initiation in early RA. A combination of a low dose of GC (i.e. 7.5–10 mg/d) and DMARDs increases remission rates and decreases the risk of medium-term structural progression in early RA. Intravenous and intramuscular administration of GC associated with DMARD initiation or intra-articular GC injections in symptomatic joints in tight control strategies increase remission rates in early RA. However, due to the risk of adverse events such as infections, cardiovascular events, or increased mortality induced by long-term use of GC, even at low-doses (e.g. 5 mg/d), GC should be prescribed at a minimal dose, for the shortest possible duration, and in association with DMARD initiation in early RA or DMARD change in active established RA.     

胰十二指肠切除术应用胰肠吻合与胰胃吻合的系统评价

目的 系统评价胰十二指肠术应用胰肠吻合术(PJ)与胰胃吻合术(PG)的临床疗效.方法 计算机检索中英文数据库,对纳入的4篇随机对照试验使用RevManS.0.18软件进行系统评价.结果 纳入患者553例.Meta分析显示,PG胆瘘发生率低(0.51％,RR =0.17,P＜0.05)、腹腔积液发生率低(8.70％,RR =0.5,P＜0.01)、腹腔内多发并发症发生率低(5.70％,RR =0.26,P＜0.01),差异有统计学意义.PG组发生胃排空障碍发生率低(10.20％,RR=0.61,P＞0.05)、腹腔内并发症发生率低(29.60％,RR =0.76,P ＞0.05),差异无统计学意义,但倾向于PG.两组胰瘘率、病死率差异均无统计学意义(P＞0.05).结论 在胰十二指肠切除术中应用PG是安全的,还需更多高质量的临床随机对照试验(RCT)详细论证.     

Engineered glove to evaluate hand disability in rheumatoid arthritis: A pilot-study

ObjectiveThe Hand Test System (HTS) is an engineered-sensorized glove that has been originally developed in the neuroscientific field for the evaluation of hand fingers’ speed movement. This pilot-study aimed to evaluate the reproducibility of HTS analysis in rheumatoid arthritis (RA), correlating glove-derived parameters with clinical disease activity indexes, self-reported disability-related questionnaires and hand strength.MethodsFifty-five RA patients and fifty age and sex matched healthy controls (HCs) performed HTS analysis. The glove recognized the touch speed between the finger tips during standard sequences of movements, providing three quantitative parameters: touch duration (TD), inter-tapping interval (ITI) and movement rate (MR). These variables were correlated with Health Assessment Questionnaire (HAQ), Health Assessment Questionnaire-Disease Index (HAQ-DI), Hand Disability Index (HDI), Hand Grip Strength (HGS), DAS28-CRP, CDAI and SDAI.ResultsIntraclass correlation coefficient was 0.93 (CI: 0.92, 0.95). RA patients showed significantly slower TD, ITI and MR than HCs, for all classes of disease activity (P < 0.001). All HTS parameters correlated significantly with HAQ, HAQ-DI, HDI, HGS, DAS28-CRP, SDAI, CDAI (between P < 0.05 and P < 0.001). Of note, also RA patients in clinical remission showed a significantly higher TD compared with HCs (P < 0.001).ConclusionHTS seems a new safe and fast tool to evaluate rheumatoid hand's functionality, measuring the speed of finger movements. Furthermore, the HTS parameters significantly correlate with quality of life, disease activity, hand strength and perceived hand disability, evaluating also potential hand motor impairment in RA clinical remission.     

Rituximab in rheumatoid arthritis and the risk of malignancies: report from a French cohort

Objective

To determine in real-life conditions the safety of treatment with rituximab (RTX) in patients with rheumatoid arthritis (RA) regarding malignancies.

Methods

Analysis of safety data from a cohort of RA patients who received at least one course of RTX. RA patients with previous malignancies were followed-up and compared to the group of patients with no history of malignancy.

Results

One hundred and eighty-six RA patients, 33 (17.7%) males, the mean age and disease duration were 55.8 ± 13.0 and 14.5 ± 11.1 years, respectively. The mean follow-up was 22.3 ± 15.1 months, corresponding to a follow-up of 346 pt-years of RTX exposure. Among these, 24 (12.9%) patients had a history of a prior malignancy. Five cancers were diagnosed during follow-up with four new malignancies (1 prostate, 1 breast, 1 colon and 1 cervical cancers) and one recurrence of a known breast cancer. The overall cancer rate was 1.45/100 pt-years (95%CI: 0.19 to 2.70), which is comparable to previously studied DMARD-treated cohorts. No new hematopoietic neoplasms were reported and the six lymphomas that have been in remission prior to RTX-therapy remained under follow-up. The baseline demographic and disease characteristics and the cancer-risk of the 24 patients who presented with a prior malignancy were similar to those with no cancer history (162 patients).

Conclusions

Although based on a modest number of observed cancers, and despite selection bias (12.9% of prior malignancies in our RTX treated RA), this observational study suggests that RTX does not increase the cancer risk in RA patients.     

Recurrent constrictive pericarditis associated with seropositive rheumatoid arthritis: A case report

IntroductionConstrictive pericarditis is an uncommon disease characterized by impaired diastolic filling of the ventricles, encased in a fibrotic pericardium resulting from an inflammatory process.Rheumatoid arthritis is a rare cause of constrictive pericarditis, usually due to a concomitant acute or chronic serositis.Presentation of caseThis paper presents a unique case of recurrent constrictive pericarditis associated with seropositive rheumatoid arthritis, requiring pericardiectomy and complicated three years later by recurrent fibrosis, demanding a second pericardiectomy.DiscussionDefining this entity as recurrent constrictive “pericarditis” might be a mistake, given that a total pericardiectomy was performed in first instance.No risk factors for recurrent fibrosis have been identified in the current medical literature, apart from partial pericardiectomy. We cannot demonstrate exclusively that rheumatoid arthritis is a risk factor for recurrent pericardial/epicardial fibrosis due to the rare nature of the disease.ConclusionFurther large scale studies are necessary to identify the risk factors for recurrence.