Impact of comorbidities on fatigue in rheumatoid arthritis patients: Results from a nurse-led program for comorbidities management (COMEDRA)

Objectives

To analyze the factors associated with fatigue focusing on comorbidities in a large cohort of rheumatoid arthritis (RA).

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。     

Validity of the rheumatoid arthritis impact of disease (RAID) score and definition of cut-off points for disease activity states in a population-based European cohort of patients with rheumatoid arthritis

Objectives

To assess the validity of the rheumatoid arthritis impact of disease (RAID) for measuring disease activity of rheumatoid arthritis (RA) and to determine cut-off values for defining the disease activity states.

Lumbar fusion outcomes in patients with rheumatoid arthritis

Although outcomes after cervical fusion in rheumatoid arthritis (RA) patients are widely published, outcomes of lumbar fusion in RA patients has not been reported. Ninteen patients with RA, identified using ICD-9 and CPT codes, who underwent instrumented posterolateral lumbar fusion were matched for age, gender, smoking status, date, and level of surgery to a contemporaneous non-RA group. Medical records and radiographs were reviewed by the primary author who had no role in the treatment of these patients. The average age was 64 years in the RA group and 65 years in the non-RA group. The male to female ratio was 2:17 and 1:18, respectively. There were three smokers and two diabetics in each group. An average of 1.5 levels was fused in each group. Average follow-up was 24 and 27 months, respectively. In the RA group, 15 patients were taking DMARDs with 7 of those also taking oral steroids; 4 patients were taking NSAIDs only. There were seven complications (37%) in the RA group versus four (21%) in the non-RA group; wound infections in three patients (16%) in the RA group versus one (5%) in the non-RA group; and non-union in two patients (11%) in the RA group versus three (16%) in the non-RA group. Clinical outcomes were similar between the two groups with 74% of patients achieving good to excellent results in the RA group compared to 63% in the non-RA group (p = 0.692). Surgeons and their RA patients who undergo an instrumented lumbar fusion can expect a slightly higher complication rate than patients without RA which may be related to osteopenia and immunosuppression.     

Economic analysis of a nurse-led programme for comorbidities management of rheumatoid arthritis patients

Objectives

Rheumatoid arthritis (RA) cause major functional, psychological, social and occupational repercussions for patients and has important economic consequences for society. The principal objective of this work was to determine the economic pertinence of a staff nurse specialised in preventive management for these patients.

The course of fatigue during the development of rheumatoid arthritis and its relation with inflammation: a longitudinal study

ObjectiveFatigue is a prominent and disabling symptom in patients with rheumatoid arthritis (RA), that is only partially explained by inflammation and responds poorly to DMARD-therapy. We hypothesized that inflammation explains fatigue to a larger extent in the phase of clinically suspect arthralgia (CSA), when persistent clinical arthritis is still absent and fatigue has not yet become chronic. We therefore studied the course of fatigue in CSA during progression to RA and the association with inflammation at CSA-onset and at RA-diagnosis.Methods600 consecutive CSA-patients were followed for RA-development. Additionally, 710 early RA-patients were studied at diagnosis. Fatigue was assessed every study visit and expressed on a 0-100 scale. Inflammation was measured with the DAS44-CRP, with and without including subclinical inflammation. The course of fatigue over time was studied with linear mixed models. Associations between fatigue and inflammation were studied with linear regression. Analyses were stratified by ACPA-status.ResultsIn 88 CSA-patients who developed RA, pre-arthritis fatigue-levels increased gradually with 7 points/year, towards 48 (95%CI=41-55) at RA-development (P=ns). Fatigue decreased in CSA-patients who did not develop RA (4 points/year, P<0.001). At CSA-onset, inflammation was associated with fatigue (β=18, meaning 18 points more fatigue per point increase DAS-score, P<0.01). This association was stronger than at RA-diagnosis (β=5, P<0.001). Fatigue-levels were lower in ACPA-positive pre-RA, but its association with inflammation was stronger compared to ACPA-negative pre-RA.ConclusionFatigue increased gradually during progression from arthralgia to clinical arthritis, and fatigue was better explained by inflammation in CSA than in RA. This implies a ‘phase-dependent relation’ between inflammation and fatigue.     

Immunogenicity of tocilizumab in patients with rheumatoid arthritis

Objective

The immunogenicity of tocilizumab (TCZ) has been poorly studied. We assessed the immunogenicity of TCZ and serum TCZ trough levels in rheumatoid arthritis (RA) patients and the preexisting TCZ-specific CD4+ T cell repertoire in healthy controls.

Clinical characteristics and outcomes in polyarticular septic arthritis

Objectives

Septic polyarthritis is rarer than septic monoarthritis, but associated with higher mortality. Septic polyarthritis may be difficult to distinguish clinically from noninfectious inflammatory arthritis. We describe one of the largest samples of septic polyarthritis with the aim of distinguishing septic monoarthritis from polyarthritis.

Persistence of ultrasound synovitis in patients with rheumatoid arthritis fulfilling the DAS28 and/or the new ACR/EULAR RA remission definitions: Results of an observational cohort study

ObjectiveThe primary aim of the study was to evaluate whether rheumatoid arthritis (RA) patients considered to be in remission according to clinical criteria sets still had persisting ultrasound (US) synovitis. We further intended to evaluate the capacity of our US score to discriminate between the patients with a clinically active disease versus those in remission.MethodsThis is an observational study nested within the Swiss Clinical Quality Management in Rheumatic Diseases (SCQM) rheumatoid arthritis cohort. A validated US score (SONAR score) based on a semi-quantitative B-mode and Doppler (PwD) score as part of the regular clinical workup by rheumatologists in different clinical settings was used. To define clinically relevant synovitis, the same score was applied to 38 healthy controls and the 90st percentile was used as cut-off for ‘relevant’ synovitis.ResultsThree hundred and seven patients had at least one US examination and concomitant clinical information on disease activity. More than a third of patients in both DAS28 and ACR/EULAR remission showed significant gray scale synovitis (P = 0.01 and 0.0002, respectively) and PwD activity (P = 0.005 and 0.0005, respectively) when compared to controls. The capacity of US to discriminate between the two clinical remission groups and patients with active disease was only moderate.ConclusionThis observational study confirms that many patients considered to be in clinical remission according the DAS and the ACR/EULAR definitions still have residual synovitis on US. The prognostic significance of US synovitis and the exact place of US in patients reaching clinical remission need to be further evaluated.     

补肾法对类风湿性关节炎患者血液流变学的影响

目的：探讨补肾中药对类风湿性关节炎患者血液流变学的影响。方法：采用补肾中药青娥丸加味片对46例类风湿性关节炎患者进行为期1个月的治疗，检测患者治疗前后血液流变学指标，并观察其变化。结果：患者治疗后症状及体征有明显改善，与治疗前比较有显著差异。全血粘度、血浆粘度、红细胞压积、红细胞电泳时间、血沉等较治疗前也明显降低。结论：补肾中药通过改善类风湿性关节炎患者的微循环而达到在一定程度治疗该病的目的。     

Intubation difficulties in patients with rheumatoid arthritis

Background : Fibreoptic intubation has been suggested to be the best method to manage a compromised airway. This retrospective study was designed to compare endotracheal intubation with the help of a rigid laryngoscope or a fibrescope in patients with rheumatoid arthritis.
Methods : Intubation difficulties with the laryngoscope and the fibrescope in patients with rheumatoid arthritis were investigated during a period of five and a half years. The anaesthesia records were used for analysis. The patients were divided into two groups (group I with 41 patients and group II with 37 patients) reflecting the change in the routine airway management in patients with rheumatoid arthritis in our hospital from the beginning of 1993. Before that time the patients were usually intubated orotracheally under general anaesthesia, but since 1993 rheumatoid patients with anticipated difficulties in endotracheal intubation have been preferably intubated fibreoptically awake under sedation and topical anaesthesia with a fibrescope.
Results : Major difficulties in endotracheal intubations were encountered in 13% of patients in group I and in 8% in group II. On two occasions in group I tracheostomy was needed. In one of these patients, emergency tracheostomy was performed. In the latter group, the main reason for prolonged fibreoptic intubations was lack of experience.
Conclusion : The introduction of fibreoptic intubation technique has had a favourable influence on the safety in the airway management of surgical patients with rheumatoid arthritis.     

Efficacy of baricitinib on periodontal inflammation in patients with rheumatoid arthritis

ObjectiveDespite a widely recognized bidirectional pathobiologic relationship between rheumatoid arthritis (RA) and periodontal disease, the impact of innovative anti-rheumatic drugs in modulating not only inflammatory and immune articular damage, but also periodontal microenvironment remains debatable. We aimed to evaluate the periodontal status in RA with and without baricitinib, a Janus kinase (JAK) inhibitor, and to better describe association between these entities.MethodsWe performed a prospective longitudinal 24-weeks study in 21 active RA initiating baricitinib. Standard assessments included a dual rheumatologic (RA activity, disability, serological, inflammatory profile) and dental evaluation comprising plaque index, gingival index, bleeding on probing, probing depth, clinical attachment level.ResultsMore than half of RA presented at baseline with chronic periodontitis, as suggested by high prevalence of sites with dental plaque, abnormal bleeding on probing, probing depth and clinical attachment level. Aggressive periodontal disease was reported particularly in disease subsets with excessive inflammatory (serum C reactive protein level) and serologic biomarkers (anti-citrullinated peptide antibodies). Furthermore, significant correlations between dental pathology, disease activity and ACPA levels were also reported (P < 0.05). Consistent improvement was noticed in both rheumatoid arthritis characteristics and periodontal status after 24 weeks of baricitinib (P < 0.05).ConclusionRA, particularly severe active ACPA-positive disease, is basically associated with altered periodontal health. JAK blockade through oral baricitinib may be efficient in patients with active RA and potentially able to modulate the inflammatory process in the periodontal tissue.     

Clinical significance of tocilizumab-related neutropenia in patients with rheumatoid arthritis

ObjectiveTo determine the risks and clinical significance of tocilizumab (TCZ)-related neutropenia, in real-world settings, for patients with rheumatoid arthritis (RA).MethodsMedical records of RA patients treated with TCZ at a tertiary referral hospital in South Korea were collected. Infectious complications were defined as cases confirmed by clinical diagnosis and treated with antibiotics.ResultsA total of 277 RA patients with TCZ treatment (intravenous: 152 [54.9%], subcutaneous: 125 [45.1%]) were included in our study. During the observational period, 22 (7%) patients experienced grade 3 neutropenia. No patients discontinued TCZ due to neutropenia, while the dosage of conventional synthetic DMARD (csDMARD) was either reduced or discontinued for 8 patients. Patients, who experienced neutropenia while using csDMARD, had a higher risk for grade 3/4 neutropenia during TCZ treatment (hazard ratio [HR]: 3.120, 95% CI: 1.189–8.189, P = 0.021). Among infections, pulmonary infections were the most common (10.35 per 100 patient-years). Age over 60 years (HR: 2.133, 95% CI: 1.118–4.071, P = 0.022) and the presence of extra-articular manifestations (adjusted HR: 11.096, 95% CI: 5.353–22.999, P < 0.001), but not neutropenia (adjusted HR: 1.263, 95% CI: 0.269–5.945, P = 0.77), were risk factors for infections during TCZ treatment.ConclusionApproximately 7% of RA patients treated with TCZ developed grade 3 neutropenia. The previous history of neutropenia during csDMARD was a risk factor for TCZ-related neutropenia. Age and extra-articular manifestations, but not neutropenia, were risk factors for infection during TCZ treatment, suggesting that TCZ treatment can be maintained in the presence of neutropenia unless infection occurs.     

Concordance between clinical and ultrasound findings in rheumatoid arthritis

BackgroundClinical joint examination is less time-consuming than ultrasound in rheumatoid arthritis. Knowledge of clinical and ultrasound concordance of joints groups could help in selecting joints for a best ultrasonographic assessment.ObjectiveTo evaluate concordance between clinical examination and ultrasound of joints in a heterogeneous group of patients with rheumatoid arthritis.MethodForty patients were included in a prospective, transversal, single-center study, whatever disease activity, duration or treatment. In each patient, 40 joints were evaluated for a total of 1600 joints. Synovitis was scored using clinical examination, B-mode, power Doppler and both B-mode and power Doppler. Concordance between swelling joint by clinical examination, synovitis thickening by B-mode (grade 1 or higher) and inflammation by power Doppler (grade 1 or higher) was assessed by computing the kappa coefficient.ResultsClinical joint examination and ultrasound concordance was very low at the shoulders and metatarsophalangeal joints (κ < 0.1) and was low at wrists (κ: 0.23 to 0.30). B-mode and power Doppler found 2.4 and 1.4 more synovitis than swollen joint count using clinical examination and up to 30 times more at metatarsophalangeal joints. Concordance was strong at tibio-talar joints (κ: 0.65 to 0.82) and moderate at others joints sites (κ: 0.4 to 0.6).ConclusionAssessment of a heterogeneous group showed that ultrasound adds information to clinical examination, most notably at the shoulders, wrists and metatarsophalangeal joints. Concordance was moderate to strong at other joint sites.     

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.     

女性类风湿关节炎患者骨密度的研究

目的探讨女性类风湿关节炎(RA)患者骨密度(BMD)的变化和骨质疏松(OP)的发生情况及其与临床指标的相关性.方法采用双能X线骨密度仪,测量了45例女性RA患者和45例女性正常人的前臂、腰椎2～4以及股骨颈、Ward区和大转子的骨矿含量,并同时测定握力、关节功能、X线分期、关节压痛数和肿胀数、日常生活能力评估(以健康评估表HAQ积分表示)和血沉、血清类风湿因子、C反应蛋白、钙、磷、碱性磷酸酶等指标.结果女性RA患者中除股骨Ward区骨量丢失较对照组差异有显著性(P＜0.05)外,其余各测定部位的BMD与对照组间差异无显著性(P＞0.05).45例女性RA患者中发生骨质疏松较非骨质疏松组年龄更大(P＜0.005),关节功能更差(P＜0.01),HAQ积分更高(P＜0.05),握力更低(P＜0.05),CRP更高(P＜0.05).女性RA患者中服用糖皮质激素组与未服用糖皮质激素组间BMD及OP发生情况的差异无显著性(P＞0.05).绝经后女性RA患者的骨量丢失较绝经前明显(P＜0.05);除桡骨远端外,绝经后患者各测定部位BMD均低于绝经前患者(P＜0.05).Logistic Regression分析显示年龄:OR=1.085[(1.019-1.156),P=0.011]和关节功能:OR=4.828[(1.368-17.039),P=0.014]为RA患者骨质疏松发生的相关因素.结论女性RA患者的总体骨量变化与正常人相近,但股骨Ward区的骨量丢失明显高于正常人.其BMD的降低和OP的发生与年龄、绝经和关节炎的严重程度有关.     

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.