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.     

风湿活动度预测绝经后女性类风湿关节炎患者骨密度的研究

目的探讨能够预测绝经后女性类风湿关节炎(Rheumatoid Arthritis RA)患者骨质疏松的指标。方法收集100例绝经后女性RA患者一般临床资料包括年龄、病程、血沉、C反应蛋白、类风湿因子、抗环瓜氨酸肽抗体、关节疼痛数目、关节肿胀数目,采用双能量X线骨密度仪测量腰椎、股骨及全身总的平均骨密度,比较临床资料并分析可能影响骨密度的因素。结果1.绝经后女性类风湿关节炎患者骨质疏松比例为33%,骨量减少比例47%,骨量正常比例20%。2.骨质疏松组的年龄、病程、血沉、关节疼痛数目、DAS28均高于非骨质疏松组,且有统计学意义。3.采用Logistic回归分析结果显示,年龄和DAS28是绝经后女性RA患者骨密度的独立危险因素。4.骨密度T值为诊断骨质疏松的金标准绘制受试者工作曲线,计算DAS28、年龄诊断骨质疏松的切点为5.3分和59.5岁。结论风湿活动度和年龄对于绝经后女性RA患者有较强的骨质疏松预警作用。     

Efficacy and safety of rituximab with and without methotrexate in the treatment of rheumatoid arthritis patients: Results from the GISEA register

IntroductionRituximab (RTX) is a monoclonal anti-CD20 antibody approved for the treatment of rheumatoid arthritis (RA) in association with methotrexate (MTX).ObjectivesTo evaluate the efficacy and safety of RTX–MTX combination therapy compared with RTX alone in the treatment of RA.MethodsWe analyzed data from a prospective cohort study, the Italian biologic register GISEA, to investigate the efficacy and safety of rituximab. Moreover, the adverse events (AE) and the causes of discontinuation therapy were analyzed.ResultsWe identified 338 RA patients, 162 treated with RTX and 176 with RTX–MTX. After 52 and 104 weeks of therapy the disease activity score in 28 joints and the Health Assessment Questionnaire Score were available in 168 patients (78 with RTX–MTX and 60 with RTX alone), showing significant reduction without differences among the two groups. AE were reported in 142 patients (42%), for a total of 368 recorded side effects. The majority (90.5%) of AE were mild to moderate in severity. Comparable percentages of severe AE were reported in the 2 groups (9.9% for RTX alone and 9.3% for RTX + MTX). A poor disease control was observed in 14.2% and 13.5% of patients treated with RTX + MTX and RTX, respectively; while 12 patients (4.5% in RTX + MTX, and 2.5% in RTX group) suspended therapy for AE.ConclusionsRTX showed a good efficacy and safety profile in the real-life management of RA patients regardless of the association with MTX.     

50例绝经后高疾病活动期的女性类风湿关节炎骨密度的临床观察

目的观察绝经后高疾病活动期的女性类风湿关节炎患者骨矿物质密度水平的变化。方法收集50例绝经后女性RA患者一般临床资料,包括年龄、RA病程、绝经年龄、ESR、CRP、RF、抗CCP抗体、DSA28评分及雌二醇水平,应用双能X线吸收法(DXA)测定50例患者腰椎L_(1-4)和左髋关节部位的骨密度,分析其骨密度(BMD)的情况。结果 1.50例绝经后女性RA的DSA28评分大于5.1,属高疾病活动期,骨质疏松组发生率52%;远高于骨量减少组(30%)及骨密度正常组(18%)。2.骨质疏松组的绝经年龄比非骨质疏松组明显提前(P=0.005),抗CCP抗体水平明显升高(P=0.037),有统计学意义,但在年龄、病程、RF、DSA28评分及雌激素方面两者无统计学差异。3.Logistic回归分析结果显示抗CCP抗体(OR值1.025,P=0.041)是绝经后高疾病活动女性RA骨质疏松的独立危险因素。4.骨质疏松组,腰椎总骨密度较髋关节显著降低(P0.001);腰椎组内比较以腰1椎体BMD最低,而后依次为腰2,腰3、腰4(P=0.0003),左髋关节组内比较以大转子BMD最低,而后依次为股骨颈、小转子(P0.0001)。结论绝经后高疾病活动期的女性RA患者存在明显的骨质疏松,以腰椎骨密度(特别L_1)下降最明显;抗CCP抗体可能是高疾病活动期的女性类RA患者发生骨质疏松的危险因素。     

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).

Recommendations of the French Society for Rheumatology for managing rheumatoid arthritis

IntroductionThis article reports the latest recommendations of the French Society for Rheumatology (SFR) regarding the management of rheumatoid arthritis (RA).MethodsNew recommendations were developed by hospital- and community-based rheumatologists having extensive experience with RA and a patient self-help organization representative. They rest on the recently issued EULAR recommendations and a literature review.ResultsPoints emphasized in the 15 recommendations include the need to share treatment decisions between the rheumatologist and the patient, the acquisition by patients of self-management skills, remission or minimal disease activity as the treatment target, the need for initiating disease-modifying drugs as early as possible, and the usefulness of regular disease activity assessments to allow rapid treatment adjustments if needed (i.e., tight disease control). First-line methotrexate monotherapy is recommended, with concomitant short-term glucocorticoid therapy if indicated by the risk/benefit ratio. Patients who fail this approach (no response after 3 months or target not achieved after 6 months) can be considered for another synthetic disease-modifying antirheumatic drug (DMARD: leflunomide or sulfasalazine), combined synthetic DMARD therapy, or methotrexate plus a biologic, depending on the prognostic factors and patient characteristics. If the first biologic fails, switching to a second biologic is recommended. In the event of a sustained remission, cautious dosage reduction of the biological and/after synthetic DMARDs is in order.ConclusionThese recommendations are designed to improve the management of patients with RA.     

应用FRAX工具评估类风湿关节炎患者骨折风险及其风险因素的相关性研究

目的探讨骨折风险评估工具(FRAX)预测类风湿关节炎(RA)患者骨质疏松性骨折的临床应用价值并对其骨折风险因素进行相关性分析。方法回顾性分析2015年1月至2016年2月期间经确诊的74例类风湿关节炎患者以及正常对照组76例的相关临床指标以及骨密度值;评估FRAX对类风湿关节炎患者的骨折风险预测值以及FRAX与类风湿临床风险因素之间的关系。结果类风湿组股骨颈、腰椎的骨密度值均低于对照组,而类风湿组中10年主要骨质疏松性骨折发生概率和10年髋部骨折发生概率均高于对照组。多重线性回归分析提示FRAX评分与易激动、口味偏淡、体重指数、S-CTX具有一定的相关性。结论 FRAX工具对临床评估RA患者骨质疏松性骨折风险、预后评价等方面具有良好的应用价值。     

Association of microRNAs genes polymorphisms with rheumatoid arthritis in Egyptian female patients

ObjectiveTo investigate whether miRNA-499 (rs3746444) and miRNA-146a (rs2910164) genes polymorphisms are independent factors for rheumatoid arthritis (RA) in Egyptians, and whether they influence disease severity and activity.MethodsTwo hundred and seventeen RA patients and 245 healthy controls were enrolled in this study. Polymorphisms of miRNA-146a and miRNA-499 genes were detected using polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP).ResultsThe miRNA-499 CT genotype was an independent factor of RA. The miRNA-499 CT, CC genotypes and C allele frequencies were significantly increased in erosive RA group. Moreover, the heterozygote CT had more severe and more active form of the disease compared with homozygote CC or TT. However, we did not find any significant association of miRNA-146a polymorphism with RA risk, severity, and activity.ConclusionThe miRNA-499 polymorphism is an independent factor of RA, and influences disease severity and activity.     

Impact of multimorbidity on disease modifying antirheumatic drug therapy in early rheumatoid arthritis: Data from the ESPOIR cohort

ObjectiveMultimorbidity is frequent in rheumatoid arthritis (RA) and could interfere with the therapeutic response. The aim of this study was to evaluate multimorbidity in the French cohort of early arthritis, the ESPOIR cohort, and its possible impact on the therapeutic response.MethodsWe included patients fulfilling 2010 ACR/EULAR criteria for RA. An adapted MultiMorbidity Index (aMMI) was developed. Each patient was assigned scores of binary aMMI (0 = no comorbidity, 1 = at least 1 comorbidity) and counted and weighted aMMI. The primary endpoint was achievement of Clinical Disease Activity Index (CDAI) low disease activity after initiation of a first disease-modifying antirheumatic drug (DMARD) according to the aMMI. We collected data from the visit preceding the first DMARD initiation and the visit after at least 3 months of treatment. The impact of aMMI on therapeutic maintenance at 1, 3, 5 and 10 years was evaluated.ResultsAnalyses involved 472 patients: 302 (64%) had at least 1 comorbidity. Overall, 45.3% and 44.7% with binary aMMI = 0 or 1, respectively (non-significant), achieved CDAI low disease activity. Similar results were found with counted and weighted aMMI. Therapeutic maintenance was significantly better with binary aMMI = 1 than binary aMMI = 0 (OR at 10 years = 14.0 [CI 95% 3.3–59.4]). Increased counted aMMI was associated with increased probability of still being on the first initiated DMARD at each time point.ConclusionIn the ESPOIR cohort, therapeutic response to a first DMARD was not affected by multimorbidity but therapeutic maintenance was better in multimorbid patients.     

Incidence of paradoxical reactions in patients treated with tocilizumab for rheumatoid arthritis: Data from the French registry REGATE

Objectives

Assess the frequency of paradoxical reactions encountered in daily practice under tocilizumab, using the REGATE (Registry-RoActemra) registry. The secondary objectives were to determine the type of paradoxical reaction and the consequences of these reactions.

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.     

Involvement of interleukin-6 and prostaglandin E2 in periarticular osteoporosis of postmenopausal women with rheumatoid arthritis

In experimental arthritis, blocking of the receptor activator of nuclear factor κB ligand (RANKL) by osteo-protegerin (OPG) treatment prevents bone loss but not inflammation, suggesting that there are inflammation-related factors that regulate RANKL and OPG. However, it is not known which factors regulate RANKL and OPG in human inflammation-induced bone loss. To clarify the inflammation-related factors that play a role in periarticular osteoporosis in patients with rheumatoid arthritis (RA), the synovial fluid and synovium of the knee joint, and the periarticular cancellous bone of the femoral condyle were collected at surgery from postmenopausal women with RA or osteoarthritis (OA). All patients with RA had radiologic bone loss on the femoral condyles, while such a loss was not observed in patients with OA. The present study examined: (i) tumor necrosis factor α (TNFα), interleukin (IL)-1β and IL-6 levels in synovial fluid; (ii) TNFα, IL-1β and IL-6 messenger RNA (mRNA) expression in the synovium and the cancellous bone that contained bone marrow; and (iii) IL-6 and prostaglandin E₂ (PGE₂) production in cultured osteoblast-lineage cells derived from collagenase-treated cancellous bone fragments. Inflammation of the knee joints in patients with RA was confirmed by significantly higher proinflammatory cytokine levels in the synovial fluid and the synovium than those seen in patients with OA. In patients with RA, mRNA expression of IL-6, but not TNFα and IL-1β, in the cancellous bone and IL-6 and PGE₂ production in the osteoblast-lineage cells were significantly higher than in patients with OA. These findings suggest, for the first time, that IL-6 is involved in periarticular osteoporosis in postmenopausal women with RA. IL-6 and PGE₂ released from osteoblast-lineage cells could be, at least in part, responsible for human inflammation-induced bone loss. Received: August 28, 2000 / Accepted: November 9, 2000     

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.     

老年类风湿关节炎患者发生骨质疏松的危险因素分析

目的调查老年类风湿关节炎(RA)患者骨质疏松(OP)的发生情况并分析其危险因素,为有效预防和干预提供依据。方法选取2012年1月至2017年9月我院收治的老年RA患者684例,根据其发生OP的情况分为OP组(383例)和非OP组(301例),记录患者一般资料及OP的相关因素。应用二分类非条件Logistic回归分析老年RA患者发生OP的危险因素。结果在684例老年RA患者中383例发生OP,发生率高达56.0%。随着年龄的增长,男、女性骨质疏松症患病率均明显增加,差异有统计学意义(P0.05)。OP组的腰椎(-2.98±0.94 vs-0.85±0.62)、股骨颈(-2.53±0.76 vs-0.82±0.57)、全髋(-1.95±0.81 vs-0.29±0.24)骨密度T值均明显低于非OP组(P0.05)。二分类非条件Logistic回归分析显示,年龄[OR=1.805(95%CI:1.613~2.274)]、病程[OR=1.603(95%CI:1.431~1.968)]、ESR[OR=1.583(95%CI:1.286~1.815)]、DAS28评分[OR=1.729(95%CI:1.504~2.063)]是老年RA患者发生OP的独立危险因素,而BMI[OR=0.752(95%CI:0.674~0.926)]、摄入钙[OR=0.584(95%CI:0.318~0.720)]、ALB[OR=0.803(95%CI:0.725~0.993)]、25(OH)D[OR=0.713(95%CI:0.620~0.857)]可能是OP保护因素。结论老年RA患者OP的发生率较高,影响其发生的危险因素较多,应做到早预防、早发现,以减少或延缓OP的发生。     

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。     

女性类风湿关节炎患者前臂骨密度测定在诊断骨质疏松中的应用价值及影响因素分析

目的探讨绝经后女性类风湿关节炎患者前臂骨密度扫描的分布规律,并通过与椎体、髋部双能X线(DXA)进行对比,确定其在类风湿关节炎(RA)患者骨质疏松诊断中的价值。方法采用DXA法,同时测量200例女性绝经后RA患者非优势侧前臂远端以及腰椎、左髋部骨密度。比较不同扫描部位之间骨密度值的关系,并探讨以诊断中轴骨密度异常的诊断界值,以及可能影响外周骨密度的因素。结果 (1)200例女性绝经RA患者平均年龄(55.9±13.8)岁。根据中轴DXA结果及骨折病史,170例(85.0%)骨密度异常(T值-1.0)。(2)RA患者中轴骨密度异常组前臂远端骨密度(0.33±0.13)g/cm~2,低于正常组(0.44±0.06)g/cm~2,(t=4.29,P0.01)。(3)病程1年以上、抗CCP抗体阳性RA患者前臂骨密度降低。(4)前臂骨密度与中轴骨密度呈正相关。(5)使用前臂骨密度诊断腰椎和左髋骨质疏松的最佳T值分别为-2.65(敏感度为0.702,特异度为0.774)和-2.50(敏感度为0.741,特异度为0.706)。(6)Logistic回归分析显示,年龄(P=0.012)、病程(P=0.011)、以及抗CCP抗体阳性(P=0.05)分别是造成RA患者前臂BMD异常的独立危险因素。结论 RA患者前臂骨密度可以作为筛查女性类风湿关节炎患者中轴骨质疏松的辅助工具,高龄、疾病病程长以及抗CCP抗体阳性患者更容易出现骨密度下降。     

Gout and rheumatoid arthritis,both to keep in mind in cardiovascular risk management: A primary care retrospective cohort study

Objectives

To assess in one time window cardiovascular risks for both patients with gout and patients with rheumatoid arthritis in a Dutch primary care population.