重组人肿瘤坏死因子受体-抗体融合蛋白治疗类风湿关节炎65例的疗效与安全性观察

目的 研究注射用重组人肿瘤坏死因子受体-抗体融合蛋白依那西普(Etanercept,ETA)治疗类风湿关节炎(rheumatoid arthritis,RA)的疗效及安全性.方法 65例患者以抽签方式随机分为试验组(31例)和对照组(34例).试验组每周1次口服空白模拟甲氨蝶呤10 mg或来氟米特片20 mg/a,同时每周2次皮下注射ETA 25 mg;对照组每周1次口服甲氨蝶呤10 mg或来氟米特片20mg/d,同时每周2次皮下注射空白模拟ETA 25 mg,疗程3月.疗效评价采用美国风湿病学会(ACR)疗效评定标准.结果 试验组治疗后的类风湿因子滴度(RF)、血沉(ESR)、c反应蛋白(CRP)水平及DAS28评分明显低于对照组(P<0.05),达到ACR50及ACR70的患者试验组均明显高于对照组(P=0.02,P<0.001).两组不良反应发生率差异无统计学意义.结论 ETA用于治疗RA具有良好的安全性和显著的疗效.     

Efficacy, safety and tolerability of lumiracoxib in patients with rheumatoid arthritis

A randomised, double-blind study was performed to assess the efficacy and tolerability of lumiracoxib in patients with rheumatoid arthritis (RA). Patients received lumiracoxib 200mg once daily (o.d.) (n= 280), lumiracoxib 400mg o.d. (n= 281), naproxen 500 mg twice daily (n= 279) or placebo (n= 284) for 26 weeks. The primary efficacy variable was response to treatment according to ACR20 criteria (adjusted for prohibited concomitant or excessive rescue medication use and discontinuations due to unsatisfactory therapeutic response) at week 13. Safety and tolerability was also assessed. Significantly more patients receiving lumiracoxib than placebo were responders according to ACR20 criteria at week 13 (41.1 and 42.7% for lumiracoxib 200 and 400 mg o.d., respectively; 32.4% for placebo; both p < 0.05). The proportion responding to naproxen (39.1%) was not significantly different from placebo. Prespecified gastrointestinal adverse events were more frequent with naproxen than with either lumiracoxib dose or placebo. Lumiracoxib is therefore an effective and well-tolerated therapy for RA.     

Clinical assessment of pain, tolerability, and preference of an autoinjection pen versus a prefilled syringe for patient self-administration of the fully human, monoclonal antibody adalimumab: the TOUCH trial

BACKGROUND: Adalimumab is a therapeutic monoclonal antibody for SC administration by 2 single-use injection devices providing bioequivalent amounts of adalimumab: a ready-to-use, prefilled syringe and an integrated, disposable delivery system, the autoinjection Pen. Although pens have been shown to be preferred over syringes by patients requiring long-term SC administration of medications, there are no data on preference and pain in the use of biologics in patients with chronic inflammatory diseases. OBJECTIVE: The aim of this study was to assess injection-site pain, tolerability, and patient preference of 2 delivery systems of adalimumab. METHODS: Patients with rheumatoid arthritis were enrolled in a Phase II, multicenter, open-label, single-arm, sequential trial. Patients self-administered a standard dose of adalimumab 40 mg SC every other week at each of 3 monitored clinical visits: visit 1 (syringe), visits 2 and 3 (Pen). At each visit, patients rated their pain on an 11-point scale (0 = none to 10 = pain as bad as it could be) immediately after injection and 15-30 minutes after injection and provided their impressions of and preferences for each delivery system. Safety events were recorded throughout the study and 70 days after final study dose. RESULTS: Fifty-two patients were enrolled in the trial and completed all 3 visits (32 women, 20 men; mean [SD] age, 53.8 [12.1] years). Forty (76.9%) patients reported that the Pen was less painful than the syringe, 4 (7.7%) patients found the syringe to be less painful, and 8 (15.4%) patients had no preference. Patients had statistically significant reductions in injection-pain scores from visit 1 to visit 2 and from visit 1 to visit 3. No new safety signals or apparent differences regarding tolerability between the syringe and Pen were observed. In addition, 46 (88.5%) patients preferred the Pen, 3 (5.8%) preferred the syringe, and 3 (5.8%) had no preference. Overall, patients evaluated the Pen as easier to use (94.2%), more convenient (92.3%), requiring less time to inject (82.7%), and safer (88.5%). CONCLUSIONS: Patients experienced less pain self-administering adalimumab via the Pen and preferred it versus the syringe. Further, patients perceived the Pen to be easier to use and more convenient. Both delivery systems were generally well tolerated.     

Efficacy and safety of the monoclonal anti-tumor necrosis factor antibody F(ab')2 fragment afelimomab in patients with severe sepsis and elevated interleukin-6 levels

OBJECTIVE: To evaluate whether administration of afelimomab, an anti-tumor necrosis factor F(ab')2 monoclonal antibody fragment, would reduce 28-day all-cause mortality in patients with severe sepsis and elevated serum levels of IL-6. DESIGN: Prospective, randomized, double-blind, placebo-controlled, multiple-center, phase III clinical trial. SETTING: One hundred fifty-seven intensive care units in the United States and Canada. PATIENTS: Subjects were 2,634 patients with severe sepsis secondary to documented infection, of whom 998 had elevated interleukin-6 levels. INTERVENTIONS: Patients were stratified into two groups by means of a rapid qualitative interleukin-6 test kit designed to identify patients with serum interleukin-6 levels above (test positive) or below (test negative) approximately 1000 pg/mL. Of the 2,634 patients, 998 were stratified into the test-positive group, 1,636 into the test-negative group. They were then randomly assigned 1:1 to receive afelimomab 1 mg/kg or placebo for 3 days and were followed for 28 days. The a priori population for efficacy analysis was the group of patients with elevated baseline interleukin-6 levels as defined by a positive rapid interleukin-6 test result. MEASUREMENTS AND MAIN RESULTS: In the group of patients with elevated interleukin-6 levels, the mortality rate was 243 of 510 (47.6%) in the placebo group and 213 of 488 (43.6%) in the afelimomab group. Using a logistic regression analysis, treatment with afelimomab was associated with an adjusted reduction in the risk of death of 5.8% (p = .041) and a corresponding reduction of relative risk of death of 11.9%. Mortality rates for the placebo and afelimomab groups in the interleukin-6 test negative population were 234 of 819 (28.6%) and 208 of 817 (25.5%), respectively. In the overall population of interleukin-6 test positive and negative patients, the placebo and afelimomab mortality rates were 477 of 1,329 (35.9%)and 421 of 1,305 (32.2%), respectively. Afelimomab resulted in a significant reduction in tumor necrosis factor and interleukin-6 levels and a more rapid improvement in organ failure scores compared with placebo. The safety profile of afelimomab was similar to that of placebo. CONCLUSIONS: Afelimomab is safe, biologically active, and well tolerated in patients with severe sepsis, reduces 28-day all-cause mortality, and attenuates the severity of organ dysfunction in patients with elevated interleukin-6 levels.     

Long-term safety,efficacy, and immunogenicity of adalimumab biosimilar BI 695501 and adalimumab reference product in patients with moderately-to-severely active rheumatoid arthritis: results from a phase 3b extension study (VOLTAIRE-RAext)

ABSTRACT

Objective: To evaluate long-term safety, efficacy, and immunogenicity of BI 695501 in patients with moderately-to-severely active rheumatoid arthritis (RA) who have completed VOLTAIRE-RA.

Methods: Eligible patients for this phase 3b open-label extension study (VOLTAIRE-RAext), who had completed 48 weeks’ treatment with BI 695501 (Group A), 24 weeks each of adalimumab RP then BI 695501 (Group B), or 48 weeks of adalimumab RP (Group C) in VOLTAIRE-RA, were enrolled.

Results: Altogether, 430 patients received BI 695501 fortnightly for 48 weeks: Group A, n = 225; Group B, n = 103; Group C, n = 102. The proportion of patients with drug-related adverse events (AEs; overall 20.2%) was similar across Groups A, B, and C: 21.3%, 20.4%, and 17.6%, respectively. The majority of treatment-emergent AEs were non-serious and of mild/moderate intensity. Consistent with adalimumab RP’s safety profile, most drug-related AEs were in the system organ class infections and infestations. BI 695501 and adalimumab RP responses at the end of VOLTAIRE-RA were sustained during VOLTAIRE-RAext and all efficacy and immunogenicity endpoints were similar across groups.

Conclusion: Over 2 years, BI 695501 showed similar safety, efficacy, and immunogenicity to adalimumab RP, independent of initial treatment in VOLTAIRE-RA. No previously unknown adalimumab side effects were identified.

Clinical trial registration: NCT02640612.     

Efficacy and safety of a non-acetylated salicylate, choline magnesium trisalicylate, in the treatment of rheumatoid arthritis

The results of three double-blind, multicentre trials are reviewed to compare the efficacy of acetysalicylic acid (ASA) and a non-acetylated salicylate, choline magnesium trisalicylate (CMT), in the treatment of rheumatoid arthritis. In each trial, patients were randomly assigned to receive comparable doses of salicylate as either ASA or CMT. Mean values for clinical indicators of rheumatoid arthritis (number of painful joints, articular index, number of swollen joints, swelling index, duration of morning stiffness) showed similar or greater improvement among groups of patients receiving CMT, compared to those receiving ASA. In addition, the incidence of gastro-intestinal side-effects was lower among patients receiving CMT.     

Patient education program to teach energy conservation behaviors to patients with rheumatoid arthritis: a pilot study

We report a prospective, randomized pilot study comparing a new workbook-based program, designed to teach patients with rheumatoid arthritis (RA) energy conservation behaviors, with standard occupational therapy (OT). Sixteen patients took part in the new program and nine received the standard therapy. Data on the number of tender or swollen joints, grip strength, walk time, activities of daily living, psychologic adjustment to illness, and daily activity log, were measured before and three months after intervention. Eleven percent of those who received standard therapy and 50% of those who received the workbook increased their amount of physically active time (p = .10). Twenty-two percent of the control group and 50% of those in the workbook group achieved a better balance of rest and physical activity (p = .07). We conclude that the adoption of energy conservation behaviors is different in the two groups. This initial study suggests that interrupting physical activity with rest periods may result in increased physical activity in patients with RA.     

注射用重组人Ⅱ型肿瘤坏死因子受体-抗体融合蛋白联合甲氨蝶呤治疗类风湿关节炎的临床效果

目的探讨注射用重组人Ⅱ型肿瘤坏死因子受体-抗体融合蛋白联合甲氨蝶呤治疗类风湿关节炎的临床效果。方法选取2017年1月至2018年12月西安市第五医院收治的136例类风湿关节炎患者作为研究对象,按照随机数字表法将其分为试验组与对照组,各68例。两组患者均采用醋氯芬酸进行常规治疗,在此基础上,对照组采用甲氨蝶呤+硫酸羟氯喹治疗,试验组采用甲氨蝶呤+注射用重组人Ⅱ型肿瘤坏死因子受体-抗体融合蛋白治疗。比较两组患者治疗3、6个月后的治疗总有效率、治疗前、后的机体关节症状严重程度、血清相关细胞因子水平及不良反应发生情况。结果治疗3、6个月后,试验组的治疗总有效率均显著高于对照组(P<0.05)。治疗后,两组的DAS28评分均显著降低,且试验组低于对照组(P<0.05)。治疗后,两组的血清COX-2、TNF-α、IL-6、M-CSF水平均降低,且试验组低于对照组(P<0.05)。两组的不良反应总发生率比较,差异无统计学意义(P>0.05)。结论注射用重组人Ⅱ型肿瘤坏死因子受体-抗体融合蛋白联合甲氨蝶呤治疗类风湿关节炎临床效果显著,可加快关节症状改善,减轻机体炎性反应,促进患者恢复,且可有效保证治疗安全性。     

Step performance in persons with rheumatoid arthritis: a case-control study

Smulders E, van Lankveld W, Eggermont F, Duysens J, Weerdesteyn V. Step performance in persons with rheumatoid arthritis: a case-control study.

Objective

To investigate factors that could lead to falls in patients with rheumatoid arthritis (RA).

Design

Case-control study.

Setting

Hospital.

Participants

Patients with RA (n=15) and age- and sex-matched controls (n=15; mean ± SD age, 60.5±7.1y).

Interventions

Not applicable.

Main Outcome Measures

Performance of participants on a step task. Furthermore, manual performance was assessed, as well as questionnaires for balance confidence, fear of falling, and activity level.

Results

Patients with RA showed nonsignificantly increased RTs (time to anticipatory postural adjustment and foot lift) and significantly increased movement times (MTs). Push-off force and step velocity were significantly lower in patients with RA. During a manual task, delayed RTs and MTs were seen. Moreover, lower levels of balance confidence and more fear of falling were reported in patients with RA. There were no differences in activity levels.

Conclusions

When performing a quick step, patients with RA show delayed MT and step velocity and decreased push off. Because quick stepping often is used to avoid falls, the increase in step execution time might have undesirable consequences. Furthermore, patients with RA have lower balance confidence and more fear of falling than healthy controls; these factors also contribute to higher fall risk.     

Diagnostic value of anti-cyclic citrullinated peptide antibody combined with rheumatoid factor in rheumatoid arthritis in Asia: a meta-analysis

ObjectiveThis meta-analysis explored the diagnostic value of anti-cyclic citrullinated peptide antibody (anti-CCP) and rheumatoid factor (RF) for rheumatoid arthritis (RA) in the Asian population.MethodsEmbase, Medline, Cochrane Library, Chinese Science and Technology Periodicals, China National Knowledge Infrastructure, and China Wanfang Databases were searched from 1 January 2000 to 1 February 2021 to collect studies on the combined detection of anti-CCP and RF for diagnosing RA. The sensitivity, specificity, diagnostic odds ratio (DOR), positive likelihood ratio (+LR), and negative likelihood ratio (−LR) were combined and analyzed. Summary receiver operating characteristic (SROC) curves were drawn.ResultsTwenty-four published papers were analyzed, including 21 combined in series and 8 combined in parallel. In the tandem analysis, the sensitivity = 0.64 [95% confidence interval (CI): 0.58–0.70], specificity = 0.97 (95%CI: 0.95–0.98), +LR = 19.70 (95%CI: 12.74–30.46), −LR = 0.37 (95%CI: 0.31–0.43), DOR = 53.43 (95%CI: 34.46–82.40), and area under the SROC curve = 0.89. In the parallel combination, the sensitivity = 0.87 (95%CI: 0.80–0.92), specificity = 0.76 (95%CI: 0.67–0.84), +LR = 3.68 (95%CI: 2.62–5.17), −LR = 0.17 (95%CI: 0.11–0.26), DOR = 21.56 (95%CI: 11.63–39.99), and area under the SROC curve = 0.89.ConclusionAnti-CCP and RF combined detection improves the diagnostic efficiency of RA, providing a potential strategy for early clinical screening in the Asian population.This trial was retrospectively registered in the INPLASY/Research Registry (https: //inplasy.com/) with the registration number INPLASY202180106.     

Quality of life and life-space mobility after total knee arthroplasty in patients with rheumatoid arthritis: a pilot case-controlled study

[Purpose] The purpose of this study was to identify factors inhibiting improvement in the quality of life after total knee arthroplasty in patients with rheumatoid arthritis. [Participants and Methods] This was a pilot case-control study. The sample comprised of five participants with rheumatoid arthritis and 11 participants with osteoarthritis, who underwent total knee arthroplasty. We compared the groups in terms of physical function, walking ability, Japanese Knee Osteoarthritis Measure, and Life-Space Assessment. Measurements were taken before surgery and at four weeks and five months post-surgery. All patients underwent rehabilitation for five months postoperatively, first as inpatients, and then as outpatients after discharge. [Results] In the period from 4 weeks to 5 months post-surgery, physical function improved similarly in both groups in terms of muscle strength and walking ability. Despite the patients with rheumatoid arthritis being younger, their self-health assessment score by the Japanese Knee Osteoarthritis Measure and measures of life-space mobility by Life-Space Assessment were lower. [Conclusion] It is important to consider exercise therapy, and gait instruction to alleviate anxiety about health status and improve the quality of life and life-space mobility in patients with rheumatoid arthritis who undergo total knee arthroplasty.     

Etodolac, aspirin, and placebo in patients with rheumatoid arthritis: a 12-week study

Etodolac, aspirin, and placebo were evaluated for efficacy and safety in 18 patients with adult-onset, active rheumatoid arthritis. This was a 12-week, double-blind, parallel-group study divided into drug titration and maintenance periods and preceded by a washout period of up to two weeks. The mean daily maintenance doses of etodolac and aspirin were 394 mg and 4,414 mg, respectively. Etodolac was significantly (P less than or equal to 0.05) more effective than placebo in five of ten clinical variables of efficacy: number of painful joints, number of swollen joints, pain intensity, erythrocyte sedimentation rate, and patients' overall assessments. Aspirin was significantly more effective than placebo in only two assessments: number of painful joints and pain intensity. One patient on etodolac, two patients on aspirin, and four patients on placebo had to be withdrawn from the trial because of insufficient therapeutic response. One patient in the placebo group was withdrawn from the study because of a pruritic rash. Mild to moderate gastrointestinal complaints occurred in all three treatment groups: in three patients taking etodolac, three taking aspirin, and two taking placebo.     

Validity and reliability of an internet-based temporal gait assessment tool with healthy adults: a pilot study

OBJECTIVES: To assess in healthy adults the validity and the inter- and intrarater reliability of the Internet-based Shaw Gait Assessment (SGA). DESIGN: Concurrent test-retest reliability and validity study with participants, 4 raters, and the Elite motion analysis system (used as the criterion standard). SETTING: Motion analysis laboratory in a university physical therapy department. PARTICIPANTS: Convenience sample of 16 healthy men and women (age range, 28-53y). INTERVENTION: Each subject performed 2 consecutive walks "at a comfortable pace" on a 6-m walkway. A video camera from the Elite motion analysis system filmed reflective markers, which were attached to subjects' shoes, and the reflective markers provided the criterion standard. Four raters simultaneously recorded each walk by using laptop computers and the SGA. MAIN OUTCOME MEASURES: Paired t test (5% level) for average differences between each test and retest for raters and the Elite; Pearson correlations, limits of agreement, and coefficients of variation (CVs) for validity of the tool; intraclass correlation coefficients (ICCs) for inter- and intrarater reliability. RESULTS: Pearson product moment correlation coefficients between each of the raters and the Elite ranged from .92 to .95 for speed, from .85 to .97 for cadence, from .87 to .92 for step length, from .61 to .84 for left advance limb time, and from .68 to .83 for right advance limb time. Pooled CVs for all variables were below 8% for all raters and the Elite. Pooled ICCs for intrarater reliability were .89 for speed, .99 for cadence, .84 for step length, .76 for left limb advance time, and .84 for right limb advance time. Interrater ICCs were .89 for speed, .82 for cadence, .76 for step length, .66 for left limb advance time, and .81 for right limb advance time. CONCLUSIONS: The SGA is a valid and reliable tool for several key temporal measures of gait in a healthy adult population.     

Chronic pericardial disease in patients with rheumatoid arthritis: a longitudinal study

We have reviewed the clinical and investigative findings in 13 patients with chronic pericardial disease and seropositive rheumatoid arthritis. In eleven cases the diagnosis was made on clinical grounds, while the diagnosis was confirmed only at post-mortem in two patients. Pleural effusions were present in seven patients, while pulsus paradoxus was found in only one case. Echocardiograms were undertaken in ten patients and all showed evidence of pericardial effusions, which were usually small and sited posteriorly. A delayed ventricular filling pattern indicating abnormal ventricular relaxation was seen in two patients with cardiac tamponade. The surviving 11 patients were reviewed a median of three years after diagnosis of their pericardial disease. Pericardectomy had been performed in six, all of whom were asymptomatic and had a normal chest radiograph. Steroids alone had been given to the other five, and three of these remained dyspnoeic with cardiomegaly. The clinical features distinguishing chronic pericardial disease from other causes of right heart failure in rheumatoid arthritis patients are subtle. As management is fundamentally different, serious consideration should be given to the diagnosis of chronic pericardial disease in any patient with rheumatoid arthritis who presents with right-sided heart failure.     

Yoga for pain and sleep quality in rheumatoid arthritis: study protocol for a pilot randomized controlled trial

Background:

Yoga is a popular complementary and alternative medicine (CAM) therapy among people with rheumatoid arthritis (RA), perceived as offering self-management options for physical and psychosocial symptoms associated with RA.

Objectives:

The primary aims of the current pilot study are (1) to assess the feasibility and safety of a relaxation-focused yoga intervention tailored for people with RA and (2) to estimate the effect of yoga on RA-related pain, sleep quality, functional disability, disease activity, quality of life, anxiety, depression, and fatigue.

Method:

Twenty-eight participants with at least minimum levels of RA-related pain and sleep disturbance will be recruited from a local public hospital database. Participants meeting inclusion criteria will be randomized into either a yoga group (receiving an 8-week program of once-weekly 75-minute relaxation-based yoga classes and thrice-weekly home practice), or a usual care control group. Outcomes will be assessed at baseline, 9, and 12 weeks. Feasibility is operationalized as acceptability (recruitment, adherence, participant retention, and participant satisfaction) and safety of the yoga intervention. Effect sizes for changes in pain, sleep quality, functional disability, disease activity, quality of life, mental health, and fatigue will be estimated.

Discussion:

Results of this pilot study will provide empirical data to determine if a larger, statistically powered main trial is feasible and safe in a national RA population. Additionally, participant feedback will provide information regarding further adaption and tailoring of the study protocol to a clinical RA population.

Trial registration:

Australian New Zealand Clinical Trials Registry ACTRN12612001019897 (registered 20/09/2012).