Comparison of efficacy of arthroscopic lavage plus administration of corticosteroids, arthroscopic lavage plus administration of placebo, and joint aspiration plus administration of corticosteroids in arthritis of the knee: A randomized controlled trial

OBJECTIVE: To compare the efficacy of arthroscopic lavage plus administration of corticosteroids (ALC), arthroscopic lavage plus administration of placebo (ALP), and joint aspiration plus administration of corticosteroids (JAC) in knee arthritis, and to evaluate whether clinical or histologic characteristics determine outcome. METHODS: Patients with knee arthritis (not due to gout, osteoarthritis, or septic arthritis) were randomized over 3 treatment arms: ALC, ALP, and JAC. The primary end point was event-free survival, with events defined as 1) recurrence or persistence of symptomatic knee swelling necessitating local re-treatment, or 2) nonimprovement of the knee joint score. Synovial tissue specimens were collected and analyzed histologically to identify predictive factors of responsiveness. RESULTS: A total of 78 patients were enrolled; 3 patients did not receive their allocated therapy and 3 were lost to followup. The median time until recurrence was 9.6 months after ALC, 3.0 months after JAC, and 1.0 month after ALP, corresponding to a relative risk (RR) of arthritis recurrence of 2.2 for JAC (95% confidence interval [95% CI] 1.2-4.2, P = 0.02) and 4.7 for ALP (95% CI 2.3-9.4, P < 0.0001) compared with ALC. A high versus low synovial extent of fibrosis conferred an RR for recurrence of 5.7 (95% CI 1.6-20.5, P < 0.01) after ALC. CONCLUSION: Arthroscopic lavage plus administration of corticosteroids was more effective than arthroscopic lavage plus administration of placebo or joint aspiration plus injection of corticosteroids. The absence of fibrosis was a histologic predictor of a beneficial response.     

Immunohistological Indication for Arthroscopic Synovectomy in Rheumatoid Knees: Analysis of Synovial Samples Obtained by Needle Arthroscopy

To determine the histological indication for arthroscopic synovectomy in rheumatoid knees, 23 patients underwent lavage and biopsy by needle arthroscopy. Eighty-one patients were treated with arthroscopic knee synovectomy after needle arthroscopy, and 51 of these patients underwent only arthroscopic synovectomy. Thirty patients who showed no improvement following arthroscopic synovectomy underwent open surgical synovectomy. Intra-articular lavage of knee joints by needle arthroscopy did not result in any clinical improvements. In the patients who underwent only arthroscopic synovectomy, two groups (only macrophages, no macrophages or B cells) showed clinical improvement (symptoms of the knee, ESR, RF). Patients in whom open surgical synovectomy was performed because of the failure of arthroscopic synovectomy showed clinical improvement. However, there was a significant loss of movement in the knee joint and more severe radiological deterioration in patients who underwent open surgical synovectomy than in those who underwent only arthroscopic synovectomy. Arthroscopic synovectomy should be used for rheumatoid patients with synovial tissue containing only macrophages or none of these two cells. Received: 26 February 2001 / Accepted: 13 July 2001     

Volume of a wash and the other conditions for maximum therapeutic effect of arthroscopic lavage in rheumatoid knees

The objective of this study was to determine the appropriate volume of saline to obtain a beneficial effect of arthroscopic lavage and the prognostic factors related to the clinical effect in a refractory rheumatoid knee. Arthroscopic lavage or arthrocentesis was performed in a random manner in 142 patients with relapsing rheumatoid arthritis. All patients were followed up for 24 months. Intra-articular lavage with 5 l (p<0.01) or 3 l (p<0.05) of saline gave better clinical results than did arthrocentesis. There was no significant difference between the cumulative incidence of recurrence of knee synovitis in patients who underwent arthrocentesis and that in patients who underwent lavage with 1 l of saline. Cox regression analysis showed that patients with knee arthritis of more than 6 months in duration and with Larsen grade II or less were more responsive to lavage with 5 or 3 l of saline. The duration of the effect of lavage with 3 l of saline was increased 2.9-fold (p=0.04) by injection of both steroids and high molecular weight hyaluronan. No bleeding or infectious complications occurred after those procedures. Arthroscopic lavage with 5 l of saline is safe and has good therapeutic effects for rheumatoid knees with mild destruction in which arthritis has persisted for more than 6 months. Lavage with 3 l of saline is recommended when intra-articular injection of corticosteroid and high molecular weight hyaluronan is performed after lavage.     

EFFECTS OF JOINT LAVAGE ON KNEE SYNOVITIS IN RHEUMATOID ARTHRITIS

Ten patients with rheumatoid arthritis and persistent knee synovitishad synovial fluid aspirated through a 14 gauge wide-bore needlefollowed by joint lavage and intra-articular triamcinolone.This resulted in the removal of variable quantities of intra-articulardebris including rice bodies. When compared to a control groupof patients, the addition of joint lavage to the standard procedureof aspiration and injection of corticosteroid resulted in moresustained resolution of synovitis after 12 weeks as judged byknee tenderness and circumference, recurrence of effusion, andsynovial fluid leucocyte count. This study suggests that kneejoint lavage may be a useful adjunct to therapy in rheumatoidarthritis patients having persistent knee synovitis. KEY WORDS: Rheumatoid arthritis, Knee synovitis, Joint lavage     

The prevalence of subclinical amyloidosis in Polish patients with rheumatoid arthritis

The aims of this study were to determine the proportion of rheumatoid arthritis (RA) patients attending hospital in whom amyloid deposits were present in abdominal fat aspiration (AFA) samples, and to assess possible risk factors for amyloid development in RA. One -hundred and twenty-one patients (16 males, 105 females) with RA referred to the Department of Rheumatology in Wroclaw between 1996 and 2001 were studied regardless of RA duration or laboratory findings. Abdominal subcutaneous fine-needle aspiration was performed, and samples of adipose tissue stained with alkaline Congo red then examined by polarized light microscopy. The presence or absence of amyloid fat deposits (AFD) was determined according to whether typical apple-green birefringence was observed. Amyloid deposits were found in 35 (29%) patients. Amyloidosis was significantly more common in males and in patients with longer disease duration. Patients with AFD had previously undergone less treatment with disease-modifying antirheumatic drugs (DMARDs) than those without AFD, and significantly fewer patients with AFD had previously taken methotrexate than those without AFD (25% vs 45%; p<0.01). Renal involvement was found in 12 of 35 patients with AFD (34%). Using the AFA technique, amyloid deposits were found commonly in RA patients, particularly in males with longer disease duration and in patients not treated intensively with DMARDs, especially methotrexate. AFA has potential useful application as a method for detecting amyloidosis before the overt occurrence of renal or other pathology related to amyloid deposits.Abbreviations AFA Abdominal fat aspiration - AFD Amyloid fat deposits - DMARDs Disease-modifying antirheumatic drugs - RA Rheumatoid arthritis     

Effects of Needle-Arthroscopic Lavage with Different Volumes of Fluid on Knee Synovitis in Rheumatoid Arthritis

To determine the appropriate volume of physiological fluid needed to effectively reduce synovitis and to determine the indications for intra-articular lavage of knee joints with rheumatoid arthritis (RA), intra-articular lavage with different volumes of physiological fluid via needle arthroscopy were performed on 102 rheumatoid knees in 98 patients (25 males, 77 females) with an average age of 46 years at the time of operation. Intra-articular lavage of a knee joint with 5 or 10 l of physiological fluid gave better clinical results than did intra-articular lavage with 0.5–1.5 l. There was no difference between the beneficial effects of intra-articular lavage using 5 l or 10 l of fluid. The preoperative conditions (CRP, frequency of the susceptible factors of HLA-DRB1 alleles, radiological change in the knee joint) and the intraoperative chondroscopic assessments were correlated with clinical improvement. Our study demonstrated that intra-articular lavage with 5 l of physiological fluid performed using needle arthroscopy was beneficial. The following points at least should be checked before performing intra-articular lavage: (1) CRP is not elevated to a high level (≥5 mg/dl), (2) the patient does not have susceptible factors in both HLA-DRB1 alleles, (3) the grade of rheumatoid knee is below Larsen II in preoperative X-ray findings, and (4) the degree of cartilage damage is not more than grade 3 in arthroscopic findings. Received: 5 July 2000 / Accepted: 31 March 2001     

Treatment of refractory chronic Lyme arthritis with arthroscopic synovectomy

Of 20 patients who underwent arthroscopic synovectomy for refractory chronic Lyme arthritis of the knee, 16 (80%) had resolution of joint inflammation during the first month after surgery or soon thereafter, and they have remained well during the 3-8-year followup period. Three of these 16 patients who were more disabled preoperatively, still had mild functional limitation at long-term followup. The remaining 4 patients (20%) had persistent or recurrent synovitis. We conclude that arthroscopic synovectomy is effective in treating chronic Lyme arthritis in patients in whom the disease does not respond to antibiotic therapy.     

Abatacept initiation in rheumatoid arthritis and the risk of serious infection: A population-based cohort study

ObjectiveTo assess whether abatacept as initial biologic disease-modifying antirheumatic drug (DMARD) in the treatment of rheumatoid arthritis is associated with an increased risk of serious infections, including bone and joint, gastrointestinal, respiratory tract, skin and soft tissue, and urinary tract, when compared with other biologic DMARDs.MethodsWe performed a population-based cohort study among patients newly-treated with biologic DMARDs within the US-based Truven MarketScan® population and Supplemental US Medicare from 2007 to 2014. Cox proportional hazards models were used to estimate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) of serious infections requiring hospitalisation associated with initiation of abatacept, compared with initiation of other bDMARDs, after controlling for age and deciles of the propensity score.ResultsThe cohort included 5,752 patients who initiated abatacept and 78,556 who initiated another biologic DMARD, of whom 193 and 1531 had a serious infection during follow-up (crude incidence rate 4.45 per 100 person-years and 3.62 per 100 person-years, respectively). Compared with other biologic DMARDs, the use of abatacept was not associated with an increased incidence of serious infections overall (HR 1.04, 95% CI 0.89–1.21). The risk did not vary by duration of use (<1 year: HR 1.03, 95% CI 0.87–1.22; >1 year: HR 1.08, 95% CI 0.77–1.52). In addition, the risk was not increased for the site-specific infections.ConclusionThe use of abatacept as first biologic DMARD in the treatment of rheumatoid arthritis was not associated with different risks of serious infections compared with other biologic DMARDs.     

Unwillingness of rheumatoid arthritis patients to risk adverse effects

OBJECTIVE: To evaluate patient willingness to accept the risk of adverse effects (AEs) commonly associated with arthritis medications. METHODS: Rheumatoid arthritis patients were asked to rate their willingness to take a medication associated with 17 specific AEs using a visual analogue scale. RESULTS: We interviewed 100 patients. Eighty-one were currently using one or more disease-modifying anti-rheumatic drugs (DMARDs) and 29 had previously experienced AEs related to DMARDs. Seventy-five stated that they were doing very well or well with respect to their arthritis compared with other people their age. Thirty-five per cent of those interviewed were unwilling to accept the risk of cosmetic changes, 38% were unwilling to accept the risk of temporary discomfort and 45% were unwilling to accept the risk of major toxicity. Patients who had previously experienced AEs were more willing to accept the risk of cosmetic changes (83 vs. 58%, P=0.02), temporary discomfort (79 vs. 55%, P=0.02) and major toxicity (83 vs. 44%, P=0.001) compared with those who had not previously experienced AEs. CONCLUSIONS: Many rheumatoid arthritis patients are very concerned about potential drug toxicity. However, risk adversity appeared to be attenuated by past experience with AEs. Our results suggest that certain patients, especially those with milder disease activity, might be reluctant to accept commonly used arthritis medications if they are fully informed of their potential toxicity.     

Quantitative magnetic resonance imaging as marker of synovial membrane regeneration and recurrence of synovitis after arthroscopic knee joint synovectomy: a one year follow up study

OBJECTIVES: By repeated magnetic resonance imaging (MRI) to study synovial membrane regeneration and recurrence of synovitis after arthroscopic knee joint synovectomy in patients with rheumatoid arthritis (RA) and other (non-RA) causes of persistent knee joint synovitis. METHODS: Contrast enhanced MRI was performed in 15 knees (nine RA, six non-RA) before and one day, seven days, two months, and 12 months after arthroscopic synovectomy. Synovial membrane volumes, joint effusion volumes, and cartilage and bone destruction were assessed on each MRI set. Baseline microscopic and macroscopic assessments of synovitis and baseline and follow up standard clinical and biochemical examinations were available. RESULTS: Synovial membrane and joint fluid volumes were significantly reduced two and 12 months after synovectomy. However, MRI signs of recurrent synovitis were already present in most knees at two months. No significant differences between volumes in RA and non-RA knees were seen. Synovial membrane volumes at two months were significantly inversely correlated with the duration of clinical remission, for all knees considered together (Spearman's correlation r(s)=-0.67; p<0.05), for RA knees (r(s)=-0.76; p<0.05), and for non-RA knees (r(s)=-0.83; p<0.05). Baseline volumes were not significantly correlated with clinical outcome. Only three knees (all RA) showed erosive progression. The rate of erosive progression was not correlated with MRI volumes or with clinical or biochemical parameters. CONCLUSION: The synovial membrane had regenerated two months after arthroscopic knee joint synovectomy and despite significant volume reductions compared with baseline it often showed signs of recurrent synovitis. MRI seems to be valuable as a marker of inflammation, destruction and, perhaps, as a predictor of therapeutic outcome in arthritis.     

重组人Ⅱ型肿瘤坏死因子受体-抗体融合蛋白对炎性关节炎患者关节置换术后恢复的影响

目的 探讨重组人Ⅱ型肿瘤坏死因子受体-抗体融合蛋白(rhTNFR:Fc)对炎性关节炎患者关节置换术后恢复的影响.方法 回顾分析67例应用rhTNFR:Fc或传统改变病情抗风湿药(DMARDs)治疗的炎性关节炎患者行关节置换术后伤口感染发生例数、伤口愈合时间、炎症期时间(体温≥37.5 ℃)及抗生素应用时间.根据所应用药物分为rhTNFR:Fc组和传统DMARDs组.其中,rhTNFR:Fc组单用rhTNFR:Fc或rhTNFR:Fc联合传统DMARDs;传统DMARDs组单用或联合应用2种或2种以上传统DMARDs.统计学处理根据数据类型选择t检验或非参数检验.结果 67例患者中,rhTNFR:Fc组18例,传统DMARDs组49例.rhTNFR:Fc组1例出现伤口感染,传统DMARDs组0例,差异无统计学意义(P＞0.05).rhTNFR:Fc组炎症期时间为(4±3) d,传统DMARDs组为(3±3)d,差异无统计学意义(P＞0.05).rhTNFR:Fc组伤口愈合时间为(14.0±3.1)d,传统DMARDs组为(14.7±2.9)d,差异无统计学意义(P＞0.05).rhTNFR:Fc组术后抗生素应用时间为(14.8±9.3)d,传统DMARDs组为(10.3±2.7)d,差异有统计学意义(P＜0.05).结论 炎性关节炎患者围手术期应用rhTNFR:Fc不增加关节置换术后伤口感染发生率,不延长伤口愈合时间及炎症期时间.

Abstract：

Objective To investigate the affect of rhTNFR:Fc on the postoperative recovery of patients with inflammatory arthritis after arthroplasty. Methods Patients with inflammatory arthritis undergoing arthroplasty were included and divided into rhTNFR:Fc group (rhTNFR:Fc only or combined with conven-tional DMARDs) and conventional DMARDs group (monotherapy with or combination of conventional DMARDs). We retrospectively analyzed the incidence of postoperative infection, wound healing time, the febrile period (body temperature ≥37.5 ℃) and the duration of antibiotics treatment after arthroplasty. x2 test and t test were used for statistical analysis. Results Sixty-seven patients were included, 18 in the rhTNFR: Fc group and 49 in the conventional DMARDs group. One postoperative infection occurred in rhTNFR :Fc group but none in the DMARDs group. There was no significant difference by Fisher's exact test (P＞0.05). The febrile duration was (4±3) days in the rhTNFR :Fc group and (3±3) days in the conventional DMARDs group, the difference was not statistically significant (P＞0.05). The wound healing time was (14.0±3.1) days in the rhTNFR :Fc group and (14.7±2.9) days in the conventional DMARDs group, which was not statistically different(P＞0.05). The duration of antibiotics treatment after operation was (14.8±9.3) days in the rhTNFR: Fc group and (10.3±2.7) days in the conventional DMARDs group, the difference was statistically significant (P＜0.05). Conclusion Using rhTNFR:Fc during perioperative period in patients with inflammatory arthritis does not increase the risk of infectious complications or extending wound healing time and the febrile duration.     

改善病情抗风湿药治疗类风湿关节炎167例临床分析

目的 比较使用改善病情抗风湿药(DMARD)治疗类风湿关节炎(RA)的临床效果及对RA转归的影响,提高对DMARD治疗RA的认识和评价.方法 回顾性总结了1999年1月至2003年4月门诊有随访病历RA患者一般情况、临床症状及治疗情况.通过统计学分析比较单用、二联、三联治疗组(一联组、二联组、三联组)疾病临床缓解的差异;3组间远期疗效、双手正位X线的变化;队列比较各组中不同病程的疗效;同时比较各组药物不良反应.结果 共有256例患者初治选择了DMARD,除外89例合用激素者,共167例作为研究对象.3组近期疗效比较:红细胞沉降率和(或)C反应蛋白、缓解晨僵差异无统计学意义;对关节肿、痛,二联组和三联组优于一联组.3组近期疗效比较差异有统计学意义(X2=9.858,P=0.002).3组远期疗效比较差异有统计学意义(p=0.048);远期疗效与联合治疗有关(Spearman等级相关系数rs=0.228 43,P=0.0132;CMH非零相关统计量为6.059,P=0.014).初诊时不同病程的远期疗效比较差异有统计学意义(p=0.019).3组药物副作用差异无统计学意义.结论 早期联合使用DMARD治疗RA远期与近期疗效,均优于单一药物治疗.     

Newer disease-modifying antirheumatic drugs and the risk of serious hepatic adverse events in patients with rheumatoid arthritis

BACKGROUND: Spontaneous cases of hepatic adverse events have been reported in patients with rheumatoid arthritis who were being treated with leflunomide, one of the newer disease-modifying antirheumatic drugs (DMARDs). We assessed the risk of hepatic events associated with the use of leflunomide and other DMARDs. METHODS: Two cohorts comprising 41,885 patients with rheumatoid arthritis who had been dispensed a DMARD between September 1, 1998, and December 31, 2001, were formed using claims databases. Follow-up was from the first dispensing date to the occurrence of a serious or nonserious hepatic event. A nested case-control approach was used to estimate adjusted rate ratios of hepatic events associated with DMARDs dispensed during the prior year, as compared with methotrexate monotherapy. RESULTS: There were 25 cases of serious hepatic events (rate, 4.9 per 10,000 per year) and 411 nonserious hepatic events (rate, 80.0 per 10,000 per year). There was no increase in the rate of serious hepatic events with either leflunomide (rate ratio [RR] = 0.9; 95% confidence interval [CI]: 0.2 to 4.9) or traditional DMARDs (RR = 2.3; 95% CI: 0.8 to 6.5). However, the rate was increased with biologic DMARDs (RR = 5.5; 95% CI: 1.2 to 24.6). The rate of nonserious hepatic events was also increased with biologic DMARDs (RR = 1.5; 95% CI: 1.0 to 2.3), but not with leflunomide (RR = 0.9; 95% CI: 0.7 to 1.3) and traditional DMARDs (RR = 1.1; 95% CI: 0.8 to 1.4). CONCLUSIONS: We found no evidence of an excess risk of serious or nonserious hepatic events with the use of leflunomide as compared with methotrexate. Still, the increased risk observed with the new biologic DMARDs should be investigated further.     

Leflunomide in rheumatoid arthritis in daily practice: treatment discontinuation rates in comparison with other DMARDs

OBJECTIVE: To evaluate the treatment discontinuation rate of leflunomide in rheumatoid arthritis (RA) in comparison with the discontinuation of other disease modifying anti-rheumatic drugs (DMARDs), in daily practice, in a single center and during the same period of time. METHODS: Study design: 3-year, retrospective, monocenter. Patients: RA patients for whom leflunomide or another DMARD was initiated between 1998 and 2001 (several DMARDs could be initiated for a given patient during this period). Collected data: For each patient, demographic and disease data. For each treatment course, date of initiation, if relevant date of discontinuation and reason for discontinuation. Analysis: Percentage of patients discontinuing treatment over time (life table method; Kaplan-Meier), comparison between leflunomide and the "any other DMARD" or methotrexate groups using the Log-Rank test. RESULTS: During the study period, 515 DMARDs were initiated in 285 patients. Leflunomide was initiated in 161 patients who were older and had a longer disease duration than the other treated patients (59 +/- 13 years and 14 +/- 9 years versus 54 +/- 15 years and 11 +/- 10 years in the leflunomide group and other DMARDs group respectively). Discontinuation rate of leflunomide after 1 year was 56.7%, mainly because of adverse drug reactions (41.6%). The discontinuation rate whatever the reason and for toxicity was higher for leflunomide than for other DMARDs studied. However discontinuation for inefficacy was similar in both groups. CONCLUSION: This study conducted in conditions of daily practice when leflunomide was first available suggests a higher discontinuation rate of leflunomide because of adverse events when compared to other DMARDs.     

单次膝关节腔注射依那西普治疗炎性膝关节炎的随机、单盲、平行、对照临床研究

目的 评价单次膝关节腔内注射依那西普对类风湿关节炎(RA)和脊柱关节病(SpA)所致的膝关节炎的疗效与安全性.方法 随机、单盲、平行、阳性药(复方倍他米松)对照的临床试验.受试者为确诊RA或SpA并伴有至少一侧膝关节肿胀及积液,但X线显示膝关节无变形、无中重度骨破坏及关节间隙明显狭窄,入组前经常规改善病情的抗风湿药(DMARDs)治疗至少6周.受试者按2∶1比例随机分为试验组和对照组,分别予以目标膝关节腔穿刺,吸净关节积液后注射1次依那西普(25 mg)或复方倍他米松(2 ml).注射后第4周随访,评价疗效和不良反应.主要疗效指标为改良(纽约)特种外科医院(HSS)膝关节评分.结果 (1)试验组47例、对照组23例受试者入选本研究.(2)改良HSS膝关节评分试验组基线值为(65.6±14.0)分,治疗4周后为(84.3±11.1)分,治疗前后比差异有统计学意义(P＜0.0001);对照组基线值为(68.2±11.4)分,治疗4周后为(79.4±15.5)分,治疗前后比,差异有统计学意义(P=0.0015);试验组改良HSS膝关节评分改善率为(34.9±38.9)%,对照组为(17.9±24.5)%,2组比较差异有统计学意义(P=0.0467).(3)试验组有8例(19.0%)、对照组有8例(44.4%)受试者发生不良事件,有7例次被研究者判断为与使用研究药物有相关性,试验组有2例次(4.8%),分别为注射点轻度疼痛和月经提前;对照组有5例次(27.8%),分别为面部潮红,失眠,耳鸣,头昏、困倦,口干、口苦;2组比较差异有统计学意义(P=0.0352).无1例受试者因不良事件而退出试验,未发生结核感染和关节腔内感染,未发生严重不良事件.结论 单次膝关节腔内注射25 ng依那西普对X线改变不明显的炎性膝关节炎是一种有效、安全的治疗选择,其疗效优于2 ml复方倍他米松.     

Treatment of chronic knee synovitis with arthroscopic synovectomy after failure of intraarticular injection of radionuclide

Although satisfactory results have been obtained with conventional synovectomy of the knee, there are frequent complications, and a long period of rehabilitation is necessary after this surgery. We performed arthroscopic synovectomy of the knees of 30 patients (33 knees), 22 of whom had rheumatoid arthritis. These patients underwent the procedure after failure to respond to an intraarticular injection of either osmic acid or yttrium 90. The operated knee was moved 3-5 hours after the arthroscopy, and the patients walked the next day. No rehabilitation was needed. The followup period ranged from 6 months to 36 months, with an average of 17.7 months. Except for 1 patient with severe arthritis, all patients experienced improvement. Results were rated as "good" or "very good" in 27 knees. Six months after synovectomy, the patients were asked to rate their improvement; the mean +/- SEM degree of improvement was 79.1 +/- 22.9%. All patients had significant improvement in the range of motion of the knee. One patient required manipulation of the knee (while under anesthesia) soon after the arthroscopy. There were no other complications. There was no detectable radiographic evidence of disease progression in 24 patients who were seen 1 year after the procedure or in 9 patients who were seen 2 years after the arthroscopy. Thus, arthroscopic synovectomy appears to be an effective and simple treatment for chronic knee synovitis, and has a low morbidity rate.     

Disease-modifying anti-rheumatic drug use according to the 'sawtooth' treatment strategy improves the functional outcome in rheumatoid arthritis: results of a long-term follow-up study with review of the literature

OBJECTIVES: To investigate long-term functional outcomes of early rheumatoid arthritis (RA) patients treated actively with disease-modifying anti-rheumatic drugs (DMARDs) from diagnosis, according to the 'sawtooth' principle, and to compare the results to historical data. METHODS: The surviving 46 and 65 patients from two early RA cohorts were examined on average 13.0 (cohort 1) and 8.5 (cohort 2) yr, respectively, after onset of disease. Functional outcome was measured by the Health Assessment Questionnaire (HAQ) and compared with the HAQ scores of 57 RA patient cohorts found through a Medline computer search. RESULTS: The respective cross-sectional mean HAQ scores of cohorts 1 and 2 were 0.75 and 0. 55, and were more favourable than the mean HAQ scores of 1.27 (27 cohorts, disease duration >10 yr) and 1.13 (13 cohorts, disease duration 5-10 yr) of the comparator cohorts. The median time that our patients were treated with DMARDs out of the total follow-up period was 88%, while in the majority of comparator cohorts the use of DMARDs was less extensive or poorly described. CONCLUSIONS: The observation of better preserved function in patients with RA over 13 and 8.5 yr, compared to earlier reports which indicated more severe declines, is a hopeful sign for the rheumatology community.     

Intra-articular treatment with the TNF-alpha antagonist, etanercept, in severe diffuse pigmented villonodular synovitis of the knee

Pigmented villonodular synovitis (PVNS) is a rare pre-malignant disease that require aggressive treatment as surgical synovectomy, eventually followed by radiosynovectomy. Nevertheless, the disease often reoccurs after these treatments. To determine the safety and efficacy of intra-articular (IA) TNFalpha blockade with etanercept (ETN), before extended arthroscopic synovectomy, in severe PVNS of the knee, two patients, (a 26-year-old man with B27+ undifferentiated spondylarthropathy and a 32-year-old femal with seronegative oligoarthritis), affected by diffuse knee PVNS (diagnosis made by histological examination), resistant to IA corticosteroid injections and to repeated arthroscopic synovectomy, were submitted, after protocol approval by human research committee and patient's written informed consent to intra-articular etanercept (IA-ETN) treatment with a different dosage schedule: 12.5 mg weekly IA-ETN injection for 4 weeks, followed by extended arthroscopic synovectomy and of 25 mg IA-ETN injection for 4 weeks, respectively. Previous DMARDs treatment was continued in stable appropriate doses. Any adverse events were recorded throughout the study. The following parameters were considered as clinical endpoints: 1) Knee Joint Index (KJI: range 0-14); 2) Thompson index (THI: range 0-9) At the study entry and at the end of follow-up, high frequency ultrasound grey scale synovial thickening (US-ST) was also assessed. No adverse events were observed due to IA-ETN and to arthroscopic synovectomy. Marked improvement of knee disease activity over time and sustained functional recover was obtained. US-ST evaluation before treatment initiation and at the end of follow-up confirmed the regression of knee joint synovial proliferation.     

Immunohistological analysis of the synovial membrane: search for predictors of the clinical course in rheumatoid arthritis.

Immunohistological features which might predict the clinical course and outcome of rheumatoid arthritis were sought by examining multiple synovial membrane samples obtained by needle biopsy from the knee joints of 57 patients who had not received disease modifying antirheumatic drugs. Clinical measurements, but not biopsies, were repeated one year and three years after starting treatment. A correlation between both the intensity of synovial lining layer thickening and mononuclear cell infiltration and the clinical status at the time of biopsy was seen. After three years of treatment the correlations were maintained in patients who had presented and persisted with milder disease but not in patients who had presented with more active disease.