Comparison of ultrasonographic assessment of synovitis and joint vascularity with radiographic evaluation in a randomized, placebo-controlled study of infliximab therapy in early rheumatoid arthritis

OBJECTIVE: To investigate sensitive ultrasonographic imaging methods for detection of synovial thickness and vascularity to discriminate between patients with early rheumatoid arthritis (RA) receiving infliximab + methotrexate (MTX) versus placebo + MTX over 18 weeks, and to compare the relationship between synovial thickening and vascularity at baseline and radiologic damage to joints of the hands and feet at 54 weeks. METHODS: Patients with early RA (duration <3 years) receiving stable dosages of MTX were randomly assigned to receive blinded infusions of 5 mg/kg infliximab (n = 12) or placebo (n = 12) at weeks 0, 2, 6, and then every 8 weeks until week 46. At baseline and week 18, clinical assessments were performed, and metacarpophalangeal joints were assessed by high-frequency ultrasonography and power Doppler ultrasonography measurements. Radiographs of the hands and feet taken at baseline and at 54 weeks were evaluated using the van der Heijde modification of the Sharp method (vdH-Sharp score). RESULTS: Using changes in the total vdH-Sharp score over 54 weeks and changes in synovial thickening and joint vascularity at 18 weeks, we were able to distinguish those patients receiving infusions of infliximab + MTX from those receiving placebo + MTX. Sonographic measurements of synovial thickening and vascularity at baseline in the placebo + MTX group demonstrated clear relationships with the magnitude of radiologic joint damage at week 54. Infliximab + MTX treatment abolished these relationships. CONCLUSION: The delay or reversal of inflammatory and joint-destructive mechanisms in patients with early RA was already apparent following 18 weeks of treatment with infliximab + MTX and was reflected in radiologic changes at 54 weeks.     

Infliximab inhibits progression of radiographic damage in patients with active psoriatic arthritis through one year of treatment: Results from the induction and maintenance psoriatic arthritis clinical trial 2

OBJECTIVE: To evaluate the effect of infliximab on progression of structural damage over 1 year in patients with active psoriatic arthritis (PsA) enrolled in the Induction and Maintenance Psoriatic Arthritis Clinical Trial 2. METHODS: In this double-blind, placebo-controlled study, 200 patients with active PsA were randomly assigned (1:1 ratio) to receive infusions of infliximab (5 mg/kg) or placebo at weeks 0, 2, and 6, and every 8 weeks thereafter through week 54. At week 24, patients initially assigned to receive placebo crossed over to receive infliximab (5 mg/kg). Based on predefined criteria, patients randomized to receive placebo could enter early escape by receiving infliximab (5 mg/kg) starting at week 16, and patients randomized to receive infliximab could have the dose increased to 10 mg/kg starting at week 38. Patients were analyzed according to the treatment they were randomized to receive. Radiographs of hands and feet were obtained at baseline and at weeks 24 and 54. Two readers blinded to treatment assignment and radiograph sequence independently evaluated erosions and joint space narrowing using the Sharp/van der Heijde scoring method modified for PsA. RESULTS: At week 24, patients randomized to receive infliximab 5 mg/kg had significantly less radiographic progression compared with patients randomized to receive placebo, with mean +/- SD changes from baseline in the total Sharp/van der Heijde score of -0.70 +/- 2.53 and 0.82 +/- 2.62, respectively (P < 0.001). At week 54, mean +/- SD changes from baseline in the total Sharp/van der Heijde score were -0.94 +/- 3.40 in patients randomized to receive infliximab and 0.53 +/- 2.60 in those receiving placebo/infliximab (P = 0.001). CONCLUSION: Infliximab significantly inhibits radiographic progression in patients with PsA as early as 6 months after starting treatment, and the beneficial effect continues through 1 year of infliximab therapy.     

Predictors of joint damage in patients with early rheumatoid arthritis treated with high-dose methotrexate with or without concomitant infliximab: results from the ASPIRE trial

OBJECTIVE: To identify disease characteristics leading to progression of joint damage in patients with early rheumatoid arthritis (RA) treated with methotrexate (MTX) versus those treated with infliximab plus MTX. METHODS: Patients who had not previously been treated with MTX with active RA were randomly assigned to receive escalating doses of MTX up to 20 mg/week plus placebo or infliximab at weeks 0, 2, and 6, and every 8 weeks thereafter through week 46. Radiographic joint damage was assessed using the modified Sharp/van der Heijde score (SHS). The relationship between disease activity measures at baseline and week 14, as well as those averaged over time, were examined in relation to the change in SHS from baseline through week 54. RESULTS: C-reactive protein (CRP) levels, erythrocyte sedimentation rate (ESR), and swollen joint count were associated with greater joint damage progression in the MTX-only group, while none of these parameters was associated with progression in the infliximab plus MTX group. Mean changes in SHS among patients in the highest CRP (> or = 3 mg/dl) and ESR (> or = 52 mm/hour) tertiles in the MTX-only group were 5.62 and 5.89, respectively, compared with 0.73 and 1.12 in the infliximab plus MTX group (P < 0.001). Patients with greater joint damage at baseline (SHS > or = 10.5) showed less progression with infliximab plus MTX compared with MTX alone (-0.39 versus 4.11; P < 0.001). Patients receiving MTX alone who had persistently active disease at week 14 showed greater radiographic progression of joint damage than those taking MTX plus infliximab. CONCLUSION: High CRP level, high ESR, or persistent disease activity was associated with greater radiographic progression in the group taking MTX alone, while little radiographic progression was seen in patients receiving both MTX and infliximab, regardless of the abnormal levels of these traditional predictors.     

Combination of infliximab and methotrexate therapy for early rheumatoid arthritis: a randomized, controlled trial

OBJECTIVE: To compare the benefits of initiating treatment with methotrexate (MTX) and infliximab (anti-tumor necrosis factor alpha [anti-TNFalpha] monoclonal antibody) with those of MTX treatment alone in patients with rheumatoid arthritis (RA) of < or =3 years' duration. METHODS: RA patients were eligible if they had active disease and no prior treatment with MTX or a TNFalpha inhibitor. One thousand forty-nine patients were randomly assigned in a 4:5:5 ratio to 3 treatment groups: MTX-placebo, MTX-3 mg/kg infliximab, and MTX-6 mg/kg infliximab. MTX dosages were rapidly escalated to 20 mg/week, and infliximab or placebo infusions were given at weeks 0, 2, and 6, and every 8 weeks thereafter through week 46. RESULTS: At week 54, the median percentage of American College of Rheumatology improvement (ACR-N) was higher for the MTX-3 mg/kg infliximab and MTX-6 mg/kg infliximab groups than for the MTX-placebo group (38.9% and 46.7% versus 26.4%, respectively; P < 0.001 for both comparisons). Patients in the MTX-3 mg/kg infliximab and MTX-6 mg/kg infliximab groups also showed less radiographic progression than those receiving MTX alone (mean +/- SD changes in van der Heijde modification of the total Sharp score at week 54: 0.4 +/- 5.8 and 0.5 +/- 5.6 versus 3.7 +/- 9.6, respectively; P < 0.001 for each comparison). In addition, physical function improved significantly more in the MTX-3 mg/kg infliximab and MTX-6 mg/kg infliximab groups than in the MTX-placebo group. Infliximab therapy was associated with a significantly higher incidence of serious infections, especially pneumonia. CONCLUSION: For patients with active RA in its early stages, combination therapy with MTX and infliximab provides greater clinical, radiographic, and functional benefits than treatment with MTX alone.     

Evidence of radiographic benefit of treatment with infliximab plus methotrexate in rheumatoid arthritis patients who had no clinical improvement: a detailed subanalysis of data from the anti-tumor necrosis factor trial in rheumatoid arthritis with concomitant therapy study

OBJECTIVE: To assess the relationship between inflammation and joint destruction in rheumatoid arthritis (RA) patients who have not responded clinically to treatment. METHODS: Changes from baseline to week 54 in clinical variables and measures of radiographic progression were compared between patients who received infliximab (3 mg/kg or 10 mg/kg every 4 or 8 weeks) plus methotrexate (MTX) and those who received MTX plus placebo in the Anti-Tumor Necrosis Factor Trial in RA with Concomitant Therapy trial. RESULTS: At week 54, patients who did not show 20% improvement by American College of Rheumatology criteria (ACR20 nonresponders) while receiving infliximab plus MTX exhibited mild but statistically significant improvement in clinical variables, including the 28-joint Disease Activity Score (DAS28) (P < 0.001), tender joint count (P = 0.014), swollen joint count (P < 0.001), and C-reactive protein (CRP) level (P < 0.001). Whereas the clinical and CRP changes among ACR20 nonresponders to infliximab plus MTX were small and much lower than among ACR20 responders to this treatment, radiographic progression among ACR20 nonresponders to infliximab plus MTX was significantly inhibited (P < 0.001) compared with ACR20 nonresponders to MTX plus placebo. Radiographic progression was much greater in patients receiving MTX plus placebo than in patients receiving infliximab plus MTX, irrespective of ACR response status (mean change in modified Sharp/van der Heijde score 6.0 in ACR20 responders and 7.2 in ACR20 nonresponders in the MTX plus placebo-treated group, versus 0.1 in ACR20 responders and 1.2 in ACR20 nonresponders in the infliximab plus MTX-treated group). Furthermore, among patients who were ACR20 nonresponders through week 54, patients who were DAS nonresponders at weeks 30 and 54, and patients without any improvement in individual clinical variables, those receiving infliximab plus MTX still demonstrated inhibition of structural damage that was statistically significant compared with inhibition in patients who received MTX plus placebo (P < 0.05 to P < 0.001). CONCLUSION: Even in patients without clinical improvement, treatment with infliximab plus MTX provided significant benefit with regard to the destructive process, suggesting that in such patients these 2 measures of disease are dissociated.     

Overestimation of serum levels of rheumatoid factor caused by the presence of an incorrect calibrator in the Dade Behring kit

Abstract

The anti-TNF-α chimeric monoclonal antibody infliximab is the first biologic to be approved for rheumatoid arthritis (RA) in Japan, and post-marketing surveillance of all of the Japanese cases treated with infliximab has been conducted to explore the safety of infliximab therapy. In addition, a retrospective clinical study on the notable efficacy and related factors of infliximab therapy in an RA management group in Japan (RECONFIRM and RECONFIRM-2) has demonstrated clinical responses. However, information on the effect of infliximab on joint destruction in Japanese RA patients remains insufficient. In this study, we retrospectively analyzed X-ray data from 67 patients in whom both hand and foot X-rays at baseline and at 54 weeks had been available among the 410 cases in the RECONFIRM-2 study. By scoring the X-rays according to the modified van der Heijde (vdH)–Sharp method, we found that the total vdH–Sharp score in the RA patients before infliximab therapy was 104.40 ± 87.34 and the yearly progression was 21.33, indicating relatively rapid progression. After infliximab therapy for 54 weeks, the total vdH–Sharp score at 54 weeks was 104.37 ± 86.87 and the estimated yearly progression was ?0.03, indicating the almost complete inhibition of progression. The RECONFIRM-2J study confirmed the significant ability of infliximab to halt joint destruction in Japanese RA patients, and showed that joint destruction was significantly associated with disease activity and the dose of MTX in the patients with moderate and advanced disease durations, respectively, before infliximab therapy.     

Infliximab and methotrexate as induction therapy in patients with early rheumatoid arthritis

OBJECTIVE: To evaluate the efficacy of infliximab plus methotrexate (MTX) as induction therapy in patients with early rheumatoid arthritis (RA). METHODS: Disease-modifying antirheumatic drug (DMARD)-naive patients with active, early RA who were included as group 4 of the BeSt study were initially treated with infliximab (3 mg/kg) in combination with MTX (25 mg/week). The Disease Activity Score (DAS) was measured every 3 months. In patients with persistent low disease activity (DAS 2.4, the infliximab dosage was increased (maximum 10 mg/kg), and they were subsequently switched to another DMARD. Except for intraarticular administration, corticosteroids were not permitted. Functional ability and the modified Sharp/van der Heijde score were determined after 2 years of therapy. RESULTS: Of the 120 patients, 67 responders (56%) had persistent low disease activity and discontinued infliximab after a median of 9.9 months, with a median MTX dosage of 10 mg/week after 2 years. Ten other patients experienced a disease flare after discontinuation and resumed infliximab after a median of 3.7 months. Thirteen patients did not achieve persistent low disease activity and received infliximab at various dosages. Treatment was unsuccessful in 30 patients. In the 67 responders, the progression of joint damage was lower than in the 30 patients in whom treatment failed. CONCLUSION: Fifty-six percent of patients with active early RA, initially treated with infliximab plus MTX, could discontinue infliximab after achieving a DAS of 相似文献   

Retrospective clinical study on the notable efficacy and related factors of infliximab therapy in a rheumatoid arthritis management group in Japan: one-year outcome of joint destruction (RECONFIRM-2J)

The anti-TNF-α chimeric monoclonal antibody infliximab is the first biologic to be approved for rheumatoid arthritis (RA) in Japan, and post-marketing surveillance of all of the Japanese cases treated with infliximab has been conducted to explore the safety of infliximab therapy. In addition, a retrospective clinical study on the notable efficacy and related factors of infliximab therapy in an RA management group in Japan (RECONFIRM and RECONFIRM-2) has demonstrated clinical responses. However, information on the effect of infliximab on joint destruction in Japanese RA patients remains insufficient. In this study, we retrospectively analyzed X-ray data from 67 patients in whom both hand and foot X-rays at baseline and at 54 weeks had been available among the 410 cases in the RECONFIRM-2 study. By scoring the X-rays according to the modified van der Heijde (vdH)–Sharp method, we found that the total vdH–Sharp score in the RA patients before infliximab therapy was 104.40 ± 87.34 and the yearly progression was 21.33, indicating relatively rapid progression. After infliximab therapy for 54 weeks, the total vdH–Sharp score at 54 weeks was 104.37 ± 86.87 and the estimated yearly progression was −0.03, indicating the almost complete inhibition of progression. The RECONFIRM-2J study confirmed the significant ability of infliximab to halt joint destruction in Japanese RA patients, and showed that joint destruction was significantly associated with disease activity and the dose of MTX in the patients with moderate and advanced disease durations, respectively, before infliximab therapy.     

Limited efficacy of conventional DMARDs after initial methotrexate failure in patients with recent onset rheumatoid arthritis treated according to the disease activity score

OBJECTIVES: To determine the efficacy of subsequent disease modifying antirheumatic drug (DMARD) therapies after initial methotrexate (MTX) failure in patients with recent onset rheumatoid arthritis (RA), treated according to the DAS for 2 years. METHODS: In groups 1 and 2 of the BeSt study, 244 RA patients were initially treated with MTX 15-25 mg/week. Patients who discontinued MTX because of insufficient clinical response (disease activity score, DAS >2.4) or toxicity were classified as "MTX failures." In group 1, these patients switched to sulfasalazine (SSA), then leflunomide and finally to MTX + infliximab (IFX). In group 2, "MTX failures" added SSA to MTX, then hydroxychloroquine (HCQ), then prednisone, and eventually switched to MTX + IFX. "MTX successes" were patients who achieved a DAS 相似文献   

Infliximab treatment maintains employability in patients with early rheumatoid arthritis

OBJECTIVE: To evaluate the impact of infliximab therapy on the employment status of patients with early rheumatoid arthritis (RA). METHODS: Methotrexate (MTX)-naive patients with active early RA were randomly allocated to receive MTX plus placebo or MTX plus infliximab (3 mg/kg or 6 mg/kg) at weeks 0, 2, and 6 and then every 8 weeks through week 46. Data for patients younger than age 65 years were included in the analyses. A patient was categorized as employable if he or she was employed or felt well enough to work if a job were available. RESULTS: The change in actual employment was not significantly different between patients receiving MTX plus infliximab and those receiving MTX plus placebo (0.5% versus 1.3%; P > 0.5). However, the proportion of patients whose status changed from employable at baseline to unemployable at week 54 was smaller in the group receiving MTX plus infliximab compared with that in the group receiving MTX alone (8% versus 14%; P = 0.05). Patients who were treated with infliximab plus MTX had a significantly greater likelihood of improvement rather than deterioration in employability (odds ratio 2.4; P < 0.001); this likelihood was not significantly greater in patients receiving MTX alone. The proportion of employed patients who lost workdays during the trial was smaller in the MTX plus infliximab group than in the MTX-alone group (P = 0.010). CONCLUSION: The actual employment rates among patients in the 2 treatment groups were not different. However, patients with early RA who were treated with MTX plus infliximab had a higher probability of maintaining their employability compared with those who were treated with MTX alone.     

IgG and IgM anticardiolipin antibodies following treatment with infliximab plus methotrexate in patients with early rheumatoid arthritis

OBJECTIVE: To assess the occurrence of anticardiolipin antibodies (aCL) in patients with early rheumatoid arthritis (RA) receiving treatment with infliximab plus methotrexate (MTX) versus MTX alone. METHODS: The first 299 patients enrolled in the randomized, Active-Controlled Study of Patients Receiving Infliximab for the Treatment of Rheumatoid Arthritis of Early Onset (ASPIRE) trial who had baseline (week 0) samples available for aCL testing were included in this study. Sera were collected at weeks 0, 30, and 54 from 110 patients taking infliximab 3 mg/kg plus MTX, 98 patients taking infliximab 6 mg/kg plus MTX, and 91 patients taking placebo plus MTX. IgG and IgM aCL were measured using an anticardiolipin assay. RESULTS: IgG and IgM aCL positivity at baseline was similar in all treatment groups. Most patients were negative for IgG aCL at baseline and remained so at the last followup evaluation. One percent (2 of 208) of patients who received infliximab plus MTX and were negative for IgG aCL at baseline were positive for IgG aCL at weeks 30 and 54. A slightly higher proportion of patients who received infliximab plus MTX and were negative for IgM aCL at baseline were positive for IgM aCL at weeks 30 and 54 (4.8% [10 of 208]) as compared with patients who received placebo plus MTX (1.1% [1 of 91]), but the difference was not significant. CONCLUSION: There was a low incidence of the development of aCL in patients with early RA who received infliximab in combination with MTX, and the difference was not significant compared with patients who received placebo plus MTX.     

Reproducibility and sensitivity to change of 5 methods for scoring hand radiographic damage in patients with rheumatoid arthritis

OBJECTIVE: To compare intrarater and interrater reproducibility and sensitivity to change of 5 scoring methods for radiographic damage on hand radiographs in patients with rheumatoid arthritis (RA). METHODS: Radiographs of 22 patients from Norway and France with average 2 years' disease duration at baseline and mean 30 months' followup were assessed by 2 readers according to Larsen, Larsen/Rau, Sharp, Sharp/van der Heijde, and Simple Erosion Narrowing Score (SENS) methods. Reproducibility at baseline and on progression was assessed using intraclass correlation coefficients (ICC) and Bland-Altman graphs. Sensitivity to change was compared across methods by computing the country-adjusted standardized response means (SRM) ratio. RESULTS: Intrarater reproducibility varied with the reader (ICC ranging from 0.90 to 0.97), with Larsen and Larsen/Rau ranking highest. Interrater reproducibility was highest with Sharp and Sharp/van der Heijde (ICC 0.76 to 0.93). Bland-Altman graphs showed a decrease of concordance in cases of more severe damage. Sensitivity to change was higher with Sharp and Sharp/van der Heijde modified for erosions (SRM ratio 1.44 and 1.70), than with Larsen/Rau and SENS. The differences between Sharp, Sharp/van der Heijde, and Larsen were less for joint space narrowing. There was a significant reader effect (p < 0.05) in all but the Sharp method. Expressed as percentage of the maximum score, the smallest detectable difference varied between 3.5% (Sharp/van der Heijde) and 14.2% (SENS erosion). CONCLUSION: All methods have high intraobserver and interobserver reliability. The interrater reproducibility decreases with disease severity. Recent modified methods perform best to detect changes, but the advantages of SENS seemed to be lost when applied on hand radiographs alone. Training the readers appears to be essential.     

The safety of infliximab, combined with background treatments, among patients with rheumatoid arthritis and various comorbidities: a large, randomized, placebo-controlled trial

OBJECTIVE: To assess the risk of serious infections following 22 weeks of infliximab therapy, and to further characterize the safety profile of infliximab in combination with background treatments during 1 year in patients with rheumatoid arthritis (RA) with various comorbidities. METHODS: Patients with active RA despite receiving methotrexate (MTX) were randomly assigned to receive infusions of placebo (group 1, n=363), 3 mg/kg infliximab (group 2, n=360), or 10 mg/kg infliximab (group 3, n=361) at weeks 0, 2, 6, and 14. At week 22, patients in placebo group 1 began receiving 3 mg/kg infliximab, and patients in group 3 continued to receive an infliximab dose of 10 mg/kg. Patients in group 2 who failed to meet predefined response criteria received increasing doses of infliximab in increments of 1.5 mg/kg. RESULTS: At week 22, the relative risk of developing serious infections in groups 2 and 3, compared with group 1, was 1.0 (95% confidence interval [95% CI] 0.3-3.1, P=0.995) and 3.1 (95% CI 1.2-7.9, P=0.013), respectively. The incidence of serious adverse events was 7.8% in groups 2 and 3 compared with 7.5% in group 1. From week 22 to week 54, 11.8%, 9.9%, and 10.3% of patients in groups 1, 2, and 3, respectively, reported occurrences of serious adverse events. Through week 54, 1 patient in group 1, 2 patients in group 2, and 4 patients in group 3 developed active tuberculosis. CONCLUSION: The risk of serious infections in patients receiving the approved infliximab dose of 3 mg/kg plus MTX was similar to that in patients receiving MTX alone. Patients receiving the unapproved induction regimen of 10 mg/kg infliximab plus MTX followed by a 10 mg/kg maintenance regimen had an increased risk of serious infections through week 22.     

Changes in biomarkers of inflammation and bone turnover and associations with clinical efficacy following infliximab plus methotrexate therapy in patients with early rheumatoid arthritis

OBJECTIVE: To determine if changes in biomarkers of inflammation and bone turnover in response to treatment with infliximab plus methotrexate (MTX) versus MTX alone are associated with improvement in clinical measures of signs, symptoms, and structural damage in early rheumatoid arthritis. METHODS: Sera were collected from patients in the ASPIRE study who received 3 mg/kg (n = 48) or 6 mg/kg infliximab plus MTX (n = 55), or MTX alone (n = 41). Several baseline biomarker levels correlated with changes in median percentage of American College of Rheumatology improvement (ACR-N), 50% improvement in ACR response (ACR50), and van der Heijde-modified Sharp score (vdHSS) at Week 54. RESULTS: Infliximab plus MTX treatment resulted in more rapid decreases in levels of matrix metalloproteinase-3 (MMP-3), intercellular cell adhesion molecule-1, interleukin 8 (IL-8), and tumor necrosis factor-a than treatment with MTX alone. Baseline levels and decreases from baseline to Weeks 6 and 54 in MMP-3 correlated with improvement in ACR-N response at Week 54. An increase in IL-8 levels from baseline to Week 54 correlated with worsening in vdHSS at Week 54 in the MTX-alone group. Regression analysis of markers at baseline showed that MMP-3 was the only variable associated with ACR50 response and less worsening in vdHSS at Week 54. CONCLUSION: Treatment with infliximab plus MTX resulted in a rapid decrease in inflammation markers. MMP-3 levels at different timepoints were consistently associated with clinical improvements at Week 54 in the infliximab plus MTX group, while increases in IL-8 levels correlated with a worsening in vdHSS at Week 54 in the MTX-alone group.     

英夫利西单抗对类风湿关节炎患者外周血单核细胞CD147表达的影响

目的 探讨抗肿瘤坏死因子-α人鼠嵌合单克隆抗体英夫利西单抗(infliximab)治疗前后类风湿关节炎(RA)患者外周血单核细胞CD147表达的变化.方法 30例经甲氨蝶呤(MTX)治疗至少3个月病情仍处于活动期的RA患者按3:1:1比例由计算机程序产生随机分配方案分为A、B、C 3组,A组接受为期14周的英夫利西单抗(3 mg/kg)治疗;B组接受为期6周的英夫利两单抗(3 mg/kg)治疗;C组接受为期14周的安慰剂治疗.治疗期间继续口服原剂量的MTX.流式细胞术检测RA患者外周血CD14+单核细胞CD147平均荧光强度水平(MFI)变化,并观察其与临床相关指标的关系.数据采用SPSS 13.0软件进行单因素方差分析、Spearman相关分析和Kruskal-Wallis秩和检验.结果 ①治疗前RA患者外周血CD14+单核细胞CD147 MFI为(101±25),健康志愿者为(78±18),差异有统计学意义(P=0.019).RA患者外周血CD147 MFI与病情活动指标DAS28(r=0.471,P=0.000)、红细胞沉降率(ESR)(r=0.371,P=0.000)、C反应蛋IQ(CRP)(r=0.249.P=0.010)、晨僵持续时间(r=279,P=0.010)呈正相关.②3组患者治疗后外周血CD14+单核细胞CD147 MFI均有下降,第18周与基线相比,A组平均改变差值(-26.9±21.7)、B组平均改变差值(-35.4±15.5)与C组平均改变差值(-10.0±6.0)相比,差异有统计学意义(P<0.05).结论 活动期RA患者外周血CD14+单核细胞CD147表达增高;与单用MTX相比,英夫利西单抗联合MTX治疗CD147 MFI表达下降更明显.     

Radiographic progression in early rheumatoid arthritis: a 12-month randomized controlled study comparing the combination of cyclosporin and methotrexate with methotrexate alone

OBJECTIVE: To determine whether patients with early rheumatoid arthritis (RA) treated with cyclosporin A (CsA) and methotrexate (MTX) in combination for 12 months show a lower rate of radiographic deterioration than those treated with MTX alone. METHODS: In this controlled and randomized single-blind trial, 61 consecutive patients with untreated RA of less than 2 yr duration were treated with either CsA + MTX combination therapy (n = 30) or MTX alone (n = 31). The primary end-point was radiographic progression after 12 months, measured using the damage score (DS) of the Sharp and van der Heijde method. RESULTS: Although there was a significant difference between the mean baseline and 12-month DS in both treatment groups (MTX/CsA, 1.93 +/- 0.90; MTX, 7.47 +/- 2.03), it was significantly less in the combination arm (P = 0.018). Of the 30 evaluable CsA + MTX patients, 16 (53%) were ACR20 responders, 15 (50%) ACR50 and 14 (47%) ACR70; the corresponding figures in the MTX arm were 19 (61%), 13 (44%) and 6 (19%). Toxicity was acceptable in both groups. CONCLUSIONS: In patients with early RA, CsA + MTX combination therapy led to a significantly lower rate of 12-month radiographic progression, was effective on inflammatory articular symptoms, and was well tolerated.     

Hand bone loss in early rheumatoid arthritis during a methotrexate-based treat-to-target strategy with or without adalimumab—a substudy of the optimized treatment algorithm in early RA (OPERA) trial

This study aims to investigate 1-year hand bone loss (HBL_1-year) in early rheumatoid arthritis (RA) patients treated with a methotrexate (MTX) and intra-articular triamcinolone treat-to-target strategy +/? adalimumab and to determine if HBL_6months is associated with radiographic progression after 2 years. In a clinical trial (OPERA) of 180 treatment-naive early RA patients, bone mineral density (BMD) was estimated from hand radiographs with digital X-ray radiogrammetry (DXR) at baseline, after 6 (n = 90) and 12 months (n = 70) of follow-up. Baseline and 2-year radiographs were scored according to the Sharp/van der Heijde method. Baseline characteristics and HBL_6months (0–6 months changes in DXR-BMD) were investigated as predictors of structural damage by univariate linear (? total Sharp/van der Heijde score (TSS) as dependent variable) and logistic (+/?radiographic progression (?TSS >0) as dependent variable) regression analyses. Variables with p < 0.10 were included in multivariable models. In 70 patients with available HBL_1-year data, HBL_1-year was median (interquartile range (IQR)) ?1.9 (?3.3; ?0.26 mg/cm²) in the MTX + placebo group and ?1.8 (?3.6; 0.06) mg/cm² in the MTX + adalimumab group, p = 0.98, Wilcoxon signed-rank. Increased HBL (compared to general population reference values) was found in 26/37 and 23/33 patients in the MTX + placebo and MTX + adalimumab groups, chi-squared = 0.99. In 90 patients with HBL_6months data and 2-year radiographic data, HBL_6months was independently associated with ?TSS after 2 years (β = ?0.086 (95% confidence interval = ?0.15; ?0.025) TSS unit/mg/cm² increase, p = 0.006) but not with presence of radiographic progression (?TSS >0) (OR 0.96 (0.92–1.0), p = 0.10). In early RA patients treated with a methotrexate-based treat-to-target strategy, the majority of patients had increased HBL_1-year, irrespective of adalimumab; HBL_6months was independently associated with ?TSS after 2 years.     

英利昔单抗联合甲氨蝶呤治疗类风湿关节炎的随机双盲临床研究

目的评价英利昔单抗与甲氨蝶呤(MTX)联合使用与单独使用MTX,在治疗类风湿关节炎(RA)中的疗效与安全性。方法本研究为随机、双盲、平行对照的临床试验。49例接受过至少3个月稳定剂量MTX治疗的活动性RA患者随机分为试验组(24例)和对照组(25例)。两组受试者在第0、2、6、14周分别接受3mg/kg的英利昔单抗或安慰剂静脉滴注,同时每周按固定剂量继续服MTX。并于试验的第0、2、6、14、18周随访,评价疗效和不良反应。以美国风湿病学会(ACR)疗效评价指标ACR20为主要疗效指标,ACR50、ACR70、晨僵时间、关节肿胀数、关节肿胀指数、关节压痛数、关节压痛指数；次要疗效指标为疼痛目视模拟测量表(VAS)评分、疲乏VAS评分、疾病总体状况的医生评价VAS评分、疾病总体状况的病人评价VAS评分、健康评价问卷(HAQ)评分。结果治疗后第2周时,英利昔单抗联合MTX组ACR20有效率为62．5%,对照组仅为8．0%(P=0．002)；晨僵时间、关节压痛数、关节压痛指数、关节肿胀数、关节肿胀指数、疼痛VAS、疲乏VAS、医生总体评价VAS、病人总体评价VAS、HAQ和血沉等较对照组也均有显著的改善(P＜0．05或P＜0．01)。第18周时,英利昔单抗联合MTX组ACR20有效率为79．2%,对照组只有48．0%(P=0．024)。两组之间不良事件发生率差异无统计学意义。结论英利昔单抗联合MTX治疗RA的疗效明显优于单用MTX的疗效,能迅速改善与RA有关的各项症状、体征和实验室炎性活动指标,具有良好的安全性。     

Improvement of the HAQ score by infliximab treatment in patients with RA: its association with disease activity and joint destruction

Abstract

We conducted a two-year prospective study to clarify the efficacy of infliximab at improving the health assessment questionnaire (HAQ) score and associated factors in 67 patients with advanced rheumatoid arthritis (RA). All patients were scheduled to receive infliximab at a dose of 3 mg/kg at weeks 0, 2, 6 and every eight weeks thereafter through to week 102, and were fully examined at the time of each infusion. Parameters of disease activity such as the serum level of C-reactive protein (CRP), the serum level of matrix metalloproteinase-3 (MMP-3) and the 28-joint disease activity score (DAS28) were obtained, and the functional capabilities of the patients were assessed using the HAQ score. The serum CRP, the MMP-3, the DAS28(CRP) level, and the mean HAQ score decreased rapidly at two weeks after the start of infliximab treatment (CRP from 3.7 to 0.9 mg/dl, MMP-3 from 362.3 to 192.8 ng/ml, DAS28(CRP) from 5.6 to 3.7, and HAQ score from 1.5 to 0.9). Compared with the baseline values, the mean progression of the modified van der Heijde (vdH)–Sharp score after one year was 4.4 ± 5.8 (median: 3.0), and that after two years was 3.1 ± 6.9 (median: 1.0). A 93% reduction in the rate of joint destruction, as measured using the vdH–Sharp score, was estimated after infliximab therapy. Patients with less joint damage (shorter disease duration or lower vdH–Sharp score) regained more of their daily activities. The present study demonstrated the importance of activity control before the progression of irreversible factors, such as joint destruction, for maintaining the functional capacities of RA patients.     

Significant improvement in synovitis,osteitis, and bone erosion following golimumab and methotrexate combination therapy as compared with methotrexate alone: A magnetic resonance imaging study of 318 methotrexate‐naive rheumatoid arthritis patients

Objective

To evaluate the effects of golimumab on inflammation/structural damage detected by magnetic resonance imaging (MRI) in patients with rheumatoid arthritis (RA).

Methods

Methotrexate (MTX)–naive RA patients (n = 637) were randomized to placebo plus MTX, golimumab 100 mg plus placebo, golimumab 50 mg plus MTX, or golimumab 100 mg plus MTX (subcutaneous golimumab every 4 weeks). Of these, 318 patients participated in an MRI substudy. MRIs (contrast‐enhanced; 1.5T) of the wrist and second through fifth metacarpophalangeal joints of the dominant hand were obtained at baseline and weeks 12 and 24. MRIs were scored by 2 independent readers (blinded to image sequence/chronology, patient identity, and treatment group) for synovitis, bone edema/osteitis, and bone erosions using the Rheumatoid Arthritis Magnetic Resonance Imaging Scoring (RAMRIS) system. Radiographs (hands, wrists, forefeet at baseline and week 28) were scored by 2 other readers (blinded as above) using the modified Sharp/van der Heijde (SvdH) scoring system. Changes from baseline were compared between treatment groups (two‐sided analysis of variance on van der Waerden normal scores).

Results

At weeks 12 and 24, combined therapy with golimumab plus MTX versus placebo plus MTX significantly improved RAMRIS scores for synovitis (mean −1.92 versus 0.14 [P < 0.001] at week 12; −2.45 versus −1.04 [P < 0.001] at week 24), osteitis (mean −1.82 versus 0.56 [P < 0.001] at week 12; −2.27 versus −0.32 [P < 0.001] at week 24), and bone erosion (mean −0.40 versus 0.24 [P = 0.016] at week 12; −0.40 versus −0.24 [P = 0.010] at week 24). Results of sensitivity analyses (no missing doses/data and using linear extrapolation) were generally consistent with results of the primary analyses. Changes in SvdH scores among the MRI substudy patients at week 28 showed no significant difference between golimumab plus MTX therapy and placebo plus MTX (mean 0.49 versus 0.92; P = 0.19). Radiographic SvdH scores demonstrated inhibition of structural damage progression by treatment with golimumab plus MTX as compared with placebo plus MTX in the overall study population but required double the number of patients (637 versus 318) and double the length of followup (28 versus 12 weeks) as needed for MRI to demonstrate this.

Conclusion

Improvements in inflammation (synovitis and osteitis) and erosions with golimumab plus MTX therapy exceeded those with placebo plus MTX therapy from week 12 onward, confirming the overall clinical/radiologic findings. MRI was more sensitive than conventional radiography in detecting the progression of erosions.