Magnetic resonance imaging for accelerated assessment of drug effect and prediction of subsequent radiographic progression in rheumatoid arthritis: a study of patients receiving combined anakinra and methotrexate treatment

OBJECTIVES: By MRI to assess the efficacy of addition of anakinra for controlling synovitis and stopping erosive progression in patients with clinically active RA despite receiving methotrexate, and to determine the predictive value of MRI for subsequent radiographic erosive progression. METHODS: 100 mg anakinra subcutaneously/day was added to the treatment of 17 patients with clinically active RA despite methotrexate. MRI of the non-dominant wrist and 2nd-5th MCP joints (OMERACT evaluation) was performed at weeks 0, 12, and 36, and radiography of both hands and wrists (modified Sharp evaluation) at weeks 0 and 36. RESULTS: MRI synovitis scores were not significantly changed. Radiography of both hands and wrists after 36 weeks showed erosive progression in 11 patients, and MRI after 12 weeks in 10 patients. Nine of 10 patients with MRI progression at 12 weeks had radiographic progression at 36 weeks. Baseline MRI synovitis and erosion scores, but no clinical/biochemical parameters, correlated significantly with subsequent erosive progression. CONCLUSION: Addition of anakinra did not significantly reduce MRI signs of synovitis, and most patients had progressive joint destruction. Baseline MRI findings predicted subsequent radiographic erosive progression. Unilateral wrist and MCP joint MRI after 12 weeks had a similar sensitivity for detection of erosive progression as bilateral hand and wrist radiography after 36 weeks.     

No erosive progression revealed by MRI in rheumatoid arthritis patients treated with etanercept,even in patients with persistent MRI and clinical signs of joint inflammation

The aim of this study is to investigate the course of magnetic resonance imaging (MRI) signs of inflammatory and destructive changes in rheumatoid arthritis (RA) wrist and metacarpophalangeal (MCP) joints during etanercept treatment. MRI of the non-dominant wrist and second to fifth MCP joints was performed in five clinical active RA patients before and 4 and 16 weeks after initiation of etanercept treatment. MRI was evaluated according to the EULAR–OMERACT RA MRI reference image atlas. The median 28-joint count disease activity score (DAS28; erythrocyte sedimentation rate based) was 5.6 (range 5.0–6.8) at baseline and 3.5 (1.5–4.1) at week 16 (decreased in all patients compared to baseline, Wilcoxon–Pratt, p < 0.05). The median MRI synovitis score was 18 (14–21), 18 (10–20) and 16 (10–20) at baseline, week 4 and 16, respectively (decreased in all patients compared to baseline, Wilcoxon–Pratt, p < 0.05), while corresponding MRI bone oedema scores were 4 (0–13), 3 (0–9) and 1 (0–3; NS). The median MRI bone erosion score was 27 (11–111; NS) at all time points. Four patients had identical total bone erosion scores at baseline and week 16, whereas one patient showed a reduced score. In conclusion, one patient showed erosive regression, while no patient showed erosive progression on MRI during 16 weeks of etanercept therapy; even though clinical and MRI signs of joint inflammation remained. This small study supports that erosive progression judged by MRI is minimal in RA patients treated with etanercept, even in joints with persistent inflammation.     

Clinical outcome and imaging changes after intraarticular (IA) application of etanercept or methylprednisolone in rheumatoid arthritis: magnetic resonance imaging and ultrasound-Doppler show no effect of IA injections in the wrist after 4 weeks

OBJECTIVE: To assess the magnetic resonance imaging (MRI) and ultrasound (US) changes in the wrist of patients with rheumatoid arthritis (RA) 4 weeks after an US guided intraarticular (IA) injection. METHODS: Contrast enhanced MRI and US-Doppler were performed at baseline and 4 weeks after IA injection of either 40 mg methylprednisolone (n = 12) or 25 mg etanercept (n = 13) in 25 patients with RA taking disease modifying antirheumatic drugs with a therapy-resistant wrist joint. All injections were US guided. RESULTS: There was an improvement in swollen target joint score (p < 0.001), tender target joint score (p < 0.002), and physician visual analog scale score (p < 0.001) after 4 weeks. Baseline MRI synovitis score was mean 5.08 (range 3-9) and was unchanged at followup in the whole group (p = 0.52) and between treatment groups (p = 0.43). MRI edema score (mean 4.46, range 0-29) in the total group was unchanged after 4 weeks (p = 0.13), whereas MRI erosion score increased in the total group from baseline, 17.88 (range 7-40), to 4 weeks, 18.25 (range 7-40) (p < 0.001). Neither US-Doppler color fraction (0.07) nor Resistive Index (RI) (p = 0.36) changed from baseline to 4 week followup. CONCLUSION: In contrast to the clinical evaluation, imaging measures of relevance for the estimation of inflammation, US-Doppler, US RI, MRI synovitis, and bone-marrow edema did not change 4 weeks after a single IA injection of either methylprednisolone or etanercept in the wrist. Within the same period, erosive progression in some patients suggested that joints with active disease may deteriorate within as little as 1 month, and that this development is not arrested by 1 injection. Given the small sample size of our study further studies are required to confirm our results.     

双重滤过血浆置换联合免疫抑制剂治疗对重度活动性类风湿关节炎患者磁共振成像的影响

目的 探讨双重滤过血浆置换(DFPP)联合免疫抑制剂(来氟米特+甲氨蝶呤)治疗对重度活动性类风湿关节炎(RA)患者磁共振成像(MRI)的影响.方法 纳入58例RA患者,病程6个月至12年,采用计算机自动生成的随机号,将患者随机分为治疗组和对照组.对照组予以来氟米特10 mg,每日2次,甲氨蝶呤15 mg,每周1次;治疗组在对照组治疗的基础上予以DFPP治疗3～4次,每次问隔7～14 d.随访至6个月.通过右腕关节MRI平扫加增强观察基线和治疗1、6个月时滑膜炎、关节腔积液及骨髓水肿的变化,应用RA磁共振评分标准(RAMRIS)判断对MRI滑膜炎的影响.组内比较采用配对t检验,组间比较采用独立样本t检验.结果 治疗组6个月时滑膜、血管翳、骨髓水肿计分分别为(1.4±1.6)、(0.13±0.35)、(5±4),显著低于对照组[分别为(7.9±1.3)、(2.76±0.43)、(16±12),P均<0.01];治疗组30例(100%)关节腔积液均消失,对照组无一例消失(P<0.01).治疗组达到MRI滑膜炎完伞缓解(滑膜、血管翳见强化,关节腔无积液)+疾病活动指数(DAS)28缓解标准的为16例(53%),对照组无一例达到此标准(P<0.01).1个月时治疗组DAS28、健康评估问卷(HAQ)分别由(7.5±1.0)、(2.23±0.58)下降至(3.5±1.2)、(0.50±0.73),差异有统计学意义(P<0.01);MRI影像滑膜、血管翳、关节腔积液、骨髓水肿无明显变化(P>0.05).结论 DFPP联合免疫抑制剂治疗对重度活动性RA MRI滑膜炎症有明显缓解作用.MRI对疾病活动的判断及治疗方案的选择可作为必要的手段之一.     

Diagnostic value of magnetic resonance imaging of the forefeet in early rheumatoid arthritis when findings on imaging of the metacarpophalangeal joints of the hands remain normal

OBJECTIVE: To investigate the diagnostic role of magnetic resonance imaging (MRI) of the forefeet in patients with early rheumatoid arthritis (RA) in whom findings on MR images of the hands are normal and conventional radiographs of the hands and feet do not show erosions. METHODS: The study group comprised 25 patients with early RA (disease duration of <12 months) in whom erosions were not demonstrated on conventional radiographs of the hands and feet. These patients underwent MRI of the clinically dominant hand to detect signs of arthritis. If results of MRI of the hand were normal according to the Outcome Measures in Rheumatology Clinical Trials (OMERACT) RA-MRI scoring system (RAMRIS), MRI of the dominant forefoot was performed. The MRI protocol comprised coronal and sagittal T1-weighted spin-echo (before and after administration of contrast medium), coronal fat-suppressed short tau inversion recovery sequences, coronal and sagittal T2-weighted turbo spin-echo sequences, and axial fat-suppressed T1-weighted spin-echo sequences after administration of contrast medium. MRI of the forefeet was analyzed on the basis of a modified RAMRIS. RESULTS: MRI revealed pathologic findings in the hands of 15 of 25 patients (edema in 9 patients, synovitis in 12, erosions in 6, defects in 3). In 10 patients with a mean disease duration of 9.4 weeks, hand MRI scans were normal according to RAMRIS. Four of these 10 patients had tenosynovitis of the finger flexor tendons (there was no OMERACT criterion for tenosynovitis). RAMRIS analysis of the corresponding MRI scans of the forefeet of these patients revealed signs of edema in 7 patients, synovitis in all 10 patients (at the third metatarsophalangeal [MTP] joint in 7, at the fourth MTP joint in 6, at the first MTP joint in 4, and at the fifth MTP joint in 2 patients), tenosynovitis of the foot flexor tendons in 2 patients, erosions at the second and third MTP joints in 1 patient, and a single defect at the first MTP joint in 1 patient. CONCLUSION: RAMRIS analysis of MRI scans of the forefeet detected synovitis and bone edema in patients with early RA in whom MRI of the finger joints was normal. MRI of the forefeet contributes an additional tool aimed at earlier and more accurate diagnosis and thus might allow an earlier decision to start appropriate medication in patients with early RA.     

Community-based evaluation of etanercept in patients with rheumatoid arthritis

OBJECTIVES: Etanercept is one of a new subgroup of biological disease modifying antirheumatic drugs (DMARD) to treat patients with rheumatoid arthritis (RA) who are non-responsive or intolerant to conventional DMARD. We evaluated the effects of etanercept (Enbrel) therapy in patients with RA in community-based clinical practice in Canada. METHODS: Using a cohort design, patients requesting etanercept therapy were stratified into treatment and control arms based upon their individual accessibility to obtain the drug. Patients were interviewed serially during a 12-month period of monitoring. The study measured painful or tender joint count, morning stiffness, pain severity, quality of life measures, medication utilization, health services utilization, and presence of adverse events. RESULTS: The baseline demographic and clinical variables for the treatment group (n = 223) and the control group (n = 208) were similar, except for education, income, and drug plan coverage. In followup, there was greater improvement in most clinical variables in the treatment arm compared to the control arm during the first 6 months, but the magnitude of difference between the 2 groups for some clinical variables decreased or became non-significant during the second 6 months. During the 12 month followup period there were 40 (18%) patient dropouts in the treatment group. CONCLUSION: In a community based setting for the treatment of RA, etanercept can effectively improve the disease state, functional class, work disability, and quality of life during the first 6 months of use. To determine the longterm sustainability of these effects studies with more than 12 months' duration will be required.     

Magnetic resonance imaging of the spine and the sacroiliac joints in ankylosing spondylitis and undifferentiated spondyloarthritis during treatment with etanercept

OBJECTIVE: To assess the changes in inflammatory lesions of the spine and the sacroiliac (SI) joints as detected by magnetic resonance imaging (MRI) in patients with ankylosing spondylitis (AS) and undifferentiated spondyloarthritis (uSpA) with predominant axial symptoms during treatment with etanercept. METHODS: MRI of the spine and/or the SI joints of patients with active AS or axial uSpA was performed at baseline (TP0, n = 25), after 6 weeks (TP1, n = 20), and after 24 weeks of continuous treatment with etanercept (TP2, n = 12). T1 weighted spin echo pre -(T1), post-gadolinium (T1/Gd-DTPA) and short tau inversion recovery (STIR) MRI sequences were used to assess chronic and active spinal lesions using the scoring system ASspiMRI. Active and chronic SI lesions were assessed using a simple scoring system. RESULTS: By use of the definite STIR sequence, significant regression of spinal inflammation was already seen already after 6 weeks in the patients treated with etanercept (mean (SD) 11.2 (13.8) at TP0 v 6.8 (7.9) at TP1; p = 0.023) but not in patients treated with placebo. Continuous treatment with etanercept for 24 weeks reduced active spinal changes by 69% (p = 0.012). T1/Gd-DTPA sequences gave similar results. There was only a trend for a decrease of active inflammatory lesions of the SI joints. CONCLUSIONS: Etanercept treatment in patients with active AS and uSpA leads to regression of active inflammatory lesions of the spine as depicted by MRI. The potential role of etanercept on deceleration of chronic spinal changes needs further study.     

Magnetic resonance imaging examinations of the spine in patients with ankylosing spondylitis before and after therapy with the tumor necrosis factor alpha receptor fusion protein etanercept

OBJECTIVE: To assess spinal inflammation by magnetic resonance imaging (MRI) before and after treatment with the tumor necrosis factor receptor fusion protein etanercept compared with placebo. METHODS: As part of a recently published randomized, controlled trial, 40 patients with ankylosing spondylitis (AS) underwent MRI of the lower thoracic and lumbar spine at 4 different time points: baseline, 12 weeks, 24 weeks, and 48 weeks. Nineteen patients received subcutaneous etanercept twice weekly (25 mg twice daily) for 1 year, and 21 patients received placebo for 6 months before being switched to etanercept. The mean age of the patients was 39.7 years, 75% were male, 89% were HLA-B27 positive, and the mean disease duration was 13 years. MRI examinations included T1-weighted sequences before and after application of gadolinium-diethylenetriaminepentaacetic acid (Gd-DTPA) and T2-weighted fat-saturated sequences. MRI sequences were scored with an adjusted AS spinal MRI score, using predefined vertebral units (VUs) as a basis. RESULTS: After 12 weeks, spinal inflammation (as assessed by T2-weighted MRI with fat saturation) regressed by 54% in the etanercept group (mean score 1.33 per VU at baseline and 0.61 per VU at 12 weeks; P = 0.002) but worsened by 13% in the placebo group (0.94 at baseline and 1.06 at 12 weeks) (P < 0.001 between groups). After switching to etanercept, placebo patients improved similarly. T1-weighted Gd-DTPA MRI sequences performed equally well in detecting spinal changes. At baseline, >50% of all active lesions were detected in the thoracic spine. Deterioration of chronic changes was significant only in patients treated with placebo. CONCLUSION: Etanercept treatment of patients with active AS results in regression of spinal inflammation as assessed by spinal MRI. Inclusion of the thoracic spine in MRI examinations of patients with AS may be of particular importance.     

Evidence for a different anatomic basis for joint disease localization in polymyalgia rheumatica in comparison with rheumatoid arthritis

OBJECTIVE: The anatomic basis for joint disease localization in polymyalgia rheumatica (PMR) is poorly understood. This study used contrast-enhanced and fat suppression magnetic resonance imaging (MRI) to evaluate the relationship between synovial and extracapsular inflammation in PMR and early rheumatoid arthritis (RA). METHODS: Ten patients with new-onset PMR and 10 patients with early RA underwent dynamic contrast-enhanced MRI and conventional MRI of affected metacarpophalangeal (MCP) joints. Synovitis and tenosynovitis were calculated based on the number of enhancing voxels, initial rate of enhancement, and maximal enhancement of gadolinium diethylenetriaminepentaacetic acid (Gd-DTPA). Periarticular bone erosion and bone edema were scored according to the OMERACT (Outcome Measures in Rheumatology Clinical Trials) scoring system in both groups. The degree of extracapsular Gd-DTPA enhancement was assessed in both conditions using semiquantitative scoring. RESULTS: No significant differences were seen in the volume of synovitis (P = 0.294), degree of flexor tenosynovitis (P = 0.532), periarticular erosions (P = 0.579), or degree of bone edema (P = 0.143) between RA and PMR joints. However, despite comparable degrees of synovitis, the proportion of MCP joints showing extracapsular enhancement was higher in the PMR group (100%) than in the RA group (50%) (P = 0.030). One PMR patient, but none of the RA patients, had bone edema at the capsular insertion. CONCLUSION: Despite degrees of synovitis and tenosynovitis comparable with those in RA, PMR-related hand disease is associated with prominent extracapsular changes, suggesting that inflammation in these tissues is more prominent than joint synovitis, which is common in both conditions. This suggests that the anatomic basis for joint disease localization differs between RA and PMR.     

Persistent low grade synovitis without erosive progression in magnetic resonance imaging of rheumatoid arthritis patients treated with infliximab over 1?year

Disease remission is only reached by a minority of rheumatoid arthritis (RA) patients treated with infliximab. Radiological assessment reported in clinical trials support the view that even under persistent inflammatory activity there is no further structural damage. Magnetic resonance imaging (MRI) allows a highly accurate detection of synovitis, bone edema, and erosions, constituting the ideal instrument for the evaluation of treatment response. The goal of this study was to evaluate MRI changes over 1 year in RA patients treated with infliximab. Four RA patients refractory to methotrexate (MTX) therapy were treated with infliximab 3 mg/kg 8/8 weeks and followed up for 1 year. Disease Activity Score (DAS28) was measured in the day of each infliximab administration. MRI was performed at baseline, 3 months, and 1 year. A simplified OMERACT RA MRI scoring (RAMRIS) was applied to the dominant wrist: synovitis (0–3) was measured in the intercarpal–carpometacarpal joints (CMTJ); bone edema (0–39) and erosions (0–130) in the base of the metacarpal and wrist bones. Baseline DAS28 was superior to 3.2 in all patients (ranging from 4.8 up to 6.2). At 14 weeks, DAS28 was still superior to 3.2 (ranging from 3.5 up to 4.6) and at 46 weeks all patients have responded, however without having achieved clinical remission, as DAS28 was still above 2.6 (ranging from 2.6 up to 3.4). MRI showed that synovitis was reduced in all patients to a score of 1, bone edema was slightly reduced (10% reduction), and erosive score was unchanged (baseline values ranging from 2 up to 20). Despite persistent low disease activity, these four RA patients treated with infliximab had stable simplified RAMRIS erosive scores over 1 year. These results support the view that there might be an uncoupling process between inflammation and bone erosions when tumor necrosis factor alpha is targeted in RA.     

Etanercept and adalimumab treatment in patients with rheumatoid arthritis and spondyloarthropathies in clinical practice: adverse events and other reasons leading to discontinuation of the treatment

In the present study, we determined from a single-center data the treatment continuation, discontinuation and reasons for discontinuation in the patients with active rheumatoid arthritis (RA) or spondyloarthropathies (SpA) who were treated with etanercept or adalimumab. All RA and SpA patients, who were treated with etanercept (n = 53) or adalimumab (n = 43) as their first biological treatment according to national guidelines in the Center for Rheumatic Diseases, Tampere University Hospital during the years 1999–2005, were analyzed at baseline and after 1-year treatment. The treatment was regarded ineffective if the clinical response was lower than ACR50 in RA or the reduction of BASDAI was lower than 50% or 2 cm in SpA. After 1 year, the continuation rate was 74% with etanercept and 60% with adalimumab. Mean prednisolone dose among continuers was diminished by 52% in etanercept-treated patients and by 44% in adalimumab-treated patients. During 1-year follow-up, 14 (26%) of the etanercept-treated patients and 17 (40%) of the adalimumab-treated patients discontinued the medication. Eleven patients were regarded as poor responders, seven in etanercept group and four in adalimumab group. Adverse events (mainly infections and injection reactions) caused six discontinuations in etanercept-treated group and 11 discontinuations in adalimumab-treated group. Etanercept was discontinued due to other adverse event in two patients: in one patient due to adenocarcinoma of ovary and in one patient due to drug-related leukopenia. One patient treated with adalimumab developed clinical and immunological features of systemic lupus erythematosus (SLE). In the present study, etanercept and adalimumab treatments were started in patients who had active RA or SpA despite ongoing treatment with combinations of traditional disease modifying antirheumatic drugs (DMARDs). Thirty-nine (74%) patients and twenty-six (60%) patients achieved at least 50% response when etanercept or adalimumab was added to their earlier DMARD treatment. Adverse events (mainly infections and injection reactions) were in line with previous reports. Three rare adverse events were reported: one patient with ovarial carcinoma, one with leukopenia and one with features of drug-induced SLE.     

Prognostic factors in a large cohort of patients with early undifferentiated inflammatory arthritis after application of a structured management protocol

OBJECTIVE: Inflammatory arthritis of the hands is a frequent clinical presentation with a variable outcome. Patients not satisfying the classification criteria for recognized arthritides are described as having undifferentiated inflammatory arthritis, for which there are no accepted therapeutic algorithms. This study assessed the clinical outcome of patients with undifferentiated arthritis of the hands after use of a treatment algorithm, and evaluated the prognostic features in these patients. METHODS: One hundred consecutive patients with undifferentiated arthritis of the hands were assessed following use of a pragmatic treatment algorithm that was based on clinical presentation and response to treatment. The following standard step-up treatment protocol was used: 1) nonsteroidal antiinflammatory drugs (NSAIDs), 2) a single dose of corticosteroid administered by either intramuscular or intraarticular injection, and 3) disease-modifying antirheumatic drugs (DMARDs). Patients with specific rheumatologic diagnoses were excluded. The primary outcome was persistence of synovitis at 12 months. RESULTS: Seventy-eight percent of patients received NSAIDs, 72% received corticosteroids, and 30% received DMARD therapy. Among patients who had synovitis at 12 months, the prevalence of rheumatoid factor (RF) seropositivity, swollen joints, and synovitis at baseline was greater than in those without persistent synovitis. Logistic regression analysis showed baseline investigations to be poor predictors of subsequent DMARD use, with the best predictor being persistence of synovitis at 12 weeks. Rheumatoid arthritis (RA) developed in 14 patients. Logistic regression analysis showed that significant predictors of RA were RF seropositivity and the painful joint count at baseline. No patient who experienced resolution of synovitis by 12 weeks had persistent synovitis that subsequently required DMARD therapy. Only 13% of patients entered remission. Early resolution of synovitis was associated with an excellent prognosis. CONCLUSION: Undifferentiated arthritis of the hands is not a benign condition, with 30% of patients receiving DMARD therapy by 12 months and low remission rates. Results of the clinical assessment at 12 weeks is the single best predictor of future therapy. This study provides background data for use in determining future therapeutic interventions.     

Response of early active rheumatoid arthritis to tumor necrosis factor inhibitors: evaluation by magnetic resonance imaging

Inflammatory changes (synovitis and bone marrow edema) and destructive changes (bone erosion) were evaluated by magnetic resonance imaging (MRI) in patients with rheumatoid arthritis (RA), and their relations with disease activity were assessed during treatment with tumor necrosis factor (TNF) inhibitors. Ten patients with early active RA underwent MRI at 0 and 16 weeks of TNF-inhibitor treatment. The carpal bones of the dominant hand were evaluated by the outcome measures in rheumatology clinical trials MRI score for RA. After 16 weeks, the mean disease activity score (DAS 28) decreased significantly from 5.54 to 2.70, while the number of tender joints, number of swollen joints, and inflammatory parameters were also significantly improved. The mean synovitis and marrow edema scores determined by MRI showed a significant decrease from 6.1 to 2.2 and 12.8 to 6.2, respectively, while the annual bone-erosion progression score decreased from 12.6 to 2.0. Although synovitis persisted in some patients, imaging remission was achieved in two patients. In conclusion, TNF-inhibitor therapy achieved an early decrease of disease activity and MRI revealed amelioration of joint destruction. The MRI score for RA is useful for assessing the early response to TNF inhibitors.     

Rapid improvement in rheumatoid arthritis patients on combination of methotrexate and infliximab: clinical and magnetic resonance imaging evaluation

The objectives of this study was to assess, using clinical and magnetic resonance imaging (MRI) criteria, the efficacy of combination infliximab therapy in patients with active rheumatoid arthritis (RA) refractory to methotrexate (MTX) treatment and to ascertain whether the changes in MRI parameters correlate with the clinical response. Four infusions of infliximab (3 mg/kg) at weeks 0, 2, 6, and 14 were added to a stable background dose of MTX in 19 patients with active disease. Clinical parameters were assessed before each infusion and at week 14. Dynamic contrast-enhanced MRI examination of the most severely affected wrist was performed at baseline and week 14. Synovitis severity, volume of synovitis, and synovial perfusion indices were evaluated. Significant improvement in all clinical disease activity parameters was seen at week 14 with reduction in C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and DAS28. Sixty-eight percent of patients achieved ACR20. MRI disease activity parameters also significantly decreased after treatment with reduction in grading of synovitis, volume of active synovitis, and perfusion enhancement slope. Significant positive correlations were seen between the baseline volume of synovitis and the pain score (r=0.65), patient global score (r=0.68), and health assessment questionnaire (HAQ) score (r=0.46). In conclusion, addition of infliximab to methotrexate rapidly reduces inflammation in longstanding patients with RA. Assessment of enhancing synovial volume and perfusion indices on serial MRI examination was helpful in documenting the effect of treatment over this short period.     

Influence of long-term low-dose methotrexate therapy on periarticular and generalized osteoporosis in rheumatoid arthritis

Our objective was to evaluate the effect of low-dose methotrexate therapy on periarticular and generalized osteopenia in patients of rheumatoid arthritis (RA). Fifty-five women received one of four therapeutic regimens. The periarticular radial bone mineral density (BMD) was analyzed by dual energy X-ray absorptiometry. Generalized osteopenia was assessed by measuring the BMD and height of the lumbar spine (L₂-L₄). Vertebral deformity was also assessed on plain Xray film. Physical activity, age and menopausal status were similar among the four treatment groups. The decrease of lumbar BMD was greatest in the group given steroids plus another disease modifying antirheumatic drug (DMARD), followed by the steroid/methotrexate group, methotrexate group and the other DMARD group. The decreases of lumbar vertebral height was greatest in the steroid/methotrexate group, followed by the steroid/DMARD group, methotrexate group and the other DMARD group. Vertebral compression was found in 22% of the steroid/methotrexate group and 14% of the steroid/DMARD group. Radial periarticular BMD was significantly lower in patients with active wrist joint synovitis than in patients without synovitis, but was increased by methotrexate therapy. We conclude that low-dose methotrexate did not increase lumbar osteopenia or vertebral compression in RA patients and might preven periarticular osteopenia by suppressing synovitis     

Influence of long-term low-dose methotrexate therapy on periarticular and generalized osteoporosis in rheumatoid arthritis

Abstract

Our objective was to evaluate the effect of low-dose methotrexate therapy on periarticular and generalized osteopenia in patients of rheumatoid arthritis (RA). Fifty-five women received one of four therapeutic regimens. The periarticular radial bone mineral density (BMD) was analyzed by dual energy X-ray absorptiometry. Generalized osteopenia was assessed by measuring the BMD and height of the lumbar spine (L₂-L₄). Vertebral deformity was also assessed on plain Xray film. Physical activity, age and menopausal status were similar among the four treatment groups. The decrease of lumbar BMD was greatest in the group given steroids plus another disease modifying antirheumatic drug (DMARD), followed by the steroid/methotrexate group, methotrexate group and the other DMARD group. The decreases of lumbar vertebral height was greatest in the steroid/methotrexate group, followed by the steroid/DMARD group, methotrexate group and the other DMARD group. Vertebral compression was found in 22% of the steroid/methotrexate group and 14% of the steroid/DMARD group. Radial periarticular BMD was significantly lower in patients with active wrist joint synovitis than in patients without synovitis, but was increased by methotrexate therapy. We conclude that low-dose methotrexate did not increase lumbar osteopenia or vertebral compression in RA patients and might preven periarticular osteopenia by suppressing synovitis     

A randomized, double-blinded, placebo-controlled clinical trial of LY333013, a selective inhibitor of group II secretory phospholipase A2, in the treatment of rheumatoid arthritis

OBJECTIVE: To evaluate the efficacy and safety of a selective inhibitor of secretory phospholipase (sPLA2), LY333013, in the treatment of rheumatoid arthritis (RA). METHODS: Two hundred and fifty-one patients with active RA despite treatment with one or more disease modifying antirheumatic drugs (DMARD) received oral doses of LY333013 (50, 250, and 1000 mg) or placebo once daily for 12 weeks. Concomitant low-dose glucocorticoids (< or = 10 mg/day prednisone equivalent) were allowed. Clinical improvement was assessed using the response criteria of the American College of Rheumatology (ACR20), and safety was evaluated with respect to adverse events and laboratory test abnormalities. RESULTS: The demographic characteristics of the treatment groups were similar. Dose-response relationships were found for ACR20 responses (p = 0.058) and reductions in C-reactive protein (p = 0.058) at week 1. The proportions of patients with an ACR20 response subsequently increased in all study groups including the placebo group at weeks 4 and 8, and the initial treatment benefit was lost. Adverse events were generally mild in severity and not associated with treatment. CONCLUSION: Treatment with LY333013 for 12 weeks was well tolerated but ineffective as an adjunct to DMARD treatment of active RA.     

Daily practice effectiveness of a step-down treatment in comparison with a tight step-up for early rheumatoid arthritis

OBJECTIVE: To study prospectively the daily practice effectiveness of a step-down early rheumatoid arthritis (RA) treatment strategy. METHODS: Patients with severe RA and no contra-indications were proposed step-down therapy, the others step-up. Step-down patients received a modified combination therapy in early RA (COBRA) regimen: sulphasalazine (SPS), 2 g daily, and methotrexate (MTX), 15 mg weekly, combined with step-down oral prednisolone (start 60 mg daily, fast tapering to 7.5 mg over 6 weeks, discontinuation from week 28). At week 40, patients were randomized to maintenance therapy with either SPS or MTX if disease activity score-28 (DAS28) was acceptably low. The step-up group started disease-modifying anti-rheumatic drug (DMARD) monotherapy. In both groups, treatment was adjusted at follow-up, based on DAS28. DAS28, functionality Health Assessment Questionnaire (HAQ), adverse events, DMARD changes and steroid use were registered 4-monthly for 2 yrs. RESULTS: Nineteen patients received step-down and 52 step-up treatment. More patients completed the first year without unplanned DMARD changes and without dosage adjustment and fewer had DMARD changes due to side effects or inefficacy in the step-down group compared with step-up, whereas the number of adverse events was comparable. MTX proved to be the most effective maintenance therapy after step-down. The DAS response, proportion of patients in remission, HAQ response and proportion of patients without disability at 4 months was higher in the step-down group. CONCLUSIONS: In daily practice, a step-down treatment strategy for early RA is more effective than a step-up approach.     

Comparison of OMERACT-RAMRIS scores and computer-aided dynamic magnetic resonance imaging findings of hand and wrist as a measure of activity in rheumatoid arthritis

The purpose of this study was to compare the value of conventional magnetic resonance imaging (MRI) finding of rheumatoid arthritis (RA) and computer-aided dynamic MRI measurements in predicting the activity of disease. The activity of the disease in 40 RA patients was evaluated by the disease activity score in 28 joints (DAS28). The conventional MRI of the wrists of all patients were scored for bone edema, synovitis and erosions, according to the criteria of RA-MRI scoring system (RAMRIS) developed by Outcome measures in rheumatology clinical trials (OMERACT) MR Imaging Group. Synovitis was also quantified by dynamic postcontrast MRI imaging using color coded maximum slope of increase maps and measurements of early enhancement rate (EER) and relative enhancement (RE). Twenty-two (55 %) patients with a score higher than 5.1 constituted the high disease activity group, 18 (45 %) patients with a score of 5.1 or less constituted moderate disease activity group. The dynamic MRI-EER score was the most significant parameter to differentiate between the groups (p = 0.001). Among OMERACT scores, only bone edema [p = 0.020 for wrist and p = 0.037 for metacarpophalangeal joints (MCP)] had a significant difference between the two groups. Dynamic MRI RE score and OMERACT scores for erosions and synovitis for both the wrist and MCP joints did not differ significantly between the two groups. Computer-aided dynamic MRI is a reliable, noninvasive method of evaluating the RA patients, which correlates with the DAS28 scores, at a higher significance than the OMERACT-RAMRIS scores.     

Regional variation and differential response to therapy for knee synovitis adjacent to the cartilage-pannus junction and suprapatellar pouch in inflammatory arthritis: implications for pathogenesis and treatment

OBJECTIVE: To use magnetic resonance imaging (MRI) to investigate the importance of knee joint synovitis at the cartilage-pannus junction (CPJ) in rheumatoid arthritis (RA) as compared with synovitis at a distant site in the suprapatellar pouch (SPP) and as compared with CPJ synovitis in the spondylarthropathies (SpA), and to assess the relative response of knee joint synovitis to therapy at the CPJ and SPP sites. METHODS: Dynamic contrast-enhanced MRI (DEMRI) of actively involved knee joints in 24 patients (13 with RA and 11 with SpA) was undertaken. The area of synovitis was calculated at the CPJ and SPP regions of interest in patients with RA and in patients with SpA. Differences in CPJ and SPP synovitis were determined using calculated DEMRI parameters which included the initial rate of contrast enhancement (IRE) and the maximal enhancement (ME). Changes in the synovial area at the CPJ and SPP were also measured in 10 patients with early RA, following treatment with disease-modifying antirheumatic drugs (DMARDs) (either methotrexate or leflunomide). RESULTS: In patients with RA or SpA, the area of synovitis was significantly larger immediately adjacent to the CPJ compared with a distant site at the SPP (in RA, mean synovitis area 162 mm2 at the CPJ versus 114 mm2 at the SPP [P = 0.010]; in SpA, mean synovitis area 214 mm2 at the CPJ versus 143 mm2 at the SPP [P = 0.002]), but the differences in the areas of synovitis at these sites were not significant between the RA and SpA patients. The IRE and ME values were also higher at the CPJ compared with the SPP, both in the RA patients (IRE P = 0.054, ME P = 0.018) and in the SpA patients (IRE P = 0.002, ME P = 0.001). A larger reduction in the area of synovitis was seen at the SPP compared with the CPJ following DMARD therapy in the RA patients (mean reduction 35% at the SPP [P = 0.023] and 12% at the CPJ [P not significant]). CONCLUSION: The non-disease-specific variations in synovitis and the differential responses to therapy in RA patients have implications for improving our understanding of CPJ synovitis. The results suggest that the pathophysiologic events at the CPJ reflect common anatomic, immune system, or biomechanical factors that play a role in modulating the severity of arthritis, and these events are not specific to RA since the same process was observed in other arthritides.