Comparison of in-office magnetic resonance imaging versus conventional radiography in detecting changes in erosions after one year of infliximab therapy in patients with rheumatoid arthritis

Abstract

The objective of this study was to compare standard hand radiographs with in-office 0.2?T magnetic resonance imaging (MRI) in monitoring response to therapy in patients with rheumatoid arthritis (RA) who were receiving infliximab, to evaluate the frequency and location of erosions, and to determine if there were differences in outcome based on disease duration at baseline. Patients who satisfied the American College of Rheumatology criteria for RA and were receiving infliximab therapy were evaluated with a baseline and 1-year follow-up MRI. Magnetic resonance images were interpreted by two blinded, board-certified radiologists. Bone erosions were identified as well-defined defects extending through the cortical margin. The mean age of the 48 patients was 58.5 years. The median infliximab dosage was 4?mg/kg. Baseline data showed that 41 patients had abnormal MRIs. The mean time between the baseline and follow-up MRI examinations was 10.5 months. Follow-up MRI revealed regression in 11 patients. Thirty-one patients had both MRIs and radiographs. Magnetic resonance imaging was approximately twice as sensitive as radiography in detecting erosions at baseline. In-office MRI was useful in monitoring disease response after the initiation of infliximab treatment. Magnetic resonance imaging is potentially a very valuable diagnostic tool and prognostic indicator for use in patients with RA.     

Assessment of structural damage progression in established rheumatoid arthritis by conventional radiography,computed tomography,and magnetic resonance imaging

Structural damage progression in patients with established rheumatoid arthritis (RA) has traditionally been assessed by conventional radiography (CR), which has proven its value in clinical practice and clinical trials over the past decades. The most prominent abnormalities visualized by CR in RA patients are erosions as a consequence of bone destruction and joint space narrowing (JSN) as a consequence of cartilage damage. Several validated scoring systems to quantify the structural joint damage and progression herein are available. Computed tomography and magnetic resonance imaging are newer, more sensitive methods for detection and monitoring of structural joint damage. A validated scoring system for magnetic resonance imaging of the hands and wrists exists, while no consensus has been reached on a scoring system for computed tomography. Structural damage identified by either CR or magnetic resonance imaging predicts a poorer disease course in patients with both early and established rheumatoid arthritis.     

Evaluation of changes in magnetic resonance images following 24 and 52 weeks of treatment of rheumatoid arthritis with infliximab,tocilizumab, or abatacept

Objectives. To compare MRI findings in rheumatoid arthritis (RA) patients treated with biologic disease-modifying anti-rheumatic drugs (DMARDs).

Methods. The study subjects were 43 RA patients treated with biologic DMARDs (13 with infliximab, 15 with tocilizumab, and 15 with abatacept). They were evaluated using Simplified Disease Activity Index (SDAI) and low-field extremity MRI at baseline, and at 24 weeks and 52 weeks of treatment.

Results. Synovitis scores were significantly lower by 24 weeks in all groups, compared with baseline (P < 0.05). Significant improvement in bone marrow edema (BME) scores were noted from baseline to 24 weeks in infliximab and abatacept groups (P < 0.05), but from 24 weeks to 52 weeks in tocilizumab group (P < 0.01). No significant change was found in erosion score. The synovitis score at baseline correlated significantly with SDAI at 24 weeks (P < 0.05), and the score at 24 weeks correlated significantly with SDAI at 52 weeks (P < 0.05).

Conclusions. The results suggest that the inflammatory improvement by infliximab and abatacept may express earlier than those by tocilizumab, despite similar improvement in SDAI. MRI-detected synovitis could be a useful predictor of SDAI at 24 weeks of treatment. The MRI remains the best tool to detect and assess the effects of biologic DMARDs in RA.     

New-onset demyelination induced by infliximab therapy in two rheumatoid arthritis patients

Therapies aimed at inhibiting tumor necrosis factor, a proinflammatory cytokine implicated in autoimmune disease, are effective for rheumatoid arthritis (RA) and Crohn’s disease. We report two patients who newly developed multiple demyelinating lesions in the central nervous system in the course of infliximab therapy for active RA. Neurological symptoms and the number of gadolinium-diethylenetriamine pentaacetic acid-enhanced lesions in magnetic resonance imaging gradually diminished with steroid treatment.     

Efficacy of radiosynovectomy of the knee in rheumatoid arthritis: Evaluation with magnetic resonance imaging

The intra-articular injection of a radiopharmaceutical agent (radiosynovectomy) produces a reduction of the synovial inflammatory process. The inflammed synovial membrane can be identified with magnetic resonance imaging after the intravenous administration of gadolinium (MRI-Gd). A 6-month prospective study was carried out in 10 patients with rheumatoid arthritis after radiosynovectomy of the knee. The efficacy was evaluated with clinical parameters and MRI-Gd. A progressive amelioration of synovial effusion, pain, articular range of mobility, total leucocytes count in synovial fluid and synovial membrane thickness through MRI-Gd was observed. The global efficacy was considered to be good in six patients, fair in three and bad in one. The study shows for the first time that MRI-Gd allows the evaluation of the response of the synovial membrane to radiosynovectomy.     

Utility of in-office extremity magnetic resonance imaging in rheumatology

Introductionof magnetic resonance imaging (MRI) in diagnosis and management of inflammatory arthritides has ushered robust changes in patient outcomes. The efficacy of MRI in detecting inflammation and damage together has raised the expectation of imaging in rheumatology. In-office extremity MRI (eMRI) systems, designed to image the peripheral joints of upper and lower extremities, are small enough to be used in clinics, have smaller fringe magnetic field, are less expensive, and reduce patient discomfort, with comparable diagnostic power. Though less sensitive in detecting osteitis, these systems have been shown to be effective in early diagnosis and monitoring of treatment outcome in patients with rheumatoid arthritis. This review focuses on eMRI systems, outlining their principle, utility in different inflammatory arthritides, and shortcomings.     

Magnetic resonance imaging versus musculoskeletal ultrasound in the evaluation of temporomandibular joint in rheumatoid arthritis patients

Aim of the work

To evaluate temporomandibular joint (TMJ) affection in rheumatoid arthritis (RA) patients by magnetic resonance imaging (MRI) versus musculoskeletal ultrasound (MSUS) and to correlate the findings with clinical manifestations, disease activity and functional status.

Analysis of subclinical synovitis detected by ultrasonography and low-field magnetic resonance imaging in patients with rheumatoid arthritis

Abstract

Objective To assess the utilities of ultrasonography (US) and low-field magnetic resonance imaging (compacTscan, cMRI) in the diagnosis of subclinical synovitis of hand joints of patients with rheumatoid arthritis (RA).

Methods A total of 1,540 joints of 77 RA patients were examined clinically, using US, using cMRI, and the baseline X-ray examination was performed. Clinical synovitis was defined as joint tenderness or swelling. Subclinical synovitis was diagnosed by US and by cMRI. The incidence of bone erosion and joint space narrowing was assessed by X-ray examination performed at approximately 40 weeks of follow-up.

Results Of the hand joints examined, 294 (19.1 %) were diagnosed with clinical synovitis, and 218 joints (14.1 %) were diagnosed with subclinical synovitis. The remaining 1,028 joints (66.8 %) were synovitis-free on clinical examination and imaging. For the diagnosis of subclinical synovitis, cMRI (11.4 %) was significantly more sensitive than power Doppler signals detected by US (US-PD; 6.8 %) (P < 0.01), and the combination of US-PD and cMRI was more useful (14.1 %) than US-PD or cMRI alone (P < 0.05). Follow-up X-ray examination of 600 joints showed a significantly higher incidence of bone erosion in joints with subclinical synovitis than in synovitis-free joints (P < 0.05).

Conclusion US-PD and cMRI are useful for detecting subclinical synovitis in patients with RA. Subclinical synovitis of the small joints of the hand can progress to bone destruction.     

Histological changes in bone marrow after treatment of infliximab for rheumatoid arthritis

To investigate histological evidence of bone remodeling in response to infliximab for rheumatoid arthritis (RA), bone marrow tissues were extracted from ten RA patients at the time of total knee arthroplasty after treatment of infliximab for an average of 16 months (range, 8–24 months). The patients had a mean age of 65.3 years (range, 57–76 years) with 4.8 mg/week of methotrexate (MTX; 4–6 mg) and 3.8 mg/day of prednisolone (2–5 mg). Control samples were obtained from ten RA patients who did not undergo infliximab therapy. These patients had an average age of 67.6 years (range, 59–78 years) and received 5.2 mg/week of MTX (4–6 mg) and 4.0 mg/day of prednisolone (2–5 mg). Histological examination of structural differences between the infliximab and control groups in bone marrow was performed using hematoxylin and eosin (H & E) to evaluate differences. In immunohistochemical examination, the expressions of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), receptor activator of nuclear (kappa) B ligand (RANKL), osteoprotegerin (OPG), and osteopontin (OPN) were compared between both groups. H & E staining revealed that the bone marrow tissues of the RA patients who underwent infliximab therapy demonstrated newly formed thickness of interstitial septum among the trabeculae as compared with the control group. Moreover, immunohistochemical examinations revealed that TNF-α, IL-6, RANKL, OPG, and OPN were expressed in this newly formed bone after infliximab therapy. Therefore, treatment with infliximab improved the histological changes with respect to bone metabolism in the newly formed bone marrow tissues.     

Synovial membrane enhancement and bone erosion by magnetic resonance imaging for prediction of radiologic progression in patients with early rheumatoid arthritis

Objective The aim of this study was to determine the prognostic factors related to radiographic progression in patients with early rheumatoid arthritis (RA) (less than 1 year after onset) undergoing enhanced MRI at entry.Methods Demographic characteristics, disease duration, and enhanced MRI of the dominant wrists were recorded at entry. Duration of morning stiffness, number of swollen joints, serum rheumatoid factor (RF), erythrocyte sedimentation rate, C-reactive protein (CRP) level, and radiographs of hands and feet (Sharp/van der Heijde score) were assessed at each follow-up. Outcome was defined as damage seen on radiography.Results One hundred fourteen patients were followed up for 10 years. Logistic regression analysis showed that high MRI score, CRP, and RF positivity were associated with radiologic progression. The MRI score at baseline was a better predictor than CRP level and RF positivity at entry.Conclusion The assessment of synovial membrane enhancement and bone erosion by MRI of the wrist in early RA is very helpful to predict erosive outcome.     

The effect of infliximab on chemokines in patients with rheumatoid arthritis

Rheumatoid arthritis (RA) is an autoimmune disease characterized by infiltration of lymphocytes, macrophages, and plasma cells into synovial membrane. The chemokines family promotes chemotactic activity in various leukocyte cell types. Chemokines thus play an essential role in the pathological formation of RA. The aim of the present study was to evaluate the influence of infliximab on serum levels of various chemokines. Twenty-four RA patients were involved in this study, which took place between March 2003 and February 2006. Infliximab was administered by intravenous infusion at a dosage of 3 mg/kg. All patients underwent general and physical examinations and routine blood and urinary analysis at the baseline, at 14 weeks, and at 30 weeks after the initial treatment. To determine whether serum and synovial fluid from RA also contained significant levels of chemokines compared with osteoarthritis patients (OA), GRO-α, MIP-1α, MIP-1β and regulated on activation normal T cell expressed and secreted (RANTES) levels of serum and synovial fluid were measured by ELISA in 20 RA patients and 20 OA patients. GRO-α, MIP-1β, and RANTES levels were significantly higher in RA compared with normal volunteers, while MIP-1α levels showed no significant differences. The mean GRO-α levels in serum from RA patients treated with infliximab decreased significantly after the initial treatment. The mean RANTES and MIP-1β levels did not change significantly after the treatment. Infliximab treatment significantly lowered the serum GRO-α levels of RA patients. GRO-α is one of the crucial cytokines affected by infliximab treatment. The blocking therapy of RANTES and MIP-1β combined with infliximab treatment may have an additional effect without competition in the TNFα cascade.     

Confirmation of effectiveness of tocilizumab by ultrasonography and magnetic resonance imaging in biologic agent-naïve early-stage rheumatoid arthritis patients

Efficacy of tocilizumab in active early-stage RA patients despite methotrexate was evaluated for 12 months. One out of 5 patients was quitted by infusion reaction whereas tocilizumab continued for 12 months in the remaining 4 patients. Power Doppler articular synovitis was reduced in every patient and disappeared in 2 patients. Marked MRI osteitis, found in 1 patient, had disappeared at 12 months. Present results confirm the efficacy of tocilizumab by ultrasonography and MRI.     

Efficacy of mizoribine pulse therapy in patients with rheumatoid arthritis who show a reduced or insufficient response to infliximab

The efficacy of infliximab, a chimeric antibody against tumor necrosis factor-α used to treat patients with rheumatoid arthritis (RA), tends to decrease as patients develop human antichimeric antibody against infliximab (HACA). The clinical study reported here was designed to evaluate the efficacy of mizoribine (MZR) pulse therapy in patients who show a reduced or insufficient response to infliximab. Ten RA patients who had active arthritis despite infliximab therapy were treated with MZR pulse therapy at a dose of 100 mg MZR and methotrexate (MTX) and the disease activity assessed at baseline and at weeks 4–8, 12–16, and 20–24. The dose was increased to 150 mg in those patients who showed an insufficient response to MZR. The mean 28-joint disease activity score (DAS28) at weeks 12–16 and 20–24 of therapy was significantly lower than that at baseline. A moderate or good European League against Rheumatism (EULAR) response was achieved in seven patients (70%) at weeks 12–16 and in five patients (50%) at weeks 20–24. The dose of 150 mg MZR was effective in one of the three patients who showed an insufficient response to pulse therapy with 100 mg MZR. Based on these results, we propose that MZR pulse therapy should be attempted before the patient is switched to other biologics.     

Discontinuation of infliximab in rheumatoid arthritis patients in clinical remission

Biologic drugs are effective but are also expensive, and it is difficult to evaluate the duration of treatment. Infliximab, an anti-TNFα antibody, suppresses arthritic activity and inhibits bone destruction in patients with rheumatoid arthritis (RA). Here, we document that infliximab could be discontinued after clinical remission in RA patients. Among 172 patients with RA who reached clinical remission following infliximab (3 mg/kg) and methotrexate (MTX, >6 mg/w), nine patients with sustained remission discontinued it. Clinical assessment was based on a disease activity score (DAS) that included a 28-joint count/erythrocyte sedimentation rate (DAS28-ESR). The disease was assessed before and after the start of infliximab treatment, and concomitant drug treatment—in the order of corticosteroid, nonsteroidal anti-inflammatory drugs (NSAIDs), and disease-modifying anti-rheumatic drugs (DMARDs) other than MTX—was gradually discontinued. We considered patients for discontinuation of infliximab treatment after remission (DAS28-ESR < 2.6) had been sustained for more than 24 weeks. The nine patients able to discontinue treatment were all females, with a mean age of 53.8 years; eight patients were at stage I or II. The mean duration of disease was 28.7 months, and these patients were on corticosteroid treatment equivalent to a mean of 2.28 mg prednisolone (PSL). These nine patients all met the remission standard—that DAS28-ESR < 2.6 for ≥24 weeks) —and so their treatment with concomitant drugs was discontinued. After the discontinuation of infliximab, the mean period of sustained remission was 14.2 months and the longest period was 29 months. The duration of disease was significantly shorter and the points from Steinbrocker’s stage-classification were significantly lower in the infliximab-discontinued group than in the infliximab-continued group. Strategic reductions and/or discontinuations of concomitant treatment were performed in RA patients who attained clinical remission (DAS28 < 2.6) through treatment with infliximab and MTX. Nine patients successfully discontinued infliximab after maintaining clinical remission for more than 24 weeks. After infliximab was discontinued, clinical remission and suppression of joint destruction were maintained with MTX alone, especially in early RA patients.     

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.     

Discontinuation of infliximab in rheumatoid arthritis patients in clinical remission

Abstract

Biologic drugs are effective but are also expensive, and it is difficult to evaluate the duration of treatment. Infliximab, an anti-TNFα antibody, suppresses arthritic activity and inhibits bone destruction in patients with rheumatoid arthritis (RA). Here, we document that infliximab could be discontinued after clinical remission in RA patients. Among 172 patients with RA who reached clinical remission following infliximab (3 mg/kg) and methotrexate (MTX, >6 mg/w), nine patients with sustained remission discontinued it. Clinical assessment was based on a disease activity score (DAS) that included a 28-joint count/erythrocyte sedimentation rate (DAS28-ESR). The disease was assessed before and after the start of infliximab treatment, and concomitant drug treatment—in the order of corticosteroid, nonsteroidal anti-inflammatory drugs (NSAIDs), and disease-modifying anti-rheumatic drugs (DMARDs) other than MTX—was gradually discontinued. We considered patients for discontinuation of infliximab treatment after remission (DAS28-ESR < 2.6) had been sustained for more than 24 weeks. The nine patients able to discontinue treatment were all females, with a mean age of 53.8 years; eight patients were at stage I or II. The mean duration of disease was 28.7 months, and these patients were on corticosteroid treatment equivalent to a mean of 2.28 mg prednisolone (PSL). These nine patients all met the remission standard—that DAS28-ESR < 2.6 for ≥24 weeks) —and so their treatment with concomitant drugs was discontinued. After the discontinuation of infliximab, the mean period of sustained remission was 14.2 months and the longest period was 29 months. The duration of disease was significantly shorter and the points from Steinbrocker’s stage-classification were significantly lower in the infliximab-discontinued group than in the infliximab-continued group. Strategic reductions and/or discontinuations of concomitant treatment were performed in RA patients who attained clinical remission (DAS28 < 2.6) through treatment with infliximab and MTX. Nine patients successfully discontinued infliximab after maintaining clinical remission for more than 24 weeks. After infliximab was discontinued, clinical remission and suppression of joint destruction were maintained with MTX alone, especially in early RA patients.     

Etanercept response in patients with rheumatoid arthritis after secondary loss of efficacy of infliximab

Abstract

This study was carried out to determine the effectiveness of half-dose administration of etanercept in patients with rheumatoid arthritis (RA) who exhibited secondary loss of efficacy of infliximab. Seventeen patients were administered 25 mg of etanercept once weekly for at least 1 year after secondary loss of efficacy of infliximab. The mean duration of treatment with infliximab was 32.5 ± 1.3 months. The patient cohort consisted of 3 males and 14 females, with a mean age of 56.3 ± 11.4 years and mean weight of 57.2 ± 10.9 kg. The mean duration of RA was 16.2 ± 10.9 years. The mean Disease Activity Score 28 was decreased significantly, from 5.8 at the initiation of infliximab therapy to 3.6 at the end of observation. There were no withdrawals due to adverse reactions during the study period, although in 2 subjects the agent was changed to tocilizumab due to lack of effect, one after 18 months and the other after 36 months, and 1 subject withdrew after 18 months for financial reasons. A good response can be expected to a half dose of etanercept in patients with secondary loss of efficacy of infliximab. Reduction of the patient’s cost burden also makes this a superior treatment.     

Antibodies against cyclic citrullinated peptides in patients affected by rheumatoid arthritis before and after infliximab treatment

To evaluate antibodies against cyclic citrullinated peptides (anti-CCP) together with rheumatoid factor (RF), antinuclear antibodies (ANA) and C-reactive protein (CRP), in patients affected by rheumatoid arthritis (RA), before and after infliximab treatment. Twenty-seven patients (five men and 22 women, mean age of 51.9 years, mean duration of disease 12.6 years) affected by RA, refractory to conventional DMARDs, were treated with infliximab, at the conventional dosage. Before starting infliximab and after 22 weeks, on the occasion of the fifth infusion, anti-CCP antibodies were tested by ELISA method. At the same time IgM RF, ANA and CRP level were measured. Before infliximab therapy, anti-CCP antibodies resulted positive in 23 patients (85.1%); the serum level did not change after infliximab treatment; only one case negative at baseline became slightly positive after treatment. Before and after therapy RF resulted positive in 22 cases (81.4%) and 21 cases (77.7%) respectively; comparing values at baseline with those after 22 weeks of treatment with infliximab, RF levels significantly decreased, as well as CRP values. In contrast to both anti-CCP antibodies, which remained stable, and to RF, which fell after infliximab, ANA were positive 1: 160 in four cases at baseline and in 12 after treatment. The titre of anti-CCP antibodies did not significantly change after anti-TNF blocker administration; instead the positivity of RF significantly decreased. As opposed to antinuclear and anti-dsDNA antibodies, which may appear or increase in titre during infliximab treatment, the typical autoantibodies detectable in RA show a different trend; in fact, anti-CCP antibodies remained stable and RF decreased.     

Improved response to infliximab after leukocytapheresis in a patent with rheumatoid arthritis

This is the first report on effective leukocytapheresis (LCAP) in an acquired infliximab (IFM) resistant patient with rheumatoid arthritis (RA). A 44-year-old Japanese woman with RA was treated with prednisolone, cyclosporine A, and methotrexate, which failed to stabilize the disease. Infliximab was then administered and the disease activity was controlled on December 2003. However, RA became active again on June 2004 so that LCAP was administered weekly for 5 weeks. After the LCAP treatment, the ACR20% response was obtained again and IFM has regained its efficacy.