Biomedical subjects

J Braun

Publications and source records attributed to J Braun.

At least 73 records · Page 4Linked to original sources

PubMed2004

Prediction of a major clinical response (BASDAI 50) to tumour necrosis factor alpha blockers in ankylosing spondylitis.

BACKGROUND: TNFalpha blockers have been shown to be highly efficacious in patients with active ankylosing spondylitis (AS). OBJECTIVE: To identify parameters predicting the clinical response to TNF blockers in AS. METHODS: Patients with active AS participated in two placebo controlled, randomised trials conducted in Germany with infliximab (n = 69) and etanercept (n = 30), respectively. For inclusion in either trial patients had to have high disease activity (BASDAI >or=4) and a spinal pain score (numerical rating scale 0-10) >or=4 despite treatment with NSAIDs. A major clinical response was defined as a 50% improvement of the initial BASDAI (BASDAI 50) after 12 weeks' treatment with active drug. Logistic regression likelihood ratio tests (univariate and multivariate), Student's t test, and chi(2) tests were performed. RESULTS: Univariate analysis showed the following to be predictors of a major response (BASDAI 50) to treatment: shorter disease duration (p = 0.003); lower BASFI (p = 0.007); younger age (p = 0.009); raised ESR (p = 0.033); raised CRP (p = 0.035). After adjustment for disease duration, BASFI, ESR, and CRP, but not age, remained significantly associated. After adjustment for disease duration and for BASFI, ESR, CRP, and in addition, a higher BASDAI were significantly associated with response. The best multivariate model built by stepwise regression contained the covariables disease duration, BASFI, BASDAI, and CRP. CONCLUSION: A shorter disease duration, younger age, and a lower BASFI are predictors of a major clinical response to TNF blockers in active AS. Raised CRP and a higher BASDAI may also be valuable predictors. These data need to be confirmed in further studies.

Adult↗

PubMed2004

[Fecal incontinence].

Diagnosis and management of fecal incontinence requires exact understanding of the anatomic and pathophysiologic principles involved and demands a methodical, stepwise approach. Despite the potential appeal of surgical intervention, a considerable number of patients can be helped by comparatively simple, noninvasive measures. Initial treatment should be medical, including biofeedback in combination with a bowel management program. In the presence of a severely denervated pelvic floor, physiotherapeutic techniques rarely give rise to a satisfactory and long-lasting response. Obvious external sphincter defects and patients who failed medical management are treated surgically. Many injuries of the external sphincter can be treated by direct sphincter repair. If patients with intact external sphincters are unresponsive to medical measures, descending perineum and resultant idiopathic fecal incontinence will improve by radio-frequency delivery, sacral nerve stimulation, or postanal plication. Patients with complex neurologic disorders or extensive sphincter defects or who have undergone previous unsuccessful attempts at repair of the puborectalis itself should be considered for dynamic gracilis plastic or an artificial sphincter.

Aged↗

PubMed2004

[Magnetic resonance tomography of sacroiliitis: anatomy, histological pathology, MR-morphology, and grading].

The diagnosis of spondyloarthropathy is based on radiography of the sacroiliac joints, beside the patient's history and clinical examination. In cases where the clinical examination and radiography yield discrepant findings, contrast-enhanced magnetic resonance imaging (MRI) is a sensitive modality for the diagnosis of early sacroiliitis. Knowledge of the morphologic anatomy of the sacroiliac joints and of their abnormal micro- and macroanatomy in sacroiliitis and enthesitis are helpful for interpreting MR images. Arthritis of the sacroiliac joints is characterized by subchondral sclerosis, erosions, transarticular bone bridges, accumulation of periarticular fat, juxta-articular osteitis, synovtis, capsulitis, and enthesitis. The major histologic finding in active sacroiliitis is the presence of proliferative, pannus-like connective tissue destroying cartilage and bone. This tissue contains fibroblasts and fibrocytes as well as T cells and macrophages with a shift of the CD4/CD8 ratio toward the CD4 T helper cell population. The well-established grading of MRI findings by means of a chronicity and activity index, which are determined quantitatively from dynamic MR images, is supplemented by an alternative, semi-quantitative grading of activity. The following grades were defined for the short tau inversion recovery (STIR) sequence or the T1-weighted, fatsaturated spin-echo sequence for each quadrant (iliac anterior, iliac posterior, sacral anterior, sacral posterior): 0: no signal increase, 1: local increase in the joint cavity or within erosions, 2: small areas of increased juxta-articular signal, 3: moderate sized areas of increased juxta-articular signal, 4: large areas of increased juxta-articular signal. Values of the 4 quadrants are summed to an activity score (range 0-16). The new grading system is proposed to facilitate the examination and shorten image interpretation time.

Diagnosis, Differential↗

PubMed2004

[Epidemiology and prognostic aspects of ankylosing spondylitis].

The spondyloarthritides (SpA) comprise ankylosing spondylitis (AS), psoriatic SpA (PsSpA), reactive SpA (ReSpA), arthritis associated with chronic inflammatory bowel disease (SpAIBD) and undifferentiated SpA (uSpA). There are characteristic clinical features of SpA: inflammatory back pain (IBP), asymmetric peripheral arthritis, enthesitis, anterior uveitis, positive family history and others. The SpA, mainly AS, are strongly associated with HLA B27. AS is the most frequent and potentially most severe subtype, next to PsSpA. The prevalence of all SpA is rather high and not much different from rheumatoid arthritis (RA) and AS patients carry a burden of disease similar to RA patients. The prognosis of AS has not been extensively studied but some factors have been identified. There is a clear role for imaging modalities in the diagnosis of AS. Changes in the sacroiliac joint as detected by radiography still constitute the basis for the diagnosis of AS (New York criteria 1984). A diagnosis of sacroiliitis as made by magnetic resonance imaging (MRI) provides more objective evidence to a diagnosis of IBP arguing in favour of SpA which is defined on the basis of the ESSG criteria 1991 mainly on a clinical basis. Radiographic spinal changes such as syndesmophytes are important for the staging and outcome of AS. MR based assessment of spinal changes in are now being increasingly used to assess disease activity of AS patients. The presence of spinal radiographic changes at time of presentation was found to be the best predictor of further deterioration using the score modified SASSS' in a recent study. Other clinical features such as hip arthritis, early onset of disease, dactylitis, oligoarthritis, limitation of spinal mobility and poor efficacy of nonsteroidal antiinflammatory drugs were found to also have negative prognostic value.

Diagnosis, Differential↗

PubMed2004

[Specialties in therapy of osteoporosis in inflammatory joint disease].

The therapeutic specialties of osteoporosis in inflammatory rheumatic diseases has gained mounting interest in the last year. The paper describes special aspects of osteoporosis in rheumatoid arthritis, ankylosing spondylitis and systemic lupus erythematodes. The problems of glucocorticoid therapy are discussed intensively with regard to the recently published recommendations for glucocorticoid-induced osteoporosis. Risk factors of osteoporosis and the therapeutic implications are demonstrated intensively as well as the modifications of the recommendations.

Arthritis, Rheumatoid↗

PubMed2004

[Measurement of quality of life in patients with active ankylosing spondylitis being treated with infliximab-a comparison of SF-36 and SF-12].

BACKGROUND: Quality of life as a part of the WHO definition of health is an important assessment tool for measuring the success in the treatment of chronic diseases. The short form 36 questionnaire (SF-36), which is measuring health related quality of life, was used in a multicentre placebo controlled study in patients with ankylosing spondylitis (AS) treated with the anti-TNF-alpha antibody infliximab. As previously reported, substantial changes of almost all outcome parameters were observed in this study because of the substantial clinical improvement that is known to occur in most patients treated with anti-TNF agents. The short form 12 questionnaire (SF-12) is shorter and quicker to complete as the SF-36. The summary scales of both questionnaires were compared in this study to answer the question whether the SF-12 can also be used in AS patient populations without too much loss of information. Using the shorter from could be an advantage for further studies in patients with AS, for example, the inception cohort for spondyloarthritides within the German Network of competence in rheumatology. Furthermore the data can be compared to the German standard population. METHODS: In this multicentre placebo controlled study 70 patients with active disease were enrolled: 35 AS patients received placebo, 35 were treated with infliximab, 5 mg/kg at week 0/2/6. Thereafter all patients were treated in an open study with infliximab at 5 mg/kg every 6 weeks. The disease activity (BASDAI), function (BASFI), mobility (BASMI), pain (NRS) and CRP as well as SF-36 were assessed. Data to calculate the SF-12 were extracted from the SF-36 questions and compared concerning agreement of individual levels, correlation with each other and with the BASFI, sensitivity to change and missing values. RESULTS: All outcome parameters for disease activity as well as all subscales of health related quality of life improved in patients with active AS treated with infliximab. The comparability of the sum components for SF-12 and SF-36 were high (physical health r=0.912 and mental health r=0.957). CONCLUSION: These data suggest that the shorter version of the SF-36, the SF-12, is capable to measure quality of life in clinical studies with AS patients.

Activities of Daily Living↗

PubMed2004

[Value of inpatient care in rheumatoid arthritis-an evidence based report].

Our aim was to analyze the existing body of evidence about inpatient care of patients suffering from rheumatoid arthritis (RA). The report was induced by the executive board of the German Society of Rheumatology which assigned the "Oliver-Sangha committee" to dissect and point out the tasks of inpatient care during the next few years. A systemic search of the literature was performed covering the years 1966 to 2001. A total of 16 studies were selected and thoroughly appraised in a systematic way. Four randomized controlled trials addressing the question could be identified. All of them included only patients in a clinical condition allowing outpatient care as well. Two studies indicate some advantage of inpatient care in comparison to outpatient treatment. Two studies, both equivalence studies from design, reveal that RA patients do not generally experience additional benefit from hospitalization. Consideration of two additional cohort studies demonstrates the increased need of inpatient care in RA patients. None of the studies was derived from the German health care system. Emergency cases were not the subject of any of these trials. General statements about the value of inpatient care of RA patients can not be drawn from the analyzed studies. The committee makes suggestions for future investigations that may help to answer this important question considering the special circumstances of the German health care system.

Ambulatory Care↗

PubMed2004

[Current therapy with TNFalpha blocking agents for ankylosing spondylitis and undifferentiated spondyloarthritis].

The Spondyloarthritides (SpA) comprise a group of inflammatory rheumatic diseases which mostly affect the spine and the larger peripheral joints. The most common entities in this group are ankylosing spondylitis (AS) and undifferentiated spondyloarthritis (uSpA). Treatments with disease-modifying or remission-inducing properties for patients with AS are so far not available. However, in the light of relevant individual and socioeconomic consequences this is an unmet medical need. Recently, etanercept in addition to infliximab has shown substantial efficacy which might even be disease controlling. For both TNFalpha blocking agents, large randomized placebo-controlled trials have proven their efficacy with an acceptable profile of adverse events. In open trials these drugs also work in patients with uSpA. There is some hope now that the TNFalpha blocking agents could stop the development of AS in patients starting with uSpA.

Antibodies, Monoclonal↗

PubMed2004

How to diagnose axial spondyloarthritis early.

BACKGROUND: Chronic low back pain (LBP), the leading symptom of ankylosing spondylitis (AS) and undifferentiated axial spondyloarthritis (SpA), precedes the development of radiographic sacroiliitis, sometimes by many years. OBJECTIVE: To assign disease probabilities and to develop an algorithm to help in the early diagnosis of axial SpA. METHODS: Axial SpA comprises AS and undifferentiated SpA with predominant axial involvement. Clinical features include inflammatory back pain (IBP), alternating buttock pain, enthesitis, arthritis, dactylitis, acute anterior uveitis, a positive family history, psoriasis, inflammatory bowel disease, and good response to NSAIDs. Associated laboratory findings include raised acute phase reactions, HLA-B27 association, and abnormalities on skeletal imaging. Sensitivities, specificities, and likelihood ratios (LRs) of these parameters were determined from published studies. A 5% prevalence of axial SpA among patients with chronic LBP was used. The probability of the presence of axial SpA, depending on the presence or absence of the above clinical features of SpA, was determined. A probability of > or = 90% was used to make a diagnosis of axial SpA. RESULTS: The presence of inflammatory back pain features increased the probability of axial SpA from the background 5% prevalence to 14%. The presence of 2-3 SpA features was necessary to increase the probability of axial SpA to 90%. The highest LRs were obtained for HLA-B27 and MRI. Diagnostic algorithms to be used in daily practice were suggested. CONCLUSIONS: This approach can help clinicians to diagnose with a high degree of confidence axial SpA at an early stage in patients with IBP who lack radiographic sacroiliitis.

Axis, Cervical Vertebra↗

PubMed2004

Impact of anti-tumour necrosis factor alpha treatment on admissions to hospital and days of sick leave in patients with ankylosing spondylitis.

OBJECTIVE: To analyse the impact of infliximab treatment on the number of hospital inpatient days and days of sick leave in patients with active ankylosing spondylitis (AS). METHODS: The data of a 2 year open extension study of a 12 week, double blind, randomised, placebo controlled trial, in which all patients with AS were treated with 5 mg/kg infliximab, were used to investigate the effect of anti-TNF treatment on admissions to hospital and days of sick leave. All patients were interviewed at baseline and at regular intervals during the study to collect this information by questionnaires. Patients who completed 2 years of treatment (n = 49) and those who did not (n = 20) were analysed separately. Sick leave analysis was restricted to currently employed patients (n = 38). RESULTS: During the 12 months before the screening visit, 20/49 (41%) completers had been admitted to hospital. After 1 and 2 years of treatment this percentage was reduced to 5/49 (10%; p<0.01), corresponding to a significant decrease in the mean number of inpatient days: from 11.1 to 0.6 after 1 year (p<0.01) and 2.9 after 2 years (p<0.01), respectively. No changes were seen in the dropout group. CONCLUSION: The use of infliximab in patients with active AS reduces some important costs of AS, but additional studies with detailed cost calculations are needed.

Adult↗

PubMed2004

Long-term comparison of a calcium-free phosphate binder and calcium carbonate--phosphorus metabolism and cardiovascular calcification.

BACKGROUND: Calcium carbonate used as a phosphate binder may contribute to cardiovascular calcification. Long-term comparisons of sevelamer, a non-calcium polymeric phosphate binder, and calcium carbonate (CC) are lacking. METHODS: 114 adult hemodialysis patients were randomly assigned to open label sevelamer or CC for 52 weeks. Study efficacy endpoints included changes in serum phosphorus, calcium, calcium-phosphorus product, and lipids. In addition, initial and sequential electron beam computerized tomography scans were performed to assess cardiovascular calcification status and change during follow-up. Safety endpoints were serum biochemistry, blood cell counts and adverse events. RESULTS: Patients receiving sevelamer had a similar reduction in serum phosphorus as patients receiving CC (sevelamer -0.58 +/- 0.68 mmol/l, CC -0.52 +/- 0.50 mmol/l; p = 0.62). Reductions in calcium-phosphorus product were not significantly different (sevelamer -1.4 +/- 1.7 mmol2/l2, CC -0.9 +/- 1.2 mmol2/l2; p = 0.12). CC produced significantly more hypercalcemia (> 2.8 mmol/l in 0% sevelamer and 19% CC patients, p < 0.01) and suppressed intact parathyroid hormone below 150 pg/ml in the majority of patients. Sevelamer patients experienced significant (p < 0.01) reductions in total (-1.2 +/- 0.9 mmol/l, -24%) and LDL cholesterol (-1.2 +/- 0.9 mmol/l, -30%). CC patients had significant increases in coronary artery (median +34%, p < 0.01) and aortic calcification (median +32%, p < 0.01) that were not observed in sevelamer-treated patients. Patients on sevelamer required more grams of binder (sevelamer 5.9 g vs. CC 3.9 g) and experienced more dyspepsia than patients on calcium carbonate. CONCLUSIONS: Sevelamer is an effective phosphate binder that unlike calcium carbonate is not associated with progressive cardiovascular calcification in hemodialysis patients.

Adult↗

PubMed2003

Navigated diffusion-weighted imaging with interpolated phase-correction for high-resolution imaging of stroke.

Stroke imaging was revolutionised with the introduction of diffusion-weighted MRI (DWI). The commonly used echoplanar DWI suffers from geometrical distortion near the skull base and the frontal regions and from reduced spatial resolution and fat suppression. To allow a voxel-by-voxel comparison between high-resolution spin-echo images, we implemented spin-echo-based DWI. Motion artefacts were eliminated by phase correction in hybrid frequency-Fourier domain using navigator echoes. In a novel approach, distorted navigator echoes which did not eliminate motion artefacts were replaced with interpolated navigator echoes, leading to restored image information. Navigated DWI yielded high-resolution images in 21 of 24 patients with brain ischaemia, allowing diagnosis of even small or diffuse zones of ischaemia. We determined the spatial distribution and mean of T(2)- and DWI signal intensity and apparent diffusion coefficients (ADC), using a multidimensional histogram-based analysis. Mean ADC were decreased in ischaemic areas less than 9 days old. The technique may also be useful for high-resolution DWI of tissue other than the brain.

Aged↗

PubMed2003

Altered cerebral vasoregulation in hypertension and stroke.

BACKGROUND: Autoregulation of blood flow that maintains steady perfusion over the range of systemic blood pressure is compromised by stroke. OBJECTIVES: To determine whether cerebral vasoregulation is impaired in stroke during orthostatic stress. METHODS: Subjects included 30 control subjects, 30 with hypertension, and 20 with minor stroke and were studied using transcranial Doppler. Bilateral blood flow velocities (BFVs) from middle cerebral arteries, heart rate, blood pressure (BP), and CO2 were obtained during hyperventilation and CO2 rebreathing during supine rest and tilt at 80 degrees. Side-to-side BFV difference, vasomotor range (VMR), and cerebrovascular resistance (CVR) were calculated during normo-, hypo-, and hypercapnia. RESULTS: Mean BFVs were similar between groups in supine position but differed during tilt. BFV diminished on the stroke side during tilt with hyperventilation and CO2 rebreathing (p < 0.0001). CVR increased (p < 0.0001) and VMR decreased (p < 0.01) on the stroke side. Vasoregulation was preserved on the normal side. BFV asymmetry differentiated patients with stroke from the other groups (p < 0.0001). BFV difference between the normal vs stroke side was the largest in stroke-normotensive (n = 7) compared with stroke-hypertensive (n = 13) patients and the two other groups (p < 0.0001). BFV asymmetry in stroke was associated with lower orthostatic BP (p < 0.0001). CONCLUSIONS: Cerebral vasoregulation is impaired with minor stroke, and cerebral blood flow depends on blood pressure. Decline of blood flow velocities during orthostatic stress may pose a risk of silent hypoperfusion.

Blood Flow Velocity↗

PubMed2003

Volume-selective 1H MR spectroscopy for in vivo detection of valproate in patients with epilepsy.

We performed volume-selective 1H MR spectroscopy (1H-MRS) on 12 patients on valproate monotherapy to detect valproate in vivo in the brain. We also acquired reference valproate spectra in vitro in subphysiological 15 g/l albumin solution in saline, in which valproate showed two resonance peaks at 0.7 and 1.2 ppm and a minimum detection threshold of 240 mg/l. In vivo 1H-MRS spectra in brain showed peaks between 0.6 and 1.6 ppm. Simultaneous serum valproate concentrations did not correlate with these integrated MRS peaks. On follow-up, changes in these signals also did not correlate with increasing serum valproate levels. The inconsistency of in vivo 1H-MRS signals at varying serum levels and the high detection levels in vitro suggest that valproate signals are missed in vivo because valproate is metabolised or strongly bound, presumably to brain macromolecules.

Adult↗

PubMed2003

Predominant cellular immune response to the cartilage autoantigenic G1 aggrecan in ankylosing spondylitis and rheumatoid arthritis.

OBJECTIVES: Based on their HLA association, both ankylosing spondylitis (AS) and rheumatoid arthritis (RA) seem to be T-cell-driven diseases in which the autoantigens remain to be defined. One possible autoantigen is the G1 domain of aggrecan, the major cartilage proteoglycan. In BALB/c mice immunized with this protein, spondylitis and erosive polyarthritis have been reported. Immune reactivity to the G1 has been described in patients with RA and AS in an earlier study. Using novel and more sensitive techniques and relevant controls we sought to define the role of G1 as an autoantigen more precisely and to extend the specific analyses to the peptide level. METHODS: Peripheral blood (PB) mononuclear cells (MNC) from 47 AS patients, 22 RA patients and 20 healthy normal controls were exposed in vitro for 6 h to the cartilage-derived autoantigens G1, human cartilage (HC) gp-39 and collagen II. Synovial fluid (SF) MNC from seven AS and four RA patients were similarly analysed. Furthermore, PB MNC of 15 AS and 10 RA patients were examined with overlapping 18-mer peptides covering the whole G1 protein to identify the immunodominant epitopes. T cells were stained by monoclonal antibodies directed against the surface markers CD4, CD69 and against the intracellular cytokines interferon-gamma (IFN gamma), tumour necrosis factor-alpha (TNF alpha), interleukin 4 (IL-4) and IL-10. The percentage of reactive T cells was quantified by flow cytometry. RESULTS: After antigen-specific stimulation with the G1 protein, the CD4+ T cells of 30 AS patients (61.7%) and of 12 RA patients (54.5%) secreted significant amounts of IFN gamma and TNF alpha, while, in contrast, only 10% of the normal controls showed a response (P < 0.05). The synovial CD4+ T cells of five AS (71.5%) and of all four RA patients showed antigen-specific responses to the G1. In contrast, stimulation with HC gp-39 and collagen II showed no significant IFN gamma and TNF alpha secretion of MNC in all groups. Several G1-derived T-cell epitopes were identified as immunodominant in PB MNC of AS and RA patients and were partly overlapping. CONCLUSIONS: These data show that a cellular immune response to G1 is present in most AS and RA patients. G1-immunodominant epitopes were identified. The relevance of this finding for the pathogenesis of AS and RA remains to be established.

Adipokines↗

PubMed2003

Magnetic resonance imaging examinations of the spine in patients with ankylosing spondylitis, before and after successful therapy with infliximab: evaluation of a new scoring system.

OBJECTIVE: To evaluate a magnetic resonance imaging (MRI) scoring system for the assessment of spinal inflammation in patients with ankylosing spondylitis (AS) who participated in a randomized, placebo-controlled trial of infliximab, and to examine whether infliximab is also effective for the reduction of MRI-proven spinal inflammation. METHODS: Twenty patients with AS (9 women and 11 men, mean age 40.9 years) were examined at baseline and after 3 months. Nine patients had received infusions of infliximab (5 mg/kg body weight) at weeks 0, 2, and 6, and 11 patients had received placebo. Three MRI sequences and 2 scoring systems were used. Chronic lesions were evaluated by T1-weighted turbo spin-echo (TSE) sequences and were assigned a chronicity score. Active lesions were evaluated either by repetition of T1-weighted TSE sequences after infusion of gadolinium-diethylenetriaminepentaacetic acid (Gd-DTPA) or by short tau inversion recovery (STIR) sequences, and were assigned an activity score. The 40 images were evaluated twice by 2 readers who were blinded to the names of the patients and the dates of the examinations, and were analyzed in relation to the clinical results. RESULTS: Active spinal lesions were detected in 15 of 20 patients (75%); the frequency as determined by STIR was equal in the 2 groups. At baseline, the total MRI scores determined using Gd-DTPA, STIR, and T1 were 112.5, 156, and 253.5, respectively. The interrater variance and intrarater variance were, respectively, 6.4 and 7.7 for the active lesion score as determined by Gd-DTPA, 15.7 and 5.3 for the active lesion score as determined by STIR sequence, and 167.3 and 75.5 for the chronic lesion score as determined by T1 sequence. Based on the means of the scores assigned by the 2 readers, the active lesion score as determined by Gd-DTPA improved by 40% in the infliximab group compared with 6% in the placebo group, the active lesion score as determined by STIR improved by 60% in the infliximab group but deteriorated by 21% in the placebo group, and the chronic lesion score as determined by T1 improved by 7% in the infliximab group but worsened by 35% in the placebo group. Five patients in the infliximab group and 2 in the placebo group were clinical responders. The acute MRI changes correlated with clinical improvement as assessed by the Bath Ankylosing Spondylitis Disease Activity Index. CONCLUSION: This novel MRI scoring system performed well in assessing acute inflammation by using STIR and post-Gd-DTPA sequences. In correlation with clinical improvement in patients with active AS who were treated with infliximab, significant regression of spinal inflammation was shown by using the MRI activity scores.

Adult↗

PubMed2003

Anatomic structures involved in early- and late-stage sacroiliitis in spondylarthritis: a detailed analysis by contrast-enhanced magnetic resonance imaging.

OBJECTIVE: To localize inflammatory and chronic changes to defined areas in the sacroiliac joints in patients with early-stage compared with late-stage spondylarthritis (SpA), using magnetic resonance imaging (MRI). METHODS: Using MRI, 93 patients with SpA and inflammatory back pain who had radiographs of the sacroiliac joints were examined, comprising 31 patients with ankylosing spondylitis (AS) and 62 with other SpA subsets, including 48 with undifferentiated SpA (uSpA). MRI was performed using T1-weighted, T2*-weighted, STIR, and dynamic contrast-enhanced (gadolinium diethylenetriaminepentaacetic acid) sequences. Two readers retrospectively analyzed the images by differentiating 9 areas of the sacroiliac joints: the ventral and caudal joint capsule, cavum, subchondral bone, bone marrow, ligament entheses, and ligaments; the sacral and iliac sides were tabulated separately. RESULTS: By MRI, sacroiliitis was more often bilateral in AS (84%) than in uSpA (48%) (P = 0.01). Inflammatory changes were found in a mean +/- SD 4.7 +/- 2.9 regions/joint, with involvement of 4.5 +/- 3.2 regions in early disease versus 5.2 +/- 2.3 regions in late disease (P not significant [NS]). Involvement of the iliac side of the sacroiliac joints was found to be more frequent than the sacral side in early disease (58% versus 48%; P < 0.01) as compared with that in late disease (58% versus 63%; P NS). The dorsocaudal parts of the synovial joint and the bone marrow were the most frequently inflamed structures in early disease (P < 0.001 for ventral versus dorsal joint capsule). In contrast, involvement of the entheses was more common in advanced disease (early 43% versus late 86%; P < 0.001). Similarly, the ligaments were more frequently involved in the late stages (early 26% versus late 40%; P = 0.06). Both patterns of bone marrow inflammation (focal and diffuse) were observed in equal frequencies in early and late disease (17% and 42% versus 26% and 43%, respectively; P NS). HLA-B27-positive patients (n = 80) had more entheseal involvement than did HLA-B27-negative patients (n = 13) (60% versus 39%; P = 0.05). HLA-B27-negative patients had a shorter disease duration (2.2 years versus 4.4 years; P = 0.05) and were more often female (62%; P = 0.02). When all pathologic changes were assessed, the STIR sequence (performed in 62 patients) was less sensitive than the contrast-enhanced sequences in that it was not able to show all relevant changes in 27% of these patients (n = 17), failing to reveal inflammation of the cavum in 15 patients and of the bone marrow and joint capsule in 1 patient each. CONCLUSION: As visualized by MRI, sacroiliitis in SpA is characterized by involvement of different joint structures. Whereas the iliac and the sacral side of the sacroiliac joints are almost equally affected, the dorsocaudal synovial part of the joint is involved significantly more often than the ventral part, especially in early disease. Sacroiliac enthesitis is not a special feature of early sacroiliac inflammation.

Adult↗

PubMed2003

Six-month results of a double-blind, placebo-controlled trial of etanercept treatment in patients with active ankylosing spondylitis.

OBJECTIVE: There is increasing evidence that tumor necrosis factor alpha (TNFalpha) is centrally involved in the pathogenesis of ankylosing spondylitis (AS) and other spondylarthritides. This study was designed to investigate the efficacy of anti-TNFalpha therapy with etanercept, a 75-kd receptor fusion protein, in active AS. METHODS: This multicenter trial had 2 phases: an initial placebo-controlled period of 6 weeks' duration and an observational phase lasting 24 weeks. Thirty patients with active AS were included. They were randomized into 2 groups, which received either etanercept (25 mg twice weekly) (n = 14) or placebo (n = 16) for 6 weeks. Then both groups were treated with etanercept. Nonsteroidal antiinflammatory drug (NSAID) treatment could be continued, but disease-modifying antirheumatic drugs (DMARDs) and steroids had to be withdrawn prior to the study. All patients received etanercept for a total of 12 weeks and were followed up for at least 24 weeks. The Bath AS Disease Activity Index (BASDAI), Bath AS Functional Index, Bath AS Metrology Index, pain level on a numeric rating scale, quality of life by the Short Form 36, and C-reactive protein (CRP) level were assessed. The primary outcome parameter was a >or=50% improvement in the BASDAI. RESULTS: Treatment with etanercept resulted in at least a 50% regression of disease activity in 57% of these patients at week 6, versus 6% of the placebo-treated patients (P = 0.004). After the placebo-treated patients switched to etanercept, 56% improved. The mean +/- SD BASDAI improved from 6.5 +/- 1.2 at baseline to 3.5 +/- 1.9 at week 6 in the etanercept group, with no improvement in the placebo group (P = 0.003 between groups). Similarly, pain, function, mobility, and quality of life improved with etanercept but not with placebo at week 6 (P < 0.05). Mean CRP levels decreased significantly with etanercept but not with placebo (P = 0.001). There was ongoing improvement in all parameters in both groups until week 12 and week 18, respectively (i.e., throughout the period of etanercept treatment). Disease relapses occurred a mean +/- SD of 6.2 +/- 3.0 weeks after cessation of etanercept. No severe adverse events, including major infections, were observed during the trial. CONCLUSION: This study shows that on a short-term basis (3 months), treatment with etanercept is clearly efficacious in patients with active AS who are receiving NSAID therapy but not DMARDs or steroids. After cessation of therapy, almost all patients experienced a relapse within a few weeks. Thus, it seems probable that etanercept must be administered continuously in most AS patients to achieve permanent inhibition of the inflammatory process.

Adult↗