Christian E. Althoff

Effects of etanercept versus sulfasalazine in early axial spondyloarthritis on active inflammatory lesions as detected by whole-body MRI (ESTHER): a 48-week randomised controlled trial

Purpose To evaluate the potential of etanercept versus sulfasalazine to reduce active inflammatory lesions on whole-body MRI in active axial spondyloarthritis with a symptom duration of less than 5 years. Methods Patients were randomly assigned to etanercept (n=40) or sulfasalazine (n=36) treatment over 48 weeks. All patients showed active inflammatory lesions (bone marrow oedema) on MRI in either the sacroiliac joints or the spine. MRI was performed at weeks 0, 24 and 48 and was scored for active inflammatory lesions in sacroiliac joints and the spine including posterior segments and peripheral enthesitis by two radiologists, blinded for treatment arm and MRI time point. Results In the etanercept group, the reduction of the sacroiliac joint score from 7.7 at baseline to 2.0 at week 48 was significantly (p=0.02) larger compared with the sulfasalazine group from 5.4 at baseline to 3.5 at week 48. A similar difference in the reduction of inflammation was found in the spine from 2.2 to 1.0 in the etanercept group versus from 1.4 to 1.3 in the sulfasalazine group between baseline and week 48, respectively (p=0.01). The number of enthesitic sites also improved significantly from 26 to 11 in the etanercept group versus 24 to 26 in the sulfasalazine group (p=0.04 for difference). 50% of patients reached clinical remission in the etanercept group versus 19% in the sulfasalazine group at week 48. Conclusion In patients with early axial spondyloarthritis active inflammatory lesions detected by whole-body MRI improved significantly more in etanercept versus sulfasalazine-treated patients. This effect correlated with a good clinical response in the etanercept group.

MRI of enthesitis of the appendicular skeleton in spondyloarthritis

Entheses are sites where tendons, ligaments, joint capsules or fascia attach to bone. Inflammation of the entheses (enthesitis) is a well-known hallmark of spondyloarthritis (SpA). As entheses are associated with adjacent, functionally related structures, the concepts of an enthesis organ and functional entheses have been proposed. This is important in interpreting imaging findings in entheseal-related diseases. Conventional radiographs and CT are able to depict the chronic changes associated with enthesitis but are of very limited use in early disease. In contrast, MRI is sensitive for detecting early signs of enthesitis and can evaluate both soft-tissue changes and intraosseous abnormalities of active enthesitis. It is therefore useful for the early diagnosis of enthesitis-related arthropathies and monitoring therapy. Current knowledge and typical MRI features of the most commonly involved entheses of the appendicular skeleton in patients with SpA are reviewed. The MRI appearances of inflammatory and degenerative enthesopathy are described. New options for imaging enthesitis, including whole-body MRI and high-resolution microscopy MRI, are briefly discussed.

Relationship between active inflammatory lesions in the spine and sacroiliac joints and new development of chronic lesions on whole-body MRI in early axial spondyloarthritis: results of the ESTHER trial at week 48

Aim To investigate the relationship between active inflammatory lesions on whole-body MRI (wb-MRI) and new development of chronic lesions on T1 MRI in patients with early axial spondyloarthritis (SpA) treated either with etanercept (ETA) or sulfasalazine (SSZ). Methods Wb-MRIs of 65 patients treated either with ETA (n=35) or SSZ (n=30) over 1 year were scored for active inflammation, fatty lesions, erosions and ankylosis in the 23 vertebral units (VUs) of the spine and in the sacroiliac joints (SI joints). Scoring was performed by two blinded radiologists. Results If there was no previous inflammation in the bone no new fatty lesions occurred in SI joint quadrants and only a few (0.6%) in spine VUs. There was a significant relationship between disappearance of inflammation and the appearance of fatty lesions: if baseline inflammation resolved fatty lesions occurred in 10.5% of SI joint quadrants and 17.9% of VUs. If inflammation did not resolve over 1 year, fatty lesions occurred less frequently: 2.4% (SI joint quadrants) and 7.2% (VUs). There was a significantly higher increase of the mean fatty lesion score between baseline and week 48 in the ETA (4.0 vs 4.8 for the SI joints and 1.9 vs 2.7 for the spine) compared to the SSZ (3.0 vs 3.2 for the SI joints and 1.1 vs 1.2 for the spine, respectively) group (p=0.001 and p=0.020 for the differences). No significant changes in the erosion or ankylosis score were observed in any of the two groups during this time. Conclusions These data indicate that there is a close interaction between inflammation, tumour necrosis factor blockade and the development of fatty lesions in subchondral bone marrow of patients with axial SpA.

Knee Osteoarthritis Efficacy of a new method of contrast-enhanced musculoskeletal ultrasonography in detection of synovitis in patients with knee osteoarthritis in comparison with magnetic resonance imaging

Objective: To develop a new method of digital synovial vascularisation quantification by using contrast-enhanced musculoskeletal ultrasonography (MUS) in detecting synovitis in patients with knee osteoarthritis (OA) compared with healthy subjects and MRI. Methods: Evaluation of 41 patients with painful knee OA and 6 healthy subjects. The severity of knee pain was evaluated. All patients and all 6 healthy subjects underwent contrast medium-enhanced (CE)-MUS with SonoVue®, and 36 patients additionally underwent CE-MRI with Magnevist. Joint effusion, synovial thickening and pain were assessed and compared with B-mode and Power Doppler sonography (PDS) as well as contrast medium enhancement. Results: Pain evaluated by the visual analogue scale (VAS) hardly correlated with other markers of disease activity measured by ultrasound (US) in B-mode or MRI. US of the superior recess revealed an effusion or synovial thickening in 58%. PDS findings were positive in 63%, and CE-MUS in the superior knee recess was positive in 95%. MRI showed effusion in the superior recess in 61% and showed positive findings in 82% when using contrast medium. The kappa value was 0.48 between US and MRI with regard to the effusion in the superior recess, and 0.53 between PD signal in the superior recess and effusion in the superior recess by US. Using MRI as the reference standard, there was a sensitivity of 72% for assessing effusion in the superior recess and 81% for assessing effusion in the lateral recess. Conclusion: Assessment of disease activity (synovitis) in knee OA by VAS is not sufficient. US PDS was more sensitive than B-mode, and CE-MUS was more sensitive than PDS and CE-MRI in detecting synovitis in patients with painful knee OA. Also, CE-MRI was more sensitive in detecting inflammatory changes in the superior recess than without contrast medium. Using CE-MUS and performing time/intensity analysis has shown to be a good model for evaluation of an inflammatory process in the setting of knee OA in the superior recess.

Similar response rates in patients with ankylosing spondylitis and non-radiographic axial spondyloarthritis after 1 year of treatment with etanercept: results from the ESTHER trial

Objective We assessed whether there is a difference to etanercept (ETA) treatment in patients with ankylosing spondylitis (AS) compared with non-radiographic axial SpA (nr-axSpA) patients with a disease duration <5 years. Method AS (n=20) and nr-axSpA (n=20) patients who were treated with ETA for 1 year were compared for differences in baseline data and treatment effect. Clinical, laboratory and MRI of sacroiliac joints (SI-joints) and spine were analysed. Results At baseline, there were no significant differences between the 20 AS and the 20 nr-axSpA patients regarding age, disease duration, gender, HLA-B27 and clinical disease activity in terms of Bath AS Disease Activity Index (BASDAI), C-reactive protein and MRI SI-joint and spine scores in the AS compared with the nr-axSpA group. After 1 year of treatment with ETA the treatment effect was similarly good in AS and nr-axSpA (reduction of BASDAI by 3.3 (95% CI 2.2 to 3.8) vs 3.6 (95% CI 2.8 to 4.4) and reduction of AS Disease Activity Score by 1.8 (95% CI 1.5 to 2.2) vs 1.8 (95% CI 1.5 to 2.1), respectively. Conclusions The response rate to TNF-blockers does not differ between AS and nr-axSpA if the baseline data regarding symptom duration and disease activity are similar for the two groups.

Claustrophobia and premature termination of magnetic resonance imaging examinations

To evaluate the incidence of MRI‐related claustrophobia and prematurely terminated MRI (ptMRI) examinations due to claustrophobia in a large‐scale cohort study.

Tenosynovitis of the flexor tendons of the hand detected by MRI: an early indicator of rheumatoid arthritis

OBJECTIVE To evaluate the potential of MRI of finger and wrist joints for diagnosing early RA. MRI was evaluated as a stand-alone tool and in combination with ACR criteria and serum markers such as RF. METHODS Ninety-nine patients (31 men, 68 women; median age 46 years) with unspecified arthritis or suspected RA and negative X-ray findings were included. MR images of the hand and wrist of these patients were retrospectively evaluated for the presence of synovitis, erosions and tenosynovitis. The clinical diagnosis (early RA or non-RA) was made by a rheumatologist after clinical follow-up for 6-41 months. Clinical and laboratory data were collected from all patients. RESULTS Fifty-eight patients had a clinical diagnosis of RA and 41 were diagnosed as non-RA. Step-wise logistic regression of all MR parameters evaluated identified tenosynovitis of the flexor tendons to be the most powerful predictor of early RA (sensitivity = 60%, specificity = 73%). Including ACR criteria in the analysis, positive serum RF and tenosynovitis were the strongest predictors of early RA (sensitivity = 83%, specificity = 63%). When serum anti-cyclic citrullinated peptides (CCP), ANA and CRP were included as additional parameters, anti-CCP and flexor tenosynovitis were the strongest predictors of early RA (sensitivity = 79%, specificity = 73%). CONCLUSIONS Flexor tenosynovitis diagnosed by MRI of the hand is a strong predictor of early RA. Combining flexor tenosynovitis on MRI with positive serum anti-CCP or positive RF is an even stronger predictor of early RA.

Magnetic resonance imaging of active sacroiliitis: Do we really need gadolinium?

INTRODUCTION Magnetic resonance imaging (MRI) of active inflammatory changes of the sacroiliac joint (SIJ) in spondyloarthritis (SpA) is performed with short tau inversion recovery (STIR) sequences and fat-saturated T1-weighted fast spin-echo (FSE) sequences after administration of gadolinium-based contrast medium (T1/Gd). The aim of the present study was to compare these two pulse sequences in terms of diagnosis, diagnostic confidence, and quantification of inflammatory changes. MATERIALS AND METHODS The study included 105 patients with suspected SpA; 72 patients developed clinical SpA over time. All patients were examined with STIR and T1/Gd and each of the two sequences was analyzed separately in conjunction with unenhanced T1 FSE images. For quantitative estimation of inflammatory changes, each sacroiliac joint (SIJ) was divided into 4 quadrants (and severity per quadrant was assigned a score of 0-4, resulting in a maximum sum score of 16 per SIJ). Diagnostic confidence was assessed on a visual analogue scale ranging from 0 to 10. RESULTS Active sacroiliitis was diagnosed in 46 patients and ruled out in 34 using STIR, whereas findings were inconclusive in 25 patients. The corresponding numbers for T1/Gd were 47, 44, and 14. Diagnostic confidence was significantly lower for STIR (7.3+/-2.6) compared with T1/Gd (8.7+/-1.9) (p<0.001). The sum scores were 2.5 (+/-3.3) for STIR and 2.2 (+/-3.2) for T1/Gd for the right SIJ and 2.2 (+/-2.9) (STIR) and 1.9 (+/-3.1) (T1/Gd) for the left SIJ. Agreement was high with intraclass correlation coefficient (ICC) values of 0.86 for the right SIJ and 0.90 for the left SIJ and positive correlation (r=0.62 right, 0.60 left). SUMMARY STIR sequences alone are sufficient for establishing a reliable diagnosis and quantify the amount of inflammation in active sacroiliitis. A contrast-enhanced study is dispensable in patients with established disease or in the setting of clinical follow-up studies. However, a contrast-enhanced MR sequence is beneficial to ensure maximum diagnostic confidence when patients with early sacroiliitis are examined.

Contrast-enhanced ultrasound in monitoring the efficacy of a bradykinin receptor 2 antagonist in painful knee osteoarthritis compared with MRI

Objectives: To evaluate contrast-enhanced ultrasound (CE-US) as a monitoring tool to assess hypervascularisation of synovial processes in knee osteoarthritis (OA) treated with intra-articular injections of the bradykinin-receptor 2 antagonist icatibant compared to contrast-enhanced magnetic resonance imaging (CE-MRI). Patients and methods: In a randomised, double-blind, placebo-controlled trial, 41 patients with painful knee OA underwent US (12.5 MHz for B-mode and 3–8 MHz for CE-US), and 36 of the patients underwent additional MRI (0.2T) at baseline and after 3 injections of the study drug (after a mean of 22.2 days). A total of 15 patients received placebo (group A), 12 patients 500 μg icatibant (group B) and 14 patients 2000 μg icatibant (group C). Pain and the synovial process (B-mode, power Doppler US (PD-US), CE-US, CE-MRI) were assessed at both time points. Results: At baseline, the placebo group showed more activity in terms of effusion in the superior and lateral recess in ultrasound as well as in PD-US in the lateral recess. Pain improved significantly in all subgroups. Effect sizes were 0.43 (pain at rest) and 0.52 (pain during activity) in group B vs 0.48 and 1.11 in group C. There was no change of US and MRI parameters. We found moderate to good correlation (r) and kappa values (κ) for effusion in the superior recess (r = 0.591, k = 0.453), effusion in the lateral recess (r = 0.304, k = 0.440) and contrast enhancement (r = 0.601, k = 0.242) between US and MRI. Conclusions: Our results show that CE-US and CE-MRI have good agreement in assessing inflammatory changes in knee OA. For the 41 patients with OA, an analgesic effect of icatibant could clearly be shown, especially for pain during activity in the high dose icatibant group. However, we could not find an anti-inflammatory effect of icatibant by CE-US compared to CE-MRI.

Active inflammation and structural change in early active axial spondyloarthritis as detected by whole-body MRI

Objective To evaluate active inflammatory lesions (AIL) and structural changes (SC) in patients with active non-radiographic axial spondyloarthritis (nr-axSpA) compared with patients with ankylosing spondylitis (AS) on whole-body MRI (wb-MRI). Method 75 patients with active disease and a symptom duration of <5 years (39 with AS and 36 with nr-axSpA) were investigated with a comprehensive wb-MRI protocol and scored for AIL and SC in the spine, sacroiliac joints (SIJs) and non-axial manifestations. Results 92% of patients with AS showed active inflammation in the SIJ, 53% in the spine and 94% and 39%, respectively, in the nr-axSpA group. There was a non-significant trend towards more inflammation in patients with AS compared with patients with nr-axSpA in SIJs and spine. Peripheral enthesitis/osteitis was more common in patients with AS (n=22) than in those with nr-axSpA (n=12) (p=0.05). SC were more common in patients with AS than in those with nr-axSpA, with significantly higher scores for SIJ fatty bone marrow deposition (FMD) in patients with AS (4.8±3.2) compared with those with nr-axSpA (2.4±2.7; p=0.001) and more frequent bone proliferation in the spine and the SIJ (p=0.02 and p=0.005, respectively). SIJ erosions were more common in AS (score 4.2±2.3) than in nr-axSpA (score 3.8±1.8) patients (not significant). Conclusions Wb-MRI detects active inflammation and SC more frequently in the SIJs than in the spine. Half of the patients showed inflammation in non-axial sites. Active inflammatory and structural lesions were present both in patients with AS and those with nr-axSpA, being only slightly more common in patients with AS.