Evolution of radiographic joint damage in rituximab-treated versus TNF-treated rheumatoid arthritis cases with inadequate response to TNF antagonists

Observational studies have suggested that patients with rheumatoid arthritis (RA) who experience inadequate response to anti-tumour necrosis factor (anti-TNF) agents respond more favourably to rituximab (RTX) than to an alternative anti-TNF agent. However, the relative effectiveness of these agents on long-term outcomes, particularly in radiographic damage, remains unclear.

Anti-inflammatory and immunosuppressive drugs and reproduction

Rheumatic diseases in women of childbearing years may necessitate drug treatment during a pregnancy, to control maternal disease activity and to ensure a successful pregnancy outcome. This survey is based on a consensus workshop of international experts discussing effects of anti-inflammatory, immunosuppressive and biological drugs during pregnancy and lactation. In addition, effects of these drugs on male and female fertility and possible long-term effects on infants exposed to drugs antenatally are discussed where data were available. Recommendations for drug treatment during pregnancy and lactation are given.

Assessing the intra- and inter-reader reliability of dynamic ultrasound images in power Doppler ultrasonography

OBJECTIVE: To assess the intra-reader and inter-reader reliabilities of interpreting ultrasonography by several experts using video clips. METHOD: 99 video clips of healthy and rheumatic joints were recorded and delivered to 17 physician sonographers in two rounds. The intra-reader and inter-reader reliabilities of interpreting the ultrasound results were calculated using a dichotomous system (normal/abnormal) and a graded semiquantitative scoring system. RESULTS: The video reading method worked well. 70% of the readers could classify at least 70% of the cases correctly as normal or abnormal. The distribution of readers answering correctly was wide. The most difficult joints to assess were the elbow, wrist, metacarpophalangeal (MCP) and knee joints. The intra-reader and inter-reader agreements on interpreting dynamic ultrasound images as normal or abnormal, as well as detecting and scoring a Doppler signal were moderate to good (kappa = 0.52-0.82). CONCLUSIONS: Dynamic image assessment (video clips) can be used as an alternative method in ultrasonography reliability studies. The intra-reader and inter-reader reliabilities of ultrasonography in dynamic image reading are acceptable, but more definitions and training are needed to improve sonographic reproducibility.

Infliximab inhibits bone resorption by circulating osteoclast precursor cells in patients with Rheumatoid Arthritis and Ankylosing Spondylitis

OBJECTIVE: To examine the effects of infliximab on bone resorption by osteoclast precursor cells (OCPs) in patients with rheumatoid arthritis (RA) and ankylosing spondylitis (AS) and to compare the results with changes in disease activity. METHODS: Before and during 24 weeks of infliximab treatment peripheral blood mononuclear cells of 9 RA and 10 AS patients were seeded onto ivory wafers and adherent cells, including OCPs, were grown in medium promoting osteoclast differentiation. Bone resorption was evaluated morphometrically and correlated to disease activity. 19 healthy individuals were studied in parallel. In addition, biochemical bone markers were assessed in all patients at baseline and after 24 weeks. RESULTS: OCPs from RA patients showed a higher bone resorption at baseline when compared to AS patients. Blocking of TNFalpha with infliximab resulted in a strong reduction of bone resorption by OCPs in both cohorts and did occur faster in RA compared to AS patients. This inhibition coincided with reduction of clinical disease activity in both patient cohorts and with an increase of serum osteocalcin levels and a relative decrease of collagen crosslinks in RA compared to AS patients. CONCLUSION: These results provide an explanation on the cellular level for the anticatabolic effect of TNF neutralization on bone. The variation in the kinetics of bone resorption by the OCPs in patients with RA and AS suggests disease-specific differences in the type or in the preactivation of OCPs.

A randomised controlled trial of spinal manipulative therapy in acute low back pain

OBJECTIVE: To determine whether treatment with spinal manipulative therapy (SMT) administered in addition to standard care is associated with clinically relevant early reductions in pain and analgesic consumption. METHODS: 104 patients with acute low back pain were randomly assigned to SMT in addition to standard care (n = 52) or standard care alone (n = 52). Standard care consisted of general advice and paracetamol, diclofenac or dihydrocodeine as required. Other analgesic drugs or non-pharmacological treatments were not allowed. Primary outcomes were pain intensity assessed on the 11-point box scale (BS-11) and analgesic use based on diclofenac equivalence doses during days 1-14. An extended follow-up was performed at 6 months. RESULTS: Pain reductions were similar in experimental and control groups, with the lower limit of the 95% CI excluding a relevant benefit of SMT (difference 0.5 on the BS-11, 95% CI -0.2 to 1.2, p = 0.13). Analgesic consumptions were also similar (difference -18 mg diclofenac equivalents, 95% CI -43 mg to 7 mg, p = 0.17), with small initial differences diminishing over time. There were no differences between groups in any of the secondary outcomes and stratified analyses provided no evidence for potential benefits of SMT in specific patient groups. The extended follow-up showed similar patterns. CONCLUSIONS: SMT is unlikely to result in relevant early pain reduction in patients with acute low back pain.

Pregnancy induces numerical and functional changes of CD4+CD25 high regulatory T cells in patients with rheumatoid arthritis

OBJECTIVE: In a prospective study we investigated whether numerical and functional changes of CD4+CD25(high) regulatory T cells (Treg) were associated with changes of disease activity observed during pregnancy and post partum in patients with rheumatoid arthritis (RA). METHODS: The frequency of CD4+CD25(high) T cells was determined by flow cytometry in 12 patients with RA and 14 healthy women during and after pregnancy. Fluorescence-activated cell sorting (FACS) was used to sort CD4+CD25(high) T cells and CD4+CD25- T cells were stimulated with anti-CD3 and anti-CD28 monoclonal antibodies alone or in co-culture to investigate proliferation and cytokine secretion. RESULTS: Frequencies of CD4+CD25(high) Treg were significantly higher in the third trimester compared to 8 weeks post partum in patients and controls. Numbers of CD4+CD25(high) Treg inversely correlated with disease activity in the third trimester and post partum. In co-culture experiments significantly higher amounts of IL10 and lowered levels of tumour necrosis factor (TNF)alpha and interferon (IFN)gamma were found in supernatants of the third trimester compared to postpartum samples. These findings were independent from health or disease in pregnancy, however postpartum TNFalpha and IFN gamma levels were higher in patients with disease flares. CONCLUSION: The amelioration of disease activity in the third trimester corresponded to the increased number of Treg that induced a pronounced anti-inflammatory cytokine milieu. The pregnancy related quantitative and qualitative changes of Treg suggest a beneficial effect of Treg on disease activity.

Hip MRI and its implications for surgery in osteoarthritis patients

Osteoarthritis (OA) of the hip joint stems from a combination of intrinsic factors, such as joint anatomy, and extrinsic factors, such as injuries, diseases, and load. Possible risk factors for OA are instability and impingement. Different surgical techniques, such as osteotomies of the pelvis and femur, surgical dislocation, and hip arthroscopy, are being performed to delay or halt OA. Success of salvage procedures of the hip depends on the existing cartilage and joint damage before surgery. The likelihood of therapy failure rises with advanced OA. For imaging of intra-articular hip pathology, MRI represents the best technique because it enables clinicians to directly visualize cartilage, it provides superior soft tissue contrast, and it offers the prospect of multidimensional imaging. However, opinions differ on the diagnostic efficacy of MRI and on the question of which MRI technique is most appropriate. This article gives an overview of the standard MRI techniques for diagnosis of hip OA and their implications for surgery.

Novel screening tools for latent tuberculosis: time to leave an old friend?

PURPOSE OF REVIEW: Therapeutic inhibition of tumour necrosis factor-alpha strongly increases the risk of reactivation in latent tuberculosis infection. Recent blood tests based on antigen-specific T cell response and measuring production of interferon-gamma, so called interferon-gamma release assays (IGRAs), are promising novel tools to identify infected patients. The performance of diagnostic testing for latent tuberculosis infection in patients with rheumatic diseases will be discussed. RECENT FINDINGS: In patients with rheumatoid arthritis, IGRAs are more sensitive and more specific than traditional tuberculin skin testing. They are unaffected by Bacillus-Calmette-Guérin vaccination and most nontuberculous mycobacteria. Most comparative studies show a better performance of the IGRAs than tuberculin skin testing in terms of a higher specificity. The rate of indeterminate results may be affected by glucocorticoids and the underlying disease but appears independent of disease-modifying antirheumatic drugs. Despite using identical Mycobacterium tuberculosis antigens, the two commercially available tests show differences in clinical performance. SUMMARY: The current information about the performance of the tuberculin skin testing and the IGRAs in the detection of latent tuberculosis infection in patients with rheumatic diseases strongly suggest a clinically relevant advantage of the IGRAs. Their use will help to reduce overuse and underuse of preventive treatment in tumour necrosis factor inhibition.