K. Tymms

A multi‐center, observational study shows high proportion of Australian rheumatoid arthritis patients have inadequate disease control

To evaluate the disease activity and current pharmacological interventions used to achieve remission in rheumatoid arthritis (RA) patients in Australia.

Etanercept treatment of renal amyloidosis complicating rheumatoid arthritis

Rheumatoid arthritis and juvenile arthritis represent the commonest diseases complicated by AA amyloidosis in developed countries. Up to 5% of patients with rheumatoid arthritis will develop AA amyloidosis, with renal failure being the commonest cause of mortality. To date, treatment of this condition has focused on suppressing the underlying inflammatory condition with drugs such as cyclophosphamide and chlorambucil, but both these drugs are associated with myelotoxicity, leukaemia and sterility. Tumour necrosis factor‐α (TNF‐α) is thought to be involved in amyloid deposition. The efficacy of anti‐TNF‐α therapy (etanercept) in the treatment of renal amyloidosis complicating rheumatoid arthritis is demonstrated here and the current scientific data on this subject are presented. (Intern Med J 2004; 34: 570−572)

Barriers to optimal disease control for rheumatoid arthritis patients with moderate and high disease activity

To evaluate barriers that prevent rheumatoid arthritis (RA) patients from achieving Disease Activity Score in 28 joints using the erythrocyte sedimentation rate (DAS28‐ESR) scores within the current recommended levels for low disease activity (LDA) or clinical remission (DAS28‐ESR score <3.2).

Improved detection of anti-Jo-1 antibody, a marker for myositis, using purified histidyl-tRNA synthetase

The increased detection of anti-Jo-1 antibody afforded by the use of the purified antigen, histidyl-tRNA synthetase, in counterimmunoelectrophoresis is demonstrated. Using purified antigen, anti-Jo-1 antibody was detected in the sera of 16/33 (48.5%) patients with confirmed myositis and in 20/45 (44.5%) patients with confirmed or possible myositis. This rate is approximately double that obtained with commercial thymus extracts both in this study and seven others reported in the literature. The presence of antibody shows marked correlation with the activity of myositis at the time of serum sampling and with the presence of interstitial lung disease. Detection rates are similar in patients with polymyositis and dermatomyositis both with and without additional connective tissue diseases.

The SMILE Study -- Safety of Methotrexate in Combination with Leflunomide in Rheumatoid Arthritis

Objective. To assess the safety of treating patients with rheumatoid arthritis with a combination of methotrexate (MTX) and leflunomide (LEF) in comparison to MTX monotherapy, in clinical practice. Methods. The Safety of Methotrexate in Combination with Leflunomide in Rheumatoid Arthritis (SMILE) study was a multicenter, observational, cross-sectional, retrospective safety study. The study was conducted by the Optimising Patient Outcomes in Australian Rheumatology-Quality Use of Medicines Initiative (OPAL QUMI). Data were deidentified for patient, clinic, and clinician prior to collection from 13 participating rheumatology practices (25 rheumatologists). Comparative analysis of safety for the different treatments, primarily with regard to neutropenia and liver abnormalities, was performed. Results. In total, 2975 patients were included in the study: 74% female, 26% male, mean age 62 years (SD 13.6). Distribution of therapy: MTX monotherapy 52.2%, LEF monotherapy 7.3%, MTX plus LEF 13.9%, and neither MTX nor LEF 26.6%. Comorbid liver disease was reported in 8.1% of patients. Liver function abnormalities were reported in 12% of the MTX monotherapy group, 16% of the LEF monotherapy group, 19% of the MTX-LEF combination group, and 14% of the group not taking either drug. Neutropenia was reported in 2.3% of the MTX monotherapy group, 5.5% of the LEF monotherapy group, 3.9% of the MTX-LEF combination group, and 4.2% of the group not taking either drug. Conclusion. The combination of MTX and LEF was well tolerated, with adverse events comparable to those of monotherapy and the other nonbiologic disease-modifying antirheumatic drug treatment group.

An Immunochip-based interrogation of scleroderma susceptibility variants identifies a novel association at DNASE1L3

IntroductionThe aim of the study was to interrogate the genetic architecture and autoimmune pleiotropy of scleroderma susceptibility in the Australian population.MethodsWe genotyped individuals from a well-characterized cohort of Australian scleroderma patients with the Immunochip, a custom array enriched for single nucleotide polymorphisms (SNPs) at immune loci. Controls were taken from the 1958 British Birth Cohort. After data cleaning and adjusting for population stratification the final dataset consisted of 486 cases, 4,458 controls and 146,525 SNPs. Association analyses were conducted using logistic regression in PLINK. A replication study was performed using 833 cases and 1,938 controls.ResultsA total of eight loci with suggestive association (P <10−4.5) were identified, of which five showed significant association in the replication cohort (HLA-DRB1, DNASE1L3, STAT4, TNP03-IRF5 and VCAM1). The most notable findings were at the DNASE1L3 locus, previously associated with systemic lupus erythematosus, and VCAM1, a locus not previously associated with human disease. This study identified a likely functional variant influencing scleroderma susceptibility at the DNASE1L3 locus; a missense polymorphism rs35677470 in DNASE1L3, with an odds ratio of 2.35 (P = 2.3 × 10−10) in anti-centromere antibody (ACA) positive cases.ConclusionsThis pilot study has confirmed previously reported scleroderma associations, revealed further genetic overlap between scleroderma and systemic lupus erythematosus, and identified a putative novel scleroderma susceptibility locus.

Infliximab in severe active ankylosing spondylitis with spinal ankylosis.

Background:  Infliximab is an anti‐tumour necrosis factor monoclonal antibody, which significantly improves pain, stiffness and functional disability outcomes in patients with active ankylosing spondylitis. There are limited data available on the efficacy of this treatment for the subgroup with established spinal ankylosis.

Etanercept in severe active rheumatoid arthritis: first australian experience

Background: Etanercept reduces disease activity in adults with chronic rheumatoid arthritis (RA) who are resistant to other therapies. Medicare Australia Pharmaceutical Benefit Scheme subsidized treatment (since August 2003) restricts etanercept availability to a most drug‐resistant RA population. The aim of the study was to assess the efficacy of etanercept in this unique group after 12 months of therapy.

Spondyloarthropathy in inflammatory bowel disease patients on TNF inhibitors.

Musculoskeletal symptoms are the most common extra‐intestinal manifestation associated with inflammatory bowel disease (IBD). Spondyloarthritis (SpA) is an umbrella term applied to a group of rheumatic diseases with some features in common and others distinct from other inflammatory arthritides.

Autologous hematopoietic stem cell transplant for systemic sclerosis improves anemia from gastric antral vascular ectasia

To the Editor: Systemic sclerosis (SSc) is a severe autoimmune condition characterized by both fibrotic and vascular complications. This can progress to functionally devastating subcutaneous fibrosis, as well as death from pulmonary, cardiac, renal, or gastrointestinal (GI) involvement1. High-dose chemotherapy followed by autologous hematopoietic stem cell transplantation (HSCT) is the first therapy to show evidence of clinically significant improvement in skin and lung function as well as quality of life in SSc when compared to intravenous cyclophosphamide (CYC)2. The multi-center, phase III randomized trial, Autologous Stem Cell Transplantation International Scleroderma, also showed a significant benefit in longterm, event-free survival with autologous HSCT compared to CYC, despite a higher early treatment-related mortality3. A publication from the European Group for Blood and Marrow transplantation (EBMT) has updated guidelines for autologous HSCT in autoimmune diseases, including SSc4. GI involvement is the presenting feature of the disease … Address correspondence to Dr. A. Bhattacharyya, St. Vincent’s Hospital, Haematology, 390 Victoria St., Sydney, New South Wales 2010, Australia. E-mail: abir123{at}gmail.com