Alan Tyndall

American College of Rheumatology/European League Against Rheumatism provisional definition of remission in rheumatoid arthritis for clinical trials

Objective Remission in rheumatoid arthritis (RA) is an increasingly attainable goal, but there is no widely used definition of remission that is stringent but achievable and could be applied uniformly as an outcome measure in clinical trials. This work was undertaken to develop such a definition. Methods A committee consisting of members of the American College of Rheumatology, the European League Against Rheumatism, and the Outcome Measures in Rheumatology Initiative met to guide the process and review prespecified analyses from RA clinical trials. The committee requested a stringent definition (little, if any, active disease) and decided to use core set measures including, as a minimum, joint counts and levels of an acute-phase reactant to define remission. Members were surveyed to select the level of each core set measure that would be consistent with remission. Candidate definitions of remission were tested, including those that constituted a number of individual measures of remission (Boolean approach) as well as definitions using disease activity indexes. To select a definition of remission, trial data were analysed to examine the added contribution of patient-reported outcomes and the ability of candidate measures to predict later good radiographic and functional outcomes. Results Survey results for the definition of remission suggested indexes at published thresholds and a count of core set measures, with each measure scored as 1 or less (eg, tender and swollen joint counts, C reactive protein (CRP) level, and global assessments on a 0–10 scale). Analyses suggested the need to include a patient-reported measure. Examination of 2-year follow-up data suggested that many candidate definitions performed comparably in terms of predicting later good radiographic and functional outcomes, although 28-joint Disease Activity Score–based measures of remission did not predict good radiographic outcomes as well as the other candidate definitions did. Given these and other considerations, we propose that a patients RA can be defined as being in remission based on one of two definitions: (1) when scores on the tender joint count, swollen joint count, CRP (in mg/dl), and patient global assessment (0–10 scale) are all ≤1, or (2) when the score on the Simplified Disease Activity Index is ≤3.3. Conclusion We propose two new definitions of remission, both of which can be uniformly applied and widely used in RA clinical trials. The authors recommend that one of these be selected as an outcome measure in each trial and that the results on both be reported for each trial.

Autologous haemopoietic stem cell transplantation in a patient with severe pulmonary hypertension complicating connective tissue disease.

Bone marrow transplantation, especially with autologous haemopoietic stem cells, is increasingly being discussed as a treatment for severe life or organ threatening autoimmune diseases. In this context we describe a case so treated. A 47 year old female was referred to our hospital for assessment of increasing chronic cough over three years, associated with NYHA (New York Heart Association) grade II dyspnoea and Raynaud syndrome. She complained of symptoms compatible with reflux oesophagitis but no true dysphagia. Barium swallow was normal. There were no skin changes proximal to the fingers and no telangiectasia. Capillary microscopy showed changes seen with systemic sclerosis. Antinuclear antibodies were positive at 1:640 with a centromere pattern, and the anticentromere antibody was also positive by EUSA to a titre of 1/10 240. Other autoantibodies, including anticardiolipin, were negative, as was the lupus inhibitor test. The hepatic enzymes were raised less than threefold of normal. Tests for antibodies to hepatitis A, B, and C, and smooth muscle and mitochondrial antibodies were negative. Pulmonary assessment showed a normal x ray and high resolution computerised tomography scan of the lungs, normal lung volumes, and a slightly reduced diffusion capacity (69% ofpredicted). Bronchoalveolar lavage revealed normal total cell count but lymphocytosis of 32% (CD4/CD8 3.5). Maximum oxygen uptake was reduced to 72% predicted values (N02max 20.6 ml kg- min-) on exercise testing. Doppler echo showed estimated systolic pulmonary artery pressure (sPAP) of 28 mm Hg, suggesting pulmonary hypertension. Treatment with 0.5 mg kg- prednisolone was given over eight weeks with some improvement of cough and exercise induced hypoxaemia, but it was withdrawn because of side effects. Further management consisted of felodipine (5-10 mg) and omeprazole 20 mg with reasonable control for the next nine months, when a recurring cough and increasing dyspnoea (NYHA grade III) prompted re-evaluation. At this time pulmonary hypertension, with estimated systolic pulmonary artery pressure (PAP) 60 mm Hg and signs of tricuspid incompetence, was observed. VO2max had fallen to 31% predicted (8.9 ml min- kg-). Otherwise the clinical and laboratory observations were unchanged. Prednisone 40

Items for developing revised classification criteria in systemic sclerosis: Results of a consensus exercise

Classification criteria for systemic sclerosis (SSc; scleroderma) are being updated. Our objective was to select a set of items potentially useful for the classification of SSc using consensus procedures, including the Delphi and nominal group techniques (NGT).

Late-onset systemic sclerosis—a systematic survey of the EULAR scleroderma trials and research group database

OBJECTIVEnThe clinical course of SSc depends on subtype, organ involvement and age. Few data are reported on patients suffering from late-onset SSc.nnnMETHODSnWe analysed data from 8554 patients prospectively followed in the EULAR Scleroderma Trials and Research (EUSTAR) group database. Late-onset SSc was defined as onset of non-RP disease features at or beyond 75 years of age. Disease characteristics, clinical features, disease course and mortality were evaluated.nnnRESULTSnA total of 123 patients with SSc onset at or beyond 75 years of age were identified. Compared with patients<75 years they had more frequently limited than diffuse SSc and a higher prevalence of anti-centromere autoantibodies. Fewer old patients had digital ulcers. The modified Rodnans skin score, the prevalence of lung fibrosis and renal crisis did not differ significantly between groups. Pulmonary hypertension (PH) measured by echocardiography was more prevalent in the late-onset group, as well as arterial hypertension and diastolic dysfunction. Late-onset SSc remained a positive predictor for PH in multivariate analyses. No significant difference of the two groups in skin score or diffusion capacity was observed during follow-up. Mortality due to SSc was higher in the late-onset group, but the survival time from diagnosis was longer compared with the younger patients.nnnCONCLUSIONnLate-onset SSc shows a distinct clinical presentation and outcome. Patients with late-onset SSc suffer more frequently from the limited subtype and PH, but fewer patients have digital ulcers. PH may in part be determined by underlying cardiovascular disease.

Hematopoietic stem cell transplantation for the treatment of severe autoimmune diseases

The role of stem cell transplantation in the treatment of severe, therapyrefractory AD remains experimental, with data on around 700 patients being sufficiently encouraging to proceed to randomized prospective trials in the major diseases: SSc, RA, MS, and soon JIA and SLE. An impressive international collaboration has and is reducing duplication of efforts with shared databases, protocols, patient selection, and end points. The concept of resetting a dysbalance in the complex immune network, rather than total eradication of clonal autoimmunity, is emerging. Further clinical trials are required to establish the place, if any, HSCT has in such treatment, and a basic science program continues to explain the pathophysiological mechanisms of these immune-modulating strategies.