J A Hunter

Effect of disease modifying agents on the lipid profiles of patients with rheumatoid arthritis

OBJECTIVE To determine the effect of intramuscular gold and oral hydroxychloroquine(HCQ) on the lipid profile of patients with rheumatoid arthritis (RA). METHOD A prospective randomised clinical trial of 12 months’ duration was performed in 100 RA patients. Data on clinical and laboratory parameters of disease activity, and fasting serum lipid samples was collected at baseline and at three monthly intervals over one year. RESULTS The expected second line response was seen with no significant difference in efficacy between the groups at 12 months. The HCQ group had a significant overall improvement in their lipid profile while there was a trend for lipid profiles in the gold group to worsen. CONCLUSIONS HCQ is an effective second line agent that has beneficial effects on serum lipids. This should be taken into account when choosing a disease modifying anti-rheumatic drug in patients who suffer from RA and who have significant cardiovascular risk factors.

Combination therapy with sulfasalazine and methotrexate is more effective than either drug alone in patients with rheumatoid arthritis with a suboptimal response to sulfasalazine: results from the double-blind placebo-controlled MASCOT study

Background: Optimal use of disease-modifying antirheumatic drugs (DMARDs) in rheumatoid arthritis is vital if progression of disease is to be reduced. Methotrexate (MTX) and sulfasalazine (SASP) are widely used inexpensive DMARDs, recently often combined despite no firm evidence of benefit from previous studies. Aim: To establish whether a combination of SASP and MTX is superior to either drug alone in patients with rheumatoid arthritis with a suboptimal response to 6 months of SASP. Methods: A randomised controlled study of step-up DMARD treatment in early rheumatoid arthritis. In phase I, 687 patients received SASP for 6 months. Those with a disease activity score (DAS) ⩾2.4 were offered additional treatment in phase II (SASP alone, MTX alone or a combination of the two). The primary outcome measure was change in DAS. Results: At 6 months, 191 (28%) patients had a DAS <2.4, 123 (18%) were eligible but did not wish to enter phase II, 130 (19%) stopped SASP because of reversible adverse events and 165 (24%) entered phase II. DAS at 18 months was significantly lower in those who received combination treatment compared with those who received either SASP or MTX: monotherapy arms did not differ. Improvement in European League Against Rheumatism and American College of Rheumatology 20, 50 and 70 scores favoured combination therapy. Conclusions: In this “true-to-life” study, an inexpensive combination of DMARDs proved more effective than monotherapy in patients with rheumatoid arthritis with a suboptimal response to SASP. There was no increase in toxicity. These results provide an evidence base for the use of this combination as a component of tight control strategies.

A risk-benefit assessment of intra-articular corticosteroids in rheumatic disorders.

The appeal of intra-articular corticosteroid therapy has increased with the growing emphasis on early disease control in rheumatoid disease. The impact on the patient’s pain and stiffness is impressive and prompt. This may encourage patient compliance with longer term therapies given to slow the course of the disease. The release of corticosteroid into the circulation also provides some generalised improvement. This can prove helpful during the management of flares of inflammatory disease.There is less evidence to support the use of intra-articular corticosteroids in other inflammatory arthritides, but experience suggests that the benefits are similar. In osteoarthritis the benefits are less certain, but intra-articular therapy may prove important in patients who cannot undergo salvage operative procedures because of intercurrent illness.The benefits of intra-articular corticosteroids may be enhanced by rest after the injection, or by the additional administration of agents such as radio-colloids, rifampicin (rifampin), or osmic acid. Most controlled trial data have been published on knee injections, but other joints can be useful targets for local therapy.The risks are mainly related to the discomfort of the procedure, localised pain post-injection and flushing, but most feared is septic arthritis which probably occurs in about 1 in 10 000 injections. Careful aseptic technique is the best protection. Tissue atrophy at the injection site, abnormal uterine bleeding, hypertension and hyperglycaemia rarely cause problems. Osteonecrosis might be as much a problem with uncontrolled painful arthritis as with a joint rendered less symptomatic by corticosteroid injections.Intra-articular corticosteroids form an important part of the management of inflammatory joint disease and might be considered where an inflammatory element occurs in osteoarthritis. They may be used at any stage in the arthritic process, but should be seen as an adjunct to other forms of symptom relief. In patients needing multiple joint injections, systemic therapy should be reviewed to see if better disease control could reduce the need for invasive therapy.

Effect of acetylator phenotype on efficacy and toxicity of sulphasalazine in rheumatoid arthritis.

A group of 54 patients with rheumatoid arthritis (31 fast, 23 slow acetylators) treated with sulphasalazine 3 g/day were studied retrospectively. At 24 weeks no difference in the efficacy of the drug could be shown between fast and slow acetylators. In a second prospective study 40 fast acetylators were allocated to 3 g/day and 20 slow acetylators to 1.5 g/day. At 24 weeks marked improvement was seen in the fast acetylators given high dose but not the slow acetylators given low dose. It was also noted in this study that the usual ratio of fast : slow acetylators was reversed, and there is some suggestion that fast acetylators may be predisposed to more severe rheumatoid arthritis. The toxicity pattern in a total of 149 patients (83 fast, 66 slow acetylators) was also studied. Significantly more slow acetylators stopped treatment because of nausea or vomiting, or both, but serious toxicity was not confined to either group. Acetylator phenotype therefore appears important in determining the incidence of nausea and/or vomiting associated with sulphasalazine therapy in patients with rheumatoid arthritis but has no effect on the occurrence of potentially serious toxicity or efficacy. Thus prior measurement of acetylator phenotype in patients with rheumatoid arthritis confers little practical benefit in their management.

Preliminary experience of 99mTc-Aprotinin scintigraphy in amyloidosis

Background and aim:  Radio‐labelled Aprotinin has been shown to bind with amyloid fibrils in vitro as well as in vivo. The aim was to test the usefulness of 99mTc‐Aprotinin imaging in systemic amyloidosis.

Health-related utility values of patients with primary Sjögren's syndrome and its predictors

Objectives EuroQoL-5 dimension (EQ-5D) is a standardised preference-based tool for measurement of health-related quality of life and EQ-5D utility values can be converted to quality-adjusted life years (QALYs) to aid cost-utility analysis. This study aimed to evaluate the EQ-5D utility values of 639 patients with primary Sjögrens syndrome (PSS) in the UK. Methods Prospective data collected using a standardised pro forma were compared with UK normative data. Relationships between utility values and the clinical and laboratory features of PSS were explored. Results The proportion of patients with PSS reporting any problem in mobility, self-care, usual activities, pain/discomfort and anxiety/depression were 42.2%, 16.7%, 56.6%, 80.6% and 49.4%, respectively, compared with 5.4%, 1.6%, 7.9%, 30.2% and 15.7% for the UK general population. The median EQ-5D utility value was 0.691 (IQR 0.587–0.796, range −0.239 to 1.000) with a bimodal distribution. Bivariate correlation analysis revealed significant correlations between EQ-5D utility values and many clinical features of PSS, but most strongly with pain, depression and fatigue (R values>0.5). After adjusting for age and sex differences, multiple regression analysis identified pain and depression as the two most important predictors of EQ-5D utility values, accounting for 48% of the variability. Anxiety, fatigue and body mass index were other statistically significant predictors, but they accounted for <5% in variability. Conclusions This is the first report on the EQ-5D utility values of patients with PSS. These patients have significantly impaired utility values compared with the UK general population. EQ-5D utility values are significantly related to pain and depression scores in PSS.

Comparative study of intramuscular gold and methotrexate in a rheumatoid arthritis population from a socially deprived area

OBJECTIVE To compare the risk-benefit ratio of intramuscular gold (gold sodium thiomalate (GST)) and methotrexate (MTX) in a population with rheumatoid arthritis (RA) from a deprived area. METHODS Patients with active RA were randomly assigned to open treatment with GST or MTX. Clinical and laboratory assessment was performed at 0, 12, 24, and 48 weeks. Results were analysed on an intention to treat basis. RESULTS 141 patients were recruited—72 were randomly allocated to GST and 69 to MTX. There were no statistically significant differences found in either the clinical or demographic variables at baseline. At 48 weeks 31 (43%) patients continued to receive GST and 43 (62%) MTX. The median MTX dose achieved was 10 mg. Gold caused significantly more withdrawals for toxicity (43% GST v 19% MTX, p=0.0026, log rank test). Both groups experienced a significant improvement in erythrocyte sedimentation rate, C reactive protein, Ritchie Articular Index, and pain score by 24 weeks (p<0.001, Friedman test). Although a trend towards an improved Health Assessment Questionnaire (HAQ) score and global wellbeing was seen in both groups, this did not reach statistical significance. No differences in efficacy were found when the two groups were compared (Mann-Whitney). CONCLUSION GST and low dose MTX showed equivalent efficacy, but toxicity was more common in patients treated with GST. GST, although more toxic, remains a useful alternative for patients in whom MTX is contraindicated.

Cardiovascular risk factors in women with primary Sjögren's syndrome: United Kingdom primary Sjögren's syndrome registry results

To determine the prevalence of traditional cardiovascular risk factors using established definitions in a large cohort of clinically well‐characterized primary Sjögrens syndrome (SS) patients and to compare them to healthy controls.

Second line (disease modifying) treatment in rheumatoid arthritis: which drug for which patient?

OBJECTIVES--The objectives were to assess (a) the comparative merits of commonly used disease modifying drugs in the treatment of rheumatoid arthritis (RA) and (b) the influence of age, gender, and disease duration on the outcome of treatment. METHODS--Collected analysis (meta-analysis) was performed on results obtained during the first year of treatment in 1140 patients with RA treated with gold, penicillamine, sulphasalazine, or auranofin from a single centre. RESULTS--Gold, penicillamine, and sulphasalazine performed similarly, with about 60% of patients continuing to receive each of these drugs for at least one year. Neither gender nor age had an influence on the response to treatment, but patients with a longer disease duration showed a greater tendency to stop treatment. The median percentage improvement was 33% in visual analogue pain score and 50% in erythrocyte sedimentation rate. CONCLUSIONS--Routine use of these drugs should at least equal these results. Any new drug should either be substantially less toxic or at least as efficacious.

Soluble molecule profiling and network analysis of primary Sjögren's Syndrome patient serum

Background Primary Sjogren’s Syndrome (pSS) is a chronic autoimmune syndrome characterised by sicca symptoms, fatigue, musculoskeletal pain and an increased risk of lymphoma. Patient populations are notably heterogeneous in their symptoms, adding to the challenge of pSS research. This study utilises serum samples from the UK Primary Sjogren’s Syndrome Registry (UKPSSR) a large cohort of clinically well-characterised pSS patients and healthy controls with an aim to determine whether serum cytokines, chemokines and adhesion molecules may be used to differentiate pSS patients from healthy controls.