Treating rheumatoid arthritis early with disease modifying drugs reduces joint damage: a randomised double blind trial of sulphasalazine vs diclofenac sodium.

BACKGROUND: Current disease management in rheumatoid arthritis (RA) has moved towards "inverting the therapeutic pyramid" by introducing disease-modifying anti-rheumatic drugs (DMARDs) early. Despite the logic of early DMARD therapy, there is a dearth of supportive evidence for this approach. We report a randomised controlled trial comparing sulphasalazine monotherapy with diclofenac monotherapy in early RA. The primary aim was to provide unequivocal evidence that early DMARDs prevent erosive damage. The secondary aim was to evaluate if sulphasalazine used alone has comparable symptomatic benefits to NSAIDs. METHODS: 117 patients with RA for under 12 months of diagnosis (mean 2 months) were randomised (62 sulphasalazine; 55 diclofenac). Sulphasalazine patients comprised 76% women, and 58% were rheumatoidfactor positive. Diclofenac patients comprised 74% women, and 54% were seropositive. 36% completed 12 months of therapy (16 sulphasalazine; 26 diclofenac); sulphasalazine was given for a mean period of 21 weeks and diclofenac for a mean period of 33 weeks. Results were analysed on an intention to treat basis. RESULTS: After 12 months the mean number of new erosions in patients randomised to receive sulphasalazine was 2.0 (95%CI 0.9, 3.1) and in patients randomised to receive diclofenac was 7.5 (95%CI 4.1, 10.9; p = 0.002 by Student's unpaired t-test). An analysis of valid compliant completers showed the mean number of new erosions in patients who received 12 months therapy with sulphasalazine was 2.3 (95%CI 0.6, 4.0) and in patients who received 12 months diclofenac was 10.5 (95%CI 5.0, 15.9; p = 0.018 by Student's unpaired t-test). The Ritchie articular index, swollen joint counts and pain scores decreased with both sulphasalazine and diclofenac, with mean falls in both groups of 15-20% at 2 weeks and 30-40% at 4 and 8 weeks. There were no differences between treatments. Disease activity scores showed similar highly significant mean decreases within both treatment groups (P < 0.001 in all cases) of 0.5 at 2 weeks and 1.0 at 4 weeks; at 12 and 26 weeks they were significantly lower with sulphasalazine (p = 0.036 and 0.045). 75% of the patients given sulphasalazine and 65% of those given diclofenac had one or more adverse events with no major differences between treatments. CONCLUSIONS: These results show that an accelerated dosing schedule of sulphasalazine has identical effects to diclofenac in reducing symptoms, indicating it is a rapidly effective DMARD. They also provide unequivocal evidence, analysed on an intention to treat basis, that early treatment with sulphasalazine significantly reduces the extent of radiological progression in active RA.

In vitro duodenal iron uptake and serum and mucosal iron protein levels, with special reference to rheumatoid arthritis.

Duodenal biopsies from control subjects, patients with iron-deficiency anaemia and rheumatoid arthritic patients with anaemia of chronic disorders (ACD) were investigated for their ability to take up 59Fe from iron ascorbate. Additionally, duodenal tissues were analysed for iron and immunoreactive ferritin and transferrin. Biopsies from iron-deficient subjects showed a 2- to 3-fold increase in the apparent Vmax for 59Fe uptake, compared to control values. Uptake was inversely related to body iron stores. ACD patients showed similar rates of 59Fe uptake to controls; the rates were independent of the degree of anaemia or serum ferritin levels. Tissue analysis showed reductions in mucosal iron and ferritin levels in iron-deficient patients, whilst transferrin levels were within the normal range. ACD patients also exhibited lower mucosal iron levels, but had iron protein levels within the normal range. It is suggested that factors distant from the intestinal mucosa influence iron absorption in ACD.

A prognostic index for erosive changes in the hands, feet, and cervical spines in early rheumatoid arthritis.

Clinical and laboratory measurements taken at the onset of rheumatoid arthritis in 149 patients were compared with the severity of radiological changes seen at 3 years in the hands and feet, and cervical spine. The strongest association with the severity of peripheral radiological damage was rheumatoid factor (p less than 0.0001 for both the latex titre and RAHA titre). Subluxation of the cervical spine was associated only with the presence of HLA-Dw2 (p less than 0.02) and HLA-B7 cross-reacting group (p less than 0.02). Discriminant function analysis utilizing latex titre, RAHA titre, haemoglobin level, and platelet count predicted the development of erosive or nonerosive disease in 79%. This method was less successful in predicting the actual severity of erosive damage and was not improved by the addition of HLA data. Radiological outcome in the cervical spine was successfully predicted in 82% using HLA-Dw2, HLA-B27 and age of onset of disease. It is concluded that the best predictors of erosive disease were standard laboratory features measured at onset, but that more powerful discriminant factors are needed if these are to influence clinical practice. Further prospective studies will establish whether rheumatoid involvement of the cervical spine is an expression of the influence of HLA determinants in this disease.