Fifty-two patients with severe rheumatoid arthritis (RA) from four Australian centres were randomised to receive cyclosporin A (CSA) (n = 25) or azathioprine (AZA) (n = 27) for six months. Initial mean doses of CSA and AZA were 4.2 mg/kg and 1.7 mg/kg respectively. The mean doses of CSA and AZA at six months were 3.4 mg/kg and 1.9 mg/kg. Assessments of side-effects and outcomes of benefit were made monthly by independent, blinded observers. Both treatment groups exhibited statistically significant improvement in standard outcome parameters when compared with baseline values. However, there were no statistically significant differences in these parameters between the two groups. There was a mean increase in serum creatinine concentration associated with CSA; no persons were withdrawn from the study for this reason. Seven CSA recipients (three gastrointestinal symptoms, two neurological symptoms, two other) and 12 AZA recipients (six gastrointestinal symptoms, four inefficacy, two other) withdrew from treatment prematurely. Seven CSA recipients became hypertensive and four required anti-hypertensive therapy. Adverse events not requiring cessation of therapy were more commonly seen among CSA patients. In this group of severely affected patients with RA both cyclosporin and azathioprine were effective therapies. CSA toxicities were predictable and manageable but required close monitoring.

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SUMMARYInclusion body myositis (IBM) is defined clinically by a characteristic pattern of progressive proximal and distal limb muscle weakness and resistance to steroid therapy, and histologically by the presence of distinctive rimmed vacuoles and filamentous inclusions as well as a mononuclear infiltrate in which CD8"^ T cells are predominant. Muscle damage is believed to be mediated by autoimmune mechanisms, but very little information is available on the immunogenic features of IBM. MHC class I and DR antigens were typed on 13 caucasoid patients with IBM using standard serological techniques or by allele-specific oligonucleotide typing. Complement components C4 and properdin factor B (Bf) were typed by immunofixation after electrophoresis. Restriction fragment length polymorphisms (RFLP) in the class ITT region were analysed using cDNA probes for C4 and 21-hydroxylase (CYP21) after Taq 1 digestion. IBM was associated with DR3 (92%), DR52 (100%) and HLA B8 (75%). The phenotype data were examined for likely haplotypes by considering together the alleles at the class T, DR and complement loci along with the C4 and CYP21 RFLP. TenoftheDR3 * subjects had a 6 4-kb C4-hybridizing fragment characteristic of a deletion of C4A and CYP21-A. These patients probably carried all, or at least the class 11 and HI regions, of the extended haplotype marked by B8/C4A*Q0/C4Bl/BfS/DR3/DR52, which has been associated with several autoimmune diseases and is present in 11 % of the healthy caucasoid population. Of the remaining subjects, two had evidence of the extended haplotype marked by B]8/C4A3/C4BQ*0/BfFl/DR3, which is present in less than 5% of the healthy population and has been associated with insulin-dependent diabetes mellitus. These data provide support for an autoimmune etiology for, and genetic predisposition to, IBM.

ResultsThe group treated with folinic acid (13 patients) and the placebo group (14 patients) were of comparable mean age (59-8 (3-6) and 62-8 (35) years respectively), sex distribution, rheumatoid factor status, and disease activity at entry (figure). The weekly doses of methotrexate were 7-9 (06) mg in the group treated with folinic