Objective: To evaluate the ability of tocilizumab (a humanised anti-IL-6 receptor antibody) monotherapy to inhibit progression of structural joint damage in patients with RA. Methods: In a multi-centre, x ray reader-blinded, randomised, controlled trial, 306 patients with active RA of ,5 years' duration were allocated to receive either tocilizumab monotherapy at 8 mg/kg intravenously every 4 weeks or conventional disease-modifying antirheumatic drugs (DMARDs) for 52 weeks. Radiographs of hands and forefeet were scored by the van der Heijde modified Sharp method. Results: Patients had a mean disease duration of 2.3 years and a disease activity score in 28 joints of 6.5 at baseline. Mean total modified Sharp score (TSS) was 29.4, which was very high despite the relatively short disease duration. At week 52, the tocilizumab group showed statistically significantly less radiographic change in TSS (mean 2.3; 95% CI 1.5 to 3.2) than the DMARD group (mean 6.1; 95% CI 4.2 to 8.0; p,0.01). Tocilizumab monotherapy also improved signs and symptoms. The overall incidences of AEs were 89% and 82% (serious AEs: 18% and 13%; serious infections: 7.6% and 4.1%) in the tocilizumab and DMARD groups, respectively. Conclusion: Tocilizumab monotherapy was generally well tolerated and provided radiographic benefit in patients with RA.
To assess the association between HLA-DRB1 and the pathogenesis of rheumatoid arthritis (RA) in the Japanese population, we typed for HLA-DRB1 alleles in 852 Japanese patients. An analysis of HLA-DRB1 allele associations was performed on the overall group and in three disease subsets of adult-onset RA, classified according to the extent of joint destruction evident on plain radiograms, i.e. least erosive subset (LES), more erosive subset (MES) and most erosive subset with mutilating disease (MUD). The Japanese RA patients with positively associated with DRB1*0101 and *0405, and negatively associated with DRB1*0701, *0802, *1302 and *1405. DRB1*0101 was associated more strongly with a milder disease subset and the relative risk (RR) was 1.9, 1.5 and 1.2 for LES, MES and MUD, respectively. On the other hand, DRB1*0405 was associated more strongly with a more severe disease subset, the RR being 1.8, 4.0 and 4.3 for LES, MES and MUD, respectively. These findings suggest that RA is a heterogeneous disease, not only clinically, but also in terms of its immunogenetic background, and that HLA-DRB1 can be a useful prognostic factor for RA.
Hydroxyapatite (HA) granules of 100 to 300 microm, 0.9 to 1.2 mm and 3.0 to 5.0 mm were mixed in a ratio of 10:45:45 and packed into massive bone deficiencies in revision operations for total hip arthroplasty. We did not use additional graft or cup support for deficiencies of the lateral and medial wall. The procedure was carried out in 40 hips between 1986 and 1992. The radiographic spaces seen at the interface between HA and bone immediately after surgery disappeared within three months. Some spaces appeared between HA granules near the bone in the lateral part of two joints, and three sockets migrated in patients with severe segmental and cavitary deficiencies. Direct bonding of HA to bone was observed radiologically without morphological changes, except in the three joints with migration. All patients could walk without pain but the three with definite loosening needed crutches.
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