Objective. To determine the safety and efficacy of intravenous (IV) pamidronate treatment in ankylosing spondylitis (AS) patients who have had a suboptimal response to nonsteroidal antiinflammatory drugs (NSAIDs).Methods. Pamidronate at 60 mg was compared with pamidronate at 10 mg rather than placebo in view of the high incidence of transient arthralgias upon first IV exposure to the drug. The drug were given monthly for 6 months in a randomized, double-blind, controlled trial. The inclusion criterion was active disease (Bath AS Disease Activity Index [BASDAI] of >4 or morning stiffness of >45 minutes) despite stable NSAID therapy. The primary outcome measure was the BASDAI, and secondary outcomes included the Bath AS Functional Index (BASFI), Bath AS Global Index (BASGI), Bath AS Metrology Index (BASMI), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) level, and percentage of patients achieving a reduction of >25% in the BASDAI. Outcome assessments were done at ؊2, 0, 12, and 24 weeks, and analysis was by intent to treat.
Results. Eighty-four AS patients (67 men and 17women; mean age 39.6 years and mean disease duration 15.1 years) were enrolled. Dosage groups were well matched at baseline for demographics, disease activity, and functional indices. At 6 months, the mean BASDAI had decreased by 2.22 (34.5%) in the 60-mg group and by 0.93 (15%) in the 10-mg group (P ؍ 0.002). Significantly greater reductions in the 60-mg group were also noted for the BASFI (P < 0.001), BASGI (P ؍ 0.01), and BASMI (P ؍ 0.03). Significantly more patients achieved a reduction of >25% in the BASDAI in the 60-mg group versus the 10-mg group (63.4% versus 30.2%; P ؍ 0.004). Differences in ESR/CRP were not significant (NS). Withdrawals included 9 (20.9%) from the 10-mg group and 3 (7.3%) from the 60-mg group (P NS). Adverse events were confined to transient arthralgias/ myalgias after the first IV infusion, occurring in 68.3% and 46.5% of patients in the 60-mg and 10-mg groups, respectively (P NS).Conclusion. Pamidronate has dose-dependent therapeutic properties in AS.
The HLA genetic region was studied in 51 patients with systemic onset juvenile rheumatoid arthritis: 35 with childhood onset and 16 with adult onset (adult Still's disease). HLA genotypes were established by including family members, 261 of whom were also typed in the study. The most marked difference between patients and controls involved the HLA-DR4 gene, which occurred with a frequency of 0.348 in the childhood onset patients and 0.170 in the controls (x2 = 8.97, P = 0.0028, adjusted P = 0.017). In contrast, the adult onset patients showed a marginal increase in HLA-DR7, but were similar to controls with respect to HLA-DR4. HLA-Bw35 was increased in children with systemic onset disease, in accordance with earlier findings. The results suggest that patients with systemic onset juvenile rheumatoid arthritis have complex HLA associations which are different in childhood onset and adult onset disease.
Takayasu's arteritis (TA) is a rare granulomatous vasculitic disease that affects the aorta and its major branches. Recent studies have suggested that anti-TNFα biological therapies are highly effective in treating TA refractory to conventional immunosuppressive therapy. We describe two patients with TA: one with progressive TA despite management with two different anti-TNFα agents, infliximab and adalimumab, and another who developed TA while treated with infliximab for the management of pre-existing Crohn's disease. From our observations, we believe that a multicentered randomized study should be designed to assess the extent of resistance to these agents when different therapeutic doses are employed for managing TA.
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