Impact of T-cell costimulation modulation in patients with undifferentiated inflammatory arthritis or very early rheumatoid arthritis: a clinical and imaging study of abatacept (the ADJUST trial).

BACKGROUND: Several agents provide treatment for established rheumatoid arthritis (RA), but a crucial therapeutic goal is to delay/prevent progression of undifferentiated arthritis (UA) or very early RA. OBJECTIVE: To determine the impact of T-cell costimulation modulation in patients with UA or very early RA. METHODS: In this double-blind, phase II, placebocontrolled, 2-year study, anti-cyclic citrullinated peptide (CCP)2-positive patients with UA (not fulfilling the ACR criteria for RA) and clinical synovitis of two or more joints were randomised to abatacept ( approximately 10 mg/kg) or placebo for 6 months; the study drug was then terminated. The primary end point was development of RA (by ACR criteria) at year 1. Patients were monitored by radiography, MRI, CCP2, rheumatoid factor and 28 joint count Disease Activity Score (DAS28) over 2 years. RESULTS: At year 1, 12/26 (46%) abatacept-treated versus 16/24 (67%) placebo-treated patients developed RA (difference (95% CI) -20.5% (-47.4% to 7.8%)). Adjusted mean changes from baseline to year 1 in Genant-modified Sharp radiographic scores for abatacepttreated versus placebo-treated patients, respectively, were 0 versus 1.1 for total score, and 0 versus 0.9 for erosion score. Mean changes from baseline to year 1 in MRI erosion, osteitis and synovitis scores were 0, 0.2 and 0.2, respectively, versus 5.0, 6.7 and 2.3 in the abatacept versus placebo groups. Safety was comparable between groups; serious adverse events occurred in one patient (3.6%) in each group. CONCLUSION: Abatacept delayed progression of UA/very early RA in some patients. An impact on radiographic and MRI inhibition was seen, which was maintained for 6 months after treatment stopped. This suggests that it is possible to alter the progression of RA by modulating T-cell responses at a very early stage of disease. Trial registration number NCT00124449.

Duodenal and gastric ulcer healing rates: a review.

The H2-receptor antagonists ranitidine and cimetidine are more effective than placebo in healing duodenal and gastric ulcers. However, the results of many studies suggest that a significant number of patients respond to treatment with placebo. In general, gastric ulcers respond somewhat more slowly to H2-receptor antagonists than do duodenal ulcers. Comparison trials between ranitidine and cimetidine indicate that both agents are equally effective in healing duodenal ulcers. With gastric ulcers, the results are variable, and neither agent is as effective as in the treatment of duodenal ulcer.

Systemic sclerosis (scleroderma). Clinical management of its major complications.

Systemic sclerosis (scleroderma) is a disease of unknown cause whose pathogenesis involves interaction between the vasculature, the immune system, and connective tissue cells. Although specific therapy awaits a better understanding of its pathogenesis, proper management may enhance not only the duration, but the quality of life for most scleroderma patients. Presently, controlled prospective trials of therapeutic agents are lacking. Published reports of drug therapy for skin, kidney, cardiac, pulmonary, and gastrointestinal complications, as well as management of Raynaud's phenomenon, are critically reviewed in this article, and the authors' approach to management of difficult clinical problems is presented.