Efficacy of B-cell-targeted therapy with rituximab in patients with rheumatoid arthritis.

BACKGROUND: An open-label study indicated that selective depletion of B cells with the use of rituximab led to sustained clinical improvements for patients with rheumatoid arthritis. To confirm these observations, we conducted a randomized, double-blind, controlled study. METHODS: We randomly assigned 161 patients who had active rheumatoid arthritis despite treatment with methotrexate to receive one of four treatments: oral methotrexate (> or =10 mg per week) (control); rituximab (1000 mg on days 1 and 15); rituximab plus cyclophosphamide (750 mg on days 3 and 17); or rituximab plus methotrexate. Responses defined according to the criteria of the American College of Rheumatology (ACR) and the European League against Rheumatism (EULAR) were assessed at week 24 (primary analyses) and week 48 (exploratory analyses). RESULTS: At week 24, the proportion of patients with 50 percent improvement in disease symptoms according to the ACR criteria, the primary end point, was significantly greater with the rituximab-methotrexate combination (43 percent, P=0.005) and the rituximab-cyclophosphamide combination (41 percent, P=0.005) than with methotrexate alone (13 percent). In all groups treated with rituximab, a significantly higher proportion of patients had a 20 percent improvement in disease symptoms according to the ACR criteria (65 to 76 percent vs. 38 percent, P< or =0.025) or had EULAR responses (83 to 85 percent vs. 50 percent, P< or =0.004). All ACR responses were maintained at week 48 in the rituximab-methotrexate group. The majority of adverse events occurred with the first rituximab infusion: at 24 weeks, serious infections occurred in one patient (2.5 percent) in the control group and in four patients (3.3 percent) in the rituximab groups. Peripheral-blood immunoglobulin concentrations remained within normal ranges. CONCLUSIONS: In patients with active rheumatoid arthritis despite methotrexate treatment, a single course of two infusions of rituximab, alone or in combination with either cyclophosphamide or continued methotrexate, provided significant improvement in disease symptoms at both weeks 24 and 48

Randomised controlled trial of Helicobacter pylori eradication in patients on non-steroidal anti-inflammatory drugs: HELP NSAIDs study

Background. The effect of Helicobacter pylori in patients receiving non-steroidal anti-inflammatory drugs (NSAIDs) is unclear. We investigated the effects of H pylori eradication in patients with current or previous peptic ulceration, dyspepsia, or both who continued to use NSAIDs. Methods. 285 patients were randomly assigned omeprazole 20 mg, amoxycillin 100 mg, and clarithromycin 500 mg, twice daily (n = 142, H pylori eradication treatment), or omeprazole with placebo antibiotics (n = 143, controls) for 1 week. All patients received omeprazole 20 mg once daily for 3 weeks until endoscopy, and, if the ulcer was not healed, 40 mg once daily until repeat endoscopy at 8 weeks. Ulcer-free patients with mild dyspepsia continued NSAIDs but not antiulcer treatment. We investigated ulcers with endoscopy at 1, 3, and 6 months and with carbon-13-labelled urea breath test at 3 months. Findings. The estimated probability of being ulcer-free at 6 months was 0.56 (95% CI 0.47-0.65) on eradication treatment and 0.53 (0.44-0.62) on on control treatment (p = 0.80). Time to treatment failure did not differ between groups for ulcers or dyspepsia alone, per-protocol analysis, or final H pylori status. 66% (58-74) of the eradication group compared with 14% (8-20) of the control group had a final negative H pylori result (p < 0.001). Fewer baseline gastric ulcers healed among eradication-treatment patients than among controls (72 vs 100% at 8 weeks, p = 0.006). Interpretation. H pylori eradication in long-term users of NSAIDs with past or current peptic ulcer or troublesome dyspepsia led to impaired healing of gastric ulcers and did not affect the rate of peptic ulcers or dyspepsia over 6 months.Articl