Diclofenac/misoprostol compared with diclofenac in the treatment of osteoarthritis of the knee or hip: a randomized, placebo controlled trial. Arthrotec Osteoarthritis Study Group.

OBJECTIVE: Gastric (GU) and duodenal ulcers (DU) are common adverse effects of nonsteroidal anti-inflammatory drugs (NSAID). Endoscopically diagnosed upper gastrointestinal (GI) ulceration occurs in about 24% of longterm NSAID users. Coadministration of misoprostol with the NSAID reduces the incidence of NSAID induced GU and DU and their complications. However, compliance is limited by the different dosing regimens of misoprostol and NSAID and GI symptoms associated with misoprostol at its recommended q.i.d. dose. We compared the efficacy, safety, and incidence of endoscopic upper GI ulceration associated with the administration of 2 combinations of diclofenac (50 or 75 mg) and misoprostol 200 microg (D50/M200 t.i.d., D75/M200 b.i.d.), diclofenac 75 mg b.i.d., and placebo in a 6 week, randomized, double blind study in patients with osteoarthritis (OA) of the knee or hip. METHODS: A total of 572 patients with symptomatic OA of the knee or hip and history of GU, DU. or 10 or more erosions were randomized to receive D50/M200 t.i.d., D75/M200 b.i.d., diclofenac 75 mg b.i.d., or placebo for 6 weeks. Arthritis assessments were performed at baseline, 2, and 6 weeks, and upper GI endoscopies at baseline and end of treatment. RESULTS: All active treatment groups were significantly better than placebo, at all visits, in improving OA symptoms. There were no significant differences in arthritis efficacy between the diclofenac/ misoprostol combinations and diclofenac. However, endoscopically diagnosed GU and/or DU were significantly less frequent in patients receiving D50/M200 t.i.d. (8%), D75/M200 b.i.d. (7%), and placebo (4%) compared to diclofenac 75 mg b.i.d. (17%). Adverse events were not different between the active treatment groups, except for higher incidences of flatulence with D75/M200 and diarrhea with D50/M200. CONCLUSION: Diclofenac 50 mg/misoprostol 200 microg t.i.d. and diclofenac 75 mg/misoprostol 200 microg b.i.d. are as efficacious as diclofenac 75 mg b.i.d. in the treatment of OA, but are associated with a significantly lower incidence of gastric and/or duodenal ulcers.

Tenidap in rheumatoid arthritis. A 24-week double-blind comparison with hydroxychloroquine-plus-piroxicam, and piroxicam alone.

OBJECTIVE: To compare the clinical efficacy, effect on serum C-reactive protein (CRP), serum amyloid A (SAA), and plasma interleukin-6 (IL-6) levels, and safety of tenidap with a combination of hydroxychloroquine-plus-piroxicam, and piroxicam alone, in the treatment of rheumatoid arthritis (RA) patients. METHODS: A double-blind, randomized, multicenter study in which patients with active RA were treated with tenidap 120 mg/day, hydroxychloroquine 400 mg/day and piroxicam 20 mg/day, or piroxicam alone 20 mg/day, for 24 weeks. RESULTS: At weeks 12 and 24, tenidap produced greater improvements than piroxicam based on 5 primary efficacy parameters; this improvement showed statistical significance in 4 of the 5 measures at week 12, and in 3 of the 5 measures at week 24. Clinical improvements in the hydroxychloroquine-plus-piroxicam-treated with tenidap. Compared with piroxicam, tenidap was associated with significantly greater reductions in serum CRP concentrations at 4, 12, and 24 weeks, and significantly greater reductions in SAA concentrations at weeks 12 and 24. The decrease in SAA concentrations was also significantly greater at weeks 4 and 24 in the tenidap-treated group than in the hydroxychloroquine-plus-piroxicam-treated group. Significant reductions in plasma IL-6 levels were observed at weeks 4, 12, and 24 within the tenidap group, and at week 24 within the hydroxychloroquine-plus-piroxicam-treated group. The overall occurrence of side effects, including gastrointestinal side effects, was similar in all 3 treatment groups. A small proportion of tenidap-treated patients (6.4%) manifested mild, nonprogressive, reversible proteinuria of presumed renal proximal tubular origin, and 3-4% of patients had elevated transaminase levels. CONCLUSION: In the treatment of patients with RA, tenidap is as effective as the combination of hydroxychloroquine-plus-piroxicam, and is more effective than piroxicam alone; moreover, tenidap's safety profile is comparable to that observed with piroxicam alone, and with hydroxychloroquine-plus-piroxicam. The clinical response observed in this study, as well as the prompt decreases in acute-phase protein levels of CRP and SAA, and in plasma IL-6 levels, suggest that tenidap represents a new type of antiarthritic medication, with properties similar to, but not identical to, a therapeutic combination of a nonsteroidal antiinflammatory drug with disease-modifying antirheumatic drugs.

Short-course ciprofloxacin treatment of acute uncomplicated urinary tract infection in women. The minimum effective dose. The Urinary Tract Infection Study Group [corrected].

BACKGROUND: Three studies were undertaken to determine the minimum effective dosing regimen of ciprofloxacin for the treatment of acute, symptomatic, uncomplicated lower urinary tract infection. METHODS: All studies were multicenter, prospective, randomized, double-blind trials. A total of 970 evaluable patients with a diagnosis of urinary tract infection received oral ciprofloxacin (200 mg to 500 mg daily in one or two divided doses for 1, 3, 5, or 7 days) or norfloxacin (400 mg twice daily [BID] for 7 days). The primary measure of efficacy was bacteriologic eradication at the end of therapy. RESULTS: In study 1, bacteriologic eradication was reported in 95 (89%) and 101 (98%) of patients in the groups who received ciprofloxacin, 500-mg single dose and 250 mg BID for 7 days, respectively. Clinical success occurred in 101 patients (94%) who received a 500-mg single dose and in 103 patients (100%) who were administered 250 mg BID for 7 days. In study 2, eradication rates in the groups who received ciprofloxacin, 100 mg BID for 3 days, 250 mg BID for 3 days, and 250 mg BID for 7 days, were 98 (93%), 95 (90%), and 98 (93%), respectively. Clinical success was reported in 102 (97%), 105 (100%), and 104 (98%) of the patients, respectively. In study 3, the eradication rates in the groups who received ciprofloxacin in dosages of 500 mg once daily for 3 days and 500 mg once daily for 5 days and norfloxacin in a dosage of 400 mg BID for 7 days were 137 (92%), 134 (90%), and 133 (94%) of the women, respectively. Clinical success was the same (97%) in all three groups. Overall, short-course (either 3- or 5-day) therapy with ciprofloxacin was statistically equivalent to conventional (7-day) therapy with either ciprofloxacin or norfloxacin. Single-dose ciprofloxacin therapy was statistically less effective than conventional treatment. CONCLUSIONS: Ciprofloxacin at a dosage of 100 mg BID for 3 days was the minimum effective dose for the treatment of uncomplicated urinary tract infection in women.

Lack of immunosuppressive effect of low-dose oral methotrexate on lymphocytes in rheumatoid arthritis.

Whether methotrexate (MTX) is effective in rheumatoid arthritis (RA) because of immunosuppressive and/or anti-inflammatory mechanisms of action is controversial. Many lines of investigation point to the latter. We evaluated DNA synthesis in peripheral blood lymphocytes (PBL) from 33 RA patients on oral MTX (7.5-15 mg/wk) and in 30 healthy controls by flow cytometric cell cycle analysis (CCA). DNA synthesis was also evaluated with a thymidilate synthetase activity assay (TSA) (3H-deoxyuridine incorporation) in 12 patients and 21 controls (12 on MTX and NSAID, and 9 healthy subjects). The patients had taken MTX for at least 3 months and were in different stages of clinical activity. There were no significant differences in TSA or in the cell cycle phase distributions (especially the S phase) between treated RA patients and controls. These data suggest that low-dose oral MTX does not inhibit DNA synthesis and therefore does not have an immunosuppressive effect on lymphocytes from patients with RA.