Efficacy Of Nabumetone Research Articles

Tolerability and efficacy of nabumetone and naproxen in the treatment of rheumatoid arthritis

The purpose of this study was to compare the tolerability and efficacy of nabumetone and naproxen in the treatment of patients with rheumatoid arthritis (RA). The occurrence of gastrointestinal (GI) adverse events was compared. Nonsteroidal anti-inflammatory drugs (NSAIDs) have similar efficacy at equipotent doses, but the therapeutic response to various NSAIDs often differs in individual patients. This was a 3-month, randomized, double-blind, multicenter, parallel-group study conducted in adult patients with RA. The study had 2 phases: a 3- to 14-day washout period and a 12-week treatment period. During the treatment phase, the tolerability and efficacy of nabumetone 2000 mg/d were compared with those of naproxen 1000 mg/d. The change from baseline in efficacy variables, including global assessments, number of tender or swollen joints, and pain, was evaluated. The study was sized to provide an 80% power to detect a 15% difference in the percentage improvement on the physician's global assessment (alpha = 0.05). GI safety was assessed by monitoring the occurrence of clinically important adverse GI events. A total of 346 RA patients at 31 US rheumatology centers were randomly assigned to treatment (173 patients per group). The study population was predominantly white (87.0%) and female (70.5%), with a mean age of 54 years. Both treatments improved the signs and symptoms of RA, with no statistically significant differences between groups for any efficacy variables. No serious GI adverse events occurred with either NSAID. The most frequent treatment-related adverse events in both groups were predominantly GI in origin, as were those that resulted in withdrawal from the study. Diarrhea with lower abdominal pain was the most common adverse event in the nabumetone group; upper abdominal pain was the most common adverse event in the naproxen group. The only significant difference between the 2 groups was a higher incidence of diarrhea (P < 0.01) in patients receiving nabumetone. Nabumetone 2000 mg/d was as effective as naproxen 1000 mg/d in relieving the signs and symptoms of RA. In this study, no serious GI adverse events were observed with either NSAID, but nabumetone was associated with a higher incidence of diarrhea.

Efficacy of nabumetone versus diclofenac, naproxen, ibuprofen, and piroxicam in osteoarthritis and rheumatoid arthritis

The efficacy of nabumetone was compared with that of diclofenac, naproxen, ibuprofen, and piroxicam in patients with osteoarthritis (OA) or rheumatoid arthritis (RA) in a randomized, controlled, open-label, multicenter trial. Patients ≥18 years with clinical and radiographic evidence of OA or RA (functional class I, II, or III), who provided written informed consent, were eligible. To mimic real-life therapy, no washout phase preceded randomization. Eligible patients were assigned in a 3:1 ratio to receive nabumetone or a comparator NSAID for 12 weeks. Thus a total of 4,411 eligible patients were randomized to receive nabumetone (N = 3,315) or one of the comparator NSAIDs (N = 1,096). Initial daily doses were: nabumetone, 1,000 mg; diclofenac, 100 mg; naproxen, 500 mg; ibuprofen, 1,200 mg; piroxicam, 10 mg. Dosage increases were permitted after a 2-week trial period. All patients were evaluated at baseline, and at 4 and 12 weeks. Of all patients randomized, approximately 46% had RA and approximately 54% had OA. Demographic characteristics were similar for the nabumetone and comparator NSAID treatment groups. In OA, nabumetone was as effective as the comparator NSAIDs in the physician and patient global assessments of disease activity, in improving the Activities and Lifestyle Index, and in decreasing the degree of pain. There was no significant difference in the percentage of patients withdrawn for lack of efficacy when treated with nabumetone or one of the comparator NSAIDs. In contrast, nabumetone was significantly (p ≤0.02) more effective than the comparator NSAIDs in RA patients for the global assessments of disease activity, pain relief, and improving the Activities and Lifestyle Index, primarily due to the poor response in the ibuprofen and piroxicam treatment groups. Furthermore, fewer nabumetone-treated RA patients (8.8%) withdrew for lack of efficacy than those treated with diclofenac (10.3%), naproxen (11%), piroxicam (13.5%), or ibuprofen (13.2%). In conclusion, in a large, randomized, open-label trial that mimicked real-life therapy, nabumetone was as effective as diclofenac, naproxen, piroxicam, and ibuprofen for the treatment of patients with OA. However, in RA, nabumetone was significantly more effective than the comparator NSAIDs, and fewer patients were withdrawn because of lack of efficacy.

Nabumetone: a "nonacidic" nonsteroidal antiinflammatory drug.

To review the pharmacology, pharmacokinetic disposition, dosage recommendations, adverse effects, drug interactions, and efficacy of nabumetone in patients with selected rheumatic disorders and soft-tissue injuries. Data from scientific literature were extracted, evaluated, and summarized for presentation. A MEDLINE search was conducted using the following indexing terms: antiinflammatory agents, nonsteroidal, nabumetone, rheumatoid arthritis (RA), and osteoarthritis (OA). Studies evaluating nabumetone reported in articles, abstracts, or proceedings involving human subjects were considered for inclusion. Special consideration was given to clinical studies using double-blind, randomized, parallel, controlled designs. Studies comparing the effectiveness and safety of nabumetone with placebo and other nonsteroidal antiinflammatory drugs (NSAIDs) were included. Data from human studies published in the English language were evaluated. Trials were assessed according to study design, sample size, and description of outcomes. Nabumetone is a nonacidic prodrug that is metabolized to an active nonsteroidal antiinflammatory moiety, 6-methoxy-2-naphthylacetic acid (6-MNA). 6-MNA is a structural analog of naproxen. Like naproxen and other NSAIDs, 6-MNA possesses analgesic, antipyretic, and antiinflammatory activity, 6-MNA has a prolonged elimination half-life, ranging from 17 to 74 hours, which allows for once-daily dosing. The efficacy of nabumetone for treating symptoms of RA and OA has been established in controlled clinical trials. Nabumetone also has been studied in ankylosing spondylitis and soft-tissue injuries. Adverse effects associated with nabumetone are similar to those associated with other NSAIDs. Gastrointestinal reactions occur most frequently in the form of abdominal pain or indigestion, nausea, or vomiting. Central nervous system adverse effects occur less frequently, and are followed in order of occurrence by rashes. Nabumetone is a prodrug metabolized to an active metabolite structurally related to naproxen. Studies have demonstrated the efficacy of nabumetone, but no advantages over the many other NSAIDs now available.

A Multicentre General Practice Trial of Nabumetone and Slow-Release Diclofenac in Osteoarthritis

A total of 243 patients were entered at 20 general practice centres in the UK in this 6 week, double-blind, randomised, parallel-group study, which was designed to compare the safety and efficacy of nabumetone (1g at night) and slow-release diclofenac (100mg at night) in the treatment of osteoarthritis. Seven parameters of efficacy were measured, adverse events were recorded and laboratory monitoring was carried out. At the end of the study, both treatment groups showed highly significant clinical improvement with no significant intergroup differences. 24 patients (20%) in the nabumetone group and 21 (17%) in the slow-release diclofenac group withdrew before the end of 6 weeks, mainly because of adverse events. Although overall the incidences of adverse events were similar in both treatment groups, significantly fewer patients complained of digestive system side effects in the nabumetone group (21) than in the slow-release diclofenac group (35) [p = 0.03]. The study was also intended to evaluate the effectiveness of study monitoring by a clinical research associate who attended study centres with a laptop microcomputer to enter trial data. Immediate correction by the trialist of errors and omissions in the data, with on-site data entry on the laptop computer, contributed to trialist motivation and resulted in rapid recruitment of patients, collection of high quality data and speedy analysis at the end of the trial.

Results of a six-month study comparing the safety and efficacy of nabumetone and aspirin in the treatment of osteoarthritis

The safety and efficacy of nabumetone (1,000 mg at bedtime) were compared with those of aspirin (900 mg four times daily) in the treatment of osteoarthritis in adult patients in a private practice setting as part of a six-month, double-blind, controlled, randomized, parallel group study. At screening, baseline, and Days 7, 14, 28, 56, 112, and 168, efficacy was evaluated according to independent assessments by the patients and the physician of overall osteoarthritic activity and pain and by the physician's assessment with respect to a defined activity. Of the 40 patients enrolled, 37 were evaluable for efficacy (19 in the nabumetone group and 18 in the aspirin group). Demographic parameters and diagnostic criteria for osteoarthritis were comparable between the groups, although there was a preponderance of women in the nabumetone group. Significant improvement from baseline in all five efficacy parameters was observed in both groups. Safety was evaluated for all 20 enrolled patients in each group. The percentage of aspirin-treated patients who withdrew from the study due to adverse experiences was greater (60 percent versus 20 percent), as was the number with at least one treatment-related adverse experience (19, or 95 percent, versus 11, or 55 percent). Treatment-related adverse experiences described as moderate or severe were reported by 70 percent of the aspirin-treated patients and by 35 percent of the nabumetone-treated patients. In this study, nabumetone 1,000 mg at bedtime had an acceptable safety profile and was as effective as aspirin 900 mg four times daily in the treatment of osteoarthritis.

Endoscopy-controlled study of the safety of nabumetone compared with naproxen in arthritis therapy

Nonsteroidal anti-inflammatory drug (NSAID) gastropathy is now a commonly recognized and reported complication of such arthritis therapy. Significant gastric lesions develop in up to 40 percent of arthritic patients treated with long-term anti-inflammatory doses of NSAIDs, 20 percent of which represents actual ulcer crater disease. This 12-week endoscopy-controlled, double-blind study was constructed to evaluate the safety and efficacy of nabumetone 1,000 mg at bedtime compared with naproxen 250 mg twice daily. A total of 37 patients completed the study, including 29 patients with a diagnosis of osteoarthritis and eight with a diagnosis of rheumatoid arthritis. By posttreatment endoscopy, nabumetone was significantly less toxic to the gastrointestinal tract than was naproxen. The nabumetone-treated group also showed greater improvement in all efficacy variables, with significant improvement noted in three of these five variables in both rheumatoid and osteoarthritic patients.

Evaluation of nabumetone in the treatment of active adult rheumatoid arthritis

The safety and efficacy of nabumetone and placebo were compared in a three-week, multicenter, double-blind, randomized, parallel evaluation involving patients with class II or III definite or classical rheumatoid arthritis. No patient received concomitant treatment with other nonsteroidal anti-inflammatory agents; however, disease-modifying agents (gold, steroids) were permitted. Of the 139 patients who entered the double-blind phase of the study, all were evaluable for safety, and 113 were evaluable for efficacy. Sixty-one patients received 1,000 mg of nabumetone per day at bedtime, and 50 were given placebo tablets; patients in both groups were permitted up to 3,250 mg of acetaminophen per day as needed for pain. After three weeks, nabumetone-treated patients exhibited a greater degree of improvement from baseline than did the placebo-treated patients, and the degree of improvement was statistically significant for four of seven variables.

Long-term treatment of rheumatoid arthritis comparing nabumetone with aspirin

This report summarizes the results of a 17-investigator multicenter six-month randomized double-blind parallel group study. The safety and efficacy of nabumetone 1,000 mg taken at bedtime was compared with that of aspirin 900 mg four times daily in the treatment of adult patients with active class II or III classical or definite rheumatoid arthritis. Two hundred sixty-four patients were entered into the study. Two hundred fifty-seven (126 nabumetone and 131 aspirin) patients were evaluable for safety. Two hundred thirty-four (113 nabumetone and 121 aspirin) patients were evaluable for efficacy. There was significant improvement in each of six clinical measurements of efficacy in both treatment groups and little difference between groups. The somewhat greater improvement in articular index and duration of morning stiffness in the nabumetone-treated group did not reach statistical significance. There was an equal percentage of patient withdrawal for lack of efficacy in each group. Overall, the rate of patient withdrawal due to adverse experiences was greater (p = 0.01) for aspirin-treated patients. These experiences were usually dispepsia, abdominal pain, and tinnitus. It was concluded that nabumetone was an effective anti-inflammatory drug in the treatment of rheumatoid arthritis with less toxicity than aspirin.

Six-month multi-center study comparing nabumetone with naproxen in the treatment of osteoarthritis

This six-month, double-blind, controlled, randomized, parallel study at 13 medical centers compared the safety and efficacy of nabumetone (1,000 mg taken at bedtime) with that of naproxen (250 mg twice daily) in the treatment of osteoarthritis in symptomatic adult outpatients. Five efficacy parameters were measured: patients' assessment of overall osteoarthritis activity and pain, physicians' assessment of overall osteoarthritis activity and pain, and physicians' assessment of pain with respect to a defined activity. All 489 patients who took medication were included in the evaluation of safety, and 455 patients (227 in the nabumetone group and 228 in the naproxen group) were evaluated for efficacy. Significant improvement in all five efficacy parameters occurred in both groups. No significant differences were found between the two groups at the end of the study in any of the five efficacy parameters. Twenty-three percent of nabumetone and 17 percent of naproxen patients withdrew from the study for lack of efficacy. At least one possible or probable treatment-related adverse experience was reported for 45 percent of nabumetone-treated patients and 42 percent of those given naproxen, and in 19 percent of the nabumetone-treated and 18 percent of the naproxen-treated patients these experiences were moderate or severe. However, only 7 percent of patients in each group withdrew from the study due to adverse experiences. Nabumetone and naproxen have comparable safety and efficacy, suggesting that a single, nighttime dose of nabumetone is a convenient, effective, and safe treatment for osteoarthritis.

Single-blind comparative study of nabumetone (relafen) versus naproxen in the treatment of rheumatoid arthritis

Forty-seven patients with active rheumatoid arthritis were entered into a single-blind study to compare the safety and efficacy of nabumetone with naproxen. Patients were randomly assigned to receive a daily dose of 2 g of nabumetone or 1 g of naproxen after a placebo-washout period of at least three days. In addition to the usual clinical and laboratory measurements of disease activity, thermographic assessment was carried out at each visit and the heat distribution index was calculated. In addition, the safety and tolerance were assessed. Patients had improvement in severity of pain, severity and duration of morning stiffness, and articular index, and there was no statistical difference between the two treatment groups. By the end of six months, 13 patients had withdrawn from treatment; five patients in the naproxen treatment group and five in the nabumetone group were withdrawn from the study due to lack of efficacy. In no patient from the nabumetone group did an adverse reaction develop. In one patient in the naproxen group, a severe decrease in white blood cell count developed, and a skin rash and swollen gums developed in another patient. We conclude that nabumetone is well tolerated and of equal efficacy to naproxen in the treatment of active rheumatoid arthritis.

Comparison of the safety and efficacy of nabumetone and aspirin in the treatment of osteoarthritis in adults

A six-month, multicenter, double-blind study compared the efficacy and safety of two therapeutic regimens in 332 patients with osteoarthritis. The patients received either 1,000 mg of nabumetone as a single bedtime dose or 900 mg of aspirin in four divided doses. At the end of the study, patients in both treatment groups showed significant improvement from baseline for all five parameters; no statistically or clinically significant differences were observed between the groups. The safety data did reveal clinically and statistically significant differences between the groups. Aspirin-treated patients experienced a greater frequency of withdrawal from the study because of adverse experiences (34 percent versus 13 percent), a greater incidence of having at least one treatment-related adverse experience (73 percent versus 52 percent), a greater percentage of patients with at least one moderate or severe treatment-related adverse experience (47 percent versus 22 percent), and a greater percentage of patients with treatment-related adverse experiences affecting the gastrointestinal system (43 percent versus 32 percent) or the inner ear (32 percent versus 10 percent). The results of this study demonstrated that nabumetone, 1,000 mg at bedtime, is as efficacious as aspirin, 900 mg four times daily, produces fewer adverse effects, and is indicated in the treatment of osteoarthritis.

Nabumetone in the treatment of skin and soft tissue injury

Nabumetone, a new nonsteroidal anti-inflammatory agent, has been evaluated for the treatment of skin and soft tissue injury, including sports injury, in clinical trials involving nearly 1,000 patients. Its efficacy, safety, and tolerance in these patients is reviewed. The efficacy of nabumetone in the treatment of soft tissue injury has been demonstrated to be similar to that of soluble aspirin, ibuprofen, and naproxen. It was not possible in these studies to demonstrate a definite advantage over placebo, and the reasons for this are discussed along with some suggestions for future studies. There were no serious adverse experiences reported, and nabumetone was well tolerated and compared favorably with the other agents used, including placebo. It caused significantly fewer gastrointestinal side effects than soluble aspirin. Nabumetone is an appropriate choice of non-steroidal anti-inflammatory drug for the treatment of sports injury.