Nabumetone Group Research Articles

Progression of macular atrophy after PDT combined with the COX-2 inhibitor Nabumetone in the treatment of neovascular ARMD

To evaluate photodynamic therapy (PDT) combined with the preferential the cyclooxygenase-2 (COX-2) inhibitor, nabumetone in the treatment of the neovascular age-related macular degeneration (ARMD). A prospective, double-blind, randomized study on 60 patients with subfoveal CNV secondary to ARMD without any previous treatment. Patients were divided into a nabumetone or placebo group. The main endpoints were the change of best-corrected visual acuity (BCVA), central macular thickness (CRT) and number of required PDT treatments. In the nabumetone group, 27 patients (90%) and 28 (93%) in the placebo group completed the follow-up of 12 months. In the nabumetone group, the mean CRT decreased from 332 μm (SD 68 μm) to 220 μm (SD 46 μm). In the placebo group, CRT decreased from 331 μm (SD 72 μm) to 254 μm (SD 61 μm). The mean BCVA was 0.68 log MAR (SD 0.22 log MAR) in the nabumetone group and 0.62 log MAR (SD 0.23 log MAR) in the placebo group at baseline. This stabilised in the placebo group to 0.66 log MAR (SD 0.33) but deteriorated in the nabumetone group to 0.86 log MAR (SD 0.41 log MAR). There was a significant reduction in the number of required PDTs in the nabumetone group, but significant progression of the RPE atrophy area. Combined PDT with oral intake of the COX-2 inhibitor, nabumetone reduced the number of required PDT retreatments, but worsening BCVA caused by macular atrophy progression. Therefore the combination of the PDT with the nabumetone is not recommended.

The Effects of Aceclofenac and Nabumetone in Osteoarthritis

Aceclofenac, a NSAID is widely used in the treatment of pain and inflammation associated with osteoarthritis. Nabumetone, a recently developed preferential cyclo-oxygenase 2 inhibitor has also proved to be equally effective. The present study was undertaken to evaluate the 'real better' drug, amongst these with better efficacy and gastro-intestinal tolerability as well. Four hundred and twenty-three patients of either sex, aged 40-64 years with uncomplicated osteoarthritis of knee joint were randomly allocated into three equal groups receiving aceclofenac, nabumetone or placebo. A baseline pain measurement was done with Visual Analogue Scale (VAS: 0-10 scale) and Investigator Global Assessment of Disease status (IGADS: 0-4 point scale). Code was broken at the end of two weeks or earlier to eliminate any real fatal outcome. Final evaluation of efficacy was done at the end of four weeks. The significance of difference between the treatment outcomes was analyzed using one way ANOVA test. During the active comparator controlled period, the most common reason for discontinuation was unacceptable adverse events. While 108 (76.6%) participants could take the full course of treatment with aceclofenac, 118 (83.7%) of the nabumetone group completed the study. Drop outs were highest in the placebo group (33.9%) followed by the aceclofenac group (12.1%) and nabumetone group (8.5%). Discontinuation due to G.I. intolerance was least in the placebo group (2.1%) followed by the nabumetone group (5%) and aceclofenac group (7.8%). The preferential inhibition of cyclo-oxygenase 2 by nabumetone was postulated to afford better clinical efficacy and gastrointestinal tolerability in osteoarthritis as compared to aceclofenac.

Safety and Efficacy of Oral Nonsteroidal Anti-Inflammatory Drugs in Patients with Rheumatoid Arthritis

To monitor the safety and efficacy profile of long-term treatment with diclofenac, nabumetone, meloxicam and celecoxib in patients with rheumatoid arthritis. This randomised, prospective clinical trial included a total of 461 subjects (313 females and 148 males) with clinically diagnosed rheumatoid arthritis. Their average age was 46.9 +/- 14.4 years (range 20-69 years), and the average disease duration was 1333.7 +/- 992.85 days. Subjects were randomly assigned daily administration of one of the following: diclofenac 75-100mg, meloxicam 15mg, nabumetone 1000mg or celecoxib 200mg. During the 6-month treatment period, a monthly patient interview was conducted to evaluate drug efficacy and safety. 407 subjects successfully completed the 6-month treatment. Sixteen patients (12.2%) withdrew from the diclofenac group, 16 (12.2%) from the nabumetone group, 17 (11.8%) from the meloxicam group and five (9.1%) from the celecoxib group. Most withdrawals occurred during the first 3 months of treatment. Reasons for withdrawals in the first three groups were lack of efficacy (44.9%) and adverse effects (38.8%). For the celecoxib group, high cost (80%) was the main reason for withdrawal. Adverse drug reactions to NSAIDs mostly occurred at an early stage of treatment, with an incidence rate of 31.9% for the diclofenac group, 19.9% for the nabumetone group, 25.2% for the meloxicam group, and 7.27% for the celecoxib group. Clinical efficacy rates for the four NSAIDs were positively related to the length of treatment. During the first 4 months, diclofenac, meloxicam and celecoxib showed better efficacy than nabumetone. There were no significant differences in efficacy during the fifth and sixth months. The overall 6-month effectiveness rates were 68.8% for diclofenac, 59.8% for nabumetone, 67.6% for meloxicam and 69.1% for celecoxib. Adverse drug reactions and their related withdrawals occurred mostly at an early stage of NSAID treatment, so it is crucial to strengthen pharmacovigilance during this period. Among the investigated NSAIDs, celecoxib did not prove to be superior to diclofenac, nabumetone or meloxicam with respect to its efficacy in the treatment of rheumatoid arthritis; however, it did show good patient compliance and safety profiles.

Effects of nabumetone, celecoxib, and ibuprofen on blood pressure control in hypertensive patients on angiotensin converting enzyme inhibitors

Nonsteroidal anti-inflammatory drugs interfere with certain antihypertensive therapies. In a double-blind study, 385 hypertensive patients stabilized on an angiotensin converting enzyme inhibitor were treated with nabumetone, celecoxib, ibuprofen, or placebo for 4 weeks. Ibuprofen caused significantly greater increases in systolic ( P < .001) and diastolic ( P < .01) blood pressures (BPs) compared to placebo, but not nabumetone or celecoxib. The proportion of patients with systolic BP increases of clinical concern at end point was significantly higher ( P < .001) for the ibuprofen group (16.7%; 15 of 90), but not for the nabumetone group (5.5%; 5 of 91) or the celecoxib group (4.6%; 4 of 87) compared to the placebo group (1.1%; 1 of 91).

A double-blind study of the effect on hemostasis of nabumetone (Relafen ®) compared to placebo

A double-blind, placebo-controlled clinical trial comparing the effect on hemostasis of nabumetone (Relafen) to placebo in patients who were about to undergo forefoot surgery was performed. Aspirin and nonsteroidal anti-inflammatory drugs (NSAIDs) are reported to inhibit platelet cyclooxygenase activity, resulting in altered platelet function and thus potentially enhanced bleeding. Nabumetone has been reported to have no effect on platelet aggregation and bleeding time in normal volunteers and in patients who have undergone knee arthroscopy. After fulfilling the inclusion criteria and after a 1-week washout period (acetaminophen controlled), 15 patients were enrolled in the nabumetone group and 15 patients were randomized in the placebo group. Hemostatic parameters [prothrombin time (PT), partial thromboplastin time (PTT), and Ivy bleeding time (IBT)] were assessed at baseline, visit 2, visit 3, and final visit. No meaningful differences were observed between treatment groups in any of the measured hemostatic parameters. No significant adverse events were reported. There was no significant change from baseline for PT, PTT, and IBT in the nabumetone group (PT, p < .06; PTT, p < .64; IBT, p < .17) versus the placebo group (PT, p < .61; PTT, p < .63; IBT, p < .25). The lack of bleeding diathesis and significant prolongation of PT, PTT, or IBT in this study suggests that nabumetone in dosages up to 1000 mg/day can be administered safely in the immediate preoperative period to patients undergoing forefoot surgery.

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.

Double-blind, placebo-controlled comparison of the safety and efficacy of orally administered etodolac and nabumetone in patients with active osteoarthritis of the knee

This 4-week, randomized, double-blind, double-dummy, placebo-controlled, parallel-group, multicenter study was designed to compare the efficacy and safety of etodolac and nabumetone in the treatment of patients with active osteoarthritis (OA) of the knee. Ninety-one patients received etodolac 400 mg twice daily, 89 received nabumetone 1500 mg once daily, and 90 received placebo. Both active treatments significantly improved the patients' condition relative to baseline ( P ≤ 0.001) at all evaluations during treatment and relative to placebo ( P ≤ 0.05) by visit 4. Improvement relative to placebo in investigator's global assessments was earlier in the etodolac group (ie, by visit 3) than in the nabumetone group. At visit 4, improvement in investigator's and patient's global assessment scores, and in the distribution of investigator's assessment scores, was significantly ( P ≤0.05) greater in the etodolac group than in the nabumetone group. Other than hypokalemia, which occurred only in three patients in the nabumetone group ( P = 0.035), there were no significant differences among the groups in the frequency of study events or premature discontinuation from the study as a result of study events. Study events considered at least possibly treatment related were reported for 26 patients in the etodolac group (28.6%), 20 in the nabumetone group (22.5%), and 23 in the placebo group (25.6%). The most frequently reported symptoms for all groups were dyspepsia, nausea, and headache. Four patients treated with nabumetone (4.5%) had elevations in aspartate aminotransferase or alanine aminotransferase during treatment. The results of this study show that etodolac 400 mg twice daily is at least as effective as nabumetone 1500 mg once daily and is equally well tolerated in the treatment of patients with active OA of the knee; etodolac may have an earlier onset of action and/or a relatively greater efficacy in patient and investigator global assessments than nabumetone.

A Controlled Study Comparing the Effects of Nabumetone, Ibuprofen, and Ibuprofen Plus Misoprostol on the Upper Gastrointestinal Tract Mucosa

This study was developed to compare the incidence of endoscopically diagnosed ulcers in elderly patients taking nabumetone, ibuprofen, or concomitant ibuprofen/misoprostol. Further research is indicated to better establish the clinical relevance of these endoscopy findings. We conducted a prospective, multicenter, randomized, endoscopist-blinded, 12-week study involving 171 patients with osteoarthritis aged 60 years and older. Patients were randomized to receive nabumetone, 1000 mg (n = 58); ibuprofen, 600 mg four times daily (n = 53); or ibuprofen, 600 mg four times daily, administered concomitantly with misoprostol, 200 micrograms four times daily (n = 60). Endoscopy was performed at baseline and at weeks 2, 6, and 12. Endoscopy results were scored on a scale of 1 to 9. Significant ulcers were defined as breaks in the mucosa greater than 5 mm with appreciable depth. Of the 171 randomized patients, 148 completed the study. There was no significant difference in the incidence of significant ulcers between the nabumetone group and the ibuprofen/misoprostol group (one vs zero). There were significantly fewer significant ulcers in the nabumetone and ibuprofen/misoprostol groups than in the ibuprofen monotherapy group (one and zero vs eight; P < .01). There also was a significant difference in the time to ulcer development, with a greater risk of developing an ulcer sooner with ibuprofen treatment (P < .01) than either nabumetone or ibuprofen/misoprostol treatment. The severity of osteoarthritis, based on physicians' assessments, improved in 64% of patients in the nabumetone group, 55% of those in the ibuprofen group, and 63% of those in the ibuprofen/misoprostol group. Nabumetone is equivalent in ulcerogenicity to concomitant ibuprofen/misoprostol and is significantly less ulcerogenic than ibuprofen alone.

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.

A Microcomputer-Assisted Study of Nabumetone and Slow Release Diclofenac in Osteoarthritis

20 UK general-practice centres entered 243 patients into a 6-week double-blind, double-dummy, randomised, parallel-group trial designed to compare nabumetone 1 g at night with slow release diclofenac 100mg at night in the treatment of osteoarthritis. Seven efficacy parameters were measured, adverse events were recorded and laboratory monitoring was performed. The study monitor entered trial data into a portable laptop microcomputer at the participating centres. Both treatment groups showed highly significant clinical improvements at the end of the 6-week study period and there were no significant inter-group differences. Overall, the incidence of adverse events was similar in the 2 groups, but significantly fewer patients in the nabumetone group (n = 21) than in the diclofenac group (n = 35) complained of gastrointestinal adverse events (p = 0.03). On-site use of the microcomputer contributed to increased monitoring efficiency and trialist motivation, resulting in rapid recruitment of patients, collection of high quality data and speedy analysis at the end of the study.

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.

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.

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.