Does colchicine work? The results of the first controlled study in acute gout. Therapeutic value of colchicine in the treatment of patients with psoriatic arthritis. Febuxostat, a novel nonpurine selective inhibitor of xanthine oxidase: a twenty-eight-day, multicenter, phase II, randomized, double-blind, placebo-controlled, dose-response clinical trial examining safety and efficacy in patients with gout. Comparison of colchicine versus prednisolone in recurrent aphthous stomatitis: A double-blind randomized clinical trial. A randomized trial comparing colchicine and ursodeoxycholic acid combination to ursodeoxycholic acid in primary biliary cirrhosis. UDCA-PBC Study Group. Comparison of adrenocorticotropic hormone and triamcinolone acetonide in the treatment of acute gouty arthritis. A prospective trial of colchicine for primary biliary cirrhosis. Efficacy and safety assessment of 0.5% and 1% colchicine cream in the treatment of actinic keratoses. Febuxostat in the treatment of gout: 5-yr findings of the FOCUS efficacy and safety study.
We have performed the first controlled study of colchicine in acute gout, to determine its efficacy and toxicity, and to define the natural history of acute gout. Two-thirds of colchicine-treated patients improved after 48 hours, but only one-third of the patients receiving placebo demonstrated similar improvement. The colchicine-treated patients responded earlier; significant differences from placebo were shown after 18-30 hours. All patients given colchicine developed diarrhea after a median time of 24 hours (mean dose of colchicine 6.7 mg). This side effect occurred before relief of pain in most patients. To test the hypothesis that colchicine is an effective treatment of psoriatic arthritis.
                Twenty five patients with psoriatic arthritis were entered into a two centre, double blind, crossover study of 23 weeks' duration comparing the therapeutic effect of colchicine (0.6-1.8 mg/day) with placebo.
                No significant difference was noted between colchicine or placebo treatment for the primary outcome measure (Lansbury joint count) or any of the seven secondary outcome measures. No change in the psoriasis was noted during active or placebo treatment. Adverse clinical effects were reported more often during treatment with colchicine (14 patients) than with the placebo (four patients), resulting in the early withdrawal of three patients receiving colchicine from the trial. Increased creatine kinase values, without weakness, occurred during treatment with colchicine (five patients) and placebo (four patients).
                In conclusion, our study did not provide evidence that colchicine is of therapeutic value in the treatment of psoriatic arthritis. Gout affects approximately 1-2% of the American population. Current options for treating hyperuricemia in chronic gout are limited. The purpose of this study was to assess the safety and efficacy of febuxostat, a nonpurine selective inhibitor of xanthine oxidase, in establishing normal serum urate (sUA) concentrations in gout patients with hyperuricemia (>or=8.0 mg/dl).
                We conducted a phase II, randomized, double-blind, placebo-controlled trial in 153 patients (ages 23-80 years). Subjects received febuxostat (40 mg, 80 mg, 120 mg) or placebo once daily for 28 days and colchicine prophylaxis for 14 days prior to and 14 days after randomization. The primary end point was the proportion of subjects with sUA levels <6.0 mg/dl on day 28.
                Greater proportions of febuxostat-treated patients than placebo-treated patients achieved an sUA level <6.0 mg/dl at each visit (P < 0.001 for each comparison). The targeted sUA level was attained on day 28 in 0% of those taking placebo and in 56% of those taking 40 mg, 76% taking 80 mg, and 94% taking 120 mg of febuxostat. The mean sUA reduction from baseline to day 28 was 2% in the placebo group and 37% in the 40-mg, 44% in the 80-mg, and 59% in the 120-mg febuxostat groups. Gout flares occurred with similar frequency in the placebo (37%) and 40-mg febuxostat (35%) groups and with increased frequency in the higher dosage febuxostat groups (43% taking 80 mg; 55% taking 120 mg). During colchicine prophylaxis, gout flares occurred less frequently (8-13%). Incidences of treatment-related adverse events were similar in the febuxostat and placebo groups.
                Treatment with febuxostat resulted in a significant reduction of sUA levels at all dosages. Febuxostat therapy was safe and well tolerated. Recurrent aphthous stomatitis (RAS) is one of the most common ulcers of the oral cavity with a reported prevalence of 5- 50%. There is still no definitive treatment for RAS; however, immunosuppressive and immunomodulant agents have been proposed. In this study, we compared the therapeutic effects of 5 mg/d prednisolone with 0.5 mg/d colchicine in the treatment of RAS.
                In a double-blind randomized clinical trial, 34 patients with RAS were randomly divided into two groups for treatment with prednisolone or colchicine. All patients took the medication for three months and were assessed at two weeks intervals. The groups were compared for size and number of lesions, severity of pain and burning sensation, duration of pain-free episodes and any side effects of the prescribed medicines. Both colchicine and prednisolone treatments significantly reduced RAS (p < 0.001). No significant differences in size and number of lesions, recurrence and severity of pain and duration of pain-free period were seen between the two treatment groups. Colchicine (52.9%) had significantly more side effects than prednisolone (11.8%).
                Low dose prednisolone and colchicine were both effective in treating RAS. Given that the two therapies had similar efficacy, yet colchicine was associated with more side effects, , 5mg/d of prednisolone seems to be a better alternative in reducing the signs and symptoms of the disease. The efficacy of colchicine combined with ursodeoxycholic acid (UDCA) and UDCA alone in the treatment of patients with nonadvanced primary biliary cirrhosis (PBC) was evaluated in a 2-year controlled study. Seventy-four patients with PBC who had been treated previously with UDCA (at least 8 months) but still had abnormal liver test results, especially elevated alkaline phosphatase activity, were randomized to be administered colchicine (1 mg/d, 5 days per week) (n = 37) or a placebo (n = 37). In addition, the patients were treated with UDCA (13-15 mg x kg(-1) x day(-1)). The patients underwent clinical examination and liver tests every 6 months and upper endoscopy and liver biopsy at entry and at 2 years. Procollagen type III aminoterminal peptide (PIIINP), hyaluronic acid, and sulfobromophthalein (BSP) elimination kinetics were determined at entry and after 2 years. After 2 years of treatment, relative to UDCA, colchicine combined with UDCA did not significantly improve symptoms, laboratory findings (serum bilirubin level, alkaline phosphatase and alanine transaminase [ALT] activities, immunoglobulin [Ig] M level), serum markers of fibrosis, or histological features, except lobular inflammation. Colchicine did tend to slightly reduce the progression of esophageal varices; however, the difference was not significant. BSP elimination kinetics (45-minute retention percentage) was significantly improved when treated with colchicine. During the 2-year study, the only clinical complications were variceal bleeding in one patient administered colchicine and two administered the placebo. Two patients died from nonliver causes. One severe adverse effect (peripheral neuromyopathy) was observed in a colchicine-treated patient. In conclusion, this study suggests that colchicine appears to provide a slight advantage relative to UDCA alone in patients with nonadvanced PBC. To determine the best alternative therapy for acute gouty arthritis when nonsteroidal antiinflammatory drugs or colchicine are contraindicated.
                Thirty-one patients with crystal proven gout presenting with an acute attack of < 5 days' duration were treated prospectively with either a single intramuscular injection of adrenocorticotropic hormone (ACTH) 40 IU or triamcinolone acetonide 60 mg. The patients were followed for 30 days.
                Resolution of all symptoms occurred at an average of 8 days for both groups. No adverse reactions were noted in either group; however, there were 11 reinjections in the ACTH group and 5 reinjections in the triamcinolone acetonide group. Two patients from the ACTH arm were transferred to the triamcinolone acetonide arm because of rebound arthritis.
                Although recent studies of ACTH and triamcinolone acetonide have demonstrated efficacy and safety comparable to indomethacin, in a direct comparison of the 2 at the doses used, triamcinolone acetonide resulted in fewer rebound attacks and treatment failures than ACTH and required fewer reinjections. We entered 60 patients with primary biliary cirrhosis in a double-blind randomized controlled trial to determine whether colchicine is therapeutically effective. Thirty patients had early disease (Stages 1 and 2), and 30 had advanced disease (Stages 3 and 4). Fifteen patients with early disease and 15 with advanced disease received colchicine (0.6 mg twice daily), and the remainder received placebo. Patients were studied about every two months; those remaining in the blind phase at two years underwent repeat liver biopsy and were then placed on open-label colchicine (0.6 mg twice daily). With a few exceptions, the results in patients with early disease were similar to those in patients with advanced disease; hence, data on patients in all stages were combined in the main analysis. During the two-year study period the colchicine-treated patients, as compared with the placebo-treated patients, had improvement in levels of serum albumin, serum bilirubin, alkaline phosphatase, cholesterol, and aminotransferases. However, there was no such improvement in the severity of symptoms or physical findings; moreover, there was no significant difference in the histologic changes noted at liver biopsy in the two treatment groups. At four years after entry, the cumulative mortality from liver disease was 21 percent in patients given colchicine and 47 percent in those given placebo (P = 0.05). The only side effect of colchicine was diarrhea, noted in three patients. The consistent and significant improvement in a number of markers of liver disease and the apparent decreased mortality from liver disease suggest that colchicine may provide some long-term clinical benefit in patients with primary biliary cirrhosis. However, the failure of colchicine to reduce hepatic inflammation and fibrosis leaves uncertain the effect of the drug on the longterm outcome of this disease. Topical colchicine has been reported to be an effective treatment for actinic keratoses, but the optimal concentration has not been fully defined.
                The aim of this study was to further support the beneficial effect of topical colchicine therapy for actinic keratoses, and to compare the efficacy and safety of two different concentrations of colchicine cream, 0.5% and 1%.
                Sixteen patients with actinic keratoses were enrolled in this comparative randomized study. Eight patients applied 1% colchicine cream, twice daily on their lesions while the other eight were treated with a 0.5% colchicine cream for 10 days. Some patients were applied a second course of 10 days' therapy. Patients were examined before treatment and at 10 days, and followed up at 1, 2 and 6 months of treatment. Visible and palpable actinic keratoses lesions in each group were counted. Safety and efficacy were also assessed by clinical examination at each study visit. Routine laboratory tests were performed before and after treatment.
                Actinic keratoses lesions showed significant clinical improvement following treatment with 0.5% and 1% colchicine cream. Complete healing of actinic keratoses were observed in six of the eight patients in the 1% colchicine group, and in seven of the eight patients in the 0.5% colchicine group. The reduction rate in number of actinic keratoses at the end of treatment in the 1% colchicine group was 73.9% (48/65) (p < 0.001), and the reduction rate in the 0.5% colchicine group was 77.7% (52/67) in total (p < 0.001). The reduction in number of actinic keratoses (mean +/- SD) at the end of treatment was similar in the 1% colchicine group (0.7 +/- 1.3), and the 0.5% colchicine group (mean 0.6 +/- 1.7) (p > 0.05). Systemic side effects were not seen in either concentration.
                Topical colchicine is an effective and safe alternative agent. Cream containing 0.5% of colchicine is equally effective as 1% colchicine cream in the treatment of actinic keratoses. This 5-yr study assessed urate-lowering and clinical efficacy and safety of long-term febuxostat therapy in subjects with gout. The primary efficacy end-point was reduction to and maintenance of serum urate (sUA) levels < 6.0 mg/dl.
                Subjects who completed a previous 28-day study were entered into an open-label extension study and initially received febuxostat 80 mg daily. Between Weeks 4 and 24, dosing could be adjusted to febuxostat 40 or 120 mg. All subjects received gout flare prophylaxis during the first 4 weeks. Gout flares were recorded and treated throughout the study, and sUA, baseline tophi and safety were monitored.
                Among 116 subjects initially enrolled, dose adjustments were made for 44 (38%) subjects. As a result, 8 subjects received febuxostat 40 mg, 79 received 80 mg, and 29 received 120 mg daily maintenance dose. At 5 yrs, 93% (54/58) of the remaining subjects had sUA < 6.0 mg/dl. Fifty-eight subjects (50%) discontinued prematurely; 38 did so in the first year. Thirteen subjects withdrew due to an adverse event. Sustained reduction of sUA was associated with nearly complete elimination of gout flares. In 26 subjects with a tophus at baseline, resolution was achieved in 69% (18/26) by last visit on study drug at any point during the study (Final Visit). There were no deaths reported during the study.
                Long-term treatment with febuxostat resulted in durable maintenance of sUA < 6.0 mg/dl for most subjects. There was nearly complete abolition of gout flares in patients completing the study. Baseline tophi resolved in a majority of subjects.
Colchicine is an effective treatment for the reduction of pain and clinical symptoms in patients experiencing acute attacks of gout, although in the regimen studied its low benefit to toxicity ratio limits its usefulness. It should be used as a second line therapy when NSAIDs or corticosteroids are contraindicated or ineffective. More evidence is needed to compare the efficacy of colchicine to that of NSAIDs or corticosteroids, the current first line therapy for acute gout.