Gout ==== þ Low-Dose Colchicine - Terkeltaub, R. A., D. E. Furst, et al. (2010). "High versus low dosing of oral colchicine for early acute gout flare: Twenty-four-hour outcome of the first multicenter, randomized, double-blind, placebo-controlled, parallel-group, dose-comparison colchicine study." Arthritis and rheumatism 62(4): 1060-1068. OBJECTIVE: Despite widespread use of colchicine, the evidence basis for oral colchicine therapy and dosing in acute gout remains limited. The aim of this trial was to compare low-dose colchicine (abbreviated at 1 hour) and high-dose colchicine (prolonged over 6 hours) with placebo in gout flare, using regimens producing comparable maximum plasma concentrations in healthy volunteers. METHODS: This multicenter, randomized, double-blind, placebo-controlled, parallel-group study compared self-administered low-dose colchicine (1.8 mg total over 1 hour) and high-dose colchicine (4.8 mg total over 6 hours) with placebo. The primary end point was > or = 50% pain reduction at 24 hours without rescue medication. RESULTS: There were 184 patients in the intent-to-treat analysis. Responders included 28 of 74 patients (37.8%) in the low-dose group, 17 of 52 patients (32.7%) in the high-dose group, and 9 of 58 patients (15.5%) in the placebo group (P = 0.005 and P = 0.034, respectively, versus placebo). Rescue medication was taken within the first 24 hours by 23 patients (31.1%) in the low-dose group (P = 0.027 versus placebo), 18 patients (34.6%) in the high-dose group (P = 0.103 versus placebo), and 29 patients (50.0%) in the placebo group. The low-dose group had an adverse event (AE) profile similar to that of the placebo group, with an odds ratio (OR) of 1.5 (95% confidence interval [95% CI] 0.7-3.2). High-dose colchicine was associated with significantly more diarrhea, vomiting, and other AEs compared with low-dose colchicine or placebo. With high-dose colchicine, 40 patients (76.9%) had diarrhea (OR 21.3 [95% CI 7.9-56.9]), 10 (19.2%) had severe diarrhea, and 9 (17.3%) had vomiting. With low-dose colchicine, 23.0% of the patients had diarrhea (OR 1.9 [95% CI 0.8-4.8]), none had severe diarrhea, and none had vomiting. CONCLUSION: Low-dose colchicine yielded both maximum plasma concentration and early gout flare efficacy comparable with that of high-dose colchicine, with a safety profile indistinguishable from that of placebo. þ Hyperuricemia - Hyperuricemia will be found in 70% of patients with their first gout attack. Ref: A Practical Approach to Emergency Medicine 2nd edition p 350 -------------------- It is my understanding, not so much from the literature, as from my perusal of medical texts, that indomethacin is indeed a more potent analgesic/anti-inflamatory agent that other NSAIDS. A few studies have compared other NSAIDS to indomethacin for acute gouty arthritis. Flurbiprofen (Ansaid) (1) and meclfenamate (Meclomen) (3) appear to be eqaully efficacious. (Incidentally, the latter study was in an issue of 'Arzneimittelforschung' which is a journal whose articles I rarely miss). I am aware of no studies directly comparing ibuprofen with indomethacin. Interestingly ACTH (2) compares quite favorably to indomethacin as well and has the advantage of significantly faster onset of action albeit with more side effects. Prednisone 40 - 60 mg p.o. with rapid taper can also be given for acute gout. Good candidates for steroid therapy might include those who are allergic to NSAIDS, have renal insufficiency, those on anticoagulants etc. H. Louzon MD (1) Lomen PL Turner LF Lamborn KR Winblad MA Sack RL Brinn EL Flurbiprofen in the treatment of acute gout. A comparison with indomethacin. Am J Med (1986 Mar 24) 80(3A):134-9 The relative efficacy and safety of flurbiprofen (Ansaid, Upjohn) and indomethacin were compared in 29 patients with monoarticular gouty arthritis of less than 48 hours' duration. A loading dose of 400 mg of flurbiprofen or 200 mg of indomethacin was administered for 24 hours, followed by 200 mg of flurbiprofen per day or 100 mg of indomethacin per day for a maximum of five days. Based on global assessment of improvement, at least 50 percent of patients in both treatment groups showed improvement within 24 hours. There were statistically significant improvements in pain, swelling, erythema, and skin temperature in both groups of patients within 48 hours of treatment. By 72 hours, the proportion of patients with improvement in the flurbiprofen group was equal to or greater than the proportion in the indomethacin group for all clinical efficacy parameters. At the end of treatment, eight of 15 patients in the indomethacin group and five of 14 patients in the flurbiprofen group were asymptomatic. There were no statistically significant differences between indomethacin and flurbiprofen in the percentage of asymptomatic patients at the end of treatment. Side effects were mild in both groups. No clinically significant between-treatment differences were noted in vital signs or in the results of laboratory assays. (2) Axelrod D Preston S Comparison of parenteral adrenocorticotropic hormone with oral indomethacin in the treatment of acute gout. Arthritis Rheum (1988 Jun) 31(6):803-5 One hundred male patients who presented with acute gouty arthritis were alternately assigned to 2 treatment groups. Seventy-six patients completed the study protocol, in which each gout attack during a 1- year period was treated. For each gout episode, 36 patients received a single intramuscular injection of 40 IU of adrenocorticotropic hormone (ACTH), and 40 patients received oral indomethacin, 50 mg 4 times daily with meals, until the pain abated. The time interval until the pain was relieved, as well as any untoward effects, were recorded for each gout attack treated. Both groups were of similar age, and had similar values for intercritical serum uric acid, 24- hour urinary uric acid, and creatinine clearance (1 month after entry into the study). The mean interval (+/- SD) to relief of pain was significantly shorter for the ACTH group (3 +/- 1 hours) than for the indomethacin group (24 +/- 10 hours). No side effects were noted in the ACTH group. However, of the 40 patients receiving indomethacin, 22 had abdominal discomfort of dyspepsia, 15 had headaches, and 12 had difficulty with mentation. Single-dose parenteral ACTH appeared to be effective more rapidly and was associated with fewer side effects than oral indomethacin in the treatment of acute gout. (3) Eberl R Dunky A Meclofenamate sodium in the treatment of acute gout. Results of a double-blind study. Arzneimittelforschung (1983) 33(4A):641-3 20 patients with an attack of acute gout participated in this double- blind study, ten patients received N-(2,6-dichloro-m- tolyl)anthranilic acid, sodium salt (meclofenamate sodium, Meclomen) and ten indometacin. The median time interval between onset of attack and onset of treatment was 11 h in the meclofenamate sodium group and 14 h in the indometacin group; medication was started with a dose of 200 mg meclofenamate sodium or 25 mg indometacin followed by 100 mg meclofenamate sodium or 25 mg indometacin every 4 h for the first 24 h. Thereafter patients received 100 mg meclofenamate sodium or 50 mg indometacin at 8-h intervals for 6 days. Similar improvement of intensity of spontaneous pain, swelling, tenderness of touch and degree of limitation of function was noted in patients of both treatment groups. This improvement could already be noted after 24 h of treatment and was sustained throughout the medication period and follow-up period. Adverse reactions were reported by 2 patients in the meclofenamate sodium group and by 5 patients in the indometacin group. The results of this double-blind study indicate that meclofenamate sodium in the dose administered was equally effective in relieving pain and inflammation and restoring restricted function in patients with acute gout as indometacin when used in the generally recommended dose for this indication. Meclofenamate sodium, even at these high dosage levels, was better tolerated than indometacin. Alloway J Rheum 993 indocin vs. steroids: no difference prednisone 40 mg with taper over 10 days [Groff Semin Arthr Rheum 90]