Objective. A dose-response relationship for hydroxychloroquine (HCQ), in terms of the proportion of patients achieving the Paulus 20% criteria for improvement, had previously been observed in patients with rheumatoid arthritis (RA) receiving a 6-week loading regimen of 400, 800, or 1,200 mg HCQ daily. This present retrospective analysis was performed to investigate possible relationships between the blood HCQ and HCQ-metabolite concentrations and measures of efficacy and toxicity. In addition, we sought to ascertain whether further investigation of HCQ/HCQ-metabolite levels might lead to testing of one of these substances as a new antirheumatic drug.Methods. Patients with active RA (n ؍ 212) began a 6-week, double-blind trial comparing 3 different doses of HCQ at 400, 800, or 1,200 mg/day, followed by 18 weeks of open-label HCQ treatment at 400 mg/day. Patients were repeatedly evaluated for treatment efficacy and toxicity. Blood samples were available from 123 patients for analysis of HCQ, desethylhydroxychloroquine (DHCQ), desethylchloroquine (DCQ), and bisdesethylchloroquine (BDCQ) levels using highperformance liquid chromatography. Achievement of the modified Paulus 20% improvement criteria for response in RA was used as the primary efficacy parameter. Spontaneously reported adverse events were categorized and analyzed as toxicity outcome variables. The relationship between response (efficacy and toxicity) and drug levels was evaluated using logistic regression analysis.Results. The subset of patients with blood concentration data was equivalent to the larger study population in all demographic and outcome characteristics. The mean HCQ, DHCQ, and DCQ elimination halflives were 123, 161, and 180 hours, respectively. There was a positive correlation between the Paulus 20% improvement criteria response and blood DHCQ concentrations during weeks 1-6 (P < 0.001). A potential relationship between ocular adverse events and BDCQ levels was found (P ؍ 0.036). Logistic regression analysis of adverse events data showed that adverse gastrointestinal events were associated with higher HCQ levels (P ؍ 0.001-0.021) during weeks 1, 2, and 3.
Objective. To investigate the usefulness of hydroxychloroquine (HCQ) dose-loading to increase the percentage of responders or rate of response in treating rheumatoid arthritis (RA).Methods. Two hundred twelve patients with early RA (mean duration 1.5 years) were enrolled in a 24-week trial. Patients were stabilized with 1,000 mg naproxen/ day and then began a 6-week, double-blind trial comparing treatment with HCQ at 400 mg/day (n ؍ ؍ ؍ 71), 800 mg/day (n ؍ ؍ ؍ 71), and 1,200 mg/day (n ؍ ؍ ؍ 66), followed by 18 weeks of open-label HCQ treatment at 400 mg/day.Results. All patients had mild, active disease at the time of initiation of HCQ treatment (31-43% rheumatoid factor positive; no previous disease-modifying antirheumatic drugs; mean swollen joint count 8.6-10.4). Based on the Paulus criteria, response during the 6-week double-blind portion of the study was 47.9%, 57.7%, and 63.6% in the 400 mg/day, 800 mg/day, and 1,200 mg/day groups, respectively (P ؍ ؍ ؍ 0.052). Discontinuations for adverse events were dose related (3 in the 400 mg/day group, 5 in the 800 mg/day group, 6 in the 1,200 mg/day group). Most involved the gastrointestinal (GI) system, with the background naproxen treatment possibly contributing. Ocular abnormalities occurred in 17 of 212 patients (8%) but were not dose related.Conclusion. Dose-loading with HCQ increased the degree of response at 6 weeks in this group of patients with early, predominantly seronegative RA. Adverse GI events were dose related, while adverse ocular events were not.
In a multicenter, randomized, double-blind, parallel trial, the efficacy and tolerability of two regimens of naproxen sodium were compared in a two-day treatment of moderate to severe pain following open surgery of the hip, shoulder, knee, and ankle joints. Of 147 patients enrolled, the data of 99 were valid for efficacy analysis, 45 in the low-dose regimen (day 1, 1,100 mg; day 2,825 mg) and 54 in the highdose regimen (1,650 mg/day). At 12 interviews each day, patients evaluated intensity of pain using numerical scales and recorded complaints. At the end of the study, overall efficacy was evaluated. Although there were no statistically significant differences between the two regimens for efficacy or tolerability, the highdose regimen achieved greater pain relief in patients who had hip or shoulder surgery, suggesting that this regimen had greater cumulative efficacy for these patients.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
customersupport@researchsolutions.com
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
This site is protected by reCAPTCHA and the Google Privacy Policy and Terms of Service apply.
Copyright © 2025 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.