E Tsakonas

McGill University, Montréal, Quebec, Canada

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Publications (3)10.39 Total impact

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    ABSTRACT: To assess the longterm effect of delaying therapy with second-line agents in patients with early rheumatoid arthritis (RA). One hundred nineteen patients who participated in a 9 month placebo controlled randomized trial of hydroxychloroquine sulfate (HCQ) were followed prospectively for an additional 3 years. Those randomized to HCQ are referred to as the early treatment group and those randomized to placebo as the delayed treatment group. Participants were assessed annually for pain [Arthritis Impact Measurement Scales (AIMS) and Stanford Health Assessment Questionnaire (HAQ)], physical disability (AIMS and HAQ), and the RA global well being scale (AIMS). Conversion of results into standard deviation (SD) units permitted defining a substantial difference as per Felson as > 0.30 SD units and a clinically indistinguishable difference as < or = 0.06 SD units. One hundred fifteen patients (97%) participated and complete data were available on 104 (87%). Compared to the early treatment group, the delayed group remained worse for both the pain and the physical disability outcomes over the additional 3 year followup. The difference in the RA global well being score became clinically indistinguishable for the early and delayed groups only after the 2 year post-trial assessment. The between-group differences were not explained by post-trial therapy with corticosteroids, other second-line agents, or nonsteroidal antiinflammatory drugs and analgesic preparations. These findings show that a delay in instituting therapy with second-line agents, even a 9 month delay in instituting a moderately powerful second-line agent such as HCQ, has significant effects on longterm patient outcome, and provides strong evidence in support of early therapy in RA.
    No preview · Article · Mar 2000 · The Journal of Rheumatology
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    ABSTRACT: The ability of antimalarials to moderate severe disease activity in systemic lupus erythematosus (SLE) is plausible but undemonstrated. We evaluated the long-term effectiveness of maintaining treatment with hydroxychloroquine sulphate (HCQ) to prevent major flares in quiescent SLE. Forty-seven patients with quiescent SLE who had been randomized to take HCQ (n = 25) or placebo (n = 22) as part of a 24-week withdrawal trial were evaluated for an additional 3 years. The primary outcome was time to a major flare of SLE which resulted in either the institution of or an increase in the current dosage of prednisone of 10 mg/day or more, or institution of therapy with immunosuppressive agents. Secondary outcomes included the specific subtype of these major flares (glomerulonephritis, vasculitis or other) and hospitalization for an exacerbation of SLE. An intent-to-treat analysis was conducted. Over the 42 months of study, 11 of 22 (50%) patients randomized initially to placebo, and seven of 25 (28%) patients randomized to continue treatment experienced a major flare. The relative risk of major flare for those randomized to continue HCQ compared with controls was 0.43 (95% CI: 0.17, 1.12). The relative risks for subtypes of flares were 0.26 (95% CI: 0.03, 2.54) for nephritis, 0.51 (95% CI: 0.09, 3.08) for vasculitis and 0.65 (95% CI: 0.17, 2.41) for flares characterized by other symptoms. The relative risk of hospitalization for major flare for patients randomized to continue hydroxychloroquine was 0.58 (95% CI: 0.13, 2.60). While the results are not statistically significant, they are compatible with the clinical belief that HCQ has a long-term protective effect against major disease flares in SLE and suggest that on average, HCQ use reduces major flares by 57% (95% CI: 83% reduction to 12% increase).
    No preview · Article · Feb 1998 · Lupus
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    ABSTRACT: PURPOSE: Studies of the efficacy of hydroxychloroquine in rheumatoid arthritis have had methodological flaws and have failed to produce definitive results. The benefits and toxicity of hydroxychloroquine sulfate in 120 patients with rheumatoid arthritis of less than 2 years duration are assessed. PATIENTS AND METHODS: A 36-week randomized double-blind, placebo-controlled trial was conducted at two university centers and four community rheumatology private practices. Patients had to have had their disease for less than 2 years and to have never received a second-line drug. Patients were randomly assigned to receive hydroxychloroquine or an equivalent number of placebo tablets in a dose of up to 7 mg/kg per day (maximum 400 mg/day). The initial dose was half the maximum dose and, if after 2 weeks of treatment there had been no side effects, the full dose was prescribed. There were four a priori primary outcomes: (1) a joint index composed of the tender joint count, the swollen joint count, the grip strength, and the duration of morning stiffness; (2) a pain index composed of the pain dimension of the Arthritis Impact measurement Scales (AIMS) and the visual analog pain scale of the Health Assessment Questionnaire (HAQ); (3) a physical function index composed of the HAQ, the physical disability dimension of the AIMS, and the McMaster-Toronto Arthritis Patient Performance Disability Questionnaire; (4) the psychological function subscale of the AIMS. Secondary outcomes included adverse events, patient and physician global assessments, hematocrit, erythrocyte sedimentation rate (ESR) and corticosteroid usage. An intent-to-treat analysis assessed improvement at 36 weeks by Student's t-test and average improvement over the course of the study by analysis of variance for repeated measures. RESULTS: Of 148 eligible patients, 120 were randomized. The characteristics of those randomized to hydroxychloroquine compared to placebo were similar at the study onset. At 36 weeks and over the course of the study there was statistically significant improvement in the joint index (P = 0.004, P = 0.034, respectively), the pain index (P = 0.007, P = 0.001, respectively), and the physical function index (P = 0.020, P = 0.011, respectively) in the group receiving hydroxychloroquine compared to the placebo group. There was no improvement in psychological function for hydroxychloroquine compared to placebo (P = 0.837 at 36 weeks, P = 0.89 over the course of the study). Among the secondary outcomes there was significant improvement only in the patient's (P = 0.01) and the outcome assessor's (P = 0.03) assessment of change and a trend towards a fewer number of intra-articular corticosteroid injections (P = 0.05) in the hydroxychloroquine-treated group. There were no important differences in the side effects between hydroxychloroquine or placebo. CONCLUSION: Over 36 weeks, hydroxychloroquine had a significant benefit on synovitis, pain, and physical disability of recent-onset rheumatoid arthritis, but did not benefit psychological function.
    No preview · Article · Feb 1995 · The American Journal of Medicine