Hydroxychloroquine sulphate in the treatment of rheumatoid arthritis: a double blind comparison of two dose regimens.

Abstract

SUMMARY A controlled, double blind, parallel group, long term study of hydroxychloroquine sulphate in the treatment of rheumatoid arthritis, comparing daily doses of 200 mg and 400 mg, is described. The trial involved 54 patients with moderate disease activity who had not previously received antimalarial drugs. Forty three patients completed the one year treatment. The groups receiving different doses were homogeneous and did not differ in any of the 25 monitored indicators. Both dose regimens were effective, and a significant reduction of disease activity was observed after one year's treatment. Of the nine laboratory and 11 clinical indices of efficacy monitored, no statistically significant differences were reported, but in the group of patients treated with the 400 mg daily dose the number of side effects was three times greater. As there have been no reports of retinopathy with hydroxychloroquine at daily doses of 200 mg the effectiveness of this dose is of practical importance.Hydroxychloroquine sulphate has been used for the treatment of rheumatoid arthritis for more than 30 years. Clinical experience with this drug has been presented in at least 250 publications, thus permitting evaluation of its position in the treatment of rheumatoid arthritis.Hydroxychloroquine is one of the so-called disease modifying drugs (formerly called basic drugs, long term effect drugs, second line antirheumatic drugs) because its ability to suppress rheumatoid arthritis activity has been repeatedly proved in double blind studies against placebo. A decrease of disease activity of at least 30% has been described in up to 63% of patients.'Most studies indicate that hydroxychloroquine is slightly less effective than gold or penicillamine, while its tolerance is substantially better than that of the other two drugs.2 There are reports of combined treatment with hydroxychloroquine and low doses of cytostatic drugs,3 and combinations with gold,4 but the combination of hydroxychloroquine and penicillamine did not produce good results.S The most undesirable complication of hydroxychloroquine treatment is possible damage to the retina. It has been proved beyond any doubt that the incidence of retinopathy during hydroxychloroquine treatment is much lower than with chloroquine in equipotent doses.6 7 The development of retinopathy depends on the dose, especially the daily dose rather than the cumulative dose.8 As the initial stages of retinopathy are fully reversible the risk of severe retinopathy at a daily dose of 400 mg is very low. No retinopathy has been described with daily doses of 200 mg hydroxychloroquine. As the role of the cumulative dose in the incidence of retinopathy6has not yet been fully explained it was necessary to verify the clinical efficacy of hydroxychloroquine in lower doses (200 mg daily), thus allowing long term administration of the drug.The purpose of this study was to compare the efficacy of daily doses of 200 mg and 400 mg hydroxychloroquine in patients with rheumatoid arthritis. Patients and methodsWe carrie...

Therapy and pharmacological properties of hydroxychloroquine and chloroquine in treatment of systemic lupus erythematosus, rheumatoid arthritis and related diseases

“…CQ in combination with the immunosuppressants, dehydro-epiandrosterone and 2-chloro-2 0 -deoxyadenosine, showed additivity in suppressing PHA stimulation, in contrast to combinations of some other immunosuppressants which showed synergistic inhibition (Klinefelter and Achurra 1973). Other studies confirmed the effects of CQ 3 lM on PHA-stimulated tritiated thymidine or deoxyuridine incorporation using salicylate 1 mM (a known inhibitor of lymphocyte proliferation) as a reference standard (Pavelka et al 1989). In view of the latter observation, the earlier comparison by Panayi and co-workers of the effects of treatment with CQ with aspirin and aspirin alone may require revision on the basis of interpreting the potential effects of salicylate from ingested aspirin alone in diminishing lymphocyte proliferation in patients with RA Panayi et al 1973).…”

“…Treatment of RA patients with HCQ (200-400 mg/day) for relatively long periods of time (months/years) has been found to reduce those biomarkers that are regulated by the cytokines IL-1 and IL-6, namely ESR and plasma levels of acute phase reactants and haptoglobin, coincident with improvement of physical signs and disease symptoms (Klinefelter and Achurra 1973;Dixon et al 1981;Pavelka et al 1989). Furthermore, plasma IgG concentrations were increased while the IgM decreased after 1 year's treatment with HCQ 200 or 400 mg/day (Kalmanson and Guze 1963).…”

High-yielding continuous-flow synthesis of antimalarial drug hydroxychloroquine

“…Additionally, hydroxychloroquine ( 1 , HCQ) is an effective non-steroidal drug with anti-inflammatory activity for the treatment of rheumatoid arthritis (RA) in patients with cardiovascular disease [ 7 – 9 ]. The World Health Organization has identified HCQ ( 1 ) as an essential antimalarial medication for a basic healthcare system, but global access to HCQ ( 1 ) has been hindered by high manufacturing costs of the API.…”

Disease activity and treatment patterns in rheumatoid arthritis in Qatar: Data from the Qatar rheumatoid arthritis registry

“…The efficacy of MTX in the treatment of RA has been demonstrated in observational studies and randomized controlled trials, and established over the long term [7]. Other conventional synthetic DMARDs (csDMARDs), including hydroxychloroquine [8], sulfasalazine [9], and leflunamide [10] have also been successfully used in RA patients and remain important therapies [5]. However, because MTX is the most extensively studied drug it is usually used as a first line unless contraindicated [6].…”