Report on chloroquine and dapsone in the treatment of rheumatoid arthritis: a 6-month comparative study.

Fowler, P. D.; Shadforth, M F; Crook, P. R.; Lawton, Angela

doi:10.1136/ard.43.2.200

Cited by 26 publications

(24 citation statements)

References 7 publications

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“…Nevertheless they both appear to produce significant clinical improvement in rheumatoid patients [19,20,21,22,28]. High doses of dapsone (100-150 mg/kg) failed to have any therapeutic effect on adjuvant arthritis in rats [29]; some activity was observed with a prophylactic schedule but this may have been due to gross toxicity of the compound.…”

Section: Discussionmentioning

confidence: 95%

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Pharmacological studies of antigen-induced arthritis in BALB/c mice II. The effects of second-line antirheumatic drugs and cytotoxic agents on the histopathological changes

1986

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The effects of treatment with second-line antirheumatic drugs and cytotoxic agents on the severity of experimental monoarticular arthritis in BALB/c mice have been investigated. The arthritis was assessed histologically in terms of synovitis and erosions of cartilage and bone. Azathioprine (20 mg/kg) and sulphasalazine (10-30 mg/kg oral; 30-100 mg/kg i.p.) produced significant suppression of synovitis and erosions when administered daily for 4 weeks commencing 2 weeks after induction of the arthritis. Dapsone (1-10 mg/kg) and to a lesser extent methotrexate (2 mg/kg) produced some suppression of erosive disease when administered daily for 4 weeks commencing 2 weeks after induction of the arthritis but this failed to reach statistical significance. Chloroquine, D-penicillamine and sodium aurothiomalate all failed to have any effect on the disease with any of the treatment schedules used. Auranofin had no effect on the disease when treatment commenced 2 weeks after intra-articular injection but produced variable suppression at high doses when administered from the day of intra-articular injection.

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Section: Discussionmentioning

confidence: 95%

“…In addition, we have investigated the activity of the orally active gold compound auranofin and two drugs which are being used increasingly for the treatment of rheumatoid arthritis, namely dapsone and sulphasalazine [19,20,21,22]. Two cytotoxic agents, azathioprine and methotrexate, have also been examined.…”

Section: Introductionmentioning

confidence: 99%

Pharmacological studies of antigen-induced arthritis in BALB/c mice II. The effects of second-line antirheumatic drugs and cytotoxic agents on the histopathological changes

1986

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“…While elevation of liver enzyme levels accounted for no dropouts in 5 of the 7 trials we used (16)(17)(18)(19)(20) and accounted for only 1 dropout in one other trial (21), it was an important cause of dropout in the trial conducted by the CSSRD group (22). In that trial, liver enzyme elevations that were greater than twice the normal level dictated a patient's withdrawal from the study; this occurred in 18 of the 95 patients randomized to receive MTX.…”

Section: Discussionmentioning

confidence: 99%

The comparative efficacy and toxicity of second‐line drugs in rheumatoid arthritis results of two metaanalyses

Felson¹,

Anderson²,

Meenan³

1990

Arthritis & Rheumatism

444

179

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We performed 2 metaanalyses of placebocontrolled and comparative clinical trials to examine the relative efficacy and toxicity of methotrexate (MTX), injectable gold, D-penicillamine (DP), sulfasalazine (SSZ), auranofin (AUR), and antimalarial drugs, the second-line drugs most commonly used to treat rheumatoid arthritis (RA). For the efficacy study, we applied a set of inclusion criteria and focused on trials which provided information on tender joint count, erythrocyte sedimentation rate, or grip strength. We found 66 clinical trials that contained 117 treatment groups of interest, and for each drug, we combined the treatment groups. For each outcome, results showed that AUR tended to be weaker than other second-line drugs. The results of the 3 outcome measures were synthesized into a composite measure of outcomes, and AUR was significantly weaker than MTX (P = 0.006), injectable gold (P < O.OOOl), DP (P < O.OOOl), and SSZ (P = 0.009) and was slightly, but not significantly, weaker than antimalarial agents (P = 0.11). We also found heterogeneity among antimalarial agents, in that patients treated with Submitted for publication January 3, 1990; accepted in revised form April 11, 1990. chloroquine did better than those treated with hydroxychloroquine. We found little difference in efficacy between MTX, injectable gold, DP, and SSZ. A power analysis showed that a trial should contain at least 170 patients per treatment group to successfully differentiate between more effective and less effective (e.g., AUR) second-line drugs. None of the reported interdrug comparative trials we reviewed were this large.For the toxicity study, our inclusion criteria captured RA trials which reported the proportion of patients who discontinued therapy because of drug toxicity and the total proportion who dropped out. We found 71 clinical trials that contained 129 treatment groups. The average proportion who dropped out and the average proportion who dropped out because of drug toxicity were computed for each drug. Overall, 30.2% of the patients in these trials dropped out; 50% of them did so because of drug toxicity. Injectable gold had higher toxicity rates (P < 0.05) and higher total dropout rates (P < 0.01) than any other drug; 30% of goldtreated patients dropped out because of side effects versus 15% of all trial patients. Antimalarial drugs and AUR had relatively low rates of toxicity; the rate for MTX was imprecise because of discrepancies between trials. Thus, of the commonly used second-line drugs, AUR is the weakest, and injectable gold is the most toxic. Agents introduced in the future will be compared with these drugs. If a curative drug is not found, large multicenter trials or data synthesis from multiple drug trials may be necessary to identify new treatment regimens that have promise.

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“…A number of studies have indicated the beneficial effects of antimalarials in rheumatoid arthritis 25–31 . Despite a low incidence of toxicity, 7,32 the long‐term drug survival rates have been low with anti‐malarials.…”

Section: Discussionmentioning

confidence: 99%

“…In several studies, chloroquine was found to be more effective than hydroxychloroquine 32,34 . Indeed, efficacy of chloroquine had been demonstrated in a few studies 27,29–31,35–40 . In one of these studies, chloroquine was found to be as effective as cyclosporin A 29 .…”

Section: Discussionmentioning

confidence: 99%

Methotrexate versus chloroquine in the treatment of rheumatoid arthritis

Alam

Haq

Majumder

et al. 2003

APLAR Journal of Rheumatology

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Aims: The cost of treatment and monitoring of rheumatoid arthritis patients with more effective disease‐modifying drugs like methotrexate and sulphasalazine is prohibitive. This open random clinical trial was carried out with a view to assessing the status of chloroquine, the cheapest disease‐modifying drug, in the treatment of rheumatoid arthritis. Method: A total of 47 cases were included in the study. Thirty subjects were randomly assigned to methotrexate and 14 to chloroquine groups. During 6 months follow‐up, five cases (three in chloroquine and two in methotrexate) dropped out because of side‐effects and inefficacy. Out of the remaining 42, 35 were female and five were male, with a mean age of 46.05 ± 14.12 years. Mean duration of the disease at the time of presentation was 5.53 ± 6.33 years. The two groups did not differ significantly in baseline demographics and disease activity variables. Results: In both groups, most indices showed significant decrease in the disease activity. The difference in decreases in swollen joint count, tender joint count, joint swelling index and duration of morning stiffness were higher in the methotrexate compared to the chloroquine group. Inter‐group differences in the magnitudes of decreases were insignificant in other variables. At the end of 6 months, the response rate, according to the WHO/ILAR criteria, were 75% and 64% in methotrexate and chloroquine groups, respectively. The difference was not significant. Anorexia and nausea were the most common side‐effects in both groups and subsided with the passage of time despite continuation of therapy. Conclusion: Considering low cost and a lesser need for close monitoring, chloroquine may be considered a choice in rheumatoid arthritis patients with mild disease and who are from underprivileged communities.

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Report on chloroquine and dapsone in the treatment of rheumatoid arthritis: a 6-month comparative study.

Cited by 26 publications

References 7 publications

Pharmacological studies of antigen-induced arthritis in BALB/c mice II. The effects of second-line antirheumatic drugs and cytotoxic agents on the histopathological changes

Pharmacological studies of antigen-induced arthritis in BALB/c mice II. The effects of second-line antirheumatic drugs and cytotoxic agents on the histopathological changes

The comparative efficacy and toxicity of second‐line drugs in rheumatoid arthritis results of two metaanalyses

Methotrexate versus chloroquine in the treatment of rheumatoid arthritis

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