Chloroquine and Rheumatoid Arthritis: A Short-Term Controlled Trial

Freedman, Allan P.

doi:10.1136/ard.15.3.251

Cited by 66 publications

(26 citation statements)

References 5 publications

(3 reference statements)

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“…Assessments were also made at 4, 8, 16 and 20 weeks and on each visit patients were questioned specifically about toxic effects. The following methods of assessment were used: 1 6. Grip strength in mm./Hg, the mean of six grips (three in each hand).…”

Section: Methods Of Assessmentmentioning

confidence: 99%

Hydroxychloroquine sulfate (“Plaquenil”) in treatment of rheumatoid arthritis

Hamilton¹,

Scott²

1962

Arthritis & Rheumatism

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A controlled therapeutic trial in 41 patients comparing hydroxychloroquine (Plaquenil) and a placebo tablet showed a small but statistically significant difference in favor of hydroxychloroquine with regard to the number of analgesic tablets which the patients found it necessary to take in addition to the drug. Less significant differences, but still in favor of hydroxychloroquine, were found with various other methods of assessment. No serious toxic effects were encountered.

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Section: Methods Of Assessmentmentioning

confidence: 99%

Hydroxychloroquine sulfate (“Plaquenil”) in treatment of rheumatoid arthritis

Hamilton¹,

Scott²

1962

Arthritis & Rheumatism

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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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“…Antimalarial drugs have been used in the treatment of rheumatic diseases, particularly rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE), since 18941 and hydroxychloroquine since at least 1956.2 Hydroxychloroquine is generally regarded as a safe, if relatively weak, member of the family of slow acting antirheumatic drugs.7 Short term studies of the use of antimalarial drugs since the 1950s have suggested clinical benefits associated with these,8 9 and longer term prospective studies, of up to one year, continue to be published.'" Prolonged continuous use of slow acting antirheumatic drugs is increasingly recommended in patients with RA," but several studies which address the long term treatment of RA have illustrated that the probability of long term use of many slow acting antirheumatic drugs, including hydroxychloroquine, is low.…”

Section: Continuation Of Long Term Treatment With Hydroxychloroquine mentioning

confidence: 99%