Chloroquine in Rheumatoid Arthritis: A Double Blindfold Trial of Treatment for One Year
Authors: A. Freedman, V. L. Steinberg
Journal: Annals of the Rheumatic Diseases (1960)

Since the preliminary report on the use of mepa- crine in the treatment of rheumatoid arthritis (Freedman and Bach, 1952), there has been a gradual appreciation of the value of 4-amino quinolone compounds for this condition.Many papers have appeared (Forestier and Certonciny, 1954;Scherbel, Schuchter, and Harrison, 1957;Erlendsson, 1958;Fuld and Horwich, 1958), but controlled trials have been few.The first (Freed- man, 1956) dealt with 66 patients each observed for a period of 16 weeks.The finding that the chloroquine-treated patients did better than the controls was confirmed by trials undertaken by Rinehart, Rosenbaum, and Hopkins (1957), Cohen andCalkins (1958), andKuipers (1959), in none of which was the period of comparison longer than 26 weeks.Bagnall (1957), convinced of the value of these drugs, abandoned his intention to conduct a controlled trial and published his findings of 4 years' treatment of patients, the longest series yet reported.With one equivocal exception (La Tona and Norcross, 1959), there has been widespread approbation by all authors for these compounds.The present report deals with observations in a double blindfold trial begun in 1956 in a group of patients each of whom was treated for a period of one year. MethodSubjects.-Patients were drawn from those attending the Department of Physical Medicine at the London Hospital, those under the care of one of us at Hackney Hospital, and those from the Department of Physical Medicine at Chase Farm Hospital, Enfield.Diagnostic Criteria.-Patientswith rheumatoid type of arthritis with active inflammation of at least four joints and a raised erythrocyte sedimentation rate were admitted irrespective of the duration of the disease or the result of the sheep-cell agglutination test.These patients all satisfied the criteria as having definite rheumatoid arthritis according to the classification of the American Rheumatism Association (Ropes, Bennett, Cobb, Jacox, and Jessar, 1957).Patients ill enough to be admitted to hospital were not accepted into the trial, and anyone within the trial was withdrawn if the condition so deteriorated as to warrant admission to hospital.Treatment.-During the trial period all patients received eight 5-gr.tablets of enteric-coated aspirin daily, and if they were anaemic oral iron was also pres- cribed.The patients also received either chloroquine or dummy tablets of identical appearance, the physician not knowing which kind the patient was having throughout the trial.These tablets were prescribed according to the serial number given to the patient as each was admitted into the trial.A list of these numbers divided randomly into two groups, P and Q, was held by the pharmacist, who dispensed either P or Q tablets according to the serial number.The dispenser did not know which was the active preparation.Those patients who were receiving the active preparation were in fact taking chloroquine sulphate 200 mg.twice daily.In a few cases in both groups side-effects occurred; these were considered to be toxic effects and a reduction of dosage to one and a half tablets daily was made.Appropriate splinting and physiotherapy were also prescribed.Assessment.-The patients were examined by one of us at a special clinic held for this purpose on a separate afternoon.At each visit they were asked specific questions concerning their symptoms and their need for analgesics other than those routinely prescribed, and about any change in their self-care and ability to work.Special note was made of their colour, and the presence of oedema, nodules, lymph-glands, and rashes.The temporo-mandibular, clavicular, and manubrial joints and the spine as well as the limb joints were separately examined.Joint tenderness was graded 1, II, or III (I representing tenderness, II wincing, and III withdrawal of the affected 243 copyright.