EXTENDED REPORTS Long term eVectiveness of antimalarial drugs in rheumatic diseases

Objective—The purpose of this study was to compare the long term eVectiveness between chloroquine (CQ) and hydroxychloroquine (HCQ). Methods—Medical charts of all patients seen by eight rheumatologists practising in two tertiary care centres and starting antimalarial treatment between January 1985 and December 1993 were reviewed. Patient characteristics, disease, and treatment information were collected. The main outcome measures were the cause of and the time to the discontinuation of antimalarial drugs resulting from all causes, principally toxicity or ineYcacy, or both. Bivariate analysis including t tests and ÷ tests were used to assess diVerences between means and proportions respectively. Survival curves were evaluated using the Kaplan-Meier method. Multivariate analysis (Cox regression) was used to adjust for potential confounders. Results—After all medical records were reviewed, 1042 eligible cases were identified. From these, 940 (90%) had usable information and they represent the cohort. Five hundred and fifty eight had rheumatoid arthritis, 178 had systemic lupus erythematosus, 127 had palindromic arthritis, and 77 had other diagnoses. Fifty seven per cent of the patients received CQ and 43% HCQ. The proportion of patients with side eVects taking HCQ and CQ was 15% and 28% respectively (p=0.001). Using Cox regression model to adjust for age at the onset of antimalarial treatment, physician diVerences, sex, disease type, disease duration before treatment, and rank selection, there were no diVerences in the hazard ratio (HR) for overall discontinuations between CQ and HCQ. While the HR for discontinuations because of toxicity was lower for HCQ (HR= 0.6, 95% CI 0.4, 0.9), the HR for discontinuations because of ineYcacy was significantly higher for HCQ (HR= 1.4, 95% CI 1.1, 1.9). Conclusions—After adjusting for time and several confounders HCQ was less toxic but less eVective than CQ. Only one case of probable/possible retinopathy was found. Therefore, we propose a careful baseline ophthalmological evaluation by an expert and then one or every two years if proper doses are used. (Ann Rheum Dis 1998;57:582–587) Antimalarial drugs have become one of the most commonly prescribed drugs in the treatment of many rheumatic diseases such as rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), palindromic arthritis (PA), and psoriatic arthritis. This seems to be related mainly to their low toxicity in comparison with the other antirheumatic agents. Chloroquine (CQ) and hydroxychloroquine (HCQ) are the only 4-aminoquinoline derivatives that are used as antirheumatic drugs, and although structural similarities between CQ and HCQ exist, it has been suggested that there are diVerences in eYcacy and in toxicity. In addition, there are considerable diVerences in costs between these two drugs, HCQ being seven times more expensive than CQ, at least in Canada. DiVerences in the prescription patterns for antimalarial drugs among rheumatologists have been reported. 17 18 Long term eVectiveness (eYcacy and toxicity under non-experimental conditions) should be considered when selecting one drug over another. However, most studies reviewing the long term eVectiveness of antimalarial drugs considered both drugs as a single group. Table 1 Patients characteristics Variable AM n (%) CQ n (%) HCQ n (%) p Value* Sex Female 719 (77) 403 (75) 316 (79) NS Male 221 (23) 136 (25) 85 (21) NS Disease duration (y)† mean (SD) 4.1 (6.6) 4.0 (6.5) 4.2 (6.8) NS Age mean (SD)† 47 (15.5) 45.3 (14.8) 49.2 (16.2) <0.0001 Drug CQ 541 (58) — — HCQ 399 (42) — — Disease RA 557 (59) 287 (53) 270 (68) <0.0001 SLE 178 (19) 113 (21) 65 (16) NS PA 128 (14) 91 (17) 37 (9) <0.001 Other 77 (8) 50 (9) 27 (7) NS Rank First 676 (72) 400 (74) 276 (69) <0.05 Other 264 (28) 139 (26) 125 (31) <0.05 Combination 174 (19) 85 (16) 89 (22) <0.01 *CQ v HCQ, †at the onset of AM therapy, NS = not significant. Ann Rheum Dis 1998;57:582–587 582 Division of Rheumatology, Department of Medicine, University of Alberta, Canada