Research on Hydroxychloroquine

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High-Dose Hydroxychloroquine During First 6 Weeks Improves RA Response

Paper: Dose-loading with hydroxycholorquine

improves the rate of

response in early, active rheumatoid arthritis.

Authors: Furst DE, Lindsley H, Baethge B, et al.

Ref: Arthritis Rheum. 1999;42:357-365.

Type: Clinical Study

Summary: Hydroxychloroquine (HCQ) is widely

recognized

as an effective treatment for rheumatoid

arthritis, but its

onset of action is slow, often requiring 3 to

6 months to

become fully effective. Now a new study shows

that

dose-loading during the first 6 weeks of

therapy significantly

improves the response during the early stages

of treatment

and this is maintained during long-term

therapy.

In this 24-week study, 212 patients with early

RA (average

disease duration of 1.5 years) were stabilized

with 1 gm of

naproxen per day. They were then assigned to a

6-week,

double-blind treatment phase with HCQ given

either 400

mg/day, 800 mg/day or 1200 mg/day. This

initial dose-loading

period was then followed by an 18-week

open-label HCQ

treatment period during which HCQ was given at

a dose of

400 mg/day.

The response (based on the us 20%

improvement

criteria) during the first 6 weeks of therapy

improved with

increasing dose of HCQ. The percentage of

patients who

met the response criteria were 48% (800mg

group), 58%

(800 mg group), and 64% (1200 mg group). The

difference

between the high-dose and low-dose group

approached

statistical significance (p=0.052), and the

investigators felt

that this was also indicative of a true

clinical difference. The

effectiveness observed in the 1200 mg group

was maintained

up to week 24, and the effectiveness observed

in the other

two groups " caught up " to that of the 1200 mg

group by the

end of the study. No dose-related ophthalmic

effects were

observed in any group.

As expected, study discontinuations due to

adverse effects

increased with dose; 4% discontinued form the

400 mg

group, 7% from the 800 mg group, and 9% from

the 1200 mg

group. These differences, however, were not

statistically

significant.

These findings indicate that using a high-dose

regimen (1200

mg/day) of hydroxychloroquine during the first

6 weeks of

therapy results in clinically relevant

improvement in a greater

proportion of patients compared to traditional

400 mg/day

dosing. This effect in sustained for up to 24

weeks when a

400mg/day maintenance dose is used.