Azathioprine in early rheumatoid arthritis

Abstract

This study compares the effect of azathioprine with those of gold and chloroquine in early (Class 11) rheumatoid arthritis (RA). Thirty-three similar patients with classic or definite R A of less than 5 years duration were randomly entered, 11 into each drug group. Assessment of standard clinical and laboratory measures at 12 and 24 weeks showed significant improvement in all three groups. In genergl, all three drugs were effective antirheumatic agents with low toxicity. However, because of serious potential toxicity, azathioprine could not be recommended over gold and chloroquine in early R A therapy.Both gold and chloroquine are established drugs with proven benefit in the medical management of rheumatoid arthritis (RA) ( 1-5). Recently immunosuppressive agents such as cyclophosphamide and azthioprine have also been demonstrated to be valuable in doubleblind controlled trials (6-9). Most of the latter studies were comprised of patients with severe (functional class 111 and IV) (10) long-standing RA, or those unresponsive to conventional therapy. The present study was undertaken to determine whether azathioprine is beneficial in earlji (class 11) RA and to compare its effect to those of gold and chloroquine. MATERIALS AND METHODSAll patients included in the study conformed to definite or classic R A according to the criteria of the ARA ( 1 I ) . The essential requirements for patient entry into the study were a ) disease duration of less than 5 years, b) n o previous therapy with either azathioprine, gold, and/or chloroquine, c) absence of contraindications to any of these three medications, and d ) informed consent. Patients thus selected were first hospitalized for a 10-day control period in the University of Toronto Rheumatic Diseases Unit (RDU), Wellesley Hospital, where they received a full program of bed rest, physiotherapy, and full-dose salicylates. Two patients on oral steroids were kept at a constant dose. Only those patients who continued to have active disease despite this treatment were accepted for the study.Thirty-three patients were entered into the study and assigned randomly into one of three treatment groups: a) azathioprine 1 .O-2.0 mg/kg/day PO, b) gold thiomalate 50 mg i.m. weekly (after standard test doses), or c) chloroquine 250 mg/day PO at bedtime. A double-blind trial was not attempted because of differences in drug preparation, method of administration, and toxicity.Each patient was admitted to the RDU for re-evaluation a t 12 and 24 weeks after beginning the study. During the initial and follow-up admissions an observer not directly involved in the patient's care took a complete history and

Serum biochemistry in relation to the action of azathioprine in rheumatoid arthritis

“…This was also reflected in part by the non-significant improvement in ESR (Fig. 2), and supports the haematological data from previous comparative studies with o-penicillamine [3] and gold [4]. The non-significant fall in ESR occurred despite highly significant improvement in CRP and plasma viscosity (p < 0.01), a phenomenon also seen during hydroxychloroquine therapy [12].…”

“…Eleven patients were strongly seropositive, but suppression of rheumatoid factor as measured by SCAT only occurred in one patient. This is contrary to a previous report which demonstrated a highly significant improvement in latex titre [4]. In view of the lack of improvement in rheumatoid factor, the increase in serum histidine was perhaps surprising considering the possible relationship between histidine and rheumatoid factor [221.…”

“…The beneficial effects of azathioprine in the treatment of rheumatoid arthritis (RA) have been demonstrated in several controlled clinical studies [1][2][3][4], though toxic effects have restricted its use 151.…”

Controlled trial of hydroxychloroquine and d‐penicillamine singly and in combination in the treatment of rheumatoid arthritis

“…Previous controlled studies also have demonstrated the effectiveness of hydroxychloroquine, although over shorter periods of followup (12)(13)(14). Althuugh hydroxychloroquine does not seem as effective as D-penicillamine in our study, about 50% of patients remain improved over 2 years, and half of those are markedly improved.…”

Bioavailability of hydroxychloroquine tablets in healthy volunteers.

“…The efficacy of hydroxychloroquine is similar to that reported for other disease modifying antirheumatic drugs, with 60-80% of adult rheumatoid arthritics improving with hydroxychloroquine therapy (Mainland & Sutcliffe, 1962;Hamilton & Scott, 1962;Kersley & Palin, 1959;Adams et al, 1983;Dwosh et al, 1977). However, the main reasons for discontinuing therapy differ between the slow acting antirheumatic drugs (Paulus, 1982).…”