860

BRITISH JOURNAL OF RHEUMATOLOGY VOL. XXXI NO. 12

P. DAVIS, A. JUBY, A. S. RUSSELL

Rheumatic Disease Unit, Department of Medicine, University of Alberta, Edmonton, Alberta, Canada Accepted 11 August 1992 Methotrexate in Older Patients with Rheumatoid Arthritis SIR—Methotrexate has been shown in long-term studies to be effective in rheumatoid arthritis (RA), although toxicity remains a frequent and occasionally serious problem [1]. Two studies report that it is at least as efficacious in patients over 65 as in younger patients, but suggest that there may be an increased withdrawal rate [2] and that there may be an increase in adverse effects, particularly of gastrointestinal and pulmonary toxicity [3]. These studies have small numbers of cases. We examined the case records of all patients aged 60 years and over as at 1 August 1991 who fulfilled the American Rheumatism Association criteria for RA, and who were prescribed methotrexate from the Auckland Hospital pharmacy any time between November 1989 and July 1991. Thirty-three patients were identified. All eligible case records were available. Twenty-three (70%) of these were female and the mean age was 69.5 years (range 60-87 years). The mean duration of disease was 16.8 years (2-48 years). Twenty-six (79%) patients were seropositive. The mean duration of therapy for all the

patients was 22 months (1-56 months). The mean cumulative dose was 740 mg (20-1925 mg), and the usual weekly dose was 7.5 mg (2.5-12.5 mg). In August 1991, 23 (70%) were still taking methotrexate. Of the 10 that had ceased therapy, seven (21%) had adverse effects (including two with neutropaenia and two with symptoms suggestive of pulmonary toxicity). All recovered on cessation of the drug, except one patient who had developed abnormal liver function tests from metastases from a colonic carcinoma that had predated the commencement of methotrexate. The remaining three (9%) had found it inefficacious. The 30% withdrawal rate compares reasonably with long-term prospective data for methotrexate therapy in all-aged rheumatoid patients. Seventy-five per cent of the initial cohort are still taking methotrexate with life table analysis projecting that 63% of the patients would be still taking methotrexate after 6 years [1]. Treatment was discontinued either early (40 months) in four patients. Four patients had a liver biopsy (one pretreatment and three for monitoring with high cumulative doses), but none were thought to indicate methotrexate liver toxicity. The 23 patients still taking methotrexate were telephoned by SY and asked about efficacy and any particular problems with methotrexate. All replied that they had no difficulty remembering to take the weekly drug, but half reported some tolerable adverse reaction. Eighteen (82%) felt it was still effective for their RA. There are many theoretical hazards of methotrexate in the elderly, such as the presence of impaired renal function, coexistent disease, or folate deficiency. Interaction with another drug is more likely because of greater numbers of medications taken by older people and altered pharmacokinetics. Compliance and monitoring are more difficult for the elderly arthritic. However, the benefit of methotrexate in elderly patients may be great, and may in fact be greater in elderly patients than in younger ones [3]. Longer term complications may not be so much of a problem. It has a more rapid onset of action and is slightly easier to monitor than i.m gold, for example [3]. Other disease-modifying agents in RA are oral, usually administered on at least a daily basis. None of our patients had difficulty with a weekly oral dosage regimen. Few studies have addressed the place of treating the older rheumatoid patient, specifically, with methotrexate. This review confirms the efficacy of methotrexate in this patient group, and there did not appear to be any untoward toxicity over what one might expect in a general rheumatoid population. P. POOLE, S. YEOMAN, D. CAUGHEY

Department Rheumatology, Auckland Hospital, New Zealand Accepted 20 August 1992 Correspondence to P. Poole, Wellington Hospital, Private Bag, Wellington South, New Zealand.

1. Weinblatt MG, Maier AL. Long-term experience with low dose weekly methotrexate in rheumatoid arthritis. J Rheumatol 1990;17:(suppl 22)33-«. 2. Dahl SL etal. Second line antirheumatic drugs in the elderly with rheumatoid arthritis: a post hoc analysis of three controlled trials. Pharmacotherapy 1990; 10:79-84. 3. Wolfe F, Cathey MA. The effect of age on methotrexate efficacy and toxicity. J Rhewnatol 1991;18:973-7.

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generally regarded as increasing with severity and duration of disease and particularly with the presence of extraarticular manifestations. Hence the patients reported by Dr Edgar and colleagues probably represents a subset of patients which lies somewhere between our patients with uncomplicated RA and those reported by us with Felty's syndrome. The other possible explanation to account for this difference relates to the standardization of assays for the detection of ANCA. As this is an immunofiuorescent technique a certain degree of subjectivity can be introduced in the reading of ANCA slides. Like Dr Edgar and colleagues, we also recognize three types of staining and in view of the high prevalence of pANCA and atypical cytoplasmic staining in our patients with Felty's syndrome we are not altogether surprised that their patients with severe RA also had a relatively high prevalence of antibodies to neutrophil cytoplasmic antigens. This certainly would account for the 24 patients who had either pANCA or atypical cytoplasmic staining. What is of interest and concern to us is the fact that seven of their 31 patients had cANCA. Our experience and those reported by others have suggested that cANCA has a relatively high degree of specificity for Wegener's granulomatosis which is not true for pANCA, which is found in other connective tissue disease and vasculitidies. These issues clearly require clarification and can only be determined with inter-laboratory standardization and exchange of positive sera between interested groups. This we have been able to achieve with our assay system thanks to exchange of serum between ourselves and colleagues in Canada and Australia. We therefore stick by our conclusion that extreme caution must be taken in the interpretation of ANCA results due to the lack of specificity of pANCA and atypical cytoplasmic staining and that in our experience cANCA is not a feature of patients with rheumatoid disease and retains a relatively high degree of specificity for Wegener's granulomatosis.

Methotrexate in older patients with rheumatoid arthritis.

860 BRITISH JOURNAL OF RHEUMATOLOGY VOL. XXXI NO. 12 P. DAVIS, A. JUBY, A. S. RUSSELL Rheumatic Disease Unit, Department of Medicine, University of...
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