Patients and methods

Over a period of five years all consecutive patients with active RA, admitted to the rheumatology ward of the University Medical Center, Utrecht, to undergo CPT to bridge the lag time of a newly started DMARD, were included in this study after informed consent. If a patient was admitted more than once for CPT in this period of five years, only the first admission was used. None of the 66 patients receiving CPT (CPT group) refused to participate. Active disease was defined as the presence of at least two of the following three criteria: Thompson joint score >10,9 erythrocyte sedimentation rate (ESR) ⩾28 mm/1st h, and early morning stiffness ⩾1 hour. Each CPT regimen comprised three doses of 200 mg dexamethasone (each dose 1000 mg methylprednisolone equivalent), given through an intravenous infusion on alternate days over a five day period.

At admission and 1–2 days before discharge from the hospital, the following variables were assessed: ESR, C reactive protein level (CRP), haemoglobin concentration, platelet count, duration of early morning stiffness, the joint score according to Thompson, and grip strength (assessed in kPa, Martin vigorimeter). In addition, the IRGL questionnaire (Impact of Rheumatic diseases on General health and Lifestyle) was administered. The IRGL is a health status questionnaire, developed from the Arthritis Impact Measurement Scales 1 (AIMS1), assessing physical, psychological, and social functioning as well as the impact of the disease on daily life.10 The scales of the IRGL differ in their individual ranges and are expressed in the original direction—for example, high values on the scale pain, and low values on the scales mobility and self care indicate a poor health status. Side effects, including psychosis or depression, were recorded by the doctor at clinical observation.

To put the (short term) effects and effect sizes of CPT in perspective we compared them with the (long term) effects and effect sizes of DMARD treatment in a historical contrast group of 181 outpatients with recent onset RA, evaluated at the start and after one year of treatment with a DMARD (starting with hydroxychloroquine, 400 mg/day or aurothioglucose, 50 mg/week or oral methotrexate, 7.5–15 mg/week).11 The two groups cannot be compared directly, obviously, because the selection criteria and the periods between assessments differ. In the DMARD contrast group, the same variables as in the CPT group were assessed.

Results

The mean ages (SD) in the CPT group and DMARD contrast group were 58 (13) and 57 (14) years, respectively; duration of RA in the CPT group was 12 (10) years. The mean duration (SD) of admission for the CPT group was 1.3 (1.0) weeks and the median time period between assessments eight days; 66% of the patients in this group had used three or more DMARDs at the time of admission.

Table 1 shows the means (SD) of the variable measures at the start and second assessment in both groups, together with the corresponding ES. Variables of disease activity and psychological wellbeing, in general, show a large ES and those reflecting functional ability a moderate ES. Figure 1 shows the percentages of patients in the CPT group with deterioration, no clinically relevant change, or improvement from baseline for each individual variable. More than 50% of patients improved by 33% or more in ESR, CRP, early morning stiffness, grip strength, pain, depressed mood, and cheerful mood. For the other variables, >50% of the patients showed no clinically relevant change. In seven patients their depressed mood deteriorated; however, the mean score before treatment for these patients was 1 (range 0–3) and the mean score after treatment 4 (range 2–7) on a scale ranging from 0 (no depression) to 24 (severe depression). These deteriorations thus were small changes in the lower, non-depressive range of the scale. Clinical observation in the CPT group disclosed in many patients a sense of euphoria after treatment, but no cases of psychosis or depression. Common short term complications of CPT encountered were increase in blood pressure, hyperglycaemia, and facial flushing, as reported earlier.3

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Figure 1

Percentages of patients with deterioration, no change, or improvement for each variable CPT group (n=66), stacked bars. Improvement on platelets is a decrease in count.

In the CPT group the percentage of patients with a clinically relevant overall response to treatment (individual patient's improvement) was 53; in the DMARD contrast group the percentage was exactly the same.

Discussion

This study aimed at qualitatively and quantitatively analysing the short term effect of CPT on health status among patients with active RA; the results may be relevant also for treatment strategies with high dose oral CT.2 After CPT, clinically relevant changes are found for the same variables that show clinically relevant changes with DMARD treatment in three domains of health status: disease activity, physical functioning, and psychological wellbeing. In the CPT group the percentage of patients with a clinically relevant overall response to treatment was the same as in the DMARD contrast group.

In the CPT group, the IRGL showed enhanced psychological wellbeing, and clinical observation disclosed no depression or psychosis. So depression and psychosis do not seem to be common short term side effects of CPT in patients with active established RA. Psychological side effects generally begin during the first weeks after the start of treatment6 ,8; however, our results do not rule out the possibility of psychological disturbances later on. The incidence of depression and psychosis due to CPT in patients with active RA who improve within days may be different from the (high) incidence of psychological disorders in patients with other diseases—for example, in patients with nephritis, in whom no short term beneficial effects occur, or in whom short term negative effects of corticosteroids may even predominate, or in patients, in whom psychological disturbances may be part of the disease—for example, systemic lupus erythematosus.