A more active treatment has profound effects on the health status of rheumatoid arthritis (RA) patients: results from a population-based RA register in Malmö, Sweden, 1997-2005.

OBJECTIVE: Population-based studies on the trends and effects of modern antirheumatic treatment are scarce. The aim of this study was to examine trends in treatment, health-related quality of life (HRQL), and disease outcome in a population-based register of patients with rheumatoid arthritis (RA) in Malmö, Sweden. METHODS: A continuously updated population-based RA register was established in the city of Malmö, southern Sweden, in 1997. Self-completed postal questionnaires issued in 1997, 2002, and 2005 were used to collect information on demographics, medication, and health status. Cross-sectional comparisons were made between data from 1997, 2002, and 2005. RESULTS: Between 1997 and 2005, the proportion of patients treated with any disease-modifying anti-rheumatic drug (DMARD) including biologics increased substantially (from 52% to 87%), as well as the proportion treated with methotrexate (from 23% to 52%) and biologics (almost exclusively tumour necrosis factor inhibitors) (from 0% to 20%). Twelve per cent of RA patients received biologics 5 years from disease onset in 2005. In parallel with changes in treatment, mean Health Assessment Questionnaire (HAQ) scores (1.19 vs. 0.89) and all Short Form 36 (SF-36) subscales improved from 1997 to 2005 (non-overlapping confidence intervals). CONCLUSION: Between 1997 and 2005, there was a substantial increase in the use of DMARDs, which was accompanied by improved mean HAQ and SF-36 scores in cross-sectional comparisons. These results support the concept that more intensive treatment with DMARDs and biologics can have profound effects on the overall health status in RA patients at the population level.

Rheumatoid arthritis: what does it cost and what factors are driving those costs? Results of a survey in a community-derived population in Malmö, Sweden.

OBJECTIVE: We sought to investigate the cost of living with rheumatoid arthritis (RA) and evaluate the influence of both demographics and specific disease characteristics on these costs. METHODS: We used a population-based questionnaire to survey 895 patients living in the city of Malmö, Sweden, during 2002. Data were obtained on direct resource consumption, investments, informal care and work capacity, as well as utility, function and patients' assessment of disease severity and pain. RESULTS: The survey was completed by 613 patients (68%). Their mean age was 66 years, 74% were female and the mean duration of disease was 16.7 years. The total mean annual cost per patient was 108,370 SEK (12,020 EUR). Direct costs represented 41% of that amount and were predominantly for drugs [14% of the participants were receiving treatment with tumour necrosis factor (TNF) blockers], community services and hospitalisation. Function measured with the Health Assessment Questionnaire (HAQ) was the main statistical predictor for all types of costs except sick leave, which was most strongly associated with patients' perception of global health. CONCLUSION: This is the first study in Sweden to include all costs incurred by a group representative of RA in the community. In comparison with previous studies, total costs had increased by more than 40%. Furthermore, direct costs were higher and constituted a great proportion of total costs because of more intensive treatments (i.e. the use of TNF blockers). Future comparisons will enable health economic evaluations on a community level.

Trends in medication and health-related quality of life in a population-based rheumatoid arthritis register in Malmo, Sweden.

OBJECTIVES: To study trends in treatment, health status and health-related quality of life (HRQL) in two cross-sectional surveys over a 5-yr period and in an observational follow-up sub-cohort based on a population-based rheumatoid arthritis (RA) register in Malmö, Sweden. MATERIAL AND METHODS: A continuously updated population-based RA register was established in Malmö city in southern Sweden in 1997. Patient-administered questionnaires in 1997 and 2002 were used to collect information on demographics, medication and health status. Cross-sectional comparisons were made between 1997 and 2002. A longitudinal analysis was also performed in the RA patients participating in both surveys. RESULTS: Increased proportions of patients were treated with disease-modifying anti-rheumatic drugs (DMARDs) (69 vs 52%), corticosteroids (30 vs 23%), methotrexate (52 vs 29%) and biologics (14 vs 0%) in 2002 compared with 1997. In the cross-sectional analysis, the visual analogue scores (VAS) for pain and general health and the short form 36 (SF-36) domains were slightly better in 2002 than in 1997. In the observational sub-cohort, patients treated with biologics improved significantly in several measures of health status, whereas those starting on methotrexate or undergoing other or no changes in DMARD therapy did not. CONCLUSIONS: In this population-based RA cohort, patients were more actively treated in 2002. Small improvements were seen in health status and these improvements were exclusively attributable to treatment with biologics.

Modelling the effect of function and disease activity on costs and quality of life in rheumatoid arthritis.

OBJECTIVE: When treatments with the potential to change the natural history of a disease are introduced, their longer-term effect on costs and quality of life (utility) has to be estimated using economic models. However, to remain useful tools, models must be updated when new information becomes available. Our earlier models in rheumatoid arthritis (RA) have been based on functional status, but it has recently been shown that disease activity might have an independent effect on utility. The objective of this study was to improve the model by incorporating the effect of a subjective measure of disease severity and activity (global VAS). METHODS: A Markov model was constructed with five states according to functional status (HAQ), and each state was subdivided according to the VAS (<40 and >40). Disease development (transition probabilities between the states) was taken from a longitudinal cohort study of patients with early RA in Sweden. A recent population-based survey of 616 patients with RA provided data on costs and utilities. The model incorporates the full distribution of costs and utilities from the survey, and long-term projections are made using Monte Carlo simulation. RESULTS: The global VAS had a highly significant effect on utilities independently of HAQ. For resource consumption, only HAQ was a significant predictor, with the exception of sick leave, which was correlated with the VAS but not with HAQ. Using the cohort distribution from the longitudinal study, expected mean costs per patient over 10 yr were 106 034 euros (s.d. 5091 euros) (1 euro = SEK 9.20) and the expected number of quality-adjusted life years (QALYs) was 5.08 (s.d. 0.09). Patients starting at HAQ <0.6 but with consistently high VAS scores would have expected costs of 102 830 euros and 4.96 QALYs, while patients with low VAS scores would have costs of 81 603 euros and 6.01 QALYs. CONCLUSION: Our new model incorporates for the first time the effect of a subjective measure of disease severity and activity on both costs and utility, making it a sensitive tool to estimate the cost-effectiveness of disease-modifying treatments. New data on resource consumption indicate a shift to higher direct costs, particularly in early disease, and lower indirect costs in more advanced disease. The large size of the data sets used in this model reduces the uncertainty and makes estimates very stable.

[The Malmo model for private and public rheumatological outpatient care. Cooperation makes it possible to introduce disease modifying treatment quickly]. / Malmömodellen för privat och offentlig reumatologisk öppenvård. Samarbete möjliggör snabbt insatt sjukdomsmodifierande behandling.

The Malmö model represents a close collaboration between private practitioners who receive public financing and hospital-based rheumatological clinics. A comparison of these two types of out-patient care was undertaken by questionnaire in 1997 (70% response rate). Of the total patient cohort in the study, 73% were seen by private rheumatologists. The evaluation showed very similar outcomes, regardless of drug treatment employed or professional personnel involved (i.e., a physician or other members of the rheumatological team). Minor differences concerned easier accessibility to physicians in private practice, and the large proportion of immigrants seen at the hospital clinic. The results of the study confirmed the similarity of care provided in both types of out-patient clinics. Improved pharmacological products for suppressing inflammation will lead to increasing demands on out-patient rheumatological care. The model described illustrates a method of meeting those demands.

Lower disease activity and disability in Swedish patients with rheumatoid arthritis in 1995 compared with 1978.

The aim of this study was to evaluate differences in disease activity, disability, and medical treatment in consecutive patients with rheumatoid arthritis seen at the outpatient clinics in Malmö, in 1978 (n = 148) and 1995 (n = 164). The groups were similar with regard to age, gender, disease duration, and the proportion having had hip or knee replacement surgery. The patients in 1995 had lower values for CRP (p<0.001), Ritchie Articular Index (mean values: 5.5 vs. 9.9, p<0.001), and Steinbrocker functional class index (mean values: 1.96 vs. 2.16, p<0.001) than the 1978 group. The 1995 patient group was also more extensively treated with DMARD:s (68 vs. 51%, p<0.01) and glucocorticosteroids (23 vs. 12%, p<0.02) and had historically been treated with almost twice as many DMARD:s (2.7 vs. 1.5, p<0.001). Similar findings regarding disease activity and disability were made when restricting the analysis to subgroups of patients that were seropositive or had a shorter disease duration (< 5 yrs). The lower disease severity in the 1995 group may be secondary to a more active medical treatment, although other possibilities such as differences in selection and secular changes in disease severity unrelated to medication cannot be excluded.

Polymyositis associated with asymptomatic primary biliary cirrhosis.

We here describe a case of polymyositis associated with asymptomatic primary biliary cirrhosis and a high titer of antimitochondrial antibodies. The patient had remarkable multiorgan engagement: polyarthritis, pericarditis, pleuritis and tachyarrythmia. Atypical changes, suggestive of mitochondrial damage, were observed in a muscle biopsy specimen. Under treatment with azathioprine and steroids, the disease had a favourable outcome.

A problem-based education program for patients with rheumatoid arthritis: evaluation after three and twelve months.

OBJECTIVE: To develop and evaluate the effect of a new arthritis education program based on a previous study. METHODS: One hundred individuals with established rheumatoid arthritis randomized to an intervention group or a control group completed self-report questionnaires. RESULTS: Three months after the education program the patients in the intervention group had increased their knowledge about their disease. They reported increased practice of exercise and joint protection and reduction of disability and pain. After 12 months, increased knowledge and practice of joint protection was maintained. However, there was no longer any difference between the intervention group and the control group regarding reported pain, disability, and practice of exercise. At both intervals the individuals in the intervention group reported an increased ability to handle their pain and a reduction of problems with their disease. The control group remained stable except for a slight increase in pain. CONCLUSION: A structured patient education program had positive impact for 3 months, and some improvements were maintained for 12 months. We suggest that patient education should become an integrated part of the total management of rheumatoid arthritis.

Contact allergy to gold and gold therapy in patients with rheumatoid arthritis.

Patients with rheumatoid arthritis were investigated for contact allergy to gold in connection with treatment with gold preparations. There were 57 patients with rheumatoid arthritis previously treated with gold, with or without cutaneous side-effects, as well as 20 patients intended for such treatment; all were exposed to patch and intradermal tests with gold sodium thiosulfate, gold sodium thiomalate and auranofin. Contact allergy to gold was demonstrated in 8 out of 77 patients (10.4%). In the retrospective material, gold allergy was found in 1.8%, in the prospective material in 35.0%. Contact allergy to gold is very frequent among patients with rheumatoid arthritis before gold therapy. In order to avoid early hypersensitivity reactions skin tests should be carried out before gold therapy is instituted.

Availability of iron and degree of inflammation modifies the response to recombinant human erythropoietin when treating anemia of chronic disease in patients with rheumatoid arthritis.

Forty-six patients with rheumatoid arthritis (RA) and documented anemia of chronic disease (Hb < 100/110 g/l) were randomized to receive either human recombinant erythropoietin (r-HuEPO, n = 36, 300 U/kg body weight) or placebo (n = 10) for 12 weeks in a multicenter study. An adequate response was defined as elevation of Hb > or = 120 g/l. Relevant clinical and laboratory assessments were made to evaluate efficacy and secure safety. A significant elevation in Hb from week 10 onwards was noted in twenty-six patients (five drop-outs) out of nine patients receiving placebo (one drop-out) (12 +/- 1.2 g/l vs 4 +/- 0.5 g/l; Hb elevation from 95 g/l to 107 g/l vs 93 g/l to 97 g/l, P < 0.05). Only 14.6%, however, were considered responders according to preset criteria. In the responders a lower initial CRP, a significant reduction in ESR but not in CRP was seen compared to the remaining r-HuEPO group. A significant elevation of energy level was noted in the r-HuEPO group; otherwise, no differences in clinical variables were seen. No serious adverse effects were noted. When analyzing patients receiving oral iron in combination with r-HuEPO and adding five additional, openly selected patients receiving both adequate iron supplementation and r-HuEPO, there was a significant weekly elevation of Hb from week 8 onwards in favor of combination therapy over the ones only receiving r-HuEPO (18 +/- 1.1 g/l vs 7 +/- 1.1 g/l, P < 0.05). The initial six responders had now reached ten of whom seven belonged to the combination therapy group. Response to r-HuEPO in RA patients appears to be dependent on availability of iron and on the degree of inflammation. If r-HuEPO treatment is considered, iron deficiency should always be corrected and strenuous efforts should have been made to control the disease itself.

A 5-year follow-up of a controlled trial of an arthritis education programme.

A 5-yr follow-up of an arthritis education programme is reported. After adjustment for those lost, deceased or moved away, the 5-yr response rate was 75% among intervention subjects and 78% among controls. Individuals who participated in the education programme maintained their increased knowledge in some aspects. The relative difference in pain and disability over 5 yr was greater in the control group. Most individuals were less active at practising exercise after 5 yr. Improvement in performing exercise and joint protection shown at 12-months follow-up did not persist. Additional questions after 5 yr showed that participants in the education programme had significantly more contact with rheumatologists, physiotherapists and occupational therapists. The participants developed an increased internal sense of control of the disease between 12 months and 5 yr. There was also a significant reduction in reported problems with their disease after 12 months, maintained after 5 yr. This may indicate that patient education contributes to the patient's feeling of responsibility for, and ability to cope with, their diseases.

Learned helplessness and its correlation to impairment, pain, anxiety and depression in rheumatoid arthritis.

A Swedish version of the self-report instrument Arthritis Helplessness Index (AHI) is presented. Validity and reliability of the translation has been analyzed. 100 consecutive patients with rheumatoid arthritis (RA) were studied, 78 of which completed 2 self-administered questionnaires with AHI, impairment, pain, anxiety and depression. Furthermore 20 of the patients were interviewed with regard to AHI. Forty-two other patients with RA were analyzed for correlation between AHI and biochemical activity and Signals of Functional Impairment (SOFI). We conclude that the Swedish version of AHI has satisfactory validity and reliability. It correlates with age, physical impairment, pain, anxiety and depression but not with sex or disease activity. Five of the original 15 items could for various reasons be omitted, leaving a 10 statement instrument. AHI is promising as a variable in future outcome studies of RA.

A controlled evaluation of arthritis education.

The benefits of patient education for those with chronic arthritis are well documented. Informed patients should practice self care more often, and may show reduced disability from their disease. An important question relates to maintenance of the knowledge and skills acquired in educational programmes. This prospective study evaluated an education programme for people with rheumatoid arthritis (RA) and osteoarthritis (OA). The intervention group participated in a comprehensively planned six session behaviourally based programme. A questionnaire was given to 100 patients and 95 matched but non-random controls before the programme, 1 month later, and at 3 and 12 months. The intervention group demonstrated improvements in knowledge, self-reported health behaviour and disability scores at 12 months, compared to the controls. No differences were reported in symptoms, compliance with therapy, pain perception, and locus of control.

Plasma salicylate levels in rheumatoid arthritis: a comparison between micro-encapsulated and conventional aspirin.

Ten patients with rheumatoid arthritis were given identical amounts of conventional aspirin (Magnecyl) tablets and micro-encapsulated aspirin (Reumyl) capsules. Steady-state salicylate levels were determined after 4 days' treatment at 8 a.m., 12 noon, 4 p.m., 10 p.m. and again at 8 a.m. No difference was noted between the levels at 12 noon or 4 p.m. The 10 p.m. levels were slightly though not significantly higher and the last set of 8 a.m. levels were significantly higher during the capsule administration. A criterion for inclusion was good tolerance of Magnecyl. The clinical effectiveness was not evaluated, but the observed good absorption features of Reumyl indicate that this preparation may prove to be of value in long-term treatment.

A comparison of ketoprofen and naproxen in rheumatoid arthritis.

Ketoprofen, 50+50+100 mg, was compared to naproxen, 250+250+250 mg, in a double-blind, cross-over twice 4-weeks' study on patients with RA. There was no significant difference in the effect on morning stiffness, pain at rest, joint count, grip strength or ESR. Among 28 patients 10 preferred ketoprofen and 7 naproxen. Two ketoprofen and 1 naproxen periods were interrupted owing to intolerable side-effects. Twenty of the patients experienced some side-effect from at least one drug. The most common complaints were gastrointestinal, seen in 12 patients on ketoprofen and 9 on naproxen. Most side-effects were mild. No abnormality in blood morphology, liver function tests, serum creatinine or fasting blood glucose was observed. No occult bleeding was detected on routine stool examination.

Endothelial and bile canalicular alkaline phosphatase in human liver and serum.

The alkaline phosphatase in homogenates of human liver was separated into two components by the addition of Triton X-100 to an agarose gel electrophoretic system. One of these components migrated at a rate identical to that of the original one and similar to alpha2-macroglobulin. The other component migrated more slowly, at a rate that resembled that of beta1-transferrin. Human serum samples regularly contained an identical fast-migrating fraction, whereas an identical slowly migrating fraction only appeared in serum obtained from patients with various diseases, especially from patients with malignant tumours, even though the liver did not contain tumour metastases. Slow isoenzyme was found in a few sera that had alkaline phosphatase activity within the normal range. Histochemical examinations of liver tissue from patients whose serum contained the slowly migrating isoenzyme showed a pronounced reaction of alkaline phosphatase in the bile canaliculi, and this isoenzyme seems to arise from the canaliculi. The fast-migrating isoenzyme might arise from the endothelial cells of the liver, to which the activity is usually confined in histochemical stainings.